Goran Petrovski

• Sharma, Sonali; Alahdab, Gieth; Haque, Muhammad Nazmul; Karkoukli, Ikbal; Assaf, Alee & Ishida, Yuichiro [Vis alle 16 forfattere av denne artikkelen] (2026). Bone morphogenetic protein signaling as a key regulator of retinal fibrosis. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 123(41), s. 1–12. doi: 10.1073/pnas.2603111123. Fulltekst i vitenarkiv
• Holen, Katrine; Karabeg, Mia; Sauesund, Ellen Steffenssen; Fosmark, Dag Sigurd; Dalby, Marius & Petrovski, Beata Eva [Vis alle 7 forfattere av denne artikkelen] (2026). Clinical, Socioeconomic, and Demographic Factors Associated with Diabetic Retinopathy in a Hospital-Based Screening Program: A Cross-Sectional Study in Oslo, Norway. Healthcare. 14(18). doi: 10.3390/healthcare14182929. Fulltekst i vitenarkiv
• Liberski, Sławomir; Skulimowski, Bartosz; Kałużna, Aleksandra; Petrovski, Goran; Cofta, Szczepan & Kocięcki, Jarosław (2026). Ocular surface and anterior segment changes in cystic fibrosis: evidence of a corneal and conjunctival epithelial phenotype - a case-control study. Journal of Cystic Fibrosis. ISSN 1569-1993. 25(5), s. 836–843. doi: 10.1016/j.jcf.2026.04.009. Fulltekst i vitenarkiv
• Haave, Hanna; Petrovski, Beata Eva; Borjan, Ivan; Lumi, Xhevat & Petrovski, Goran (2026). Anatomical and Functional Outcomes of Platelet-Rich Plasma-Assisted Surgery for Full-Thickness Macular Holes: A Retrospective Real-World Cohort Study. Journal of Clinical Medicine. 15(18). doi: 10.3390/jcm15187129.
• Liberski, Sławomir; Skulimowski, Bartosz; Waśniewski, Filip; Kałużna, Aleksandra; Wilk, Zuzanna & Petrovski, Goran [Vis alle 8 forfattere av denne artikkelen] (2026). Retinal microvascular alterations and choroidal changes in cystic fibrosis before and after CFTR modulator therapy. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 61, s. 1–9. doi: 10.1016/j.pdpdt.2026.105615. Fulltekst i vitenarkiv
• Sekáč, David; Muñoz, Georgina Faura; Eikenes, Marte; Josifovska, Natasha; Petrovski, Goran & Ellederová, Zdenka [Vis alle 7 forfattere av denne artikkelen] (2026). Polarized secretion of mitochondrial DNA by retinal pigment epithelial cells. Experimental Eye Research. ISSN 0014-4835. 272. doi: 10.1016/j.exer.2026.111225. Fulltekst i vitenarkiv
• Liberski, Sławomir; Skulimowski, Bartosz; Waśniewski, Filip; Kałużna, Aleksandra; Petrovski, Goran & Cofta, Szczepan [Vis alle 7 forfattere av denne artikkelen] (2026). Deep Optic Nerve Head Structural Alterations in Adults with Cystic Fibrosis. Journal of Clinical Medicine. 15(11), s. 1–12. doi: 10.3390/jcm15114308. Fulltekst i vitenarkiv
• Nicolaissen, Bjørn; Nguyen, Giang Huong; Beraki, Kahsai; Azqueta, Oscoz Amaya; Petrovski, Goran & Moe, Morten Carstens [Vis alle 10 forfattere av denne artikkelen] (2026). DNA Oxidation and Expression of Repair Enzymes in Organ- Cultured Human Limbal Epithelium. International Journal of Molecular Sciences. ISSN 1661-6596. 27(11). doi: 10.3390/ijms27115073. Fulltekst i vitenarkiv
• Muñoz, Georgina Faura; Amar, Marwa Ben; Petrovski, Goran; Muñoz-Berbel, Xavier & Eide, Lars (2026). Machine learning-driven sensor array for predictive detection of glutathione. Microchemical Journal. ISSN 0026-265X. 226. doi: 10.1016/j.microc.2026.118261. Fulltekst i vitenarkiv
• Ruban, Andrii; Prudyus, Vitalyi; Zolnikova, Anna; Petrovski, Beata Eva; Petrovski, Goran & Binder, Susanne [Vis alle 8 forfattere av denne artikkelen] (2026). Characteristics and surgical outcomes of combat blast-related full-thickness traumatic macular holes: insights from war eye trauma in Ukraine. International Journal of Retina and Vitreous (IJRV). 12. doi: 10.1186/s40942-026-00816-3. Fulltekst i vitenarkiv Vis sammendrag

  Background This study analyzes the clinical features and surgical outcomes of combat blast–related traumatic full-thickness macular holes (BRTMH) secondary to war-related ocular trauma in Ukraine, managed at a single civilian center. Methods Thirteen patients (14 eyes) with diagnosis of BRTMH treated with pars plana vitrectomy (PPV) were recruited for this retrospective, consecutive case, interventional study. Surgery outcome-related factors including face-down positioning were assessed and statistically analyzed. Results Blast trauma was the cause of injury in all (100%) of the MH cases, wearing no eye protection. Four eyes (28.6%) with MH were secondary to an open-globe, whereas ten eyes (71.4) were related to a closed-globe injury. MH closure was achieved in all cases (100%) after the primary surgery. The median (IQR) ocular trauma score (OTS) was 68 (56–75), while the time interval from injury to surgery was 41 (19 to 71) days. The median (IQR, interquartile range 25–75%) Minimum Linear Diameters of the MHs (µm) was 682 μm (532–889), while nine out of fourteen eyes (64.3%) had BRTMH > 600 μm. There was a direct correlation of postoperative visual acuity at 1 month with the OTS score (ρ = 0.51, p = 0.03) and preoperative visual acuity (LogMar) (ρ = 0.72, p = 0.002), and an inverse correlation with the size of the MH (ρ = -0.63 p = 0.008). Conclusion Combination of different surgical approaches with minimization of postoperative face-down position time allows to achieve high anatomical and functional results being safe and highly acceptable for wounded patients with BRTMH.

• Sauesund, Ellen Steffenssen; Brunborg, Cathrine; Jørstad, Øystein Kalsnes; Moe, Morten Carstens; Erke, Maja Gran & Fosmark, Dag Sigurd [Vis alle 7 forfattere av denne artikkelen] (2026). Implementation of diabetic retinopathy screening in the Oslo region, Norway: a 3-year pilot study. Frontiers in Medicine. 13. doi: 10.3389/fmed.2026.1748289. Fulltekst i vitenarkiv
• Helland-Hansen, Bjørn André; Sverstad, Alexander; Petrovski, Goran & Larsen, Stig Einride (2026). Eye-tracking-derived foveal biomarkers and functional alterations in dry AMD: findings from a controlled clinical study. International Journal of Retina and Vitreous (IJRV). doi: 10.1186/s40942-026-00838-x. Fulltekst i vitenarkiv
• Gupta, Santosh; Lytvynchuk, Lyubomyr; Ardan, Taras; Studenovska, Hana; Muñoz, Georgina Faura & Eide, Lars [Vis alle 11 forfattere av denne artikkelen] (2025). A model for de novo pigmentation of amelanotic retinal pigment epithelial cells. Acta Ophthalmologica. ISSN 1755-375X. 104(2), s. 212–224. doi: 10.1111/aos.17572. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: Retinal Pigment Epithelial (RPE) cells perform critical functions in thevisual cycle. Their melanin pigmentation, which is organized into specializedcompartments – melanosomes, is highly critical for proper vision. A chemicalmethod to induce pigmentation in a non-pigmented model of ARPE-19 cellswas applied using L-DOPA as a repurposed drug from the current treatment ofParkinson's disease. Methods: L-DOPA was optimized for its toxic effect on ARPE-19 cells alongwith pigmentation development. Gene expression and immunocytochemistryconfirmed upregulation of melanogenesis-related genes and proteins.Melanosomes were characterized by TEM. Results: We found 1000 μM L-DOPA to induce pigmentation of ARPE-19cells by Day 3, and achieve full pigmentation by Day 5. By Day 5, L-DOPA at1000 μM induced mitochondrial and nuclear DNA damage. However, the geneexpression of RPE-specific markers (tyrosinase, TYRP1, CRALBP, PEDF) was significantly different in L-DOPA-treated ARPE-19 cells compared tonon-treated ones. Positive expression for Tyrosinase enzyme was confirmed byICC on both Day 3 and Day 5 of L-DOPA treatment. Transmission electronmicroscopy showed the de novo melanosome formation with ultrastructuralfeatures of various stages of maturity (Stage I to IV), apical-basal polarity andmelanosome localization on the apical side of the L-DOPA-treated ARPE-19cells. Conclusion: Our study showed that L-DOPA treatment could induce de novomelanosome formation in amelanotic RPEs. We propose a newer approach ofdeveloping an ex vivo model for de novo pigmentation of RPE cells with cell-specific modification and culture condition optimization

• Karabeg, Mia; Petrovski, Goran; Holen, Katrine; Sauesund, Ellen Steffenssen; Fosmark, Dag Sigurd & Russell, Greg [Vis alle 14 forfattere av denne artikkelen] (2025). Comparison of Validity and Reliability of Manual Consensus Grading vs. Automated AI Grading for Diabetic Retinopathy Screening in Oslo, Norway: A Cross-Sectional Pilot Study. Journal of Clinical Medicine. 14(13). doi: 10.3390/JCM14134810. Fulltekst i vitenarkiv Vis sammendrag

  Background: Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Manual grading of fundus images is the gold standard in DR screening, although it is time-consuming. Artificial intelligence (AI)-based algorithms offer a faster alternative, though concerns remain about their diagnostic reliability. Methods: A cross-sectional pilot study among patients (≥18 years) with diabetes was established for DR and diabetic macular edema (DME) screening at the Oslo University Hospital (OUH), Department of Ophthalmology, and the Norwegian Association of the Blind and Partially Sighted (NABP). The aim of the study was to evaluate the validity (accuracy, sensitivity, specificity) and reliability (inter-rater agreement) of automated AI-based compared to manual consensus (MC) grading of DR and DME, performed by a multidisciplinary team of healthcare professionals. Grading of DR and DME was performed manually and by EyeArt (Eyenuk) software version v2.1.0, based on the International Clinical Disease Severity Scale (ICDR) for DR. Agreement was measured by Quadratic Weighted Kappa (QWK) and Cohen’s Kappa (κ). Sensitivity, specificity, and diagnostic test accuracy (Area Under the Curve (AUC)) were also calculated. Results: A total of 128 individuals (247 eyes) (51 women, 77 men) were included, with a median age of 52.5 years. Prevalence of any vs. referable DR (RDR) was 20.2% vs. 11.7%, while sensitivity was 94.0% vs. 89.7%, specificity was 72.6% was 83.0%, and AUC was 83.5% vs. 86.3%, respectively. DME was detected only in one eye by both methods. Conclusions: AI-based grading offered high sensitivity and acceptable specificity for detecting DR, showing moderate agreement with manual assessments. Such grading may serve as an effective screening tool to support clinical evaluation, while ongoing training of human graders remains essential to ensure high-quality reference standards for accurate diagnostic accuracy and the development of AI algorithms.

• Sverstad, Alexander; Møller, Jens Riis; Virgili, Gianni; Azuara-Blanco, Augusto; Freiberg, Josefine & Ahrensberg, Simone [Vis alle 9 forfattere av denne artikkelen] (2025). Central Contrast Sensitivity as an Outcome Measure in Randomized Controlled Trials in Glaucoma—A Systematic Review. Life. 15(7). doi: 10.3390/life15071043. Fulltekst i vitenarkiv
• Ruban, Andrii; Prudyus, Vitalyi; Zolnikova, Anna; Petrovski, Beata Eva; Petrovski, Goran & Grzybowski, Andrzej [Vis alle 7 forfattere av denne artikkelen] (2025). Foveal actual defect (FAD): A novel OCT biomarker for prognosis and surgical decision support in idiopathic full-thickness macular hole. Asia-Pacific Journal of Ophthalmology (APJO). 14(5). doi: 10.1016/j.apjo.2025.100232. Fulltekst i vitenarkiv
• Borjan, Ivan; Pleština-Borjan, Ivna; Stanić, Robert; Znaor, Ljubo; Petrovski, Beata Eva & Petrovski, Goran (2025). Open globe injuries in a croatian cohort: characteristics and prognostic value of the ocular trauma score in predicting the final visual outcome. International Journal of Retina and Vitreous (IJRV). 11(1). doi: 10.1186/s40942-025-00696-z. Fulltekst i vitenarkiv Vis sammendrag

  Background Open globe injuries (OGI) are the most severe and sight-treating ocular traumas encountered in ophthalmology. The purpose of the study is to analyze the characteristics and prognostic factors of OGI and to evaluate the prognostic value of the Ocular Trauma Score (OTS) in predicting final visual outcome. Methods A retrospective study analyzing OGI in 56 patients referred to the Eye Clinic, University Hospital Centre Split, Croatia, was conducted between January 2020 and January 2023. The characteristics of OGI and other relevant factors contributing to the final visual outcome were analyzed. The comparison between the final visual outcomes predicted by OTS system and those observed in the study was performed. Non-parametric statistical methods (Wilcoxon, Kruskal-Wallis and chi-square tests) with the Bonferroni correction for multiple comparisons were used in statistical analysis. Results The average age of patients was 45 years; 48 (86%) were males and 8 (14%) females. Most of the patients (68%) were admitted to the hospital and treated within 6 h after the injury. Most of the injuries (88%) occurred during leisure time and most often were located in zone 2 (46%). Penetrating injuries were the most frequent injury type (52%), while globe rupture was present in 16 (29%) patients. The posterior segment was affected in 27 (48%) patients. In 16 (29%) patients, final BCVA reached ≥ 0.5. The worst final BCVA– NLP was most commonly experienced in patients with globe rupture (38%). Poor final BCVA was statistically significantly associated with worse initial BCVA (P < 0.001), globe rupture (P < 0.001), lower OTS category (P < 0.001), and the presence of RAPD (P < 0.001). The final visual results were comparable with predicted visual outcome by OTS. Conclusions The study cohort from Croatia showed that the most important factors in the prognosis of final BCVA in OGI were initial BCVA, injury type, RAPD, localization and extent of the wound, and appropriate, timely surgical treatment in specialized institutions with experienced surgeons. Furthermore, our study findings are mostly consistent with those of the international OTS group and support the view that OTS is a reliable predictor of the final visual outcome.

• Confalonieri, Filippo; Hertzberg, Silvia Nanjala Walekhwa; Dziedzic, Krystian Andrzej; Lumi, Xhevat; Lytvynchuk, Lyubomyr & Znaor, Ljubo [Vis alle 8 forfattere av denne artikkelen] (2025). Cost-Effectiveness of Alternative Treatment Strategies of Subretinal Macular Hemorrhage. Healthcare. 13(13). doi: 10.3390/healthcare13131550. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To evaluate the cost-effectiveness of alternative treatment strategies for subretinal macular hemorrhage (SRMH), a condition often associated with neovascular age-related macular degeneration (AMD) and other retinal vascular disorders, leading to severe visual impairment. Methods: A retrospective cross-sectional study conducted at Oslo University Hospital assessed the cost and utility of various SRMH treatment modalities. These included intravitreal anti-VEGF monotherapy, intravitreal tissue plasminogen activator (tPA) with gas displacement (alone and in combination with anti-VEGF), and pars plana vitrectomy (PPV) with subretinal tPA and gas displacement (with and without anti-VEGF). Costs were analyzed from a healthcare perspective, encompassing direct and indirect costs. Effectiveness was measured using median best-corrected visual acuity (BCVA) improvements. Sensitivity analyses were performed to account for complications and variations in follow-up. Results: Anti-VEGF monotherapy was the most cost-effective treatment, with the lowest cost per unit of BCVA improvement (NOK 44,717) in outpatient settings. Intravitreal tPA with gas displacement emerged as a cost-effective alternative but exhibited higher costs when combined with anti-VEGF or performed as an inpatient procedure. PPV with subretinal tPA and gas displacement, with or without anti-VEGF, was the least cost-effective modality, particularly in inpatient settings. Sensitivity analyses indicated that anti-VEGF therapy remained cost-effective even with increased follow-up requirements and complications, while tPA-based therapies required significant BCVA improvements to match anti-VEGF’s cost–utility. Conclusions: Outpatient intravitreal anti-VEGF monotherapy followed by tPA with gas displacement are the most cost-effective strategies for SRMH management. Subretinal tPA-based treatments are associated with higher costs and limited economic viability, highlighting the importance of tailored treatment selection. These findings support strategic resource allocation in managing SRMH while optimizing patient outcomes.

• Hiller, John Kim; Sandås, Elise Mørk; Rootwelt, Helge; Vassli, Anja Østeby; Lumi, Xhevat & Moe, Morten Carstens [Vis alle 9 forfattere av denne artikkelen] (2025). Metabolic Deficiencies in the Vitreous of Diabetic Retinopathy: Exploring the Potential of Dietary Supplementation to Address Key Metabolite Imbalances. Clinical Ophthalmology. ISSN 1177-5467. 19, s. 2997–3007. doi: 10.2147/OPTH.S531638. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: This study aimed to investigate the metabolic alterations in the vitreous humor of patients with diabetes across different stages of diabetic retinopathy (DR) and explore potential dietary interventions to mitigate these changes. Patients and Methods: Vitreous samples were collected from 23 patients undergoing vitrectomy and grouped into controls, diabetic without DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Metabolomic analysis was performed using mass spectrometry, focusing on identifying significantly altered metabolites. Results: A total of 82 features were identified, of which several were significantly reduced in DR compared to controls. Ascorbate and taurine were notably lower in NPDR (p < 0.01), while choline and N-acetylaspartic acid were significantly reduced in NPDR and PDR (p < 0.01). Tagatose was significantly reduced in PDR (p < 0.05), while stachydrine and serine displayed biphasic trends, decreasing in NPDR (p < 0.001; p < 0.05) but increasing in PDR (p < 0.05). Conclusion: The results suggest that key metabolites involved in antioxidant defense, membrane integrity, and neuronal function are disrupted in the vitreous humor of patients with DR. Dietary supplementation targeting these metabolic deficiencies, such as increased intake of ascorbate, taurine, serine, choline, and stachydrine, may offer adjunctive support in managing DR progression.

