Morten Carstens Moe

• Nicolaissen, Bjørn; Nguyen, Giang Huong; Beraki, Kahsai; Azqueta, Oscoz Amaya; Petrovski, Goran & Moe, Morten Carstens [Show all 10 contributors for this article] (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. Full text in Research Archive
• Ryan, Stephen James; Jørstad, Anna-Katharina; Moe, Morten Carstens; Skjelland, Mona Elisabeth; Roy, Ansar & Rowe, Fiona J. [Show all 8 contributors for this article] (2026). Validation of the Vision Impairment Screening Assessment in acute stroke care: a prospective diagnostic accuracy study. European Stroke Journal. ISSN 2396-9873. 11(5). doi: 10.1093/esj/aakag053. Full text in Research Archive
• Løkken, Jacopo Francesco Taraldsrud; Moe, Morten Carstens; Sæther, Erik Magnus & Jørstad, Øystein Kalsnes (2026). Beyond drug price: A comparison of overall costs of anti-vascular endothelial growth factor therapy alternatives for neovascular age-related macular degeneration in Norway. Acta Ophthalmologica. ISSN 1755-375X. doi: 10.1111/aos.70069. Full text in Research Archive
• Ackermann, Bryan Calder; Junker, Niklas; Friedrich, Maximilian; Jørstad, Øystein Kalsnes; Moe, Morten Carstens & Augustin, Victor Aristide [Show all 8 contributors for this article] (2026). The effect of syringe design and cannula dimensions on time-force curve in intravitreal injection across different drug viscosities: area under the curve and peak injection force. International Journal of Retina and Vitreous (IJRV). 12. doi: 10.1186/s40942-026-00833-2. Full text in Research Archive Show summary

  Background New intravitreal medications can offer longer treatment duration by using higher drug concentrations, which, in turn, increase viscosity. There is also a trend toward having smaller-gauge cannulas, which require a higher injection force. While the ophthalmologist cannot control viscosity, the choice of syringe may affect the force needed to administer the drug. This study compared two standard 1-ml syringes (BD Plastipak™ and Braun Injekt®-F) with a syringe featuring a reduced plunger diameter (Zero Residual™ 0·2 mL silicone oil-free syringe) for injecting a variety of fluids with viscosity that mimics commonly used intravitreal formulations. Methods Injection force over time was measured for each combination of the three syringes, four fluids, and two cannulas (30 G and 33 G), and the results were compared using a two-way ANOVA, followed by Tukey’s post-hoc test. Plungers of the 1ml syringes had a diameter of approximately 4.70mm, while the smaller syringe had a plunger diameter of 2.48mm. Of the 1ml syringes, one was silicone oil lubricated (BD Plastipak™). The tested fluids were chosen to simulate bevacizumab (Balanced Salt Solution), pegcetacoplan (13.8 mg/0.1 ml of PEG-40,000), a high-viscosity solution (40 mg/0.1 ml of PEG-400), and a very high-viscosity solution (Tween 80 diluted with BSS). Results The Zero Residual syringe required significantly lower injection forces, as quantified by both the area under the curve (AUC) and peak force. These effects became more pronounced when using smaller-diameter cannulas and increasingly viscous fluids. The BD Plastipak needed lower forces than the Braun Injekt-F. Conclusions While silicone-oil lubrication reduced injection force, its effect was modest compared with that of plunger diameter, which was the primary determinant of the injection force required for a given viscosity and cannula diameter.

• Sauesund, Ellen Steffenssen; Brunborg, Cathrine; Jørstad, Øystein Kalsnes; Moe, Morten Carstens; Erke, Maja Gran & Fosmark, Dag Sigurd [Show all 7 contributors for this article] (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. Full text in Research Archive
• Moe, Morten Carsten; Hal, Bas van; Melo, Gustavo Barreto & Jørstad, Øystein Kalsnes (2026). Time for refrigerated syringes of biologics to reach room temperature before intravitreal injection. Eye (London. 1987). ISSN 0950-222X. doi: 10.1038/s41433-026-04414-3. Full text in Research Archive
• Ryan, Stephen James; Jørstad, Øystein Kalsnes; Skjelland, Mona; Pesonen, Maiju; Simonsen, Claus Z. & Bek, Toke [Show all 50 contributors for this article] (2026). A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion. New England Journal of Medicine. ISSN 0028-4793. 394(5), p. 442–450. doi: 10.1056/nejmoa2508515. Full text in Research Archive Show summary

  Background: Central retinal artery occlusion can result in permanent vision loss. Effective treatment is lacking. Methods: We conducted a phase 3, double-blind, double-dummy, randomized, controlled trial involving adults with acute, nonarteritic central retinal artery occlusion who had symptom onset within 4.5 hours before treatment. Patients were assigned, in a 1:1 ratio, to receive intravenous tenecteplase (at a dose of 0.25 mg per kilogram of body weight) and oral placebo or intravenous placebo and oral aspirin (at a dose of 300 mg). The primary end point was vision recovery, defined as a best corrected visual acuity (BCVA) in the affected eye at 30 days of up to 0.7 logMAR (logarithm of the minimum angle of resolution; equivalent to ≥20/100). Key secondary visual end points were a BCVA of up to 0.5 logMAR (equivalent to ≥20/63), mean improvement in BCVA, and perimetry score at 30 days. Key safety end points included symptomatic intracranial hemorrhage, major bleeding, and death. Results: A total of 78 patients at 16 sites in six countries underwent randomization, with 40 assigned to receive tenecteplase and 38 to receive aspirin. At 30 days, 8 patients (20%) in the tenecteplase group and 9 patients (24%) in the aspirin group had vision recovery (risk difference, −3.7 percentage points; 95% confidence interval, −22.0 to 14.7; P=0.69). The outcomes with regard to the secondary visual end points did not differ substantially between the groups. There was a greater incidence of adverse events in the tenecteplase group, including one fatal intracranial hemorrhage. Conclusions: Intravenous tenecteplase administered within 4.5 hours after onset of central retinal artery occlusion did not result in significantly greater vision recovery at 30 days than oral aspirin but was associated with serious safety concerns. (Funded by Oslo University Hospital and others; TenCRAOS ClinicalTrials.gov number, NCT04526951; EU Clinical Trials number, 2024-517606-29-00.)

• Karabeg, Mia; Petrovski, Goran; Holen, Katrine; Sauesund, Ellen Steffenssen; Fosmark, Dag Sigurd & Russell, Greg [Show all 14 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Hiller, John Kim; Sandås, Elise Mørk; Rootwelt, Helge; Vassli, Anja Østeby; Lumi, Xhevat & Moe, Morten Carstens [Show all 9 contributors for this article] (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, p. 2997–3007. doi: 10.2147/OPTH.S531638. Full text in Research Archive Show summary

  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.

• Hiller, John Kim; Sandås, Elise Mørk; Rootwelt, Helge; Vassli, Anja Østeby; Lumi, Xhevat & Moe, Morten Carstens [Show all 9 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Show all 32 contributors for this article] (2025). An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models. Nature Communications. 16(1), p. 1–16. doi: 10.1038/s41467-025-59353-6. Full text in Research Archive Show summary

  Although vaccines are usually given intramuscularly, the intranasal delivery route may lead to better mucosal protection and limit the spread of respiratory virus while easing administration and improving vaccine acceptance. The challenge, however, is to achieve delivery across the selective epithelial cell barrier. Here we report on a subunit vaccine platform, in which the antigen is genetically fused to albumin to facilitate FcRn-mediated transport across the mucosal barrier in the presence of adjuvant. Intranasal delivery in conventional and transgenic mouse models induces both systemic and mucosal antigen-specific antibody responses that protect against challenge with SARS-CoV-2 or influenza A. When benchmarked against an intramuscularly administered mRNA vaccine or an intranasally administered antigen fused to an alternative carrier of similar size, only the albumin-based intranasal vaccine yields robust mucosal IgA antibody responses. Our results thus suggest that this needle-free, albumin-based vaccine platform may be suited for vaccination against respiratory pathogens.

• Karabeg, Mia; Petrovski, Goran; Hertzberg, Silvia Nanjala Walekhwa; Erke, Maja Gran; Fosmark, Dag Sigurd & Russell, Greg [Show all 13 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• 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. Full text in Research Archive Show summary

  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.

• Sauesund, Ellen Steffenssen; Hertzberg, Silvia Nanjala Walekhwa; Jørstad, Øystein Kalsnes; Moe, Morten Carsten; Erke, Maja Gran & Fosmark, Dag Sigurd [Show all 7 contributors for this article] (2024). A health economic pilot study comparing two diabetic retinopathy screening strategies. Scientific Reports. 14(1). doi: 10.1038/s41598-024-66405-2. Full text in Research Archive Show summary

  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.