• Dziedzic, Krystian Andrzej; Confalonieri, Filippo; Petrovski, Beata Eva; Lytvynchuk, Lyubomyr; Bragadottir, Ragnheidur & Borjan, Ivan [Vis alle 8 forfattere av denne artikkelen] (2025). Outcomes of subretinal macular hemorrhage treatment: a 7-year retrospective cohort study at Oslo University Hospital. International Journal of Retina and Vitreous (IJRV). 11(1). doi: 10.1186/s40942-025-00749-3. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Subretinal macular hemorrhage (SRMH) is a vision-threatening condition with no consensus on optimal treatment. This study evaluated the outcomes of five treatment modalities and their correlation with patient characteristics and optical coherence tomography findings. Methods A retrospective review was conducted on 120 SRMH patients treated at Oslo University Hospital between October 24, 2015, and December 27, 2022. Best-corrected visual acuity (BCVA) was assessed before and 1-month after treatment. Statistical analyses were performed to evaluate the impact of treatment timing, hemorrhage size, and different therapeutic interventions on visual outcomes. Results Early intervention, particularly within 7 days of symptom onset, was associated with better median BCVA 1-month post-surgery. A 14-day cut-off showed no benefit. Patients with smaller hemorrhages (< 4500 μm) had significantly higher BCVA before treatment, but no statistical difference was observed 1-month after treatment. Combination therapies, including tissue plasminogen activator (tPA) with Sulfur Hexafluoride (SF6) gas and tPA with SF6 gas plus anti-vascular endothelial growth factor (anti-VEGF), resulted in significantly improved visual outcomes 1-month post-surgery, but no intervention outperformed others at the 1-month endpoint. Conclusions Early intervention, particularly within 7 days of symptom onset, may improve visual outcomes in SRMH. Combined therapies involving tPA, gas and anti-VEGF appear to be more effective. Further studies with extended follow-up are needed to establish definitive treatment guidelines.

• Muth, Daniel R.; Quérat, Laurence; Venkataraman, Abinaya P.; Dominguez-Vicent, Alberto; Petrovski, Goran & Williams, Pete A. [Vis alle 9 forfattere av denne artikkelen] (2025). Long-Term Natural History of Treatment-Naïve Geographic Atrophy in Age-Related Macular Degeneration. Translational Vision Science & Technology. 14(5). doi: 10.1167/tvst.14.5.5. Fulltekst i vitenarkiv
• Josifovska, Natasha; Niemi, Essi Maria; Ramalingam, Murugan; Manivasagam, Geetha; Scholz, Hanne & Petrovski, Goran (2025). A pilot study for decellularizing porcine cornea for future use in corneal regeneration. PLOS ONE. 20(12). doi: 10.1371/journal.pone.0339462. Fulltekst i vitenarkiv Vis sammendrag

  Porcine corneas were decellularized for future use in corneal regeneration by using various washing steps with 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) detergent, Benzonase, and Ethylenediaminetetraacetic acid (EDTA). The quality of the decellularized corneas was assessed by quantitative and qualitative measurement of DNA content, glycosaminoglycans (GAGs), immunofluorescent staining for Collagen (Col) I, V, Keratocan, Fibronectin, Laminin, Lumican and Decorin, and Transmission Electron Microscopy (TEM) to observe the structure of the collagen fibrils was used. The decellularization process showed 99.5% DNA content reduction in the corneas and a similar pattern was observed in the preservation of GAGs. Hematoxylin & Eosin (H&E) and immunofluorescent staining showed no presence of cell nuclei, while Alcian blue staining confirmed the presence of GAGs. Col I, V, Keratocan, Fibronectin, Laminin, Lumican and Decorin were still present in the decellularized corneas and TEM microscopy further confirmed the similar patterns of the collagen fibrils in the decellularized, compared to the native corneas. This pilot study showed our method is effective in decellularizing porcine corneas, with a very high amount of DNA being removed, while the GAGs being preserved to an acceptable extent, and the structure and pattern of the collagen fibrils maintained.

• Helland-Hansen, Bjørn Andre; Sverstad, Alexander; Petrovski, Goran & Larsen, Stig (2025). Dynamic Pupillary Responses in Age-Related Macular Degeneration: A Controlled Clinical Study Using High-Frequency Video-Oculography. Clinical Ophthalmology. ISSN 1177-5467. 2025(19), s. 4689–4707. doi: 10.2147/OPTH.S531353. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To investigate whether dynamic pupillary responses differ between patients with age-related macular degeneration (AMD) and healthy controls (HC), and to evaluate their potential as functional biomarkers using high-frequency, VR-based video-oculography. Methods: A controlled clinical study included 17 AMD patients and 17 age-matched HCs; four AMD participants were excluded for low recording quality. Dynamic pupillary responses were recorded with the BulbiCam video-oculography system (400 Hz), which presented independent monocular light stimuli through multiple permutations of bright (300 cd/m²) and dark (5 cd/m²) conditions. Measured variables included pupil diameter, latency, peak velocity, and pupil diameter–time integral (PDTI). Each eye was tested separately, and repeated sessions were analysed for reliability (intraclass correlation coefficient, ICC), repeatability (agreement index, AI), and stability (stability index, SI). Group differences were assessed using analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis. Results: AMD eyes showed larger steady-state pupil diameter and higher PDTI than controls (p < 0.05). First peak velocity was reduced in the worst eye only, while latencies were unchanged. PDTI and diameter demonstrated high reliability and stability across repetitions, and ROC analysis confirmed effective group discrimination. Conclusion: High-frequency VR pupillometry detected reproducible functional alterations in AMD, consistent with impaired macular photoreceptor input but preserved reflex transmission. PDTI and diameter serve as diagnostic (population-level) and monitoring (patient-level) biomarkers, offering a non-invasive and objective method for AMD detection and follow-up in clinical and research settings.

• Borjan, Ivan; Pleština-Borjan, Ivna; Znaor, Ljubo; Pavić, Maja; Josifova, Tatjana & Marković, Irena [Vis alle 8 forfattere av denne artikkelen] (2025). Proliferative Diabetic Retinopathy in Young-Onset Type 1 Diabetes in Croatia: Risk Factors and a Predictive Economic Model for National Screening. Medicina. ISSN 1010-660X. 61(12). doi: 10.3390/medicina61122168. Fulltekst i vitenarkiv Vis sammendrag

  Background and Objectives: To provide, for the first time, statistical data on risk factors for proliferative diabetic retinopathy (PDR) in young-onset type 1 diabetes (T1D) in Croatia, and to develop a predictive health economic model to evaluate the clinical and financial impact of implementing a national diabetic retinopathy (DR) screening. Materials and Methods: A cross-sectional study at University Hospital Split (June 2020–June 2022) analyzed 58 suitable T1D patients out of 562 screened. Patients were classified based on detailed fundus exams and photos into PDR and non-PDR groups. Clinical, demographic, and laboratory data were collected and analyzed using logistic regression. A health economic model was established to project the number of preventable PDR cases and the potential cost savings under various screening scenarios. Results: PDR was found in 47% of patients. Its presence was statistically significantly linked to longer diabetes duration, poor glycemic control, onset before 18 years of age, and irregular eye exams. Irregular ophthalmologic examinations increased the odds of PDR by nearly 30-fold. Health-economic modeling for 10,000 young-onset T1D patients showed that annual screening with 60% uptake could prevent about 1973 PDR cases and save €14.2 million annually. Screening remained cost-effective even with moderate uptake or less frequent intervals. Conclusions: Strict glycemic control and regular eye examinations are critical for preventing PDR in young T1D, and establishing a national screening program would be cost-effective, especially in resource-limited settings like Croatia, where providing appropriate, timely treatment may be challenging.

• Brymová, Anna Macečková; Rodriguez-Jimenez, Francisco Javier; Konrad, Annika; Nemesh, Yaroslav; Thottappali, Muhammed Arshad & Artero-Castro, Ana [Vis alle 28 forfattere av denne artikkelen] (2025). Delivery of Human iPSC-Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells. Advanced Science. 12(20). doi: 10.1002/advs.202412301. Fulltekst i vitenarkiv Vis sammendrag

  In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age-related macular degeneration (AMD), loss of retinal pigment epithelia (RPE) cells and subsequently photoreceptors in the macular area result in a dramatic decline of central visual function. Repopulating this area with functional RPE cells may prevent or decline the progression of photoreceptor loss. In the present study, the viability, survival, and integration of human induced pluripotent stem cell (hiPSC)-derived RPE cells (hiPSC-RPE) is assessed generated using clinical-grade protocol and cultured on a clinically relevant scaffold (poly-L-lactide-co-D, L-lactide, PDLLA) after subretinal implantation in immunosuppressed minipigs for up to 6 weeks. It is shown that transplanted hiPSC-RPE cells maintain the RPE cell features such as cell polarity, hexagonal shape, and cell–cell contacts, and interact closely with photoreceptor outer segments without signs of gliosis or neuroinflammation throughout the entire period of examination. In addition, an efficient immunosuppressing strategy with a continuous supply of tacrolimus is applied. Continuous verification and improvement of existing protocols are crucial for its translation to the clinic. The results support the use of hiPSC-RPE on PDLLA scaffold as a cell replacement therapeutic approach for RPE degenerative diseases.

• Hiller, John Kim; Sandås, Elise Mørk; Rootwelt, Helge; Vassli, Anja Østeby; Lumi, Xhevat & Moe, Morten Carstens [Vis alle 9 forfattere av denne artikkelen] (2025). Metabolomic biomarkers in vitreous humor: unveiling the molecular landscape of diabetic retinopathy progression. International Journal of Retina and Vitreous (IJRV). 11(1). doi: 10.1186/s40942-025-00682-5. Fulltekst i vitenarkiv Vis sammendrag

  Background Diabetic retinopathy (DR) is a progressive retinal disease that leads to vision loss if not detected early. Metabolomic analysis of vitreous humor offers a promising approach to identifying biomarkers associated with disease onset and progression. This pilot study investigates the metabolomic profiles of vitreous humor from patients at different stages of DR, aiming to uncover potential biomarkers for early detection and monitoring of disease progression. Methods Vitreous samples were collected during therapeutic pars plana vitrectomy of 23 patients without diabetes (CTRL), with diabetes and without retinopathy (DIA), non-proliferative DR (NPDR) and proliferative DR (PDR). Metabolomics was performed using high-performance liquid chromatography coupled with high-resolution mass spectrometry. Results Principal component analysis revealed distinct metabolic signatures differentiating the patient groups. Lysine, proline, and arginine levels progressively increased from DIA to NPDR and PDR stages, highlighting their association with disease progression. Methionine and threonine showed notable increases in PDR compared to all other groups, while carnitine, a key metabolite in lipid metabolism, exhibited stage-specific increases, peaking in PDR. The detection of systemic and topical drugs, including metformin and tropicamide, in the vitreous further emphasizes altered ocular permeability in DR. Conclusion Our findings suggest that metabolomic profiling could provide valuable insights into the underlying pathogenesis of DR and serve as a foundation for personalized therapeutic strategies.

• Sverstad, Alexander; Helland-Hansen, Bjørn Andre; Kristianslund, Olav; Kolko, Miriam; Larsen, Stig Einride & Petrovski, Goran (2025). Eye-tracking biomarkers for glaucoma based on saccadic reaction time: a controlled clinical study. Frontiers in Ophthalmology. 5. doi: 10.3389/fopht.2025.1636911. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Evaluate the validity and reliability of saccadic reaction time (SRT)-based variables obtained using the novel eye-tracking device Bulbicam (BCAM) in differentiating early-to-moderate glaucoma (GLA) from healthy controls (HCs) and to identify potential biomarkers for GLA. Methods A controlled clinical study was conducted, involving 18 GLA-patients, and 18 age-matched HCs. Participants underwent BCAM’s visual field (VF) test, which measures SRT at 58 symmetrically arranged locations with 6° spacing. Variables were analysed for group differences, within- and between-patient repeatability, and stability. To evaluate their potential as biomarkers, VF locations were aggregated into clusters, quadrants, hemifields, and whole VF analyses. Results Significant SRT differences (p ≤ 0.05) were observed between GLA and HC in 44 of 58 locations in the worst eye and 42 of 58 in the best eye. Eight out of ten clusters met the criteria for BCAM biomarkers having significant group differences, sufficient within- and between-patient repeatability, and adequate stability. All quadrants demonstrated excellent stability and repeatability thereby qualifying as biomarkers. Hemifield SRTs were reliable, however, the absolute difference between hemifields showed poor within-participant repeatability. The mean and standard deviation of SRT for the whole VF were identified as significant biomarkers with excellent stability. Conclusions The majority of SRT variables are capable of differentiate glaucomatous eyes from HC while maintaining sufficient reliability and stability for clinical application. 19 of 22 BCAM VF test variables were found to be potential GLA-biomarkers. Clinical Trial Registration https://clinicaltrials.gov/ , identifier NCT05449041.

• Confalonieri, Filippo; Casarini, Barbara; Papapicco, Annalaura; Stiro, Fabio; Piscopo, Raffaele & D’Andrea, Luca [Vis alle 8 forfattere av denne artikkelen] (2025). A Systematic Review of Micropulse Laser Trabeculoplasty (MLT) in Primary Open-Angle Glaucoma (POAG) Management: Efficacy, Safety, and Future Perspectives. Biomedicines. 13(1). doi: 10.3390/biomedicines13010211. Fulltekst i vitenarkiv Vis sammendrag

  Background/Objectives: Micropulse laser trabeculoplasty (MLT) is gaining attention as a non-invasive treatment option for primary open-angle glaucoma (POAG), offering an alternative to traditional surgeries and medications. This systematic review evaluates the effectiveness, safety, and potential of MLT in glaucoma management. Methods: This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, following the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) recommendations. Results: We identified 79 articles, and after removing duplicates and screening abstracts, 56 articles were eligible for further review. A detailed full-text analysis was conducted on 26 articles, of which 15 met the predefined inclusion criteria. Conclusions: MLT shows promise as a primary or adjunctive treatment for reducing intraocular pressure (IOP) in glaucoma and ocular hypertension patients. Current evidence supports its efficacy and safety; however, additional long-term studies are needed to confirm its durability and compare its effectiveness with traditional surgical and pharmacological approaches. Standardizing treatment protocols and refining patient selection criteria could enhance MLT’s clinical value and support its broader adoption in glaucoma care.

• Muñoz, Georgina Faura; Studenovska, Hana; Sekac, David; Ellederova, Zdenka; Petrovski, Goran & Eide, Lars (2024). The Effects of the Coating and Aging of Biodegradable Polylactic Acid Membranes on In Vitro Primary Human Retinal Pigment Epithelium Cells. Biomedicines. 12:966(5), s. 1–14. doi: 10.3390/biomedicines12050966. Fulltekst i vitenarkiv Vis sammendrag

  Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement of dysfunctional human retinal pigment epithelium (hRPE) cells by the transplantation of in vitro-cultivated hRPE cells to the affected area emerges as a feasible strategy for regenerative therapy. Synthetic biomimetic membranes arise as powerful hRPE cell carriers, but as biodegradability is a requirement, it also poses a challenge due to its limited durability. hRPE cells exhibit several characteristics that putatively respond to the type of membrane carrier, and they can be used as biomarkers to evaluate and further optimize such membranes. Here, we analyze the pigmentation, transepithelial resistance, genome integrity, and maturation markers of hRPE cells plated on commercial polycarbonate (PC) versus in-house electrospun polylactide-based (PLA) membranes, both enabling separate apical/basolateral compartments. Our results show that PLA is superior to PC-based membranes for the cultivation of hRPEs, and the BEST1/RPE65 maturation markers emerge as the best biomarkers for addressing the quality of hRPE cultivated in vitro. The stability of the cultures was observed to be affected by PLA aging, which is an effect that could be partially palliated by the coating of the PLA membranes.

• Karabeg, Mia; Petrovski, Goran; Hertzberg, Silvia Nanjala Walekhwa; Erke, Maja Gran; Fosmark, Dag Sigurd & Russell, Greg [Vis alle 13 forfattere av denne artikkelen] (2024). A pilot cost-analysis study comparing AI-based EyeArt® and ophthalmologist assessment of diabetic retinopathy in minority women in Oslo, Norway. International Journal of Retina and Vitreous (IJRV). 10(1). doi: 10.1186/s40942-024-00547-3. Fulltekst i vitenarkiv Vis sammendrag

  Background Diabetic retinopathy (DR) is the leading cause of adult blindness in the working age population worldwide, which can be prevented by early detection. Regular eye examinations are recommended and crucial for detecting sight-threatening DR. Use of artificial intelligence (AI) to lessen the burden on the healthcare system is needed. Purpose To perform a pilot cost-analysis study for detecting DR in a cohort of minority women with DM in Oslo, Norway, that have the highest prevalence of diabetes mellitus (DM) in the country, using both manual (ophthalmologist) and autonomous (AI) grading. This is the first study in Norway, as far as we know, that uses AI in DR- grading of retinal images. Methods On Minority Women’s Day, November 1, 2017, in Oslo, Norway, 33 patients (66 eyes) over 18 years of age diagnosed with DM (T1D and T2D) were screened. The Eidon - True Color Confocal Scanner (CenterVue, United States) was used for retinal imaging and graded for DR after screening had been completed, by an ophthalmologist and automatically, using EyeArt Automated DR Detection System, version 2.1.0 (EyeArt, EyeNuk, CA, USA). The gradings were based on the International Clinical Diabetic Retinopathy (ICDR) severity scale [1] detecting the presence or absence of referable DR. Cost-minimization analyses were performed for both grading methods. Results 33 women (64 eyes) were eligible for the analysis. A very good inter-rater agreement was found: 0.98 (P < 0.01), between the human and AI-based EyeArt grading system for detecting DR. The prevalence of DR was 18.6% (95% CI: 11.4–25.8%), and the sensitivity and specificity were 100% (95% CI: 100–100% and 95% CI: 100–100%), respectively. The cost difference for AI screening compared to human screening was $143 lower per patient (cost-saving) in favour of AI. Conclusion Our results indicate that The EyeArt AI system is both a reliable, cost-saving, and useful tool for DR grading in clinical practice.

• Arnould, Louis; Varsanyi, Balazs; Dervan, Edward; Posarelli, Chiara; Filipe, Helena Prior & Bourcier, Tristan [Vis alle 30 forfattere av denne artikkelen] (2024). Variation in eye care professional distribution across Europe, a survey. Eye (London. 1987). ISSN 0950-222X. doi: 10.1038/s41433-024-03010-7. Fulltekst i vitenarkiv
• Confalonieri, Filippo; Ferraro, Vanessa; Barone, Gianmaria; Maria, Alessandra Di; Petrovski, Beata Eva & Garcia, Josè Luis Vallejo [Vis alle 10 forfattere av denne artikkelen] (2024). Outcomes in the Treatment of Subretinal Macular Hemorrhage Secondary to Age-Related Macular Degeneration: A Systematic Review. Journal of Clinical Medicine. 13(2). doi: 10.3390/jcm13020367. Fulltekst i vitenarkiv Vis sammendrag

  Background: Subretinal macular hemorrhage (SRMH) secondary to age-related macular degeneration (AMD) is a relatively rare condition in ophthalmology characterized by blood collection between the neurosensory retina and the retinal pigment epithelium (RPE). Without prompt treatment, visual prognosis is poor. A plethora of treatment approaches have been tried over the past years ranging from intravitreal anti-vascular endothelial growth factor (anti-VEGF) monotherapy to direct subretinal surgery, with no conclusive superiority of one over the other. Materials and Methods: We conducted a systematic review of the outcomes and treatment modalities of SRMH from inception to 14 June 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence was assessed for all included articles according to the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: A total of 2745 articles were initially extracted, out of which 1654 articles were obtained after duplicates were removed and their abstracts screened. A total of 155 articles were included for full-text review. Finally, 81 articles remained that fulfilled the inclusion criteria. Conclusions: Even though there are solid results supporting a variety of treatments for SRMH, the best treatment modality has still not been conclusively demonstrated and further research is needed.

• Sverstad, Alexander; Kristianslund, Olav; Petrovski, Goran; Moe, Morten Carsten & Jørstad, Øystein Kalsnes (2024). A proof-of-concept study of a prototype needle that mitigates intraocular pressure rise following intravitreal injection. International Journal of Retina and Vitreous (IJRV). 10(1). doi: 10.1186/s40942-024-00590-0. Fulltekst i vitenarkiv Vis sammendrag

  Purpose To determine the feasibility of a prototype needle that enhances vitreous reflux (VR) to control intraocular pressure (IOP) in intravitreal injection (IVI). Methods We created an eye model to compare IVI using a standard 30-G needle with four different versions of a 30-G prototype needle with one to four surface grooves that enhanced VR. We injected 50, 70, and 100 µl saline through porcine sclera or 460-µm-thick rubber and measured the peak and 3-second pressure before we extracted the needle and measured the 10-second pressure. Results 50-µl injection through sclera with the standard needle resulted in mean (SD) pressure of 58.6 (3.8) mmHg at peak, 52.8 (4.7) mmHg at 3 s, and 39.6 (18.0) mmHg at 10 s. The prototype needle lowered the pressure; four grooves resulted in mean (SD) pressure of 29.4 (5.6) mmHg at peak, 22.0 (3.7) mmHg at 3 s, and 7.2 (6.6) mmHg at 10 s. 70-µl and 100-µl injections through sclera with the standard needle resulted in mean (SD) pressure of 68.8 (3.6) and 86.0 (6.0) mmHg at peak. Similar to 50-µl injection, the prototype needle lowered the pressure for 70-µl and 100-µl injections. At 10 s, we observed varying leakage at the injection site for sclera but not for rubber. Conclusions The study provides proof of concept for a needle design for which surface grooves enhance VR and counteract the effect of IVI on IOP. The safety and efficacy of the prototype needle must be studied further in a clinical trial.

• Svikle, Zane; Paramonova, Natalia; Siliņš, Emīls; Pahirko, Leonora; Zariņa, Līga & Baumane, Kristīne [Vis alle 8 forfattere av denne artikkelen] (2024). DNA Methylation Profiles of PSMA6, PSMB5, KEAP1, and HIF1A Genes in Patients with Type 1 Diabetes and Diabetic Retinopathy. Biomedicines. 12(6). doi: 10.3390/biomedicines12061354. Fulltekst i vitenarkiv Vis sammendrag

  We explored differences in the DNA methylation statuses of PSMA6, PSMB5, HIF1A, and KEAP1 gene promoter regions in patients with type 1 diabetes and different diabetic retinopathy (DR) stages. Study subjects included individuals with no DR (NDR, n = 41), those with non-proliferative DR (NPDR, n = 27), and individuals with proliferative DR or those who underwent laser photocoagulation (PDR/LPC, n = 46). DNA methylation was determined by Zymo OneStep qMethyl technique. The methylation of PSMA6 (NDR 5.9 (3.9–8.7) %, NPDR 4.5 (3.8–5.7) %, PDR/LPC 6.6 (4.7–10.7) %, p = 0.003) and PSMB5 (NDR 2.2 (1.9–3.7) %, NPDR 2.2 (1.9–3.0) %, PDR/LPC 3.2 (2.5–7.1) %, p < 0.01) differed across the groups. Consistent correlations were observed between the methylation levels of HIF1A and PSMA6 in all study groups. DNA methylation levels of PSMA6, PSMB5, and HIF1A genes were positively correlated with the duration of diabetes, HbA1c, and albuminuria in certain study groups. Univariate regression models revealed a significant association between the methylation level z-scores of PSMA6, PSMB5, and HIF1A and severe DR (PSMA6: OR = 1.96 (1.15; 3.33), p = 0.013; PSMB5: OR = 1.90 (1.14; 3.16), p = 0.013; HIF1A: OR = 3.19 (1.26; 8.06), p = 0.014). PSMB5 remained significantly associated with DR in multivariate analysis. Our findings suggest significant associations between the severity of DR and the DNA methylation levels of the genes PSMA6, PSMB5, and HIF1A, but not KEAP1 gene.

• Sauesund, Ellen Steffenssen; Hertzberg, Silvia Nanjala Walekhwa; Jørstad, Øystein Kalsnes; Moe, Morten Carsten; Erke, Maja Gran & Fosmark, Dag Sigurd [Vis alle 7 forfattere av denne artikkelen] (2024). A health economic pilot study comparing two diabetic retinopathy screening strategies. Scientific Reports. 14(1). doi: 10.1038/s41598-024-66405-2. Fulltekst i vitenarkiv Vis sammendrag

  To compare two screening strategies for diabetic retinopathy (DR), and to determine the health-economic impact of including optical coherence tomography (OCT) in a regular DR screening. This cross-sectional study included a cohort of patients (≥ 18 years) with type 1 or 2 diabetes mellitus (T1D or T2D) from a pilot DR screening program at Oslo University Hospital, Norway. A combined screening strategy where OCT was performed in addition to fundus photography for all patients, was conducted on this cohort and compared to our existing sequential screening strategy. In the sequential screening strategy, OCT was performed on a separate day only if fundus photography indicated diabetic macular edema (DME). The presence of diabetic maculopathy on fundus photography and DME on OCT was determined by two medical retina specialists. Based on the prevalence rate of diabetic maculopathy and DME from the pilot, we determined the health-economic impact of the two screening strategies. The study included 180 eyes of 90 patients. Twenty-seven eyes of 18 patients had diabetic maculopathy, and of these, 7 eyes of 6 patients revealed DME on OCT. When diabetic maculopathy was absent on fundus photographs, OCT could not reveal DME. Accordingly, 18 patients (20%) with diabetic maculopathy would have needed an additional examination with OCT in the sequential screening strategy, 6 (33%) of whom would have had DME on OCT. In an extended healthcare perspective analysis, the cost of the sequential screening strategy was higher than the cost of the combined screening strategy. There was a weak association between diabetic maculopathy on fundus photography and DME on OCT. The health economic analysis suggests that including OCT as a standard test in DR screening could potentially be cost-saving.

• Confalonieri, Filippo; Rosa, Antonio La; Ottonelli, Giovanni; Barone, Gianmaria; Ferraro, Vanessa & Maria, Alessandra Di [Vis alle 11 forfattere av denne artikkelen] (2024). Retinitis Pigmentosa and Therapeutic Approaches: A Systematic Review. Journal of Clinical Medicine. 13(16). doi: 10.3390/jcm13164680. Fulltekst i vitenarkiv Vis sammendrag

  Background: Retinitis pigmentosa (RP) is a group of hereditary retinal dystrophies characterized by progressive degeneration of photoreceptor cells, which results in debilitating visual impairment. This systematic review aims to evaluate the efficacy and safety of emerging treatment modalities for RP, including gene therapy, mesenchymal-cell-based approaches, and supplementary interventions. Methods: A comprehensive search of electronic databases was conducted to identify relevant studies published up to February 2024. Studies reporting outcomes of treatment interventions for RP, including randomized controlled trials, non-randomized studies, and case series, were included. Data extraction and synthesis were performed according to predefined criteria, focusing on assessing the quality of evidence and summarizing key findings. Results: The search yielded 13 studies meeting inclusion criteria, encompassing diverse treatment modalities and study designs. Gene therapy emerged as a promising therapeutic approach, with several studies reporting favorable outcomes regarding visual function preservation and disease stabilization. Mesenchymal-cell-based therapies also demonstrated potential benefits, although evidence remains limited and heterogeneous. Supplementary interventions, including nutritional supplements and neuroprotective agents, exhibited variable efficacy, with conflicting findings across studies. Conclusions: Despite the lack of definitive curative treatments, emerging therapeutic modalities promise to slow disease progression and preserve visual function in individuals with RP. However, substantial gaps in evidence and heterogeneity in study methodologies underscore the need for further research to elucidate optimal treatment strategies, refine patient selection criteria, and enhance long-term outcomes. This systematic review provides a comprehensive synthesis of current evidence and highlights directions for future research to advance the care and management of individuals with RP.

• Borjan, Ivan; Pleština-Borjan, Ivna; Hertzberg, Silvia Nanjala Walekhwa; Siničić, Alen; Znaor, Ljubo & Petrovski, Beata Eva [Vis alle 7 forfattere av denne artikkelen] (2024). Outcome of Different Surgical Repair Techniques for Rhegmatogenous Retinal Detachment—A Health Economic Analysis in the Split-Dalmatia County, Croatia. Healthcare. 12(6). doi: 10.3390/healthcare12060648. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: The goal of this research is to investigate the characteristics and surgical techniques for repairing rhegmatogenous retinal detachment (RRD) and their influence on anatomical and functional success of the treatment with a special emphasis on the economic costs and outcome quality-adjusted life years (QALYs) of the procedures. Methods: This retrospective study analyzed data from 151 patients with RRD treated at the Department of Ophthalmology, Clinical Hospital Centre Split, Croatia, in a 3-year period, using one of three surgical techniques: pneumoretinopexy (PR), scleral buckling (SB) or pars plana vitrectomy (PPV), followed-up for at least 6 months. Demographic, pre- and post-operative ophthalmic exam parameters and surgical technique used were collected accordingly. Statistical analysis of the influence of the studied parameters upon anatomical and functional outcomes was performed, as well as health economic analysis on costs and derived utilities/QALYs of these surgical methods. Results: Of all patients, 130 (86%) were successfully operated on, and 21 patients (14%) required another surgical procedure. No statistically significant differences in the anatomical success between the 3 surgical techniques were found. However, the functional outcome (based on the final best corrected visual acuity (BCVA)) differed significantly. Despite improvement in the final BCVA, BCVA ≥ 0.5 was achieved in only 52 (34.4%) patients. The final BCVA showed significant association with the time elapsed from the onset of RRD to the surgical intervention, pre-operative BCVA, macular- and preoperative lens- status and type of surgery. The estimated diagnosis-related group (DRG) cost for day and inpatient surgery was based upon existing DRG cost for PPV, which for PR and SB was calculated accordingly. Based upon the success of the procedure and visual outcome, the overall calculated QALYs for PR and SB appeared to be similar, while the QALYs were lower for PPV. Conclusions: The success rate of treating RRD mostly depends on performing an early surgical procedure (especially in the case of attached macula), identification of all retina tears and, most importantly, choosing the appropriate surgical technique. Decisions on treatment for RRD should also be based upon cost-effective and QALYs-assessed procedures, especially in countries like Croatia, where limited healthcare resources exist. This study shows PR to be efficient and most cost-effective for RRD repairment in appropriate cases.

• Liberski, Slawomir; Confalonieri, Filippo; Cofta, Szczepan; Petrovski, Goran & Kocięcki, Jarosław (2024). Ocular Changes in Cystic Fibrosis: A Review. International Journal of Molecular Sciences. ISSN 1661-6596. 25(12). doi: 10.3390/ijms25126692. Fulltekst i vitenarkiv Vis sammendrag

  Cystic fibrosis (CF), also known as mucoviscidosis, is the most common autosomal recessive genetic disease in the Caucasian population, with an estimated frequency of 1:2000–3000 live births. CF results from the mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene localized in the long arm of chromosome 7. The product of CFTR gene expression is CFTR protein, an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that regulates the transport of chloride ions (Cl−) across the apical cell membrane. Primary manifestations of CF include chronic lung and pancreas function impairment secondary to the production of thick, sticky mucus resulting from dehydrated secretions. It is well known that CF can cause both anterior and posterior ocular abnormalities. Conjunctival and corneal xerosis and dry eye disease symptoms are the most characteristic manifestations in the anterior segment. In contrast, the most typical anatomical and functional changes relating to the posterior segment of the eye include defects in the retinal nerve fiber layer (RNFL), vascular abnormalities, and visual disturbances, such as reduced contrast sensitivity and abnormal dark adaptation. However, the complete background of ophthalmic manifestations in the course of CF has yet to be discovered. This review summarizes the current knowledge regarding ocular changes in cystic fibrosis.

• Stranak, Zbynek; Ardan, Taras; Nemesh, Yaroslav; Toms, Maria; Toualbi, Lyes & Harbottle, Richard [Vis alle 12 forfattere av denne artikkelen] (2024). Feasibility of Direct Vitrectomy-Sparing Subretinal Injection for Gene Delivery in Large Animals. Current Eye Research. ISSN 0271-3683. doi: 10.1080/02713683.2024.2343335. Fulltekst i vitenarkiv
• Reyna, Erick Carlos; Öztek, Melisa; Petrovski, Goran; Binder, Susanne; Stieger, Knut & Lytvynchuk, Lyubomyr (2024). Clinical significance of signal shadowing during intraoperative optical coherence tomography-assisted vitreoretinal surgery. Scientific Reports. 14(1). doi: 10.1038/s41598-024-56125-y. Fulltekst i vitenarkiv Vis sammendrag

  This study aimed to analyze the clinical significance of signal shadowing during intraoperative optical coherence tomography (iOCT)-assisted vitreoretinal surgery caused by vitreoretinal instruments, tissue dyes, and vitreous substitutes, and to objectively quantify its impact on iOCT imaging. This is a retrospective observational study of postoperative image analysis from one hundred seventeen (117) patients who underwent iOCT-assisted vitrectomy. The image data were divided into three groups: vitreoretinal instruments, tissue dyes, and vitreous substitutes. The data was then processed using graphic software to measure the grade of picture quality distortion and compared to paired image controls without clinically perceptive interference, then analyzed statistically. The intraocular portion of all studied vitreoretinal instruments caused a high average gray level interference compared to controls ranging from 32 to 68% reduction, obscuring the area of interest significantly. The tips of the instruments produced low-grade shadowing, allowing the underlying tissue to be distinguished. The analyzed dyes demonstrated a wide interference range: ICG (− 75.12%), and triamcinolone (− 26.13%) showed dose-dependent high shadowing, while VITREODYNE™ (49.3%) and brilliant blue G (14.06%) exhibited no perceived distortions whilst increasing average gray levels. All analyzed vitreous substitutes (air, SF6, C3F8, PFCL, and silicone oil) showed an insignificant shadowing effect on iOCT. Certain dyes and vitreous substitutes produce a negligible shadowing effect compared to controls and other dyes, providing an advantage during real-time iOCT imaging. All analyzed vitreoretinal instruments showed a significant interference that should prompt the development of new imaging techniques or the implementation of materials with low-grade interference to overcome a clinically relevant shadowing effect on iOCT, maximizing the technology’s visual accuracy and surgical diagnostic aid proficiency.

• Hoel, Sissel; Moe, Kjartan; Sugulle, Meryam; Petrovski, Goran; Veiby, Nina & Staff, Anne Cathrine (2024). Retinal oximetry and microvascular assessment after hypertensive pregnancy complications. Acta Ophthalmologica. ISSN 1755-375X. 102(6), s. 653–661. doi: 10.1111/aos.16651. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Women with hypertensive disorders of pregnancy (HDP) are at increased risk of developing premature cardiovascular disease (CVD). The mechanisms behind this are not fully understood, but microvascular alterations have been documented in retinal arterioles and venules. The aim of this study was to use non-invasive retinal imaging to investigate the structural and functional properties of arterioles, venules and capillaries in this patient group. Methods We examined 27 women with previous HDP and 23 controls at 3 years postpartum. The retinal microvasculature was assessed by vessel calibre measurements, retinal oximetry and optical coherence tomography angiography. Differences were analysed using non-parametric tests and multiple regression analyses, adjusted for age and body mass index. Results Median arteriolar oxygen saturation (SaO2; 94.2% vs. 93.0%), venular oxygen saturation (SvO2; 60.1% vs. 62.4%) and arteriovenous saturation difference (AV-difference; 32.8% vs. 32.3%) were similar across groups. Capillary vessel density (VD; 46.2% vs. 46.3%), skeletonised VD (VSD; 21.3 vs. 21.1 mm/mm2) and vessel diameter index (21.65 vs. 21.86) were also comparable. In the HDP group, mean arterial pressure (MAP) was positively correlated with AV-difference (R2 = 0.209) and negatively correlated with arteriolar diameter (CRAE; r2 = 0.382). Conclusions Structural microvascular alterations appear not to be key biomarkers for CVD risk after HDP as early as 3 years postpartum in otherwise healthy women. Further studies are needed to evaluate whether such changes occur later in life. MAP was associated with AV-difference only in the HDP group, suggesting specific mechanisms affecting functional microvascular properties in these women.