• Husum, Yngvil Solheim; Moe, Morten Carsten; Fagerland, Morten; Eriksen, Erik Fink & Jørstad, Øystein Kalsnes (2024). Zoledronic acid as adjuvant therapy in neovascular age-related macular degeneration: a randomised controlled pilot study. BMJ Open Ophthalmology. 9(1). doi: 10.1136/bmjophth-2024-001964. Full text in Research Archive Show summary

  Aims To assess the feasibility of a study protocol for a randomised controlled trial of zoledronic acid (ZA) as adjuvant therapy for neovascular age-related macular degeneration (nAMD). Methods In this 1-year, randomised, double-blinded, placebo-controlled pilot study, nAMD patients were allocated 1:1 to receive intravenous ZA 5 mg or placebo at baseline and after 6 months in addition to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy following a treat-and-extend regimen. Bevacizumab was the first-line anti-VEGF drug, but eyes with refractory nAMD were switched to aflibercept. The primary outcome was mean change in best-corrected visual acuity (BCVA). Results 40 participants enrolled in the study, with 20 allocated to each treatment group. 38 participants received both study infusions, and all participants completed the final assessment. Mean (SD) change in BCVA was 7.5 (9.5) letters in the ZA group and −0.5 (11.5) letters in the control group; the between-group difference was 8.0 letters (95% CI: 1.5 to 15.0 letters). There were no between-group differences in mean change in central retinal thickness, refractory nAMD proportion or mean number of injections. Conclusion It is feasible to conduct a randomised controlled trial of ZA as adjuvant therapy for nAMD in terms of recruitment and adherence to the pilot study protocol. We found a possible visual benefit of ZA that is worth further investigation. To clarify the relationship between ZA and the need for intravitreal injections, we recommend amending the protocol by omitting switching of the anti-VEGF drug. Due to the limited sample size of the pilot study, the estimates of treatment effect are not meant to be confirmatory and should be interpreted with caution. Trial registration number 2019-001492-37 (EudraCT), 04304755 (NCT).

• 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. Full text in Research Archive Show summary

  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.

• Hiller, John Kim; Sandås, Elise Mørk; Rootwelt, Helge; Vassli, Anja Østeby; Utheim, Tor Paaske & Moe, Morten Carsten [Show all 8 contributors for this article] (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), p. 324–331. doi: 10.1089/jop.2022.0159. Full text in Research Archive
• 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. Full text in Research Archive Show summary

  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.

• Agra, Lydianne Lumack do Monte; Sverstad, Alexander; Chagas, Thiago A; Araujo, Rodrigo H.; Oliveira, Larissa & Kristianslund, Olav [Show all 11 contributors for this article] (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), p. 892–900. doi: 10.1016/j.oret.2023.06.003. Full text in Research Archive Show summary

  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 [Show all 8 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Sauesund, Ellen Steffenssen; Jørstad, Øystein Kalsnes; Brunborg, Cathrine; Moe, Morten Carsten; Erke, Maja Gran & Fosmark, Dag Sigurd [Show all 7 contributors for this article] (2023). A Pilot Study of Implementing Diabetic Retinopathy Screening in the Oslo Region, Norway: Baseline Results. Biomedicines. 11(4). doi: 10.3390/biomedicines11041222. Full text in Research Archive Show summary

  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).

• gjølberg, torleif; Wik, Jonas Aakre; Johannessen, Hanna; Krüger, Stig; Bassi, Nicola & Christopoulos, Panagiotis [Show all 15 contributors for this article] (2023). Antibody blockade of Jagged1 attenuates choroidal neovascularization. Nature Communications. 14(1). doi: 10.1038/s41467-023-38563-w. Full text in Research Archive Show summary

  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.

• Jørstad, Øystein Kalsnes; Foss, Stian; gjølberg, torleif; mester, simone; Nyquist-Andersen, Mari & Sivertsen, Magne S. [Show all 10 contributors for this article] (2023). Pharmaceutical compounding and storage of faricimab in a syringe for intravitreal injection do not impair stability and bi-specific binding properties. International Journal of Retina and Vitreous (IJRV). 9(1). doi: 10.1186/s40942-023-00507-3. Full text in Research Archive Show summary

  Background Intravitreal injection (IVI) of antibody biologics is a key treatment approach in ophthalmology. Pharmaceutical compounding and storage of prefilled syringes for IVI must take place without impairing the structure and function of the biologics. This study investigated the effect of withdrawing and storing the therapeutic antibody faricimab (Vabysmo, Roche, Basel, Switzerland) in the Zero Residual silicone oil-free, 0.2-mL syringe (SJJ Solutions, The Hague, the Netherlands). Methods To assess the effect of syringe withdrawal on faricimab, we compared samples from syringes prepared at day 0 with samples taken directly from faricimab vials. To assess the effect of syringe storage on faricimab, we kept prefilled syringes in the dark at 4 oC for 7, 14, or 37 days and compared samples from these syringes with day 0. We measured protein concentration (with spectrophotometry), stability and integrity (with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size-exclusion chromatography (SEC), and melting temperature (Tm)), as well as binding of faricimab to its cognate antigens: vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2) (with enzyme-linked immunosorbent assay (ELISA)). Results Faricimab migrated in line with its expected molecular mass under both reducing and non-reducing conditions for all time points when analyzed with SDS-PAGE, without any sign of degradation products or aggregation. The SEC elution profiles were identical for all time points. There were slight variations in Tm for different time points compared to day 0 but without consistent relationship with storage time. ELISA did not detect differences in VEGF-A or Ang-2 binding between time points, and faricimab did not bind the neonatal Fc receptor. Conclusions Withdrawal and storage of faricimab in syringes for up to day 37 did not impair the structure and bi-specific binding properties of the therapeutic antibody.

• Husum, Yngvil Solheim; Bråten, Ragnhild Haugli; Sæther, Erik Magnus; Moe, Morten Carsten; Kristiansen, Ivar Sønbø & Jørstad, Øystein Kalsnes (2023). Intravitreal anti-vascular endothelial growth factor therapy for retinal diseases in Norway from 2011 to 2021: A combined registry and survey study. Acta Ophthalmologica. ISSN 1755-375X. p. 1–11. doi: 10.1111/aos.16598. Full text in Research Archive
• Benjakul, Sopisa; Anthi, Aina Karen; Kolderup, Heidi Anette; Vaysburd, Marina; Lode, Heidrun Elisabeth & Mallery, D [Show all 20 contributors for this article] (2023). A pan-SARS-CoV-2-specific soluble angiotensin-converting enzyme 2-albumin fusion engineered for enhanced plasma half-life and needle-free mucosal delivery. PNAS Nexus. 2(12), p. 1–15. doi: 10.1093/pnasnexus/pgad403. Full text in Research Archive Show summary

  Immunocompromised patients often fail to raise protective vaccine-induced immunity against the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Although monoclonal antibodies have been authorized for clinical use, most have lost their ability to potently neutralize the evolving Omicron subvariants. Thus, there is an urgent need for treatment strategies that can provide protection against these and emerging SARS-CoV-2 variants to prevent the development of severe coronavirus disease 2019. Here, we report on the design and characterization of a long-acting viral entry-blocking angiotensin-converting enzyme 2 (ACE2) dimeric fusion molecule. Specifically, a soluble truncated human dimeric ACE2 variant, engineered for improved binding to the receptor-binding domain of SARS-CoV-2, was fused with human albumin tailored for favorable engagement of the neonatal fragment crystallizable receptor (FcRn), which resulted in enhanced plasma half-life and allowed for needle-free transmucosal delivery upon nasal administration in human FcRn-expressing transgenic mice. Importantly, the dimeric ACE2-fused albumin demonstrated potent neutralization of SARS-CoV-2 immune escape variants.

• Moe, Morten Carsten; Özmert, Emin; Baudouin, Christophe; Binadra, Abhinav; Crafoord, Sven & Jo, Young [Show all 16 contributors for this article] (2023). International Olympic Committee (IOC) consensus paper on sports-related ophthalmology issues in elite sports. BMJ Open sport & exercise medicine. 9(3). doi: 10.1136/bmjsem-2023-001644. Full text in Research Archive Show summary

  Vision plays an important role in an athletes’ success. In sports, nearly 80% of perceptual input is visual, and eye health and sports medicine are closely intertwined fields of utmost importance to athletes. The physical nature of sports activities renders individuals more prone to various eye injuries than the general population. Ocular trauma can lead to lifelong sequelae, and impaired vision requires careful follow-up and management. Apart from injuries, athletes may also experience vision problems that can hamper their performance, including blurred vision, double vision, and light sensitivity. The interdisciplinary nature of sports medicine necessitates collaboration between sports medicine professionals and ophthalmologists. Through such collaborations, athletes can receive appropriate eye care, education on proper eye protection and guidance on adopting good eye health practices. If any inconspicuous symptoms are not detected and treated promptly, athletes may acquire systemic injuries because of defective vision, preventing them from achieving high level athletic performance in competitions. The protection of the elite athlete is the responsibility of all of us in sports medicine. To advance a more unified, evidence-informed approach to ophthalmic health assessment and management in athletes and as relevant for sports medicine physicians, the International Olympic Committee Consensus Group aims for a critical evaluation of the current state of the science and practice of ophthalmologic issues and illness in high-level sports, and present recommendations for a unified approach to this important issue.

• Melo, Gustavo Barreto; Santos, Lucas Andrade; Agra, Lydianne Lumack do Monte; Meyer, Carsten; Moe, Morten Carsten & Jørstad, Øystein Kalsnes (2023). Accuracy and residual volume of intravitreal injection syringes in administration of very small volumes. Eye (London. 1987). ISSN 0950-222X. doi: 10.1038/s41433-023-02670-1. Full text in Research Archive Show summary

  Intravitreal injections (IVIs) are widely used to deliver therapeutic agents for various retinal conditions. The syringe accuracy is a critical factor in achieving optimal treatment outcomes and minimizing potential risks in IVIs, such as unpredictable variation in drug volume (and thereby therapeutic effect) and intraocular pressure (IOP) rise [1,2,3,4,5]. Smaller volumes than the typical 0.05 mL, albeit harder to deliver with common 1-mL syringes, could mitigate the impact on IOP and drug wastage. In this study, we evaluated the accuracy and residual volume of three syringe models that can potentially administer very small volumes intravitreally.