• Lemonche, Gerard Boix; Hildebrand, Torben; Haugen, Håvard Jostein; Petrovski, Goran & Nogueira, Liebert Parreiras (2024). Contrast-enhanced Micro-CT 3D visualization of cell distribution in hydrated human cornea. Heliyon. 10(3). doi: 10.1016/j.heliyon.2024.e25828. Fulltekst i vitenarkiv Vis sammendrag

  Background The cornea, a vital component of the human eye, plays a crucial role in maintaining visual clarity. Understanding its ultrastructural organization and cell distribution is fundamental for elucidating corneal physiology and pathology. This study comprehensively examines the microarchitecture of the hydrated human cornea using contrast-enhanced micro-computed tomography (micro-CT). Method Fresh human corneal specimens were carefully prepared and hydrated to mimic their in vivo state. Contrast enhancement with Lugol's iodine-enabled high-resolution Micro-CT imaging. The cells' three-dimensional (3D) distribution within the cornea was reconstructed and analyzed. Results The micro-CT imaging revealed exquisite details of the corneal ultrastructure, including the spatial arrangement of cells throughout its depth. This novel approach allowed for the visualization of cells' density and distribution in different corneal layers. Notably, our findings highlighted variations in cell distribution between non-hydrated and hydrated corneas. Conclusions This study demonstrates the potential of contrast-enhanced micro-CT as a valuable tool for non-destructive, 3D visualization and quantitative analysis of cell distribution in hydrated human corneas. These insights contribute to a better understanding of corneal physiology and may have implications for research in corneal diseases and tissue engineering.

• Larsen, Kristoffer; Petrovski, Goran & Boix-Lemonche, Gerard (2024). Alternative cryoprotective agent for corneal stroma-derived mesenchymal stromal cells for clinical applications. Scientific Reports. 14(1). doi: 10.1038/s41598-024-65469-4. Fulltekst i vitenarkiv Vis sammendrag

  Cryopreservation of human corneal stroma-derived mesenchymal stromal cells (hCS-MSCs) with dimethylsulfoxide (DMSO) as a cryoprotective agent (CPA) has not been previously compared to that with glycerol under standard conditions. The hCS-MSCs were hereby cryopreserved with both compounds using a freezing rate of 1 °C/minute. The CPAs were tested by different concentrations in complete Minimum Essential Medium (MEM) approved for good manufacturing practice, and a medium frequently used in cell laboratory culturing—Dulbecco’s modified eagle serum. The hCS-MSCs were isolated from cadaveric human corneas obtained from the Norwegian Eye Bank, and immunophenotypically characterized by flow cytometry before and after cryopreservation. The survival rate, the cellular adhesion, proliferation and cell surface coverage after cryopreservation of hCS-MSCs has been studied. The hCS-MSCs were immunofluorescent stained and examined for their morphology microscopically. The results showed that cryopreservation of hCS-MSCs in MEM with 10% glycerol gives a higher proliferation rate compared to other cryopreserving media tested. Based on the results, hCS-MSCs can safely be cryopreserved using glycerol instead of the traditional use of DMSO.

• Hadad, Rubin; Hedengran, Anne; Barnils, Alex; Petrovski, Goran; Cvenkel, Barbara & Utheim, Tor Paaske [Vis alle 9 forfattere av denne artikkelen] (2024). Effect of chlorhexidine, povidone-iodine and betadine antiseptic eye drops on cultured human conjunctival goblet cell survival. Acta Ophthalmologica. ISSN 1755-375X. doi: 10.1111/aos.16684. Fulltekst i vitenarkiv
• Lumi, Xhevat; Confalonieri, Filippo; Ravnik-Glavač, Metka; Goričar, Katja; Blagus, Tanja & Dolžan, Vita [Vis alle 9 forfattere av denne artikkelen] (2023). Inflammation and Oxidative Stress Gene Variability in Retinal Detachment Patients with and without Proliferative Vitreoretinopathy. Genes. 14(4). doi: 10.3390/genes14040804. Fulltekst i vitenarkiv Vis sammendrag

  This study investigated the association between certain genetic variations and the risk of developing proliferative vitreoretinopathy (PVR) after surgery. The study was conducted on 192 patients with primary rhegmatogenous retinal detachment (RRD) who underwent 3-port pars plana vitrectomy (PPV). The distribution of single nucleotide polymorphisms (SNPs) located in genes involved in inflammation and oxidative stress associated with PVR pathways were analyzed among patients with and without postoperative PVR grade C1 or higher. A total of 7 defined SNPs of 5 genes were selected for genotyping: rs4880 (SOD2); rs1001179 (CAT); rs1050450 (GPX1); rs1143623, rs16944, rs1071676 (IL1B); rs2910164 (MIR146A) using competitive allele-specific polymerase chain reaction. The association of SNPs with PVR risk was evaluated using logistic regression. Furthermore, the possible association of SNPs with postoperative clinical parameters was evaluated using non-parametric tests. The difference between two genotype frequencies between patients with or without PVR grade C1 or higher was found to be statistically significant: SOD2 rs4880 and IL1B rs1071676. Carriers of at least one polymorphic IL1B rs1071676 GG allele appeared to have better postoperative best-corrected visual acuity only in patients without PVR (p = 0.070). Our study suggests that certain genetic variations may play a role in the development of PVR after surgery. These findings may have important implications for identifying patients at higher risk for PVR and developing new treatments.

• Bisevac, Jovana; Moe, Morten Carsten; Drolsum, Liv Kari; Kristianslund, Olav; Petrovski, Goran & noer, agate (2023). A Novel Technique of Amniotic Membrane Preparation Mimicking Limbal Epithelial Crypts Enhances the Number of Progenitor Cells upon Expansion. Cells. 12(5). doi: 10.3390/cells12050738. Fulltekst i vitenarkiv Vis sammendrag

  We aimed to investigate whether a novel technique of human amniotic membrane (HAM) preparation that mimics the crypts in the limbus enhances the number of progenitor cells cultured ex vivo. The HAMs were sutured on polyester membrane (1) standardly, to obtain a flat HAM surface, or (2) loosely, achieving the radial folding to mimic crypts in the limbus. Immunohistochemistry was used to demonstrate a higher number of cells positive for progenitor markers p63α (37.56 ± 3.34% vs. 62.53 ± 3.32%, p = 0.01) and SOX9 (35.53 ± 0.96% vs. 43.23 ± 2.32%, p = 0.04), proliferation marker Ki-67 (8.43 ± 0.38 % vs. 22.38 ± 1.95 %, p = 0.002) in the crypt-like HAMs vs. flat HAMs, while no difference was found for the quiescence marker CEBPD (22.99 ± 2.96% vs. 30.49 ± 3.33 %, p = 0.17). Most of the cells stained negative for the corneal epithelial differentiation marker KRT3/12, and some were positive for N-cadherin in the crypt-like structures, but there was no difference in staining for E-cadherin and CX43 in crypt-like HAMs vs. flat HAMs. This novel HAM preparation method enhanced the number of progenitor cells expanded in the crypt-like HAM compared to cultures on the conventional flat HAM.

• Confalonieri, Filippo; Barone, Gianmaria; Ferraro, Vanessa; Ambrosini, Giacomo; Gaeta, Alessandro & Petrovski, Beata Eva [Vis alle 9 forfattere av denne artikkelen] (2023). Early versus Late Pars Plana Vitrectomy in Vitreous Hemorrhage: A Systematic Review. Journal of Clinical Medicine. 12(20). doi: 10.3390/jcm12206652. Fulltekst i vitenarkiv Vis sammendrag

  Background: Vitreous hemorrhage (VH) is a common vitreoretinal condition causing impairment of vision due to various etiologies. No consensus exists on the best timing for performing pars plana vitrectomy (PPV) in fundus-obscuring VH. Materials and Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, we conducted a systematic review of the timing of PPV in VH. We assessed the strength of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for all the included publications, in accordance with the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) recommendations. Results: A total of 1731 articles were identified. Following the removal of duplicates and screening of abstracts, 1203 articles remained. Subsequently, a comprehensive full-text review of 30 articles was conducted. Ultimately, 18 articles met the predefined inclusion criteria. Conclusions: Despite the small number of studies on the timing of treatment for VH, the advantage of early over late PPV seems to be a reasonable approach in selected cases, and it might be considered modern standard care.

• Hiller, John Kim; Sandås, Elise Mørk; Rootwelt, Helge; Vassli, Anja Østeby; Utheim, Tor Paaske & Moe, Morten Carsten [Vis alle 8 forfattere av denne artikkelen] (2023). Ex Vivo Pig Eye Model for Studying Diffusion of Acylcarnitines with Different Physicochemical Properties. Journal of Ocular Pharmacology and Therapeutics. ISSN 1080-7683. 39(5), s. 324–331. doi: 10.1089/jop.2022.0159. Fulltekst i vitenarkiv
• Bisevac, Jovana; Katta, Kirankumar; Petrovski, Goran; Moe, Morten Carsten & Noer, Agate (2023). Wnt/β-Catenin Signaling Activation Induces Differentiation in Human Limbal Epithelial Stem Cells Cultured Ex Vivo. Biomedicines. 11(7). doi: 10.3390/biomedicines11071829. Fulltekst i vitenarkiv Vis sammendrag

  Human limbal epithelial stem cells (hLESCs) continuously replenish lost or damaged human corneal epithelial cells. The percentage of stem/progenitor cells in autologous ex vivo expanded tissue is essential for the long-term success of transplantation in patients with limbal epithelial stem cell deficiency. However, the molecular processes governing the stemness and differentiation state of hLESCs remain uncertain. Therefore, we sought to explore the impact of canonical Wnt/β-catenin signaling activation on hLESCs by treating ex vivo expanded hLESC cultures with GSK-3 inhibitor LY2090314. Real-time qRT-PCR and microarray data reveal the downregulation of stemness (TP63), progenitor (SOX9), quiescence (CEBPD), and proliferation (MKI67, PCNA) genes and the upregulation of genes for differentiation (CX43, KRT3) in treated- compared to non-treated samples. The pathway activation was shown by AXIN2 upregulation and enhanced levels of accumulated β-catenin. Immunocytochemistry and Western blot confirmed the findings for most of the above-mentioned markers. The Wnt/β-catenin signaling profile demonstrated an upregulation of WNT1, WNT3, WNT5A, WNT6, and WNT11 gene expression and a downregulation for WNT7A and DKK1 in the treated samples. No significant differences were found for WNT2, WNT16B, WIF1, and DKK2 gene expression. Overall, our results demonstrate that activation of Wnt/β-catenin signaling in ex vivo expanded hLESCs governs the cells towards differentiation and reduces proliferation and stem cell maintenance capability.

• Gupta, Santosh; Lytvynchuk, Lyubomyr; Ardan, Taras; Studenovska, Hana; Sharma, Ruchi & Muñoz, Georgina Faura [Vis alle 14 forfattere av denne artikkelen] (2023). Progress in Stem Cells-Based Replacement Therapy for Retinal Pigment Epithelium: In Vitro Differentiation to In Vivo Delivery. Stem Cells Translational Medicine. ISSN 2157-6564. 12(8), s. 536–552. doi: 10.1093/stcltm/szad039. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Retinal pigment epithelium (RPE) is a critical cell monolayer forming the blood-retina-barrier (BRB) and a permeable bridge between the choriocapillaris and the retina. RPE is also crucial in maintaining photoreceptor function and for completing the visual cycle. Loss of the RPE is associated with the development of degenerative diseases like age-related macular degeneration (AMD). To treat diseases like AMD, pluripotent stem cell-derived RPE (pRPE) has been recently explored extensively as a regenerative module. pRPE like other ectodermal tissues requires specific lineage differentiation and long-term in vitro culturing for maturation. Therefore, understanding the differentiation process of RPE could be useful for stem cell-based RPE derivation. Developing pRPE-based transplants and delivering them into the subretinal space is another aspect that has garnered interest in the last decade. In this review, we discuss the basic strategies currently employed for stem cell-based RPE derivation, their delivery, and recent clinical studies related to pRPE transplantation in patients. We have also discussed a few limitations with in vitro RPE culture and potential solutions to overcome such problems which can be helpful in developing functional RPE tissue.

• Gupta, Santosh; Sharma, Akriti; Petrovski, Goran & Verma, Rama Shanker (2023). Vascular reconstruction of the decellularized biomatrix for whole-organ engineering—a critical perspective and future strategies. Frontiers in Bioengineering and Biotechnology. 11. doi: 10.3389/fbioe.2023.1221159. Fulltekst i vitenarkiv Vis sammendrag

  Whole-organ re-engineering is the most challenging goal yet to be achieved in tissue engineering and regenerative medicine. One essential factor in any transplantable and functional tissue engineering is fabricating a perfusable vascular network with macro- and micro-sized blood vessels. Whole-organ development has become more practical with the use of the decellularized organ biomatrix (DOB) as it provides a native biochemical and structural framework for a particular organ. However, reconstructing vasculature and re-endothelialization in the DOB is a highly challenging task and has not been achieved for constructing a clinically transplantable vascularized organ with an efficient perfusable capability. Here, we critically and articulately emphasized factors that have been studied for the vascular reconstruction in the DOB. Furthermore, we highlighted the factors used for vasculature development studies in general and their application in whole-organ vascular reconstruction. We also analyzed in detail the strategies explored so far for vascular reconstruction and angiogenesis in the DOB for functional and perfusable vasculature development. Finally, we discussed some of the crucial factors that have been largely ignored in the vascular reconstruction of the DOB and the future directions that should be addressed systematically.

• Agra, Lydianne Lumack do Monte; Sverstad, Alexander; Chagas, Thiago A; Araujo, Rodrigo H.; Oliveira, Larissa & Kristianslund, Olav [Vis alle 11 forfattere av denne artikkelen] (2023). Accuracy, Precision, and Residual Volume of Commonly Used Syringes for Intravitreal Injections and the Impact on Intraocular Pressure. Ophthalmology Retina. ISSN 2468-7219. 7(10), s. 892–900. doi: 10.1016/j.oret.2023.06.003. Fulltekst i vitenarkiv Vis sammendrag

  Purpose To compare accuracy, precision, and residual volume of commonly used syringes for intravitreal injections (IVIs) and to assess the intraocular pressure (IOP) rise by variations in volumes delivered. Design Experimental laboratory study. Subjects No subjects were involved in this study. Methods We tested 8 syringe models with 2 different needle setups, with 2 different solutions (distilled water or glycerin) and target volumes (50 and 70 μL). To obtain the delivered and residual volumes, we weighed the syringe-needle setups with scale before liquid withdrawal, with liquid, and after liquid release. We also created an experimental eye model to determine the transient rise in IOP following stepwise 10-μL increases in injection volumes. Main Outcome Measures Delivered and residual volumes, IOP rise. Results We tested a total of 600 syringe-needle setups. Becton Dickinson (BD) Ultra-Fine (0.34 ± 0.28 μL), Zero Residual (1.53 ± 1.15 μL), and Zero Residual Silicone Oil-free (1.40 ± 1.16 μL) syringes showed the lowest residual volume (P < 0.001) in comparison with the others (range: 24.86 ± 1.78 μL for Injekt-F to 51.97 ± 3.37 μL for Omnifix-F). The most accurate setups were (percentage deviation from target volume): Zero Residual Silicone Oil-free (+ 0.70%), Zero Residual 0.3 ml (+ 4.49%), BD Ultra-Fine (+ 7.83%), Injekt-F (9.42%), Norm-Ject (+ 15.88%), Omnifix-F (+ 16.96%), BD Plastipak Brazil (+17.96%), and BD Plastipak Spain syringes (+ 19.41%). There was a statistically significant difference between the Zero Residual Silicone Oil-free syringe and all other syringes (P < 0.0001), except for the Zero Residual 0.3-ml syringe (P = 0.029). The coefficient of variation was low for all syringes. The modeled IOP rise ranged from 32.3 (standard deviation [SD], 1.4) mmHg for 20-μL injection volume to 76.5 (SD, 1.0) mmHg for 80-μL injection volume. For the standard 50-μL injection volume, the peak pressure was 50.7 (SD, 0.1) mmHg, and the pressure rise duration was 28 (SD, 2) minutes. Conclusions There were significant differences in accuracy and residual volume between syringes, whereas they showed a high precision. Volume excess results in a considerable increase in IOP rise after injection. These findings may provide a relevant overview to clinicians and to both device and drug manufacturers regarding pharmacoeconomic, safety, and efficacy issues.

• Lemonche, Gerard Boix; Nagymihaly, Richard; Niemi, Essi Maria; Josifovska, Natasha; Johansen, Stian & Moe, Morten Carsten [Vis alle 8 forfattere av denne artikkelen] (2023). Intracorneal Implantation of 3D Bioprinted Scaffolds Containing Mesenchymal Stromal Cells Using Femtosecond-Laser-Assisted Intrastromal Keratoplasty. Macromolecular Bioscience. ISSN 1616-5187. 23. doi: 10.1002/mabi.202200422. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Injury of the cornea is a complex biological process. Regeneration of the corneal stroma can be facilitated by the presence of mesenchymal stromal cells (MSCs) and application of tissue equivalents. A new tissue‐engineering strategy for corneal stroma regeneration is presented using cellularized 3D bioprinted hydrogel constructs implanted into organ cultured porcine corneas using femtosecond laser‐assisted intrastromal keratoplasty. The ex vivo cultured, MSC‐loaded 3D bioprinted structures remain intact, support cell survival, and contain de novo synthesized extracellular matrix components and migrating cells throughout the observation period. At day 14 postimplantation, the cellularized tissue equivalents contain few or no cells, as demonstrated by optical coherence tomography imaging and immunofluorescent staining. This study successfully combines a laboratory‐based method with modern, patient‐care practice to produce a cell‐laden tissue equivalent for corneal implantation. Optimal bioink composition and cellularization of tissue equivalents are essential in fine‐tuning a method to promote the current technique as a future treatment modality.