• Jacobsen, Henrik Holvin; Jørstad, Øystein Kalsnes; Moe, Morten Carsten; Petrovski, Goran; Pripp, Are Hugo & Sandell, Tiril [Show all 7 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Hertzberg, Silvia Nanjala Walekhwa; Jørstad, Øystein Kalsnes; Petrovski, Beata Eva; Bragadottir, Ragnheidur; Steffensen, Leif Arthur & Moe, Morten Carsten [Show all 8 contributors for this article] (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), p. 1–16. doi: 10.3390/ijerph191912603. Full text in Research Archive Show summary

  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.

• gjølberg, torleif; Lode, Heidrun Elisabeth; Melo, Gustavo B.; mester, simone; Probst, Christine & Sivertsen, Magne S. [Show all 9 contributors for this article] (2022). A Silicone Oil-Free Syringe Tailored for Intravitreal Injection of Biologics. Frontiers in Ophthalmology. 2. doi: 10.3389/fopht.2022.882013. Full text in Research Archive
• Salvanos, Panagiotis; Bjørnsson, Helgi David; Vitelli, Valeria; Bragadottir, Ragnheidur; Moe, Morten Carsten & Utheim, Tor Paaske (2022). Autofluorescence Imaging in the Long-Term Follow-Up of Scleral Buckling Surgery for Retinal Detachment. Journal of Ophthalmology. ISSN 2090-004X. 2022. doi: 10.1155/2022/2119439. Full text in Research Archive Show summary

  Purpose. To analyse fundus autofluorescence (AF) changes in retinal reattachment following primary scleral buckling (SB) surgery for rhegmatogenous retinal detachment (RRD). Methods. Prospective noninterventional chart review study. AF images were reviewed for peripheral and central changes and compared to clinical and OCT findings. Results. A total of 73 eyes from 69 patients were included, four presenting with bilateral RRD. Mean age was 55 ± 12 years, male/female ratio 40/29, fovea-on/-off RRD 43/30, and mean follow-up time 376 ± 270 days, with a mean of 5 ± 3 postoperative visits. Preoperatively, RRD was seen as a hypofluorescent area with a hyperfluorescent leading edge. Immediately postoperatively, three types of cryopexy could be differentiated, gradually transforming to scleral hyperfluorescence. Buckle tightening produced alternating hyper-/hypofluorescent streaks, and demarcation lines showed a persistent rugged hyperfluorescent signal. Choroidal detachment led to transient hypofluorescence, whereas vortex vein compression induced persistent hypofluorescence. Peripheral retinal folds were hyperfluorescent and the drainage site was hypofluorescent. AF was highly sensitive in detecting even small amounts of hyperfluorescent persistent subretinal fluid (SRF) that showed a slow resolution during follow-up. A granular “salt-and-pepper-” like pattern in the central macula was seen in 80% of eyes with fovea-off RRD and alternating streaks in 10%. Findings from OCT imaging correlated well with AF regarding SRF, macular oedema, retinal pigment epithelial detachment, and presence of a subretinal scar, but only moderately in epiretinal membrane formation and choroidal folds. Conclusions. AF is a useful, noninvasive, adjuvant tool in the long-term follow-up after SB surgery.

• Kvernebo, Anne Kari; Moe, Morten Carsten; Sundheim, Liv Kristin Ribbskog; Capone, Luigino; Drolsum, Liv Kari & Kvernebo, Knut (2022). Human ocular surface microcirculation quantified by in vivo computer assisted video microscopy and diffuse reflectance spectroscopy. Experimental Eye Research. ISSN 0014-4835. 224, p. 1–6. doi: 10.1016/j.exer.2022.109232. Full text in Research Archive Show summary

  Non-invasive imaging techniques are increasingly used to objectively quantify anterior segment structures of the eye. In this study, we apply the novel oxygen delivery index (ODIN) concept that, quantifies microvascular capacity for oxygen delivery, to the ocular surface in healthy humans. The purpose of the study was to test the applicability of the technologies used for data acquisition from the human ocular surface. We also validated whether the ODIN concept has sufficient sensitivity to detect and differentiate between microvascular structure and function in limbal and bulbar conjunctiva. Multiple ocular surface measurements using computer-assisted video microscopy (field of view: 1.6 mm × 0.9 mm) and diffuse reflectance spectroscopy (measuring volume: ∼0.1 mm3) were obtained from limbal and bulbar conjunctiva in 20 healthy volunteers. Three parameters were extracted during analyses: Functional capillary density, capillary flow velocity, and microvascular oxygen saturation. Functional capillary density was higher at limbus than in bulbar conjunctiva (11.2 ± 1.8 c/mm versus 5.2 ± 1.2 c/mm, p < 0.01), and microvascular oxygen saturation was lower at limbus (77 ± 8%) as compared to bulbar conjunctiva (89 ± 6%), p < 0.01. More than 80% of scored capillaries had continuous blood flow and no difference was seen between the recording sites (p = 0.68). In conclusion, the ODIN concept is applicable for the assessment of human ocular surface microvascular function and has sufficient sensitivity to detect increased capillary density and oxygen extraction at limbus as compared with bulbar conjunctiva.

• 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), p. e1630–e1640. doi: 10.1111/aos.15151. Full text in Research Archive Show summary

  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 [Show all 7 contributors for this article] (2022). Video display terminal use and dry eye: preventive measures and future perspectives. Acta Ophthalmologica. ISSN 1755-375X. 100(7), p. 723–739. doi: 10.1111/aos.15105. Full text in Research Archive Show summary

  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.

• Gjølberg, Torleif Tollefsrud; Frick, Rahel; Mester, Simone; Foss, Stian; Grevys, Algirdas & Høydahl, Lene Støkken [Show all 11 contributors for this article] (2022). Biophysical differences in IgG1 Fc-based therapeutics relate to their cellular handling, interaction with FcRn and plasma half-life. Communications Biology. 5(1), p. 1–17. doi: 10.1038/s42003-022-03787-x. Full text in Research Archive Show summary

  Abstract Antibody-based therapeutics (ABTs) are used to treat a range of diseases. Most ABTs are either full-length IgG1 antibodies or fusions between for instance antigen (Ag)-binding receptor domains and the IgG1 Fc fragment. Interestingly, their plasma half-life varies considerably, which may relate to how they engage the neonatal Fc receptor (FcRn). As such, there is a need for an in-depth understanding of how different features of ABTs affect FcRn-binding and transport behavior. Here, we report on how FcRn-engagement of the IgG1 Fc fragment compare to clinically relevant IgGs and receptor domain Fc fusions, binding to VEGF or TNF-α. The results reveal FcRn-dependent intracellular accumulation of the Fc, which is in line with shorter plasma half-life than that of full-length IgG1 in human FcRn-expressing mice. Receptor domain fusion to the Fc increases its half-life, but not to the extent of IgG1. This is mirrored by a reduced cellular recycling capacity of the Fc-fusions. In addition, binding of cognate Ag to ABTs show that complexes of similar size undergo cellular transport at different rates, which could be explained by the biophysical properties of each ABT. Thus, the study provides knowledge that should guide tailoring of ABTs regarding optimal cellular sorting and plasma half-life.

• Veiby, Nina; Simeunovic, Aida; Heier, Martin; Brunborg, Cathrine; Saddique, Naila & Moe, Morten C. [Show all 9 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Kvernebo, Anne Kari; Miyamoto, Takuma; Drolsum, Liv Kari; Moe, Morten Carsten; Måsøy, Svein-Erik & Sunagawa, Gengo [Show all 10 contributors for this article] (2021). Ocular surface microcirculation is better preserved with pulsatile versus continuous flow during cardiopulmonary bypass—An experimental pilot. Artificial Organs. ISSN 0160-564X. doi: 10.1111/aor.14137. Full text in Research Archive Show summary

  Background: Non- pulsatile cardiopulmonary bypass (CPB) may induce micro-vascular dysregulation. In piglets, we compared ocular surface microcirculation during pulsatile versus continuous flow (CF) bypass.Methods: Ocular surface microcirculation in small tissue volumes (~0.1 mm3) at limbus (high metabolic rate) and bulbar conjunctiva (low metabolic rate) was ex-amined in a porcine model using computer assisted video microscopy and diffuse reflectance spectroscopy, before and after 3 and 6 h of pulsatile (n = 5 piglets) or CF (n = 3 piglets) CPB. Functional capillary density, capillary flow velocity and microvascular oxygen saturation were quantified.Results: At limbus, velocities improved with pulsatility (p< 0.01) and deterio-rated with CF (p< 0.01). In bulbar conjunctiva, velocities were severely reduced with CF (p< 0.01), accompanied by an increase in capillary density (p< 0.01). Microvascular oxygen saturation decreased in both groups.Conclusion: Ocular surface capillary densities and flow patterns are better pre-served with pulsatile versus CF during 6 h of CPB in sleeping piglets.

• Jørstad, Øystein Kalsnes; Wigers, Andreas R.; Marthinsen, Pål Bache; Evang, Johan Arild & Moe, Morten Carstens (2021). The Value of Macular Optical Coherence Tomography in Watchful Waiting of Suprasellar Masses: A 2-Year Observational Study. Journal of neuro-ophthalmology. ISSN 1070-8022. 41(4), p. e516–e522. doi: 10.1097/WNO.0000000000000993. Full text in Research Archive
• Eidet, Jon Roger; Akopian, Maja; Olstad, Ole Kristoffer; Jørstad, Øystein Kalsnes; Moe, Morten Carsten & Petrovski, Goran [Show all 7 contributors for this article] (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), p. 1–10. doi: 10.1186/s12348-021-00249-z. Full text in Research Archive Show summary

  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.

• Husum, Yngvil Solheim; Moe, Morten Carstens; Bragadottir, Ragnheidur & Jørstad, Øystein Kalsnes (2021). Switching to aflibercept versus continuing bevacizumab for treatment-resistant neovascular age-related macular degeneration: a one-year comparative observational study. Acta Ophthalmologica. ISSN 1755-375X. 99(8), p. 1–6. doi: 10.1111/aos.14825. Full text in Research Archive Show summary

  Purpose To compare outcomes of a treatment algorithm that allows for switching treatment-resistant neovascular age-related macular degeneration (nAMD) eyes to aflibercept with continuing bevacizumab. Methods Retrospective study of nAMD patients who initiated treatment in 2012 (aflibercept unavailable) and 2018 (aflibercept available). Eyes were included in the case of residual macular fluid after a minimum of 4 monthly bevacizumab injections. Only eyes in the 2018 group could then switch to aflibercept. Results The study included 40 eyes from 2012 and 88 eyes from 2018. Patient characteristics were similar across the groups at baseline and 4 months. In 2018, 59 eyes (67%) were switched to aflibercept after 4 months. Mean change in BCVA from 4 months to one year was +2.8 letters in 2018 versus −1.7 letters in 2012 (p = 0.043). Mean change in BCVA from baseline to one year was +9.4 letters in 2018 (p < 0.001) and +4.4 letters in 2012 (p = 0.073). Mean change in CRT from 4 months to one year was −36 µm in 2018 versus −23 µm in 2012 (p = 0.373). Mean change in CRT from baseline to one year was −100 µm in 2018 (p < 0.001) and −75 µm in 2012 (p < 0.001). Mean number of injections given in one year was 11.8 in 2018 versus 10.4 in 2012 (p < 0.001). After one year, a majority of eyes in both groups still received treatment at 4-week intervals. Conclusion The study suggests that the possibility of switching eyes with treatment-resistant nAMD to aflibercept leads to a modest visual benefit compared with continuing first-line bevacizumab therapy.

• Sivertsen, Magne S.; Lode, Heidrun Elisabeth; Gjølberg, Torleif Tollefsrud; Petrovski, Goran; Andersen, Jan Terje & Jørstad, Øystein Kalsnes [Show all 7 contributors for this article] (2021). Cluster of symptomatic silicone oil droplets following intravitreal injections: A 1-year observational study. BMJ Open Ophthalmology. 6:e000764(1), p. 1–5. doi: 10.1136/bmjophth-2021-000764. Full text in Research Archive Show summary

  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.

• Bøhler, Anders Djupesland; Strøm, Marianne Ekornes; Sandvig, Kjell Ulrik; Moe, Morten Carsten & Jørstad, Øystein Kalsnes (2021). Acute macular neuroretinopathy following COVID-19 vaccination. Eye (London. 1987). ISSN 0950-222X. doi: 10.1038/s41433-021-01610-1. Full text in Research Archive
• Josifovska, Natasha; Albert, Réka; Nagymihaly, Richard; Lytvynchuk, Lyubomyr; Moe, Morten Carsten & Kaarniranta, Kai [Show all 8 contributors for this article] (2020). Resveratrol as Inducer of Autophagy, Pro-Survival, and Anti-Inflammatory Stimuli in Cultured Human RPE Cells. International Journal of Molecular Sciences. ISSN 1661-6596. 21(3), p. 1–12. doi: 10.3390/ijms21030813. Full text in Research Archive Show summary

  Purpose: To investigate the mechanism by which resveratrol acts upon retinal pigment epithelial (RPE) cells and to characterize its effect upon autophagy, survival, and inflammation, with consequent implications to treatment for age-related macular degeneration (AMD). Methods: Cultured ARPE-19 cells were exposed to 10 and 50 μM resveratrol. Cell survival/death was determined by annexin-FITC/propidium iodide using flow cytometry, while autophagy was studied by detecting autophagic vacuoles formation (acridine orange and transmission electron microscopy), as well as LC3II/I ratio and p62 expression by Western blot. In addition, time-lapse confocal microscopy of a pDENDRA-LC3 expression vector was performed to detect autophagy in transfected ARPE-19 cells under the different treatment conditions. Inhibition of proteasomal and autophagy-lysosomal fusion was carried out by MG-132 and chloroquine, respectively, while induction of autophagy was achieved by rapamycin treatment. Detection of secreted cytokines by ARPE-19 cells using Human XL Cytokine Array was performed under oxidative stress (H2O2) and resveratrol treatments, respectively. Results: Resveratrol induced autophagy in ARPE-19 cells as determined by augmented presence of autophagic vacuoles, increased LC3II/I ratio and decreased p62 expression, as well as time-lapse confocal microscopy using pDENDRA-LC3 expression vector. Resveratrol acted similarly to proteasomal inhibition and downstream of mammalian target of rapamycin (mTOR), since upstream inhibition of autophagy by 3-methyladenine could not inhibit autophagy in ARPE-19 cells. Co-treatmeant by rapamycin and/or proteasome inhibition showed no additive effect upon autophagy induction. ARPE-19 cells treated by resveratrol showed lower cell death rate compared to untreated controls. Resveratrol induced a specific anti-inflammatory response in ARPE-19 cells. Conclusions: Resveratrol can induce autophagy, pro-survival, and anti-inflammatory stimuli in ARPE-19 cells, properties which could be plausible to formulate future treatment modalities for AMD.

• Veiby, Nina; Simeunovic, Aida; Heier, Martin; Brunborg, Cathrine; Saddique, Naila & Moe, Morten Carsten [Show all 9 contributors for this article] (2020). Venular oxygen saturation is increased in young patients with type 1 diabetes and mild nonproliferative diabetic retinopathy. Acta Ophthalmologica. ISSN 1755-375X. 98(8), p. 800–807. doi: 10.1111/aos.14462. Full text in Research Archive
• Ness, Charlotte Larsen; Katta, Kirankumar; Garred, Øystein; Kumar, Neena Theresa; Olstad, Ole Kristoffer & Petrovski, Goran [Show all 8 contributors for this article] (2020). Integrated differential DNA methylation and gene expression of formalin-fixed paraffin-embedded uveal melanoma specimens identifies genes associated with early metastasis and poor prognosis. Experimental Eye Research. ISSN 0014-4835. 203. doi: 10.1016/j.exer.2020.108426. Full text in Research Archive Show summary

  Purpose Uveal melanoma (UM) is an aggressive malignancy, in which nearly 50% of the patients die from metastatic disease. Aberrant DNA methylation is recognized as an important epigenomic event in carcinogenesis. Formalin-fixed paraffin-embedded (FFPE) samples represent a valuable source of tumor tissue, and recent technology has enabled the use of these samples in genome-wide DNA methylation analyses. Our aim was to investigate differential DNA methylation in relation to histopathological classification and survival data. In addition we sought to identify aberrant DNA methylation of genes that could be associated with metastatic disease and poor survival. Methods FFPE samples from UM patients (n = 23) who underwent enucleation of the eye in the period 1976–1989 were included. DNA methylation was assessed using the Illumina Infinium HumanMethylation450 array and coupled to histopathological data, Cancer Registry of Norway- (registered UM metastasis) and Norwegian Cause of Death Registry- (time and cause of death) data. Differential DNA methylation patterns contrasting histological classification, survival data and clustering properties were investigated. Survival groups were defined as “Early metastasis” (metastases and death within 2–5 years after enucleation, n = 8), “Late metastasis” (metastases and death within 9–21 years after enucleation, n = 7) and “No metastasis” (no detected metastases ≥18 years after enucleation, n = 8). A subset of samples were selected based on preliminary multi-dimensional scaling (MDS) plots, histopathological classification, chromosome 3 status, survival status and clustering properties; “Subset Early metastasis” (n = 4) vs “Subset No metastasis” (n = 4). Bioinformatics analyses were conducted in the R statistical software. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in various comparisons were assessed. Gene expression of relevant subgroups was determined by microarray analysis and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results DNA methylation analyses identified 2 clusters that separated the samples according to chromosome 3 status. Cluster 1 consisted of samples (n = 5) with chromosome 3 disomy (D3), while Cluster 2 was comprised of samples (n = 15) with chromosome 3 monosomy (M3). 1212 DMRs and 9386 DMPs were identified in M3 vs D3. No clear clusters were formed based on our predefined survival groups (“Early”, “Late”, “No”) nor histopathological classification (Epithelioid, Mixed, Spindle). We identified significant changes in DNA methylation (beta FC ≥ 0.2, adjusted p < 0.05) between two sample subsets (n = 8). “Subset Early metastasis” (n = 4) vs “Subset No metastasis” (n = 4) identified 348 DMPs and 36 DMRs, and their differential gene expression by microarray showed that 14 DMPs and 2 DMRs corresponded to changes in gene expression (FC ≥ 1.5, p < 0.05). RNF13, ZNF217 and HYAL1 were hypermethylated and downregulated in “Subset Early metastasis” vs “Subset No metastasis” and could be potential tumor suppressors. TMEM200C, RGS10, ADAM12 and PAM were hypomethylated and upregulated in “Subset Early metastasis vs “Subset No metastasis” and could be potential oncogenes and thus markers of early metastasis and poor prognosis in UM. Conclusions DNA methylation profiling showed differential clustering of samples according to chromosome 3 status: Cluster 1 (D3) and Cluster 2 (M3). Integrated differential DNA methylation and gene expression of two subsets of samples identified genes associated with early metastasis and poor prognosis. RNF13, ZNF217 and HYAL1 are hypermethylated and candidate tumor suppressors, while TMEM200C, RGS10, ADAM12 and PAM are hypomethylated and candidate oncogenes linked to early metastasis. UM FFPE samples represent a valuable source for methylome studies and enable long-time follow-up.