• Confalonieri, Filippo; Josifovska, Natasha; Lemonche, Gerard Boix; Stene-Johansen, Ingar; Bragadottir, Ragnheidur & Lumi, Xhevat [Vis alle 7 forfattere av denne artikkelen] (2023). Vitreous Substitutes from Bench to the Operating Room in a Translational Approach: Review and Future Endeavors in Vitreoretinal Surgery. International Journal of Molecular Sciences. ISSN 1661-6596. 24(4). doi: 10.3390/ijms24043342. Fulltekst i vitenarkiv Vis sammendrag

  Vitreous substitutes are indispensable tools in vitreoretinal surgery. The two crucial functions of these substitutes are their ability to displace intravitreal fluid from the retinal surface and to allow the retina to adhere to the retinal pigment epithelium. Today, vitreoretinal surgeons can choose among a plethora of vitreous tamponades, and the tamponade of choice might be difficult to determine in the ever-expanding range of possibilities for a favorable outcome. The currently available vitreous substitutes have disadvantages that need to be addressed to improve the surgical outcome achievable today. Herein, the fundamental physical and chemical proprieties of all vitreous substitutes are reported, and their use and clinical applications are described alongside some surgical techniques of intra-operative manipulation. The major upcoming developments in vitreous substitutes are extensively discussed, keeping a translational perspective throughout. Conclusions on future perspectives are derived through an in-depth analysis of what is lacking today in terms of desired outcomes and biomaterials technology.

• Sauesund, Ellen Steffenssen; Jørstad, Øystein Kalsnes; Brunborg, Cathrine; Moe, Morten Carsten; Erke, Maja Gran & Fosmark, Dag Sigurd [Vis alle 7 forfattere av denne artikkelen] (2023). A Pilot Study of Implementing Diabetic Retinopathy Screening in the Oslo Region, Norway: Baseline Results. Biomedicines. 11(4). doi: 10.3390/biomedicines11041222. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: to gain insight into the baseline parameters of a population with diabetes mellitus (DM) included in a pilot diabetic retinopathy (DR) screening program at Oslo University Hospital (OUH), Norway. Methods: This was a cross-sectional study of a cohort of adult patients (≥18 years) with type 1 or 2 DM (T1D and T2D). We measured the best-corrected visual acuity (BCVA), blood pressure (BP), heart rate (HR), intraocular pressure (IOP), height and weight. We also collected HbA1c, total serum cholesterol and urine-albumin, -creatinine and -albumin-to-creatinine ratio (ACR), as well as socio-demographic parameters, medications and previous screening history. We obtained color fundus photographs, which were graded by two experienced ophthalmologists according to the International Clinical Disease Severity Scale for DR. Results: The study included 180 eyes of 90 patients: 12 patients (13.3%) had T1D and 78 (86.7%) had T2D. In the T1D group, 5 patients (41.7%) had no DR, and 7 (58.3%) had some degree of DR. In the T2D group, 60 patients (76.9%) had no DR, and 18 (23.1%) had some degree of DR. None of the patients had proliferative DR. Of the 43 patients not newly diagnosed (time of diagnosis &gt; 5 years for T1D and &gt;1 years for T2D), 37.5% of the T1D patients and 5.7% of the T2D patients had previously undergone regular screening. Univariate analyses found for the whole cohort significant associations between DR and age, HbA1c, urine albumin-to-creatinine ratio, body mass index (BMI) and duration of DM. For the T2D group alone, there were significant associations between DR and HbA1c, BMI, urine creatinine, urine albumin-to-creatinine ratio and duration of DM. The analysis also showed three times higher odds for DR in the T1D group than the T2D group. Conclusions: This study underscores the need for implementing a systematic DR screening program in the Oslo region, Norway, to better reach out to patients with DM and improve their screening adherence. Timely and proper treatment can prevent or mitigate vision loss and improve the prognosis. A considerable number of patients were referred from general practitioners for not being followed by an ophthalmologist.Among patients not newly diagnosed with DM, 62.8% had never had an eye exam, and the duration of DM for these patients was up to 18 years (median: 8 years).

• Raudonis, Vidas; Kairys, Arturas; Verkauskiene, Rasa; Sokolovska, Jelizaveta; Petrovski, Goran & Balciuniene, Vilma Jurate [Vis alle 7 forfattere av denne artikkelen] (2023). Automatic Detection of Microaneurysms in Fundus Images Using an Ensemble-Based Segmentation Method. Sensors. 23(7). doi: 10.3390/s23073431. Fulltekst i vitenarkiv Vis sammendrag

  In this study, a novel method for automatic microaneurysm detection in color fundus images is presented. The proposed method is based on three main steps: (1) image breakdown to smaller image patches, (2) inference to segmentation models, and (3) reconstruction of the predicted segmentation map from output patches. The proposed segmentation method is based on an ensemble of three individual deep networks, such as U-Net, ResNet34-UNet and UNet++. The performance evaluation is based on the calculation of the Dice score and IoU values. The ensemble-based model achieved higher Dice score (0.95) and IoU (0.91) values compared to other network architectures. The proposed ensemble-based model demonstrates the high practical application potential for detection of early-stage diabetic retinopathy in color fundus images.

• Confalonieri, Filippo; Lumi, Xhevat & Petrovski, Goran (2023). Spontaneous Epiretinal Membrane Resolution and Angiotensin Receptor Blockers: Case Observation, Literature Review and Perspectives. Biomedicines. 11(7). doi: 10.3390/biomedicines11071976. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Epiretinal membrane (ERM) is a relatively common condition affecting the macula. When symptoms become apparent and compromise a patient’s quality of vision, the only therapeutic approach available today is surgery with a vitrectomy and peeling of the ERM. Angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACE-Is) reduce the effect of angiotensin II, limit the amount of fibrosis, and demonstrate consequences on fibrinogenesis in the human body. Case Description and Materials and Methods: A rare case of spontaneous ERM resolution with concomitant administration of ARB is reported. The patient was set on ARB treatment for migraines and arterial hypertension, and a posterior vitreous detachment was already present at the first diagnosis of ERM. The scientific literature addressing the systemic relationship between ARB, ACE-Is, and fibrosis in the past 25 years was searched in the PubMed, Medline, and EMBASE databases. Results: In total, 38 and 16 original articles have been selected for ARBs and ACE-Is, respectively, in regard to fibrosis modulation. Conclusion: ARBs and ACE-Is might have antifibrotic activity on ERM formation and resolution. Further clinical studies are necessary to explore this phenomenon.

• gjølberg, torleif; Wik, Jonas Aakre; Johannessen, Hanna; Krüger, Stig; Bassi, Nicola & Christopoulos, Panagiotis [Vis alle 15 forfattere av denne artikkelen] (2023). Antibody blockade of Jagged1 attenuates choroidal neovascularization. Nature Communications. 14(1). doi: 10.1038/s41467-023-38563-w. Fulltekst i vitenarkiv Vis sammendrag

  Antibody-based blocking of vascular endothelial growth factor (VEGF) reduces choroidal neovascularization (CNV) and retinal edema, rescuing vision in patients with neovascular age-related macular degeneration (nAMD). However, poor response and resistance to anti-VEGF treatment occurs. We report that targeting the Notch ligand Jagged1 by a monoclonal antibody reduces neovascular lesion size, number of activated phagocytes and inflammatory markers and vascular leakage in an experimental CNV mouse model. Additionally, we demonstrate that Jagged1 is expressed in mouse and human eyes, and that Jagged1 expression is independent of VEGF signaling in human endothelial cells. When anti-Jagged1 was combined with anti-VEGF in mice, the decrease in lesion size exceeded that of either antibody alone. The therapeutic effect was solely dependent on blocking, as engineering antibodies to abolish effector functions did not impair the therapeutic effect. Targeting of Jagged1 alone or in combination with anti-VEGF may thus be an attractive strategy to attenuate CNV-bearing diseases.

• Hedengran, Anne; Freiberg, Josefine; Hansen, Pernille May; Lemonche, Gerard Boix; Utheim, Tor Paaske & Dartt, Darlene Ann [Vis alle 9 forfattere av denne artikkelen] (2023). Comparing the effect of benzalkonium chloride-preserved, polyquad-preserved, and preservative-free prostaglandin analogue eye drops on cultured human conjunctival goblet cells. Journal of optometry. ISSN 1888-4296. 17(1). doi: 10.1016/j.optom.2023.100481. Fulltekst i vitenarkiv Vis sammendrag

  Purpose To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK-preserved and PF latanoprost on the cytokine secretion from GC. Methods Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)-6 and IL-8 from GC. Results BAK-preserved latanoprost and bimatoprost reduced cell survival by 28% (p = 0.0133) and 20% (p = 0.0208), respectively, in the LDH assay compared to a negative control. BAK-preserved latanoprost reduced cell proliferation by 54% (p = 0.003), BAK-preserved bimatoprost by 45% (p = 0.006), PQ-preserved travoprost by 16% (p = 0.0041), and PF latanoprost by 19% (p = 0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK-preserved latanoprost caused an increase in the secretion of pro-inflammatory IL-6 and IL-8 (p = 0.0001 and p = 0.0019, respectively) compared to a negative control, which PF latanoprost did not. Conclusion BAK-preserved PGA eye drops were more cytotoxic to GCs than PQ-preserved and PF PGA eye drops. BAK-preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ-preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK-preserved PGA eye drops.

• Borjan, Ivan; Stanić, Robert; Pleština-Borjan, Ivna; Pavić, Maja; Hertzberg, Silvia Nanjala Walekhwa & Znaor, Ljubo [Vis alle 8 forfattere av denne artikkelen] (2023). Pseudoexfoliative Syndrome in Cataract Surgery—A Quality Register Study and Health Economic Analysis in the Split-Dalmatia County, Croatia. Journal of Clinical Medicine. 13(1). doi: 10.3390/jcm13010038. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To investigate the impact of pseudoexfoliation (PEX) syndrome on intraoperative phacoemulsification (PHACO) parameters and assess the economic cost of PHACO surgery for cataracts in patients with and without PEX syndrome. Methods: This was a retrospective quality register study on 5889 patients (6236 eyes) who underwent PHACO cataract surgery in the Eye Clinic, Clinical Hospital Centre Split, Croatia, over a 7-year period (May 2015 to December 2022), in accordance with the Guidelines of the Helsinki Declaration and approval from the Research Ethics Committee of the University Hospital Centre Split, Croatia. Inclusion criteria were patients with either presenile or senile cataract or cataract related to PEX syndrome who undertook PHACO procedure by the same experienced surgeon using the same PHACO device (Infiniti Vision System, Alcon Laboratories, Inc., Fort Worth, TX, USA). Eyes were categorized according to PEX presence- (PEX group) or absence (Group without PEX). The following recorded data about intraoperative PHACO parameters were collected: Cumulative Dissipated Energy (CDE), Ultrasound total time, PHACO time, torsional time, aspiration time, estimated fluid used, and duration of the surgical procedure. In the economic analysis, all PHACO parameters were considered, with a specific focus on the duration of the surgical procedure, costs associated with additional medical materials and devices, complications during surgery, and surgery procedure Diagnosis-Related Group (DRG) codes. Results: A total of 4535 cases were eligible for inclusion in the study, 278 (6.13%) were diagnosed with PEX and 4257 (93.87%) had no PEX. Significantly higher PHACO parameters were observed in the PEX group. Similarly, a statistically significant increase in the values of all PHACO parameters was observed with the increase in nuclear lens density. Intraoperative complications were more frequent in the PEX group. Zonular weakness requiring the use of a capsular tension ring (CTR) and posterior capsular rupture occurred 30 and 13 times more often, respectively, in the PEX group. The expected cost of the PHACO procedure was found to be 1.4 times higher in patients with PEX, compared to those without PEX, for all types of nuclear cataract. Conclusions: All PHACO parameters are significantly higher in patients with PEX. The costs associated with PHACO surgery for cataracts are greater for patients with PEX and are not covered by the present DRG codes, which highlights the need to accordingly adjust the DRGs for PHACO procedures in PEX patients, in order to maintain the quality of healthcare provided for these vulnerable patients.

• Confalonieri, Filippo; Haave, Hanna; Binder, Susanne; Bober, Agnieszka Monika; Bragadottir, Ragnheidur & Bærland, Thomas Pedersen [Vis alle 40 forfattere av denne artikkelen] (2023). Macular hole Delphi consensus statement (MHOST). Acta Ophthalmologica. ISSN 1755-375X. 101, s. 815–825. doi: 10.1111/aos.15682. Fulltekst i vitenarkiv Vis sammendrag

  Purpose To derive a Delphi method-based consensus for the surgical management of Full Thickness Macular Hole (FTMH) and Lamellar Macular Hole (LMH). Methods 37 expert VR surgeons from 21 mainly European countries participated in Delphi method-based questionnaire for diagnosis and treatment of FTMHs and LMHs. Results A total of 36 items were rated in round 1 by 37 participants, of which 10 items achieved consensus: intraoperative verification of PVD; clinical superiority of OCT-based FTMH classification; practical ineffectiveness of ocriplasmin; circular 360° ILM peeling for small macular holes; use of regular surgical technique for the size of the hole in concomitant retinal detachment; performing complete vitrectomy; SF6 gas as preferred tamponade; cataract surgery if crystalline lens is mildly/moderately opaque; removal of both ILM and LHEP in LMH surgery. In round 2, 18 items with moderate consensus (45-70% agreement) in round 1 were rated by 35 participants. Final consensus was reached in 35% of questions related to both diagnosis and surgical procedures. Conclusions This Delphi study provides valuable information about the consensus/disagreement on different scenarios encountered during FTMH and LMH management as a guide tosurgical decision-making. High rate of disagreement and/or variable approaches still exist for treating such relatively common conditions.

• Lemonche, Gerard Boix; Nagymihaly, Richard; Lumi, Xhevat & Petrovski, Goran (2023). The human lens is capable of trilineage differentiation towards osteo-, chondro-, and adipogenesis—a model for studying cataract pathogenesis. Frontiers in Bioengineering and Biotechnology. 11. doi: 10.3389/fbioe.2023.1164795. Fulltekst i vitenarkiv Vis sammendrag

  The potential for trilineage differentiation of cells in tissues represents a model for studying disease pathogenesis and regeneration pathways. Human lens trilineage differentiation has not yet been demonstrated, and so has calcification and osteogenic differentiation of human lens epithelial cells in the whole human lens. Such changes can pose a risk for complications during cataract surgery. Human lens capsules ( n = 9) from cataract patients undergoing uneventful surgery were trilineage-differentiated toward osteogenesis, chondrogenesis, and adipogenesis. Furthermore, whole human healthy lenses ( n = 3) collected from cadaveric eyes were differentiated into bone and characterized by immunohistochemistry. The cells in the human lens capsules were capable of undergoing trilineage differentiation, while the whole human healthy lenses could undergo osteogenesis differentiation, expressing osteocalcin, collagen I, and pigment epithelium-derived factor. We, hereby, show an ex vivo model for cataract formation through different stages of opacification, as well as provide in vivo evidence from patients undergoing calcified lens extraction with bone-like consistency.

• Confalonieri, Filippo; Ferraro, Vanessa; Maria, Alessandra Di; Gaeta, Alessandro; Vallejo-Garcia, Josè Luis & Vinciguerra, Paolo [Vis alle 8 forfattere av denne artikkelen] (2023). Antiplatelets and Anticoagulants in Vitreoretinal Surgery: A Systematic Review. Life. 13(6). doi: 10.3390/life13061362. Fulltekst i vitenarkiv Vis sammendrag

  Background: Antiplatelets and anticoagulants have substantially influenced contemporary vitreoretinal surgical practices. The availability of new oral blood thinners has recently spurred a renewed interest in the clinical approach to vitreoretinal surgical conditions since it may be difficult for the surgeon to collect sufficient evidence-based data to decide whether to discontinue or continue such medications. Materials and Methods: We conducted a systematic review on the use of antiplatelets and/or anticoagulants in the perioperative setting in vitreoretinal surgery and their possible complications, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The level of evidence, according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines, and the quality of evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, were assessed for all included articles. Results: In total, 2310 articles were initially extracted, out of which 1839 articles were obtained after duplicates were removed and their abstracts were screened. A total of 27 articles were included in the full-text review. Finally, a remaining 22 articles fulfilled the inclusion criteria. Conclusions: Even though there is just a small number of studies with solid results, the advantage of using antiplatelets and/or anticoagulants in vitreoretinal surgery seems to outweigh the disadvantages, which are mainly related to postoperative hemorrhagic complications.

• Gupta, Santosh; Lytvynchuk, Lyubomyr; Ardan, Taras; Studenovska, Hana; Munoz, Georgina Faura & Eide, Lars [Vis alle 12 forfattere av denne artikkelen] (2023). Retinal Pigment Epithelium Cell Development: Extrapolating Basic Biology to Stem Cell Research. Biomedicines. 11(2). doi: 10.3390/biomedicines11020310. Fulltekst i vitenarkiv
• Josifovska, Natasha; Andjelic, Sofija; Lytvynchuk, Lyubomyr; Lumi, Xhevat; Dučić, Tanja & Petrovski, Goran (2023). Biomacromolecular Profile in Human Primary Retinal Pigment Epithelial Cells—A Study of Oxidative Stress and Autophagy by Synchrotron-Based FTIR Microspectroscopy. Biomedicines. 11(2). doi: 10.3390/biomedicines11020300. Fulltekst i vitenarkiv Vis sammendrag

  Synchrotron radiation-based Fourier Transform Infrared (SR-FTIR) microspectroscopy is a non-destructive and chemically sensitive technique for the rapid detection of changes in the different components of the cell’s biomacromolecular profile. Reactive oxygen species and oxidative stress may cause damage to the DNA, RNA, and proteins in the retinal pigment epithelium (RPE), which can further lead to age-related macular degeneration (AMD) and visual loss in the elderly. In this study, human primary RPEs (hRPEs) were used to study AMD pathogenesis by using an established in vitro cellular model of the disease. Autophagy—a mechanism of intracellular degradation, which is altered during AMD, was studied in the hRPEs by using the autophagy inducer rapamycin and treated with the autophagy inhibitor bafilomycin A1. In addition, oxidative stress was induced by the hydrogen peroxide (H2O2) treatment of hRPEs. By using SR-FTIR microspectroscopy and multivariate analyses, the changes in the phosphate groups of nucleic acids, Amide I and II of the proteins, the carbonyl groups, and the lipid status in the hRPEs showed a significantly different pattern under oxidative stress/autophagy induction and inhibition. This biomolecular fingerprint can be evaluated in future drug discovery studies affecting autophagy and oxidative stress in AMD.