• Eidet, Jon Roger; Jørstad, Øystein Kalsnes; Fostad, Ida; Olstad, Ole Kristoffer; Sørland, Ragnhild Ø. & Moe, Morten Carsten [Show all 8 contributors for this article] (2020). Unilateral acute anterior uveitis is associated with ipsilateral changes in the tear fluid proteome that involves the LXR/RXR pathway. Journal of Ophthalmic Inflammation and Infection. 10. doi: 10.1186/s12348-020-00204-4. Full text in Research Archive Show summary

  Purpose To determine whether unilateral acute anterior uveitis (AAU) induces ipsilateral changes in the tear fluid proteome. Methods Five patients (25–77 years old) with unilateral AAU were included. Tear fluid samples were obtained using Schirmer’s test strips. The healthy eye served as control. Proteins were identified by liquid chromatography tandem mass spectrometry. Results Two hundred forty-two tear fluid sample proteins were identified, of which 75 were present in at least three patients. Nine proteins were at least 1.5-fold increased, whereas eight were at least 1.5-fold decreased in tears from the diseased eye compared with the healthy eye. APOBEC3A was significantly increased (1.43-fold; P = 0.04), whereas TGM2 was significantly decreased (− 1.21-fold; P = 0.03) in tears from the diseased eye relative to the healthy eye. Ingenuity Pathway Analysis identified LXR/RXR (P < 1.02E−4) as a top canonical pathway. Conclusion Unilateral AAU induced detectable changes in the ipsilateral tear fluid proteome and involvement of the inflammation-associated LXR/RXR pathway.

• Khan, Ayyad Ahmad Zartasht; Utheim, Tor Paaske; Moe, Morten Carsten; Aass, Hans Christian Dalsbotten; Sapkota, Dipak & Vallenari, Evan Michael [Show all 7 contributors for this article] (2020). The silk protein sericin promotes viability of ARPE-19 and induced pluripotent stem cell-derived retinal pigment epithelial cells in vitro. Current Eye Research. ISSN 0271-3683. 46(4), p. 504–514. doi: 10.1080/02713683.2020.1809001. Full text in Research Archive Show summary

  Purpose Maintaining mature and viable retinal pigment epithelial cells (RPE) in vitro has proven challenging. Investigating compounds that can promote RPE-viability and maturation is motivated by RPE transplantation research, the quest to understand RPE physiology, and a desire to modulate RPE in pathological states. We have previously reported that the silk protein sericin promotes viability, maturation, and pigmentation of human fetal RPE. In the present study, our aim was to uncover whether these effects can be seen in adult retinal pigment epithelial cell line-19 (ARPE-19) and induced pluripotent stem cell-derived RPE (iPSC-RPE). Methods ARPE-19 and iPSC-RPE were cultured with or without 10 mg/mL sericin. After 7 days, viability was assessed with calcein-acetoxymethyl ester (CAM) and ethidium homodimer-1 (EH-1) assays, flow cytometry, and morphometric analysis. Expression levels of RPE65, tyrosinase, and Pmel17 were quantified to compare maturation between the sericin-treated and control cultures. Light microscopy and staining of the tight junction protein zonula occludens protein 1 (ZO-1) were employed to study sericin’s effects on RPE morphology. We also measured culture medium pH, glucose, lactate, and extracellular ion content. Results Sericin-supplemented RPE cultures demonstrated significantly better viability compared to control cultures. Sericin appeared to improve ARPE-19 maturation and morphology in vitro. No effects were seen on RPE pigmentation with the concentration of sericin and duration of cell culture herein reported. Conclusions This is the first study to demonstrate that supplementing the culture media with sericin promotes the viability of iPSC-RPE and ARPE-19. Sericin’s viability-promoting effects may have important implications for retinal therapeutics and regenerative medicine research.

• Veiby, Nina; Simeunovic, Aida; Heier, Martin; Brunborg, Cathrine; Saddique, Naila & Moe, Morten Carsten [Show all 9 contributors for this article] (2020). Associations between macular OCT angiography and nonproliferative diabetic retinopathy in young patients with type 1 diabetes mellitus. Journal of Diabetes Research. ISSN 2314-6745. 2020, p. 1–12. doi: 10.1155/2020/8849116. Full text in Research Archive Show summary

  Background/Objective. Optical coherence tomography angiography (OCTA) is increasingly used to supplement ophthalmoscopy in the diagnosis and follow-up of diabetic retinopathy. Our objective was to confirm if OCTA parameters can predict the development of nonproliferative diabetic retinopathy (NPDR) and to clarify if any single OCTA parameter is associated with NPDR independently of well-known risk factors in young type 1 diabetes (T1D) patients. Methods. OCTA of both eyes was performed in a cross-sectional study of 14 to 30-year-old individuals with at least 10-year duration of T1D and controls recruited from the Norwegian Atherosclerosis and Childhood Diabetes (ACD) study. Vessel density (VD) and foveal avascular zone (FAZ) area in the superficial and deep capillary plexus (SCP and DCP), total retinal volume (TRV), and central macular thickness (CMT) were calculated using automated software. Univariate and multivariate ordered logistic regression (OLR) models were used accordingly. Results. We included 168 control eyes and 315 T1D eyes. Lower VD in DCP (OR 0.65, 95% CI 0.51–0.83), longer diabetes duration (OR 1.51, 95% CI 1.22–1.87), and higher waist circumference (OR 1.08, 95% CI 1.02–1.14) were significantly associated with progression of NPDR. VD in SCP and DCP were significantly lower in T1D patients without diabetic retinopathy than in controls. Conclusions. Sparser VD in DCP is significantly associated with severity of NPDR, supporting that OCTA might detect the earliest signs of NPDR before it is visible by ophthalmoscopy.

• Kvernebo, Anne Kari; Miyamoto, Takuma; Sporastøyl, Ane Halse; Sundheim, Liv Kristin Ribbskog; Måsøy, Svein-Erik & Drolsum, Liv [Show all 10 contributors for this article] (2020). Quantification of ocular surface microcirculation by computer assisted video microscopy and diffuse reflectance spectroscopy. Experimental Eye Research. ISSN 0014-4835. 201, p. 1–7. doi: 10.1016/j.exer.2020.108312. Full text in Research Archive Show summary

  In piglets we tested the applicability of digital video microscopy and diffuse reflectance spectroscopy for non-invasive assessments of limbal and bulbar conjunctival microcirculation. A priori we postulated that the metabolic rate is higher in limbal as compared to bulbar conjunctiva, and that this difference is reflected in microvascular structure or function between the two locations. Two study sites, Oslo University Hospital (OUH), Norway and Cleveland Clinic (CC), USA, used the same video microscopy and spectroscopy techniques to record limbal and bulbar microcirculation in sleeping piglets. Recordings were analyzed with custom-made software to quantify functional capillary density, capillary flow velocity and microvascular oxygen saturation in measuring volumes of approximately 0.1 mm3. The functional capillary density was higher in limbus than in bulbar conjunctiva at both study sites (OUH: 18.1 ± 2.9 versus 12.2 ± 2.9 crossings per mm line, p < 0.01; CC: 11.3 ± 3.0 versus 7.1 ± 2.8 crossings per mm line, p < 0.01). Median categorial capillary blood flow velocity was higher in bulbar as compared with limbal recordings (CC: 3 (1–3) versus 1 (0–3), p < 0.01). Conjunctival microvascular oxygen saturation was 88 ± 5.9% in OUH versus 94 ± 7.5% in CC piglets. Non-invasive digital video microscopy and diffuse reflectance spectroscopy can be used to obtain data from conjunctival microcirculation in piglets. Limbal conjunctival microcirculation has a larger capacity for oxygen delivery as compared with bulbar conjunctiva.