• Confalonieri, Filippo; Souza, Boža Gorenjak de; Petrovski, Goran & Lumi, Xhevat (2022). Severe Retinal Necrosis Due to Klebsiella pneumoniae After Acute Prostatitis. American Journal of Case Reports. 23. doi: 10.12659/AJCR.937512. Fulltekst i vitenarkiv
• Pusnik, Ambrose; Petrovski, Goran & Lumi, Xhevat (2022). Dysphotopsias or Unwanted Visual Phenomena after Cataract Surgery. Life. 13(1), s. 1–13. doi: 10.3390/life13010053. Fulltekst i vitenarkiv Vis sammendrag

  Dysphotopsias are unwanted visual phenomena that occur after cataract surgery. They represent some of the most common reasons for patient dissatisfaction after uncomplicated surgery for cataract phacoemulsification with in-the-bag intraocular lens (IOL) implantation. Depending on the form of the optical phenomenon and the effect it poses on vision, dysphotopsias are divided into positive and negative type. Positive dysphotopsias are usually described by patients as glare, light streaks, starbursts, light arcs, rings, haloes, or flashes of light. Negative dysphotopsias are manifested as an arc-shaped shadow or line usually located in the temporal part of the visual field, similar to a temporal scotoma. In addition to their different clinical manifestations, positive and negative dysphotopsia also have different risk factors. Even though up to 67% of patients may experience positive dysphotopsia immediately after surgery, only 2.2% of the cases have persistent symptoms up to a year postoperatively. Surgical intervention may be indicated in 0.07% of cases. The incidence of negative dysphotopsias is up to 26% of all patients; however, by one year postoperatively, the symptoms usually persist in 0.13 to 3% of patients. For both types of dysphotopsia, preoperative patients’ education, accurate preoperative diagnostics, and use of an appropriate IOL design and material is mandatory. Despite all these measures, dysphotopsias may occur, and when noninvasive measures fail to improve symptoms, a surgical approach may be considered.

• Jacobsen, Henrik Holvin; Jørstad, Øystein Kalsnes; Moe, Morten Carsten; Petrovski, Goran; Pripp, Are Hugo & Sandell, Tiril [Vis alle 7 forfattere av denne artikkelen] (2022). Noninvasive Estimation of Pulsatile and Static Intracranial Pressure by Optical Coherence Tomography. Translational Vision Science & Technology. 11. doi: 10.1167/tvst.11.1.31. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To explore the ability of optical coherence tomography (OCT) to noninvasively estimate pulsatile and static intracranial pressure (ICP). Methods: An OCT examination was performed in patients who underwent continuous overnight monitoring of the pulsatile and static ICP for diagnostic purpose. We included two patient groups, patients with idiopathic intracranial hypertension (IIH; n = 20) and patients with no verified cerebrospinal fluid disturbances (reference; n = 12). Several OCT parameters were acquired using spectral-domain OCT (RS-3000 Advance; NIDEK, Singapore). The ICP measurements were obtained using a parenchymal sensor (Codman ICP MicroSensor; Johnson & Johnson, Raynham, MA, USA). The pulsatile ICP was determined as the mean ICP wave amplitude (MWA), and the static ICP was determined as the mean ICP. Results: The peripapillary Bruch's membrane angle (pBA) and the optic nerve head height (ONHH) differed between the IIH and reference groups and correlated with both MWA and mean ICP. Both OCT parameters predicted elevated MWA. Area under the curve and cutoffs were 0.82 (95% confidence interval [CI], 0.66–0.98) and -0.65° (sensitivity/specificity; 0.75/0.92) for pBA and 0.84 (95% CI, 0.70–0.99) and 405 µm (0.88/0.67) for ONHH. Adjusting for age and body mass index resulted in nonsignificant predictive values for mean ICP, whereas the predictive value for MWA remained significant. Conclusions: This study provides evidence that the OCT parameters pBA and ONHH noninvasively can predict elevated pulsatile ICP, represented by the MWA. Translational Relevance: OCT shows promise as a method for noninvasive estimation of ICP.

• Confalonieri, Filippo; Haave, Hanna; Bragadottir, Ragnheidur; Stene-Johansen, Ingar; Lumi, Xhevat & Lytvynchuk, Lyubomyr [Vis alle 7 forfattere av denne artikkelen] (2022). Intraoperative Optical Coherence Tomography in the Management of Macular Holes: State of the Art and Future Perspectives. Biomedicines. 10(11), s. 1–24. doi: 10.3390/biomedicines10112873. Fulltekst i vitenarkiv Vis sammendrag

  Background: Non-invasive diagnostic technologies in ophthalmology have substantially transformed contemporary clinical practice. Intraoperative optical coherence tomography (iOCT) systems have recently been used for various surgical interventions, including the treatment of full-thickness macular holes (FTMHs). Materials and Methods: We conducted a systematic review on the use of iOCT and its possible benefits in the management of FTMHs, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, were assessed for all included articles. Results: 1131 articles were initially extracted, out of which 694 articles were obtained after duplicates were removed and their abstracts screened. A total of 65 articles was included for full-text review. Finally, 17 articles remained that fulfilled the inclusion criteria. Conclusions: Even though there is just a small number of studies with solid results, the use of iOCT in FTMH surgery may be a helpful tool for both novice and experienced surgeons planning and managing difficult cases. Additionally, it could be used for teaching reasons and for exploring novel surgical techniques.

• Hertzberg, Silvia Nanjala Walekhwa; Jørstad, Øystein Kalsnes; Petrovski, Beata Eva; Bragadottir, Ragnheidur; Steffensen, Leif Arthur & Moe, Morten Carsten [Vis alle 8 forfattere av denne artikkelen] (2022). Transition from Laser to Intravitreal Injections for Diabetic Retinopathy: Hospital Utilization and Costs from an Extended Healthcare Perspective. International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 19(19), s. 1–16. doi: 10.3390/ijerph191912603. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To describe the trends in hospital utilization and economic outcomes associated with the transition from laser to intravitreal injection (IVI) therapy for diabetic retinopathy (DR) at Oslo University Hospital (OUH), which provides the largest retina service in Norway. Methods: This descriptive study analyzed hospital administrative data and determined the average utilization and treatment proportions of laser therapy, IVIs and vitrectomy for each patient per year. The Chi-square test was used to compare resource use between treatment groups. From an extended healthcare perspective, the annual cost per patient was calculated using Norwegian tariff data from 2020 and the National Medication Price Registry for patients seen between 2010 and 2018. Bootstrapping was performed to generate 95% confidence intervals for the cost per patient per year. Results: Among the 1838 (41% female) patients treated for DR between 2005 and 2018, OUH provided on average 1.09 laser treatments per DR patient and 0.54 vitrectomies per DR patient in 2005, whose utilization declined to 0.54 and 0.05 treatments per DR patient, respectively, by 2018. Laser treatments declined from 64% to 10%, while vitrectomies declined from 32% to 1%. In contrast, IVI treatments increased from 4.5% to 89% of the total share, representing an average increase, from 0.08 injections per patient in 2005 to 4.73 injections per patient in 2018. Both the increasing number of DR patients and the shift in the type of treatment increased the economic costs of treating DR from a total of EUR 0.605 million (EUR 2935 per patient) in 2010 to EUR 2.240 million (EUR 3665 per patient) in 2018, with IVIs contributing considerably to these costs. Conclusions: Despite the decline in the use of vitrectomies, the transition from laser to IVI therapy for DR increased the healthcare resource utilization and economic costs of its treatment over the observed time. A main cost driver was the need for long-term IVIs, in addition to the drug cost itself. Trade-offs can be achieved through effective alternative IVI delivery or appropriate drug choice that balances patient needs with the economic burden of treating DR.

• Thein, Anna-Sophie; Hedengran, Anne; Azuara-Blanco, Augusto; Arita, Reiko; Cvenkel, Barbara & Gazzard, Gus [Vis alle 13 forfattere av denne artikkelen] (2022). Adverse Effects and Safety in Glaucoma Patients: Agreement on Clinical Trial Outcomes for Reports on Eye Drops (ASGARD)—A Delphi Consensus Statement. American Journal of Ophthalmology. ISSN 0002-9394. 241, s. 190–197. doi: 10.1016/j.ajo.2022.05.007. Fulltekst i vitenarkiv Vis sammendrag

  PURPOSE The purpose of this study is to establish consensus among experts on outcomes and methods to be used in clinical trials to assess adverse effects of anti-glaucomatous eye drops. DESIGN Modified Delphi method. METHODS Clinical experts from Europe, North America, South America, the Middle East, and Asia were invited to participate in 2 sequential web-based surveys administered from June 27 to August 29, 2021. A total of 91 clinical experts were invited to participate. Of these, 71 (78%) experts from 23 different countries accepted the invitation and answered the first questionnaire. The importance of items was ranked using a 10-point scale (1 as not important, 10 as very important). RESULTS A total of 84 items were rated in round one by 71 participants. Of these, 68 (81%) reached consensus. In round 2, 19 items, including 3 additional items, were rated by 53 (75%) participants. Consensus was reached in 98% of investigated items. Eight outcomes were agreed as important to assess when conducting future trials: ocular surface, dryness, epithelial damage, local adverse effects related to eye drops as reported by patients, periocular surroundings and eyelids, quality of life questionnaires, hyperemia, visual acuity, tear film, and anterior chamber inflammation. CONCLUSION We propose a consensus-based series of outcomes and assessment methods to be used in clinical trials assessing adverse effects of antiglaucomatous eye drops. This, we hope, will improve the comparability of results from future trials and thus facilitate meta-analyses and progress in this field.

• Haave, Hanna; Petrovski, Beata Eva; Zając, Michał; Lumi, Xhevat; Melekidou, Wassiliki & Lytvynchuk, Lyubomyr [Vis alle 11 forfattere av denne artikkelen] (2022). Outcomes from the Retrospective Multicenter Cross-Sectional Study on Lamellar Macular Hole Surgery. Clinical Ophthalmology. ISSN 1177-5467. 16, s. 1847–1860. doi: 10.2147/OPTH.S351932. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To analyze the functional and anatomical parameters of lamellar macular hole (LMH) surgery with internal limiting membrane peeling and determine which surgical technique provides the best visual outcome. Methods: This is a retrospective multicenter cross-sectional study on patients who underwent pars plana vitrectomy (PPV) for LMH with or without combined phaco-vitrectomy, as well as gas-, air- or BSS-tamponade. Pre- and postoperative examination included best corrected visual acuity (BCVA) measurements for functional comparison and optical coherence tomography (OCT) scans to determine the contributing anatomical parameters. Results: A total of 66 consecutive patients were included (age: 71.79 ± 8.52 years), of which 47 (71.2%) were diagnosed as tractional type LMH, and 19 patients (28.8%) as degenerative type. An epiretinal membrane (ERM) was present in 63 of the patients (95.5%), LMH-associated epiretinal proliferation (LHEP) was present in 19 patients (28.8%), and 16 patients (24.2%) had concomitant ERM and LHEP. In the group of tractional LMH, the mean central foveal thickness (CFT) was 81.1% thicker (P < 0.05) than in the degenerative group. Thirty-one patients (47.0%) underwent a combined phaco-vitrectomy procedure, while the rest underwent 23G, 25G or 27G PPV. Seventeen of the 66 patients received gas-tamponade (25.7%)-either SF6 or C3F8, 26 received air-tamponade (39.4%), while the remaining 23 patients received balanced salt solution (BSS)-tamponade (34.9%) during vitrectomy. The total BCVA showed significant improvement postoperatively (p < 0.001) and accordingly in the following groups: tractional LMH type (p < 0.001), degenerative type (p < 0.001), simple PPV (p < 0.001), phaco-vitrectomy (p < 0.001), BSS injection (p < 0.01), gas-tamponade (p < 0.05). None of the patients included in the study developed a full thickness macular hole postoperatively. Conclusion: PPV provided a high success rate and functional improvement for treating LMH for both tractional and degenerative types, as well as combined phaco-vitrectomy treatment when cataract was present.

• Confalonieri, Filippo; NGO, Huy Bao; Petersen, Helga Huld Halldorsdottir; Eide, Nils & Petrovski, Goran (2022). Iris Racemose Hemangioma Assessment with Swept Source Optical Coherence Tomography Angiography: A Feasibility Study and Stand-Alone Comparison. Journal of Clinical Medicine. 11(21), s. 1–8. doi: 10.3390/jcm11216575. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To evaluate arteriovenous malformations (AVM) with swept-source (SS) optical coherence tomography (OCT) angiography (OCTA) in iris racemose hemangioma and compare it with traditional intravenous iris fluorescein angiography (IVFA). Methods: A cross-sectional observational clinical study was conducted on patients with iris racemose hemangioma with the ZEISS PLEX Elite 9000 SS OCT &amp; OCTA. Results: Three eyes of three patients were imaged. Iris racemose hemangiomas demonstrated a tortuous, well-defined, and continuous course of the AVM. The ZEISS PLEX Elite 9000 SS OCT &amp; OCTA allowed for a detailed visualization of the ARM and was superior to IVFA in depicting small caliber, fine vessels. Conclusions: SS-OCTA may provide a dye-free, no-injection, cost-effective method comparable to spectral domain OCTA and IVFA for diagnosing and monitoring iris racemose hemangiomas for growth and vascularity.

• Lytvynchuk, Lyubomyr; Ebbert, Annabelle; Studenovska, Hana; Nagymihaly, Richard; Josifovska, Natasha & Rais, David [Vis alle 23 forfattere av denne artikkelen] (2022). Subretinal Implantation of Human Primary RPE Cells Cultured on Nanofibrous Membranes in Minipigs. Biomedicines. 10(3). doi: 10.3390/biomedicines10030669. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: The development of primary human retinal pigmented epithelium (hRPE) for clinical transplantation purposes on biodegradable scaffolds is indispensable. We hereby report the results of the subretinal implantation of hRPE cells on nanofibrous membranes in minipigs. Methods: The hRPEs were collected from human cadaver donor eyes and cultivated on ultrathin nanofibrous carriers prepared via the electrospinning of poly(L-lactide-co-DL-lactide) (PDLLA). “Libechov” minipigs (12–36 months old) were used in the study, supported by preoperative tacrolimus immunosuppressive therapy. The subretinal implantation of the hRPE-nanofibrous carrier was conducted using general anesthesia via a custom-made injector during standard three-port 23-gauge vitrectomy, followed by silicone oil endotamponade. The observational period lasted 1, 2, 6 and 8 weeks, and included in vivo optical coherence tomography (OCT) of the retina, as well as post mortem immunohistochemistry using the following antibodies: HNAA and STEM121 (human cell markers); Bestrophin and CRALBP (hRPE cell markers); peanut agglutining (PNA) (cone photoreceptor marker); PKCα (rod bipolar marker); Vimentin, GFAP (macroglial markers); and Iba1 (microglial marker). Results: The hRPEs assumed cobblestone morphology, persistent pigmentation and measurable trans-epithelial electrical resistance on the nanofibrous PDLLA carrier. The surgical delivery of the implants in the subretinal space of the immunosuppressed minipigs was successfully achieved and monitored by fundus imaging and OCT. The implanted hRPEs were positive for HNAA and STEM121 and were located between the minipig’s neuroretina and RPE layers at week 2 post-implantation, which was gradually attenuated until week 8. The neuroretina over the implants showed rosette or hypertrophic reaction at week 6. The implanted cells expressed the typical RPE marker bestrophin throughout the whole observation period, and a gradual diminishing of the CRALBP expression in the area of implantation at week 8 post-implantation was observed. The transplanted hRPEs appeared not to form a confluent layer and were less capable of keeping the inner and outer retinal segments intact. The cone photoreceptors adjacent to the implant scaffold were unchanged initially, but underwent a gradual change in structure after hRPE implantation; the retina above and below the implant appeared relatively healthy. The glial reaction of the transplanted and host retina showed Vimentin and GFAP positivity from week 1 onward. Microglial activation appeared in the retinal area of the transplant early after the surgery, which seemed to move into the transplant area over time. Conclusions: The differentiated hRPEs can serve as an alternative cell source for RPE replacement in animal studies. These cells can be cultivated on nanofibrous PDLLA and implanted subretinally into minipigs using standard 23-gauge vitrectomy and implantation injector. The hRPE-laden scaffolds demonstrated relatively good incorporation into the host retina over an eight-week observation period, with some indication of a gliotic scar formation, and a likely neuroinflammatory response in the transplanted area despite the use of immunosuppression.

• Freiberg, Josefine C.; Hedengran, Anne; Heegaard, Steffen; Petrovski, Goran; Jacobsen, Jette & Cvenkel, Barbara [Vis alle 7 forfattere av denne artikkelen] (2022). An Evaluation of the Physicochemical Properties of Preservative-Free 0.005% (w/v) Latanoprost Ophthalmic Solutions, and the Impact on In Vitro Human Conjunctival Goblet Cell Survival. Journal of Clinical Medicine. 11(11), s. 1–12. doi: 10.3390/jcm11113137. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To examine the physicochemical properties of five preservative-free (PF) 0.005% latanoprost ophthalmic products; Monoprost®, Latanest®, Gaap Ofteno®, Xalmono®, and Xaloptic® Free. Furthermore, the study investigated the mucin production and cell survival of primary cultured human conjunctival goblet cells when treated with PF eye drops. Method: The pH value, osmolality, and surface tension were examined. Cell survival was analyzed using lactate dehydrogenase and tetrazolium dye colorimetric assays. Mucin production was analyzed with immunohistochemical staining. Results: Monoprost® (pH value 6.84 ± 0.032) had a pH value closest to the pH value of tear fluid (pH value 7.4–7.6), whereas Gaap Ofteno® (pH value 6.34 ± 0.004) and Latanest® (pH value 6.33 ± 0.003) had the lowest pH values. Gaap Ofteno® (325.9 ± 2.9 mosmol/kg) showed iso-osmolar probabilities, whereas the other products were hypo-osmolar. Gaap Ofteno® (60.31 ± 0.35 mN/m) had a higher surface tension compared to the tear fluid (40 to 46 mN/m), as described in the literature. No significant differences in goblet cell survival or mucin release were observed between the treatments and control. Conclusion: Significant differences in pH value, osmolality, and surface tension were observed. However, this did not affect the viability of the goblet cells or the release of mucin. Clinical studies are required to evaluate the long-term effects of use on efficacy and safety.