• Nagymihaly, Richard; Moe, Morten Carstens & Petrovski, Goran (2020). Isolation and Culture of Corneal Stromal Stem Cells. Methods in molecular biology. ISSN 1064-3745. 2145, p. 1–15. doi: 10.1007/978-1-0716-0599-8_1. Full text in Research Archive
• Hertzberg, Silvia Nanjala Walekhwa; Veiby, Nina; Bragadottir, Ragnheidur; Eriksen, Ketil; Moe, Morten Carsten & Petrovski, Beata [Show all 7 contributors for this article] (2020). Cost-effectiveness of the triple procedure – phacovitrectomy with posterior capsulotomy compared to phacovitrectomy and sequential procedures. Acta Ophthalmologica. ISSN 1755-375X. 98(6), p. 592–602. doi: 10.1111/aos.14367. Full text in Research Archive Show summary

  Purpose To evaluate the cost‐effectiveness of the triple procedure (phacovitrectomy + posterior capsulotomy, PhacoPPVc) compared to the double‐ (phacovitrectomy, PhacoPPV) or single sequential procedures. Methods Prospective study on 31 eyes from 31 patients (mean age: 72.1 ± 9.1 years; 55% females) was performed with a preoperative decision to undergo only pars plana vitrectomy (PPV) (26%) or PhacoPPV (74%) and/or posterior capsulotomy based upon presence or absence of lens opacification or pseudophakia. Time during and between surgeries, surgical procedure codes, medical and transport costs, outcome and likelihood of complications after surgery were all included in the analysis. Societal perspectives and visual acuity were considered as measures of quality of adjusted life years (QALYs). Results About 23 eyes underwent triple procedure and eight eyes underwent vitrectomy only (mean surgery times: 35.9 and 24.0 min, respectively). Posterior capsulotomy took on average 30 s, while preparation and cataract procedure took 13.0 min. The patients travelled on average 80km (average cost: $280.12) to the surgery unit. The average reimbursement fee for the day procedures ranged between $174.17 (YAG capsulotomy; Diagnosis Related Group (DRG): 0.034), $1045.48 (Phaco + intraocular lens (IOL); DRG: 0.204) and $1701.32 (PPV; DRG: 0.332). The combined procedures excluded lens and laser reimbursements, while the calculated reimbursements for the double/triple procedures were $2713.08/$2901.45, respectively, without significant loss of QALYs. PhacoPPVc was found to be unequivocally cost‐effective, while PhacoPPV remained cost saving compared to sequential procedures. Conclusion This study confirms that the triple procedure has benefits to the patients, health institution and surgeon. For patients, it saves them travel and healing time; for health institution, it justifies the calculated higher costs and need for higher reimbursement for the double/triple procedures, which are cost saving.

• Bisevac, Jovana; Anisimova, Natalia S.; Nagymihaly, Richard; Kristianslund, Olav; Katta, Kirankumar & Noer, Agate [Show all 11 contributors for this article] (2020). Long-term myofibroblast persistence in the capsular bag contributes to the late spontaneous in-the-bag intraocular lens dislocation. Scientific Reports. 10, p. 1–17. doi: 10.1038/s41598-020-77207-7. Full text in Research Archive Show summary

  Abstract Late spontaneous in-the-bag intraocular lens (IOL) dislocation is a complication presenting 6 months or later after cataract surgery. We aimed to characterize the cells in the lens capsules (LCs) of 18 patients with spontaneous late in-the-bag IOL dislocation. Patients' average age was 82.6 ± 1.5 years (range 72–98), and most of them had pseudoexfoliation syndrome (PEX). Cells from the LCs were positive for myofibroblast (αSMA), proliferation (Ki-67, PCNA), early lens development/lens progenitor (SOX2, PAX6), chemokine receptor (CXCR4), and transmembrane (N-cadherin) markers, while negative for epithelial (E-cadherin) marker. Moreover, the cells produced abundant fibronectin, type I and type V collagen in the nearby extracellular matrix (ECM). During ex vivo cultivation of dislocated IOL-LCs in toto, the cells proliferated and likely migrated onto the IOL’s anterior side. EdU proliferation assay confirmed the proliferation potential of the myofibroblasts (MFBs) in dislocated IOL-LCs. Primary cultured lens epithelial cells/MFBs isolated from the LC of dislocated IOLs could induce collagen matrix contraction and continuously proliferated, migrated, and induced ECM remodeling. Taken together, this indicates that long-lived MFBs of dislocated IOLs might contribute to the pathogenic mechanisms in late in-the-bag IOL dislocation.

• Bern, Malin C.; Nilsen, Jeannette; Ferrarese, Mattia; Sand, Kine Marita Knudsen; Gjølberg, Torleif Tollefsrud & Lode, Heidrun Elisabeth [Show all 24 contributors for this article] (2020). An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics. Science Translational Medicine. ISSN 1946-6234. 12(565), p. 1–13. doi: 10.1126/scitranslmed.abb0580. Full text in Research Archive Show summary

  Needle-free uptake across mucosal barriers is a preferred route for delivery of biologics, but the efficiency of unassisted transmucosal transport is poor. To make administration and therapy efficient and convenient, strategies for the delivery of biologics must enhance both transcellular delivery and plasma half-life. We found that human albumin was transcytosed efficiently across polarized human epithelial cells by a mechanism that depends on the neonatal Fc receptor (FcRn). FcRn also transported immunoglobulin G, but twofold less than albumin. We therefore designed a human albumin variant, E505Q/T527M/K573P (QMP), with improved FcRn binding, resulting in enhanced transcellular transport upon intranasal delivery and extended plasma half-life of albumin in transgenic mice expressing human FcRn. When QMP was fused to recombinant activated coagulation factor VII, the half-life of the fusion molecule increased 3.6-fold compared with the wild-type human albumin fusion, without compromising the therapeutic properties of activated factor VII. Our findings highlight QMP as a suitable carrier of protein-based biologics that may enhance plasma half-life and delivery across mucosal barriers.

• Jacobsen, Henrik Holvin; Sandell, Tiril; Jørstad, Øystein Kalsnes; Moe, Morten Carsten; Ringstad, Geir & Eide, Per Kristian (2020). In vivo evidence for impaired glymphatic function in the visual pathway of patients with normal pressure hydrocephalus. Investigative Ophthalmology and Visual Science. ISSN 0146-0404. 61:24(13), p. 1–11. doi: 10.1167/IOVS.61.13.24. Full text in Research Archive Show summary

  Purpose: Impaired ability to remove toxic metabolites from central nervous system may be an important link between cerebral and ophthalmic degenerative diseases. The aim of the present study was to compare the glymphatic function in the visual pathway in patients with idiopathic normal pressure hydrocephalus (iNPH), a neurodegenerative dementia subtype, with a reference group. Methods: We compared 31 subjects with Definite iNPH (i.e., shunt-responsive) with 13 references in a prospective and observational study. After intrathecal injection of the magnetic contrast agent gadobutrol (Gadovist, 0.5 mL, 1.0 mmol/mL, Bayer Pharma AG), serving as a tracer, consecutive magnetic resonance imaging (MRI) scans were obtained (next 24–48 hours). The normalized MRI T1 signal recorded in the cerebrospinal fluid (CSF) and along the visual pathway served as a semi-quantitative measure of tracer enrichment. Gadobutrol does not penetrate the blood-brain barrier and is thus confined to the extravascular space. Overnight measurements of pulsatile intracranial pressure were used as a surrogate marker for the intracranial compliance. Results: The tracer enriched the prechiasmatic cistern similarly in both groups, but clearance was delayed in the iNPH group. Moreover, both delayed enrichment and clearance of the tracer were observed in the visual pathway in the iNPH subjects. The enrichment in the visual pathway and the CSF correlated. Individuals with elevated pulsatile intracranial pressure showed reduced enrichment within the visual pathway. Conclusions: There was delayed enrichment and clearance of a tracer in the visual pathway of iNPH patients, which suggests impaired glymphatic function in the visual pathway in this disease.

• Blom, Kathrine; Bragadottir, Ragnheidur; Sivertsen, Magne S.; Moe, Morten Carsten & Jørstad, Øystein Kalsnes (2020). Does pharmaceutical compounding of vascular endothelial growth factor inhibitors for intravitreal use alter the risk of post-injection endophthalmitis? Ocular immunology and inflammation. ISSN 0927-3948. p. 1–5. doi: 10.1080/09273948.2020.1820530. Full text in Research Archive Show summary

  Purpose To investigate the safety of pharmaceutically compounded syringes for intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) drugs. Methods Single center, retrospective chart review. From 2015 to 2019, Oslo University Hospital, Norway gradually implemented pharmaceutical compounding and splitting of bevacizumab, ranibizumab, and aflibercept vials into multiple prefilled syringes for intravitreal use. Medical records of all post-injection endophthalmitis (PIE) cases in this 5-year period were reviewed. The incidences of PIE associated with compounded and clinician-withdrawn syringes were compared. Results In 5 years, the total number of anti-VEGF injections was 112,926; 68,150 procedures (60%) utilized compounded syringes, and 44,776 procedures (40%) utilized clinician-withdrawn syringes. A total of 11 PIE cases were identified (incidence 0.10 per 1000; 95% CI 0.05–0.17). Five PIE cases were associated with compounded syringes (incidence 0.07 per 1000; 95% CI 0.03–0.17); 3 of these were culture positive. Six PIE cases were associated with clinician-withdrawn syringes (incidence 0.13 per 1000; 95% CI 0.06–0.29); 2 of these were culture positive. The relative risk of PIE following procedures utilizing compounded versus clinician-withdrawn syringes was 0.55 (95% CI 0.17–1.79; p = 0.32). Conclusion Use of compounded anti-VEGF drugs in a large clinical setting was not associated with an altered risk of PIE. The finding adds to the evidence that splitting of vials into prefilled syringes for intravitreal injections is safe, provided that an appropriate pharmaceutical compounding procedure is strictly followed.

• Landsend, Erlend Christoffer Sommer; Pedersen, Hilde Røgeberg; Utheim, Øygunn Aass; Rueegg, Corina Silvia; Baraas, Rigmor C. & Lagali, Neil [Show all 9 contributors for this article] (2019). Characteristics and Utility of Fundus Autofluorescence in Congenital Aniridia Using Scanning Laser Ophthalmoscopy. Investigative Ophthalmology and Visual Science. ISSN 0146-0404. 60(13), p. 4120–4128. doi: 10.1167/iovs.19-26994. Full text in Research Archive Show summary

  Purpose: To investigate fundus autofluorescence (FAF) and other fundus manifestations in congenital aniridia. Methods: Fourteen patients with congenital aniridia and 14 age- and sex-matched healthy controls were examined. FAF images were obtained with an ultra-widefield scanning laser ophthalmoscope. FAF intensity was quantified in the macular fovea and in a macular ring surrounding fovea and related to an internal reference within each image. All aniridia patients underwent an ophthalmologic examination, including optical coherence tomography and slit-lamp biomicroscopy. Results: Mean age was 28.4 ± 15.0 years in both the aniridia and control groups. Fovea could be defined by subjective assessment of FAF images in three aniridia patients (21.4%) and in all controls (P = 0.001). Mean ratio between FAF intensity in the macular ring and fovea was 1.01 ± 0.15 in aniridia versus 1.18 ± 0.09 in controls (P = 0.034). In aniridia, presence of foveal hypoplasia evaluated by biomicroscopy correlated with lack of foveal appearance by subjective analyses of FAF images (P = 0.031) and observation of nystagmus (P = 0.009). Conclusions: Aniridia patients present a lower ratio between FAF intensity in the peripheral and central macula than do healthy individuals. Both subjective and objective analyses of FAF images are useful tools in evaluation of foveal hypoplasia in aniridia.

• Jelin, Elma; Wisløff, Torbjørn; Jørstad, Øystein Kalsnes; Heiberg, Turid & Moe, Morten Carsten (2019). Patient-reported outcome measures in the management of neovascular age-related macular degeneration: a 1-year prospective study. BMJ Open Ophthalmology. 4(1), p. 1–8. doi: 10.1136/bmjophth-2019-000353. Full text in Research Archive Show summary

  <i>Objective</i> - To prospectively explore the following patient-reported outcome measures (PROMs) in the management of neovascular age-related macular degeneration (nAMD): (1) self-reported visual function, (2) symptom-state, (3) general-health and (4) satisfaction of treatment.<p> <p><i>Methods and analysis</i> - Corresponding to the four PROMs, participants responded to the following questionnaires: (1) National Eye Institute Visual-Functioning-Questionnaire (NEI-VFQ-25), (2) Patient-Acceptable-Symptom-Status (PASS 5), (3) EuroQol-Group-Questionnaire (EQ-5D-3L) and (4) Dimensions of Importance in Treatment of nAMD (DITAMD). Data were collected at baseline and after 3, 6 and 12 months of intravitreal antivascular endothelial growth factor treatment. Results were evaluated with t-tests and mixed linear regression analyses.<p> <p><i>Results</i> - The study included 197 patients. At baseline NEI-VFQ-25 (79.53±14.52) and EQ-5D (0.74±0.28) had relatively high scores, whereas PASS 5 was below ‘acceptable’ (3.30±0.80). At 12 months NEI-VFQ-25 and PASS 5 showed significant improvement, whereas EQ-5D and DITAMD remained unchanged. At baseline patients receiving treatment of the better-seeing eye (BSE) (n=52) reported significantly worse NEI-VFQ-25 and PASS 5 than patients for whom treatment only involved the worse-seeing eye (WSE), (n=145). In contrast to BSE patients, there was no improvement of NEI-VFQ-25 for WSE patients at 12 months, despite a significant improvement in best-corrected visual acuity (BCVA). Two independent variables, treatment including the BSE and BCVA for the treated eye, were found to predict both NEI-VFQ-25 and PASS 5.<p> <p><i>Conclusion</i> - After 12 months of nAMD treatment, there was a significant improvement in PASS 5 and NEI-VFQ-25, the latter depending on whether therapy included BSE. EQ-5D and DITAMD remained unaltered.

• Kristianslund, Olav; Dalby, Marius; Moe, Morten Carsten & Drolsum, Liv (2019). Cost-effectiveness analysis in a randomized trial of late in-the-bag intraocular lens dislocation surgery: repositioning versus exchange. Acta Ophthalmologica. ISSN 1755-375X. 97(8), p. 1–7. doi: 10.1111/aos.14108. Full text in Research Archive Show summary

  Purpose To compare the cost‐effectiveness of two operation methods for late in‐the‐bag intraocular lens (IOL ) dislocation. Methods In this randomized clinical trial, 104 patients were randomly assigned to IOL repositioning by scleral suturing (n = 54) or IOL exchange with a retropupillary iris‐claw lens (n = 50). A cost‐effectiveness analysis (CEA ) was performed in conjunction with previously published 6‐month efficacy and safety results. An incremental cost‐effectiveness ratio was calculated as the cost difference between the operation groups relative to their difference in postoperative corrected distance visual acuity (CDVA ) (mean and 95% confidence interval: minimum and maximum), reported as the cost difference in United States Dollars ($) per logMAR difference. Results Exchange surgery was $281.20 ± 17.66 more expensive than repositioning, mainly explained by the new IOL and the frequent use of anterior vitrectomy. A previous trial publication revealed no significant difference in the 6‐month postoperative CDVA between the groups. In the CEA , the mean group difference yielded an incremental cost‐effectiveness ratio of −$281.20 per −0.11 logMAR (‐$1108/QALY ) in favour of repositioning, ranging from −$281.20 per −0.29 logMAR (‐$406/QALY ) in favour of repositioning to +$281.20 per −0.08 logMAR (+$1522/QALY ) in favour of exchange. The CEA did not include the mean 9.5 min shorter operation time for exchange. Conclusion Repositioning tended to be more cost‐effective than exchange; however, this is modified if also considering the operation time. Overall, it seems the cost‐effectiveness is not alone sufficiently different to recommend one of the operation methods over the other for late in‐the‐bag IOL dislocation.

• Kristiansen, Ivar Sønbø; Bråten, Ragnhild Haugli; Jørstad, Øystein Kalsnes; Moe, Morten Carsten & Sæther, Erik Magnus (2019). Intravitreal therapy for retinal diseases in Norway 2011-2015. Acta Ophthalmologica. ISSN 1755-375X. p. 1–7. doi: 10.1111/aos.14262. Full text in Research Archive Show summary

  Purpose During the past decade, intravitreally administered biologic drugs have advanced the treatment of retinal diseases, such as wet age‐related macular degeneration (AMD), diabetic macular oedema and retinal venous occlusions. The drugs as well as the necessary disease management imply considerable economic burden on healthcare systems. This Norwegian study documents the rates of use of intravitreal therapies and intercounty variation over a 5‐year period. Methods We collected data from the Norwegian Patient Register for all episodes of care encompassing intravitreal therapy during the period 2011–2015. For each episode, we received information on patient age, sex, county of residence, diagnosis and name of drug injected. Results During the study period, 21 277 patients had in total 236 857 episodes of care. The number of intravitreal injections doubled from 2011 to 2015, reaching 63 601 injections in 2015, of which 77% were for diagnosed wet AMD. In 2015, the age‐adjusted number of episodes varied from 19 to 55 per 1000 population aged 50+ across Norway's 19 counties. The age‐adjusted number of patients treated per 1000 population aged 50+ varied from 5.22 to 8.35. Conclusion The use of intravitreal injections increased rapidly with wet AMD as the most frequent diagnosis and with varying utilization across Norway's 19 counties. The causes of the varying use of intravitreal therapies could not be established but may reflect variation in disease prevalence, treatment capacity, travel distance to the nearest ophthalmic service and lack of national treatment guidelines. The geographic variation in utilization may challenge policy goals of equitable care and warrants further studies.

• Lode, Heidrun Elisabeth; Gjølberg, Torleif Tollefsrud; Foss, Stian; Sivertsen, Magne S.; Brustugun, Jørgen & Andersson, Yvonne [Show all 9 contributors for this article] (2019). A new method for pharmaceutical compounding and storage of anti-VEGF biologics for intravitreal use in silicone oil-free prefilled plastic syringes. Scientific Reports. 9:18021(1), p. 1–10. doi: 10.1038/s41598-019-54226-7. Full text in Research Archive Show summary

  Intravitreal injections of antibody-based biologics targeting vascular endothelial growth factor (VEGF) are highly effective and have markedly decreased the risk of visual impairment associated with prevalent retinal diseases, such as neovascular age-related macular degeneration and diabetes macular oedema. The diseases are chronic in their nature, and most patients need long-term therapy to suppress disease activity. We previously reported a compounding method for repackaging and storage of aflibercept (Eylea), a commonly used anti-VEGF biologic, in silicone oil-coated plastic syringes without compromising drug stability or activity. In addition to improving safety and time spent per patient, compounding of anti-VEGF biologics enables single-dose vials to be split into multiple syringes, thereby considerably reducing waste and drug expenses. However, symptomatic silicone oil droplets may deposit in the eye's vitreous body after repetitive injections. To fully avoid this complication, we here report on a novel pharmaceutical compounding method using silicone oil-free syringes and a 33 G × 9 mm Low Dead Space Needle hub injection needle. We evaluate the method for three anti-VEGF biologics commonly used in ophthalmology: aflibercept, ranibizumab (Lucentis) and bevacizumab (Avastin). Our results show that compounding and storage for one week does not compromise the functional activity of the biologics and allows for safe and cost-effective compounding of anti-VEGF biologics for intravitreal injections in prefilled silicone oil-free syringes.