• Hertzberg, Silvia Nanjala Walekhwa; Moe, Morten Carstens; Jørstad, Øystein Kalsnes; Petrovski, Beata Eva; Burger, Emily Annika & Petrovski, Goran (2022). Healthcare expenditure of intravitreal anti-vascular endothelial growth factor inhibitors compared with dexamethasone implant for diabetic macular oedema. Acta Ophthalmologica. ISSN 1755-375X. 100(8), s. e1630–e1640. doi: 10.1111/aos.15151. Fulltekst i vitenarkiv Vis sammendrag

  Purpose The aim of this study was to estimate the 1-year costs associated with treating diabetic macular oedema (DME) patients using current intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics compared with the dexamethasone implant. Methods We conducted a descriptive cost-evaluation analysis using data from Oslo University Hospital and literature to compare three different intravitreal drugs for DME: bevacizumab, aflibercept and dexamethasone. Stratification of patients into ‘Naive’ or ‘Switch’ group was based on treatment history. We estimated the costs from healthcare and ‘extended’ healthcare perspectives. Sensitivity analysis evaluated the impact of various parameters. Results The average injections per patient per year for the Naive group (bevacizumab), Switch group (aflibercept) and dexamethasone were 9.5, 9.1 and 3.0 respectively. From a healthcare perspective, the 1-year costs for the Naive group were 15% lower (bevacizumab, €3619), and for the Switch group, 23% higher (aflibercept, €5226) compared with dexamethasone (€4252). The ‘extended’ healthcare perspective showed the cost per patient per year for bevacizumab remained nominally lower in the Naive group, while dexamethasone remained lower for the Switch group (€5116 for dexamethasone, compared to €4987 for bevacizumab and €6537 for aflibercept). Conclusions From a primary healthcare perspective, the dexamethasone as a first-line DME treatment may increase economic costs in settings where bevacizumab is used off-label. Treating resistant DMEwith dexamethasone may reduce the costs and treatment burden compared with switching to aflibercept.

• Kamøy, Bjørnar; Magnø, Morten Scherven; Nøland, Sara Julie Maria Tellefsen; Moe, Morten Carsten; Petrovski, Goran & Vehof, Jelle [Vis alle 7 forfattere av denne artikkelen] (2022). Video display terminal use and dry eye: preventive measures and future perspectives. Acta Ophthalmologica. ISSN 1755-375X. 100(7), s. 723–739. doi: 10.1111/aos.15105. Fulltekst i vitenarkiv Vis sammendrag

  Background Dry eye disease (DED) is a common cause of ocular pain and discomfort. Dry eye disease (DED) stems from a loss-of-tear film homeostasis and is frequently seen in video display terminal (VDT) users. Video display terminal (VDT) use reduces blink rates and increases incomplete blinks, leading to tear film instability and ocular inflammation, promoting DED. Purpose To assess and evaluate the methods for preventing VDT-associated DED and ocular discomfort. Methods Studies were found using PubMed and Embase with the search terms: (digital visual terminal* OR computer use OR screen use OR smartphone OR display OR visual display terminal* OR computer vision syndrome OR tablet OR phone OR screen time) AND (dry eye OR DED). Results Thirty-one relevant articles were found. Ten described single-visit studies, whereas 21 had a prolonged follow-up. Most preventive measures of VDT-associated DED aimed to increase blink rate or directly prevent tear film instability, ocular inflammation, mucin loss or ocular surface damage. Using an adjustable chair and ergonomic training, blink animations and omega-3 supplementation improved signs and symptoms of VDT-associated DED. Taking frequent breaks was associated with fewer symptoms, but no study assessed the commonly suggested 20-20-20 rule. Conclusion Preventive measures, such as blink animation programmes, oral intake of omega-3 fatty acids and improved ergonomics act on different parts of the vicious cycle of dry eye and could supplement each other. A comparison of the efficacy of the different interventions as well as more evidence of the effect of increased humidity, VDT filters and ergonomic practices, are required.

• Ruban, Andrii; Petrovski, Beata Eva; Petrovski, Goran & Lytvynchuk, Lyubomyr M. (2022). Internal Limiting Membrane Peeling and Gas Tamponade For Full-Thickness Macular Holes of Different Etiology – Is It Still Relevant? Clinical Ophthalmology. ISSN 1177-5467. 16, s. 3391–3404. doi: 10.2147/OPTH.S373675. Fulltekst i vitenarkiv Vis sammendrag

  Background: Despite the abundance of novel surgical approaches proposed for full thickness macular hole (FTMH) treatment, the choice of the optimal technique remains debatable Vitrectomy with «classic» internal limiting membrane peeling and gas tamponade remains the standard of FTMH surgery in many cases, but there are still very limited recent publications on the outcomes of such surgery. Purpose: To investigate the anatomical and functional result and to analyze the significance of outcome-related risk factors of the classic 25-gauge pars plana vitrectomy (PPV) with ILM peeling and gas tamponade (GT) for treatment of FTMH of different etiology. Patients and methods: Thirty-eight eyes of thirty-seven patients with FTMH who underwent 25-gauge PPV, ILM peeling and GT were recruited for this retrospective, consecutive, interventional study. Four eyes with persistent holes underwent a re-operation. Outcome-related factors were discussed. Results: The primary closure rate was 89.5% (34/38). All eyes that underwent the repeated surgery (4 cases) obtained final closure. A hole size of > 500 μm has a statistically significant effect on the primary macular hole closure (F = 0.048; &phis; = 0.38; p ˂ 0.05). In the general group (N = 38), the duration of symptoms directly correlated with age (ρ = 0.34; p = 0.04), size of the hole (ρ = 0.66; p ˂ 0.001) and BCVA before surgery (ρ = 0.59; p ˂ 0.001), after 1 month (ρ = 0.36; p = 0.03), and after 3 months (ρ = 0.35; p = 0.03). Preoperative BCVA was better in initially closed cases (Group 1) (U = 26.0; p = 0.05). In the Group 2 with primary unclosed holes, 75% of the eyes (3/4) had an axial length (AL) > 26 mm, while in Group 1 such eyes were 12.5 times less (2/34) 5.9% (F = 0.004; &phis; = 0.63; р ˂ 0.01). The ELM recovery rate at 3 months was 92% (35/38 eyes) and the restoration of EZ at 3 months was 47% (18/38 eyes). Best-corrected visual acuity of all individuals improved significantly from 0.72 ± 0.35 (logMAR) (Me = 0.7; IQR: 0.5– 0.8) to 0.25± 0.14 (logMAR) (Me = 0.2; IQR: 0.2 – 0.3) at 1 month and 0.17 ± 0.13 (logMAR) (Me = 0.2; IQR: 0.1 – 0.2) at 3 months after surgery (P = 0.0001). Conclusion: 25G PPV with ILM and GT for FTMH of different etiology provide satisfactory morphologic and functional outcomes. Elongated AL, large diameter of MH and long duration of symptoms are the risk factors for initial closure. Proper second surgery can obtain satisfactory outcomes for persistent holes.

• Hedengran, Anne; Freiberg, Josefine Clement; Hansen, Pernille May; Jacobsen, Jette; Larsen, Susan Weng & Harloff-Helleberg, Stine [Vis alle 11 forfattere av denne artikkelen] (2022). Generic benzalkonium chloride-preserved travoprost eye drops are not identical to the branded polyquarternium-1-preserved travoprost eye drop: Effect on cultured human conjunctival goblet cells and their physicochemical properties. Acta Ophthalmologica. ISSN 1755-375X. 100(7), s. 819–827. doi: 10.1111/aos.15163. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To investigate the effect of polyquaternium-1 (PQ)-preserved and benzalkonium chloride (BAK)-preserved travoprost eye drops on viability of primary human conjunctival goblet cell (GC) cultures and on secretion of mucin and cytokines. Furthermore, to evaluate the physicochemical properties of the branded travoprost eye drop Travatan and available generics. Methods: The effect of travoprost eye drops was evaluated on GC cultures. Cell viability was assessed through lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Mucin secretion was evaluated by immunohistochemical staining. Secretion of interleukin (IL)-6 and IL-8 was measured using BD Cytometric Bead Arrays. pH, viscosity, droplet mass, osmolality and surface tension were measured for all included eye drops. Results: In the LDH assay, BAK travoprost caused significant GC loss after 2 hrs of incubation compared to the control. PQ travoprost caused no GC loss at any time point. Both PQ- and BAK travoprost caused secretion of mucin to the cytoplasma. No difference in IL-6 and IL-8 secretion was identified compared to controls. The pH values for the generics were lower (pH 6.0) than the pH value for Travatan (pH 6.7; p < 0.0001). The viscosity was lowest for Travatan, while the mean droplet mass was higher for Travatan (35 mg) than the generics (28–30 mg; p ≤ 0.0318). The osmolality and surface tension did not differ between the eye drops investigated. Conclusion: BAK travoprost caused GC loss, indicating that PQ preservation may be preferable in treatment of glaucoma. Furthermore, physicochemical properties of branded and generic travoprost eye drops can not be assumed to be identical.

• Nes, Dragana; Berg-Hansen, Pål; Benavent, Sigrid Aune de Rodez; Høgestøl, Einar August; Beyer, Mona K. & Rinker, Daniel Allen [Vis alle 12 forfattere av denne artikkelen] (2022). Exploring Retinal Blood Vessel Diameters as Biomarkers in Multiple Sclerosis. Journal of Clinical Medicine. 11(11). doi: 10.3390/jcm11113109. Fulltekst i vitenarkiv Vis sammendrag

  We aimed to determine whether retinal vessel diameters and retinal oxygen saturation in newly diagnosed patients with multiple sclerosis (pwMS) are different from those of a healthy population. Retinal blood vessel diameters were measured using imaging with a spectrophotometric non-invasive retinal oximeter. Twenty-three newly diagnosed untreated relapsing-remitting MS (RRMS) patients (mean age: 32.2 ± 7.5 years, age range = 18–50 years, 56.5% female) were measured and compared to 23 age- and sex-matched healthy controls (HCs) (mean age: 34.8 ± 8.1 years). Patients with Optic Neuritis were excluded. Retinal venular diameter (143.8 µm versus 157.8 µm: mean; p = 0.0013) and retinal arteriolar diameter (112.6 µm versus 120.6 µm: mean; p = 0.0089) were smaller in pwMS when compared with HCs, respectively. There was no significant difference in the oxygen saturation in retinal venules and arterioles in pwMS (mean: 60.0% and 93.7%; p = 0.5980) compared to HCs (mean: 59.3% and 91.5%; p = 0.8934), respectively. There was a significant difference in the median low contrast visual acuity (2.5% contrast) between the pwMS and the HC groups (p = 0.0143) Retinal arteriolar and venular diameter may have potential as objective biomarkers for MS.

• Lumi, Xhevat; Petrovski, Beata Eva & Petrovski, Goran (2022). Simple new technique for macular pucker peel without forceps. Frontiers in Medicine. 9, s. 1–7. doi: 10.3389/fmed.2022.947578. Fulltekst i vitenarkiv Vis sammendrag

  Purpose This study aimed to describe the effectiveness and evaluate the anatomical and functional results of surgery for macular pucker (MP) peel using a 25-gauge pars plana vitrectomy (PPV) cutter without forceps. Methods This study assessed a prospective consecutive case series of 14 eyes of 14 patients who underwent 25-gauge PPV for MP. The surgical procedure was performed using the new peeling technique. The edge of the membrane was engaged at the opening of the cutter by gradually increasing the vacuum. The peeling process was finished by holding a stable vacuum or regrasping the membrane in the same manner. Results The study included six women and eight men patients with a mean age of 72.3 (range 59–84) years. MP peel was achieved in all cases without the need for microforceps. Patients were followed for at least 6 months. Visual acuity and retinal thickness were obtained 6 months after the surgery. Best corrected visual acuity improved from a mean pre-operative 0.6 on a logMAR scale to post-operative 0.23 ( P &amp;lt; 0.001). Mean pre-operative Central Retinal Thickness was significantly reduced from 489.7 to 377.6 μm post-operatively ( P &amp;lt; 0.001). There were no intra- or post-operative complications. Conclusion MP peel with a 25-gauge vitrectomy probe could be an alternative simple and safe technique. The technique does not require extra instrumentation. It results in anatomic and functional improvement in all cases.

• Muñoz, Georgina Faura; Lemonche, Gerard Boix; Holmeide, Anne Kristin; Verkauskiene, Rasa; Volke, Vallo & Sokolovska, Jelizaveta [Vis alle 7 forfattere av denne artikkelen] (2022). Colorimetric and Electrochemical Screening for Early Detection of Diabetes Mellitus and Diabetic Retinopathy—Application of Sensor Arrays and Machine Learning. Sensors. 22(3). doi: 10.3390/s22030718. Fulltekst i vitenarkiv Vis sammendrag

  In this review, a selection of works on the sensing of biomarkers related to diabetes mellitus (DM) and diabetic retinopathy (DR) are presented, with the scope of helping and encouraging researchers to design sensor-array machine-learning (ML)-supported devices for robust, fast, and cost-effective early detection of these devastating diseases. First, we highlight the social relevance of developing systematic screening programs for such diseases and how sensor-arrays and ML approaches could ease their early diagnosis. Then, we present diverse works related to the colorimetric and electrochemical sensing of biomarkers related to DM and DR with non-invasive sampling (e.g., urine, saliva, breath, tears, and sweat samples), with a special mention to some already-existing sensor arrays and ML approaches. We finally highlight the great potential of the latter approaches for the fast and reliable early diagnosis of DM and DR.

• Pasák, Michael; Vanišová, Marie; Tichotová, Lucie; Křížová, Jana; Ardan, Taras & Nemesh, Yaroslav [Vis alle 15 forfattere av denne artikkelen] (2022). Mitochondrial Dysfunction in a High Intraocular Pressure-Induced Retinal Ischemia Minipig Model. Biomolecules. 12(10), s. 1–13. doi: 10.3390/biom12101532. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: Retinal ischemia (RI) and progressive neuronal death are sight-threatening conditions. Mitochondrial (mt) dysfunction and fusion/fission processes have been suggested to play a role in the pathophysiology of RI. This study focuses on changes in the mt parameters of the neuroretina, retinal pigment epithelium (RPE) and choroid in a porcine high intraocular pressure (IOP)-induced RI minipig model. Methods: In one eye, an acute IOP elevation was induced in minipigs and compared to the other control eye. Activity and amount of respiratory chain complexes (RCC) were analyzed by spectrophotometry and Western blot, respectively. The coenzyme Q10 (CoQ10) content was measured using HPLC, and the ultrastructure of the mt was studied via transmission electron microscopy. The expression of selected mt-pathway genes was determined by RT-PCR. Results: At a functional level, increased RCC I activity and decreased total CoQ10 content were found in RPE cells. At a protein level, CORE2, a subunit of RCC III, and DRP1, was significantly decreased in the neuroretina. Drp1 and Opa1, protein-encoding genes responsible for mt quality control, were decreased in most of the samples from the RPE and neuroretina. Conclusions: The eyes of the minipig can be considered a potential RI model to study mt dysfunction in this disease. Strategies targeting mt protection may provide a promising way to delay the acute damage and onset of RI.

• Anisimova, Natalia; Arbisser, Lisa; Tzamalis, Argyrios; Petrovski, Beata Eva; Shilova, Natalya & Petrovski, Goran [Vis alle 8 forfattere av denne artikkelen] (2022). Corectopia grading: A novel classification system. Seminars in Ophthalmology. ISSN 0882-0538. 37(1), s. 105–110. doi: 10.1080/08820538.2021.1926517. Fulltekst i vitenarkiv
• Veiby, Nina; Simeunovic, Aida; Heier, Martin; Brunborg, Cathrine; Saddique, Naila & Moe, Morten C. [Vis alle 9 forfattere av denne artikkelen] (2021). Retinal venular oxygen saturation is associated with non-proliferative diabetic retinopathy in young patients with type 1 diabetes. Acta Ophthalmologica. ISSN 1755-375X. doi: 10.1111/aos.15018. Fulltekst i vitenarkiv Vis sammendrag

  Purpose To determine the contribution of retinal vessel density (VD), central retinal vessel diameter and retinal oxygen (O2) saturation independently of other known risk factors in the development of non-proliferative diabetic retinopathy (NPDR). Methods Macular optical coherence tomography angiography (OCTA), central retinal artery/vein equivalent diameter (CRAE/CRVE) measurements and retinal oximetry were performed in a cross-sectional study of 166 eyes from 166 individuals with type 1 diabetes (T1D) aged 14–30 years. Multiple logistic regression analysis was used to investigate whether O2 saturation, retinal vessel diameters and vessel density in the deep capillary plexus (VD-DCP) were associated with NPDR, when adjusting for known risk factors. The individuals were allocated to one group without and one group with NPDR. Results Multiple logistic regression analysis showed that age (OR = 1.25, 95% CI: 1.04–1.49) and AV-difference in O2 saturation (OR = 0.85, 95% CI 0.77–0.93) were significantly associated with NPDR. Conclusion Our findings suggest that age and lower AV-O2 saturation difference contribute to explaining the grade of NPDR independently of other well-known risk factors. Reduced delivery of O2 to the retinal tissue is associated with the development of NPDR in young patients with T1D and should be given appropriate weight in the risk stratification at early stages of the disease.

• Lytvynchuk, Lyubomyr; Petrovski, Goran; Dam, Adien; Hiemstra, Joep; Wimmer, Tobias & Savytska, Iryna [Vis alle 8 forfattere av denne artikkelen] (2021). Novel Needle for Intravitreal Drug Delivery: Comparative Study of Needle Tip Aspirates, Injection Stream and Penetration Forces. Clinical Ophthalmology. ISSN 1177-5467. 15, s. 723–734. doi: 10.2147/OPTH.S297139. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To study the efficacy of a novel needle for intravitreal injection (IVI) in comparison to the conventional needle under experimental conditions. Methods: The newly designed 30-gauge (G) needle (NDN) (EP 18158 542.3, patent pending) with occluded outer orifice and a side port for drug delivery was compared to the conventional standard hypodermic 30 G needle for IVI (SHN). An animal study to obtain needle tip aspirates was performed on 10 albino rat eyes. During IVIs, cellular content, which was cut by the needle tip, was aspirated. Cellular material was studied in regard to cell types and their quantity. The injection stream was studied using trypan blue dye in vitro and pig cadaver eyes. The penetration force was tested on polyurethane Testing Foil Strips PU 04 (Melab, Leonberg, Germany) by applying a velocity of 100 mm/min. The results were analyzed using descriptive statistics, correlation matrices and t-test methods with p< 0.05 as statistically significant. Results: Cytological analysis of the needle aspirates showed the presence of cellular content in each case. The amount of conjunctival, ciliary body epithelial cells and granulated basophilic protein sediments (sign of cellular damage) in the case of the NDN tips was significantly lower compared to the SHN. The average penetration force of the NDN was 0.791 N, and in the case of the SHN was 0.566 N. The injection stream study revealed a difference in the initial injection phase between the two needle types, although the diffuse filling of the vitreous area which surrounded the needle tip appeared to be similar. Discussion: The NDN demonstrated superior performance with regard to a significantly reduced number of cells being captured by the needle tip. Delivery of the injected fluid into the vitreous cavity was comparable. In order to investigate superior properties of the NDN needle design, further studies with improved prototypes would be necessary.

• Eidet, Jon Roger; Akopian, Maja; Olstad, Ole Kristoffer; Jørstad, Øystein Kalsnes; Moe, Morten Carsten & Petrovski, Goran [Vis alle 7 forfattere av denne artikkelen] (2021). The acute phase response protein SERPINA3 is increased in tear fluid from the unaffected eyes of patients with unilateral acute anterior uveitis. Journal of Ophthalmic Inflammation and Infection. 11(1), s. 1–10. doi: 10.1186/s12348-021-00249-z. Fulltekst i vitenarkiv Vis sammendrag

  Background To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. Methods Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay. Results Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population. Conclusions The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.

• Sivertsen, Magne S.; Lode, Heidrun Elisabeth; Gjølberg, Torleif Tollefsrud; Petrovski, Goran; Andersen, Jan Terje & Jørstad, Øystein Kalsnes [Vis alle 7 forfattere av denne artikkelen] (2021). Cluster of symptomatic silicone oil droplets following intravitreal injections: A 1-year observational study. BMJ Open Ophthalmology. 6:e000764(1), s. 1–5. doi: 10.1136/bmjophth-2021-000764. Fulltekst i vitenarkiv Vis sammendrag

  Objective To describe a cluster of symptomatic intravitreal silicone oil (SiO) droplets following intravitreal injections (IVIs) and assess the effect of switching to a SiO-free syringe. Methods and analysis Observational quality registry study of patients receiving IVI at a large Norwegian ophthalmology centre between April 2018 (start of cluster) and November 2019 (1 year after switching to SiO-free syringes). At onset, anti-vascular endothelial growth factor drugs were administered using SiO-containing insulin syringes. From November 2018, SiO-free syringes were implemented. Spontaneously reported symptomatic SiO cases were confirmed by slit-lamp examination. A follow-up interview was performed after 1 year, assessing visual complaints. The prevalence of non-symptomatic cases was assessed in a sample of 50 eyes from 50 consecutive IVI patients. Results Among 13 429 IVIs, 50 eyes of 46 patients (29 women) with symptomatic intravitreal SiO droplets were identified. Forty-one patients reported floaters at regular appointments, whereas five patients contacted the department regarding symptoms between scheduled appointments. After 1 year, 34 patients (79%) still experienced floaters, 21 (49%) reported reduced symptoms and 3 (7%) reported worsened symptoms. Eighteen patients (42%) reported being bothered, and eight (18.6%) reported that their lives were negatively affected by the floaters. Among 50 non-symptomatic eyes that had received IVI during the same period, intravitreal SiO was found in 34 (68%). No cases of symptomatic intravitreal SiO droplets were identified after switching to SiO-free syringes. Conclusion Symptomatic intravitreal SiO following IVI can cause significant and prolonged distress for affected patients. It can be avoided by using SiO-free syringes.

• Klionsky, Daniel J.; Abdel-Aziz, Amal Kamal; Abdelfatah, Sara; Abdellatif, Mahmoud Khaled; Abdoli, Asghar & Abudu, Yakubu Princely [Vis alle 50 forfattere av denne artikkelen] (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. ISSN 1554-8627. 17(1), s. 1–382. doi: https:/www.tandfonline.com/doi/full/10.1080/15548627.2020.1797280. Fulltekst i vitenarkiv
• Müllertz, Olivia; Hedengran, Anne; Mouhammad, Zaynab Ahmad; Freiberg, Josefine; Nagymihály, Richárd & Jacobsen, Jette [Vis alle 13 forfattere av denne artikkelen] (2021). Impact of benzalkonium chloride-preserved and preservative-free latanoprost eye drops on cultured human conjunctival goblet cells upon acute exposure and differences in physicochemical properties of the eye drops. BMJ Open Ophthalmology. 6(1). doi: 10.1136/bmjophth-2021-000892. Fulltekst i vitenarkiv Vis sammendrag

  Objective To investigate the short-term impact on human conjunctival goblet cell (GC) survival and mucin release of acute exposure to benzalkonium chloride (BAK) preserved and preservative-free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops’ physicochemical properties. Methods and analysis Primary GC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using a lactate dehydrogenase assay. Mucin release was evaluated through mucin-specific immunostaining. pH value, osmolality, drop mass and surface tension for all LT eye drops were measured. Results After application with PF-LT for 30 min (min), the GC survival was maintained compared with control (p=0.9941), while all BAK-LT eye drops reduced survival with approximately 30% (p&lt;0.02). Following application with PF-LT for 30 min, mucin was found around the GC nucleus, as seen in the vehicle control, indicating no secretion. In contrast, BAK-LT caused diffuse staining of mucin, similar to the secretagogue histamine, indicating stimulation of secretion. The pH value of the BAK-LT and PF-LT eye drops were 6.0–6.9 and 6.8, respectively. The osmolality was 258–288 mOsm/kg for the BAK-LT eye drops and 276 for PF-LT eye drops. The mean drop mass was 26–31 mg for the BAK-LT eye drops and 30 mg for PF-LT. The surface tension was lower for all BAK-LT eye drops (31.1–32.1 mN/m) compared with PF-LT (42 mN/m). Conclusion PF-LT compared with various branded and generic LT preparations containing BAK are less cytotoxic when applied to cultured GCs.

• Eszes, Dóra Júlia; Szabó, Dóra Júlia; Russell, Greg; Lengyel, Csaba; Várkonyi, Tamás & Paulik, Edit [Vis alle 10 forfattere av denne artikkelen] (2021). Diabetic Retinopathy Screening in Patients with Diabetes Using a Handheld Fundus Camera: The Experience from the South-Eastern Region in Hungary. Journal of Diabetes Research. ISSN 2314-6745. 2021, s. 1–9. doi: 10.1155/2021/6646645. Fulltekst i vitenarkiv Vis sammendrag

  Purpose. Diabetic retinopathy (DR) is the leading cause of vision loss among active adults in industrialized countries. We aimed to investigate the prevalence of diabetes mellitus (DM), DR and its different grades, in patients with DM in the Csongrád County, South-Eastern region, Hungary. Furthermore, we aimed to detect the risk factors for developing DR and the diabetology/ophthalmology screening patterns and frequencies, as well as the effect of socioeconomic status- (SES-) related factors on the health and behavior of DM patients. Methods. A cross-sectional study was conducted on adults (>18 years) involving handheld fundus camera screening (Smartscope Pro Optomed, Finland) and image assessment using the Spectra DR software (Health Intelligence, England). Self-completed questionnaires on self-perceived health status (SPHS) and health behavior, as well as visual acuity, HbA1c level, type of DM, and attendance at healthcare services were also recorded. Results. 787 participants with fundus camera images and full self-administered questionnaires were included in the study; 46.2% of the images were unassessable. T1D and T2D were present in 13.5% and 86.5% of the participants, respectively. Among the T1D and T2D patients, 25.0% and 33.5% had DR, respectively. The SES showed significant proportion differences in the T1D group. Lower education was associated with a lower DR rate compared to non-DR (7.7% vs. 40.5%), while bad/very bad perceived financial status was associated with significantly higher DR proportion compared to non-DR (63.6% vs. 22.2%). Neither the SPHS nor the health behavior showed a significant relationship with the disease for both DM groups. Mild nonproliferative retinopathy without maculopathy (R1M0) was detected in 6% and 23% of the T1D and T2D patients having DR, respectively; R1 with maculopathy (R1M1) was present in 82% and 66% of the T1D and T2D groups, respectively. Both moderate nonproliferative retinopathy with maculopathy (R2M1) and active proliferative retinopathy with maculopathy (R3M1) were detected in 6% and 7% of the T1D and T2D patients having DR, respectively. The level of HbA1c affected the attendance at the diabetology screening (HbA1c > 7% associated with >50% of all quarter-yearly attendance in DM patients, and with 10% of the diabetology screening nonattendance). Conclusion. The prevalence of DM and DR in the studied population in Hungary followed the country trend, with a slightly higher sight-threatening DR than the previously reported national average. SES appears to affect the DR rate, in particular, for T1D. Although DR screening using handheld cameras seems to be simple and dynamic, much training and experience, as well as overcoming the issue of decreased optic clarity is needed to achieve a proper level of image assessability, and in particular, for use in future telemedicine or artificial intelligence screening programs.

• Tichotová, Lucie; Studenovska, Hana; Petrovski, Goran; Popelka, Štěpán; Nemesh, Yaroslav & Sedláčková, Miroslava [Vis alle 17 forfattere av denne artikkelen] (2021). Advantages of nanofibrous membranes for culturing of primary RPE cells compared to commercial scaffolds. Acta Ophthalmologica. ISSN 1755-375X. s. 1–14. doi: 10.1111/aos.15034. Fulltekst i vitenarkiv
• Jevnikar, Kristina; Mekjavic, Polona Jaki; Valentincic, Natasa Vidovic; Petrovski, Goran & Petrovic, Mojca Globocnik (2021). An update on COVID-19 related ophthalmic manifestations. Ocular immunology and inflammation. ISSN 0927-3948. 29(4), s. 684–689. doi: 10.1080/09273948.2021.1896008. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To summarize ophthalmic manifestations of coronavirus disease (COVID-19) reported in the literature thus far. Methods: The PubMed database was systematically searched through October 24, 2020, to identify relevant articles using the following search terms: (“COVID-19” OR “SARS-CoV-2”) AND (“eye” OR “ophthalmology” OR “retina” OR “retinal findings” OR “cornea” OR “conjunctiva”). Only articles published in English were included in this review. Results: The reported prevalence of ophthalmic manifestations is generally low, but correlates positively with the severity of the disease. Most commonly reported ocular manifestations are conjunctivitis, conjunctival hyperemia and chemosis. Retinal findings include microhemorrhages and flame-shaped hemorrhages, cotton wool spots, dilated veins, and tortuous vessels. Conclusion: Considering the COVID-19 cases have reached pandemic dimensions and are surging, yet again, it is of utmost importance to determine its ophthalmic manifestations and prevent their vision threatening complications. Further studies are warranted to establish whether the retinal findings appear due to the COVID-19 or are an incidental finding in patients with a preexisting diabetic or hypertensive retinopathy.

Se alle arbeider i NVA

• Hildebrand, Torben; Lemonche, Gerard Boix; Haugen, Håvard Jostein; Petrovski, Goran & Nogueira, Liebert Parreiras (2024). Contrast-enhanced micro-CT for visualization of cell distribution in hydrated human cornea. Fulltekst i vitenarkiv
• Ruban, Andrii; Petrovski, Beata Eva; Petrovski, Goran & Lytvynchuk, Lyubomyr M. (2023). Comments on: Internal Limiting Membrane Peeling and Gas Tamponade for Full-Thickness Macular Holes of Different Etiology - Is It Still Relevant? [Response to Letter]. Clinical Ophthalmology. ISSN 1177-5467. 17, s. 103–105. doi: 10.2147/OPTH.S402222. Fulltekst i vitenarkiv
• Lytvynchuk, Lyubomyr; Stranak, Zbynek; Studenovska, Hana; Rais, David; Popelka, Štěpán & Tichotová, Lucie [Vis alle 24 forfattere av denne artikkelen] (2022). Subretinal Implantation of RPE on a Carrier in Minipigs: Guidelines for Preoperative Preparations, Surgical Techniques, and Postoperative Care. Journal of Visualized Experiments. 2022(189), s. 1–26. doi: 10.3791/63505. Fulltekst i vitenarkiv Vis sammendrag

  Degenerative disorders of the retina (including age-related macular degeneration), which originate primarily at or within the retinal pigmented epithelial (RPE) layer, lead to a progressive disorganization of the retinal anatomy and the deterioration of visual function. The substitution of damaged RPE cells (RPEs) with in vitro cultured RPE cells using a subretinal cell carrier has shown potential for re-establishing the anatomical structure of the outer retinal layers and is, therefore, being further studied. Here, we present the principles of a surgical technique that allows for the effective subretinal transplantation of a cell carrier with cultivated RPEs into minipigs. The surgeries were performed under general anesthesia and included a standard lens-sparing three-port pars plana vitrectomy (PPV), subretinal application of a balanced salt solution (BSS), a 2.7 mm retinotomy, implantation of a nanofibrous cell carrier into the subretinal space through an additional 3.0 mm sclerotomy, fluid-air exchange (FAX), silicone oil tamponade, and closure of all the sclerotomies. This surgical approach was used in 29 surgeries (18 animals) over the past 8 years with a success rate of 93.1%. Anatomic verification of the surgical placement was carried out using in vivo fundus imaging (fundus photography and optical coherence tomography). The recommended surgical steps for the subretinal implantation of RPEs on a carrier in minipig eyes can be used in future preclinical studies using large-eye animal models.

• Petrovski, Goran; Lytvynchuk, Lyubomyr; Stieger, Knut & Petrovski, David (2022). A simple twist technique for lens-sparing one-handed peripheral vitrectomy in phakic patients: a learning approach for junior surgeons. International Journal of Retina and Vitreous (IJRV). 8(83). doi: 10.1186/s40942-022-00433-w. Fulltekst i vitenarkiv Vis sammendrag

  The evolution of vitrectomy has led to improved suturless techniques and minimally invasive surgery. Nevertheless, the procedure requires great bimanual dexterity and poses risk for lens touch, especially in the hands of less experienced junior surgeons. We hereby present a twist technique which allows for one-handed (right or left) peripheral vitrectomy without the need for one or several hand-switches with the vitreous cutter and avoids lens touch. The technique can be used as a learning approach for junior vitreoretinal surgeons.

• Confalonieri, Filippo; Stene-Johansen, Ingar; Lumi, Xhevat & Petrovski, Goran (2022). Intravitreal r-tPA Injection and Pneumatic Displacement for Submacular Retinal Hemorrhage: A Case Series. Case Reports in Ophthalmology. 13(2), s. 630–637. doi: 10.1159/000526068. Fulltekst i vitenarkiv Vis sammendrag

  We describe the results of very early pars plana vitrectomy, subretinal r-tPA, and gas tamponade in patients with subretinal macular hemorrhage secondary to neovascular age-related macular degeneration. The patients ended up with a favorable functional recovery. We conclude that very early treatment might lead to a good functional prognosis.

• Confalonieri, Filippo; Ladstein, Gunn Elin; Stene-Johansen, Ingar & Petrovski, Goran (2022). Iatrogenic central retinal artery occlusion following retrobulbar anesthesia with adrenaline for vitreoretinal surgery: a case report. Journal of Medical Case Reports. 16(1), s. 1–8. doi: 10.1186/s13256-022-03518-0. Fulltekst i vitenarkiv Vis sammendrag

  Background We describe a patient presenting with central retinal artery occlusion (CRAO) of the right eye after retrobulbar anesthesia with adrenaline for macular pucker surgery. Case presentation The patient, a 67-year-old Caucasian man, developed a CRAO postoperatively by the next-day control likely due to the retrobulbar injection of a combination of Xylocaine and Bupivacaine with adrenaline as anesthetic. Conclusions The addition of adrenaline to the standard anesthetic solution could be a risk factor for serious complications, such as CRAO.

• Hiller, John Kim & Petrovski, Goran (2026). Vitreous Metabolomics in Diabetic Retinopathy: Biomarkers, Therapeutic Targets, and Ocular Drug Assessment. Universitetet i Oslo. ISSN 9788234808821. Fulltekst i vitenarkiv Vis sammendrag

  Diabetes can damage the small blood vessels of the retina and lead to diabetic retinopathy, a major cause of vision impairment among working-age adults. The disease may progress before noticeable symptoms develop, highlighting the need for improved biomarkers of disease progression and new therapeutic targets. The thesis aimed to characterise the metabolic environment of the eye in different stages of diabetic retinopathy and to identify potential biomarkers and therapeutic targets using targeted and untargeted mass spectrometry of undiluted vitreous samples from patients undergoing vitrectomy. A second aim was to develop an ex vivo porcine eye model for studying the movement of molecules within the eye and its potential application in ocular drug development. Metabolomic profiling revealed distinct stage-associated changes in the vitreous of patients with diabetes and diabetic retinopathy, demonstrating that progression of the disease is accompanied by characteristic alterations in ocular metabolism. Several amino acids, including arginine, methionine, threonine and proline, as well as carnitine, showed increased levels with advancing disease, whereas metabolites associated with antioxidant defence, membrane integrity and neuronal function, including taurine, ascorbate, choline and N-acetylaspartate, were reduced at different stages of diabetic retinopathy. These findings provide a rationale for further investigating whether correction of selected metabolic deficiencies, including through dietary supplementation, could have a role as an adjunctive strategy in diabetic retinopathy. In the ex vivo porcine eye model, the movement of molecules between the anterior and vitreous chambers was shown to depend on time and molecular properties. The model provides a controlled experimental platform for studying ocular drug distribution and may contribute to the development and optimisation of future ocular therapies. Overall, the thesis demonstrates that metabolomic analysis of the vitreous can provide new insights into the molecular changes associated with diabetic retinopathy and identify potential biomarkers and therapeutic targets for further investigation. Additional information

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