• Jacobsen, Henrik Holvin; Ringstad, Geir; Jørstad, Øystein Kalsnes; Moe, Morten Carsten; Sandell, Tiril & Eide, Per Kristian (2019). The Human Visual Pathway Communicates Directly With the Subarachnoid Space. Investigative Ophthalmology and Visual Science. ISSN 0146-0404. 60(7), p. 2773–2780. doi: 10.1167/iovs.19-26997. Full text in Research Archive Show summary

  Purpose: Explore in vivo whether there is direct communication between the cerebrospinal fluid (CSF) and extravascular compartment of human visual pathway structures. Methods: A prospective and observational study included 10 subjects who underwent intrathecal gadolinium–enhanced magnetic resonance imaging (MRI) for suspected CSF circulation disorder, but with a negative result and with no known ophthalmic diseases. After precontrast T1-weighted MRI, 0.5 mL of gadobutrol (Gadovist, 1.0 mmol/mL) was injected intrathecally. Gadobutrol distributes in the extravascular space, and served as a CSF tracer. Consecutive MRI scans were obtained throughout 24 to 48 hours. To assess gadobutrol contrast enrichment, regions of interest (ROIs) were placed at multiple locations along the visual pathway, from the primary visual cortex to the eye's vitreous body. CSF tracer dependent T1 signal was measured in each ROI. A linear mixed-model was used for statistical analyses. Results: CSF tracer enrichment was found within the optic nerve, optic chiasm, optic tract, and primary visual cortex (P < 0.001). Peak tracer enrichment in the visual pathway generally occurred after 24 hours and was preceded by peak enhancement in the prechiasmatic cistern after 4 to 6 hours. Conclusions: The results indicate direct communication between CSF of subarachnoid space and the extravascular space of the human visual pathway. Extravascular entry of the CSF tracer is a prerequisite for a glymphatic system, the present findings may suggest its presence. The existence of a glymphatic system in the human visual pathway could bring novel perspectives on the pathophysiology and treatment of ophthalmic diseases.

• Jørstad, Øystein Kalsnes; Steffensen, Leif Arthur; Eriksen, Ketil; Bragadottir, Ragnheidur & Moe, Morten Carsten (2019). Thirteen years of intravitreal anti-vascular endothelial growth factor therapy: the promises and burdens of a paradigm shift told from the perspective of the largest retina service in Norway. Acta Ophthalmologica. ISSN 1755-375X. p. 1–6. doi: 10.1111/aos.14177. Full text in Research Archive Show summary

  Purpose To describe the first 13 years of anti‐vascular endothelial growth factor (anti‐VEGF) therapy from the perspective of a public ophthalmic department serving a local community of almost one million people. Methods Retrospective registry study. Data from Oslo University Hospital, Norway were collected from 2006 through 2018. Hospital episode statistics were searched for episodes of care encompassing intravitreal anti‐VEGF procedures. Patient‐specific ID numbers, diagnoses, and drug codes were registered. In general, bevacizumab was used as first‐line treatment, with aflibercept reserved for resistant cases from 2013. Results The number of unique patients treated per year increased from 130 in 2006 to 3428 in 2018. In 2018, 2488 (73%) patients had also received treatment the previous year. The number of yearly injections increased from 228 in 2006 to 25 570 in 2018. In 2018 the diagnosis macular degeneration constituted 69% of injections, diabetic retinopathy constituted 15%, retinal vein occlusion constituted 13%, and other diagnoses constituted 3%. In the same year 49% of injections were with bevacizumab, 46% with aflibercept, 4% with ranibizumab, and 1% with dexamethasone implants. The bevacizumab to aflibercept ratio was almost 1:1 for macular degeneration and diabetic retinopathy; for retinal vein occlusion the ratio was 13:7. Conclusion In 13 years there was an approximately 100‐fold increase in the number of yearly intravitreal injections. A majority of patients received long‐term treatment. Macular degeneration was the most common diagnosis. Using bevacizumab as first‐line treatment, with aflibercept reserved for resistant cases from 2013, eventually resulted in a nearly 1:1 ratio in drug usage.

• Jelin, Elma; Wisløff, Torbjørn; Moe, Morten Carsten & Heiberg, Turid (2019). Psychometric properties of the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) in a Norwegian population of patients with neovascular age-related macular degeneration compared to a control population. Health and Quality of Life Outcomes. 17(1), p. 1–9. doi: 10.1186/s12955-019-1203-0. Full text in Research Archive Show summary

  Background Although visual acuity and optical coherence tomography (OCT) are most widely used as outcomes in treatment of neovascular age-related Macular Degeneration (nAMD), patient reported outcome measures are increasingly recognized. National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) was developed to capture the perceived visual function. Yet, evidence of psychometric performance in the target population is required. The aim of this study was to examine the psychometric properties of NEI-VFQ 25 in a Norwegian cohort of newly diagnosed nAMD patients followed with a Treat and Extend (T/E) protocol. Methods Patients receiving intravitreal anti–vascular endothelial growth factor (anti-VEGF) injection treatment according to a T/E protocol completed a Norwegian translation of NEI-VFQ 25, EuroQoL Health Questionnaire (EQ-5D), and Patient acceptable symptom state (PASS 5) at baseline, 3, 6 and 12 months. In addition, a control population completed the same questionnaires. Visual acuity was assessed with LogMar for best/treated eye. Validity testing comprised face validity by a 0–10 numeric rating scale about relevance of NEI-VFQ 25 as well as regression analyses and correlations between NEI-VFQ 25 and other relevant variables. Reliability was examined with Intraclass Correlation Coefficient (ICC) and Cronbach’s alpha for internal consistency were performed. Responsiveness, discriminatory power and predictive value were also explored. Results Number of respondents at baseline, after 3, 6 and 12 months was 197, 186, 176 and 168, respectively. The control population comprised 26 individuals. Face validity of NEI-VFQ 25 had a mean (SD) of 7.8 (1.7) (n = 84). NEI-VFQ was significantly correlated to visual acuity and PASS 5 as well as EQ-5D at baseline. Reliability (ICC) of the overall and sub scores for the patients/controls ranged from 0.49–0.97/0.59–0.97. Cronbach’s alpha was 0.61–0.85. Discriminatory power was confirmed by significant differences of the overall score between controls and patients (P < 0.001). NEI-VFQ 25 indicates responsiveness showing overall score improved significantly (P ≤ 0.001) from baseline to 3 months. NEI-VFQ 25, general health and visual acuity at baseline were the strongest predictors for how patients reported vision after 6 months follow-up. Conclusion NEI-VFQ 25 showed acceptable psychometric performance, which supports that the Norwegian version can be used to monitor patients treated for nAMD.

• Lorenzo, Yolanda; Haug, Kristiane; Ringvold, Amund; Petrovski, Goran; Moe, Morten Carsten & Collins, Andrew Richard [Show all 7 contributors for this article] (2018). Levels of oxidative DNA damage are low in ex vivo engineered human limbal epithelial tissue. Acta Ophthalmologica. ISSN 1755-375X. 96(8), p. 1–7. doi: 10.1111/aos.13811. Full text in Research Archive Show summary

  Purpose To examine levels of oxidative DNA base damage and expression of selected genes and proteins related to DNA damage repair in human limbal epithelium engineered ex vivo. Methods Cells were expanded from limbal tissue on cell culture‐treated inserts in medium containing fetal bovine serum, recombinant growth factors, hormones and cholera toxin (COM) and in medium with human serum as the single growth‐promoting additive (HS). Cells were analysed after two, three and four weeks in culture for DNA strand breaks and oxidized purine bases (Comet assay using the enzyme formamidopyrimidine DNA glycosylase, Fpg) and for expression of DNA repair enzymes APE1, OGG1 and Polβ by in situ hybridization (ISH) and by immunohistochemistry (IHC). Results Levels of strand breaks were substantial while levels of net Fpg‐sensitive sites (8‐oxoguanine and ring‐opened FaPy bases) were relatively low in cells engineered in COM and in HS. Both types of medium were found to support expression of base excision repair (BER) enzymes APE1, OGG1 and Polβ at the gene level. At the protein level, expression of APE1 and OGG1 was noticeable in both conditions while expression of Polβ was low. Conclusion Our findings indicate low levels of oxidative stress and/or efficient DNA purine base damage repair in human limbal epithelium engineered in a medium with human serum as the single growth‐promoting additive as well as in traditional medium with xenobiotics.

• Jørstad, Øystein Kalsnes; Wigers, Andreas Reidar; Marthinsen, Pål Bache; Moe, Morten Carsten & Evang, Johan Arild (2018). Loss of horizontal macular ganglion cell complex asymmetry: an optical coherence tomography indicator of chiasmal compression. BMJ Open Ophthalmology. 3(1), p. 3000195–3000195. doi: 10.1136/bmjophth-2018-000195. Full text in Research Archive
• Jelin, Elma; Wisløff, Torbjørn; Moe, Morten Carsten & Heiberg, Turid (2018). Development and testing of a patient-derived questionnaire for treatment of neovascular age-related macular degeneration: dimensions of importance in treatment of neovascular age-related macular degeneration. Acta Ophthalmologica. ISSN 1755-375X. 96(8), p. 804–811. doi: 10.1111/aos.13847. Full text in Research Archive
• Salvanos, Panagiotis; Moe, Morten Carsten; Utheim, Tor Paaske; Bragadottir, Ragnheidur & Kerty, Emilia (2018). Ultra-wide-field fundus imaging in the diagnosis and follow-up of susac syndrome. Retinal cases & brief reports. ISSN 1935-1089. 12(3), p. 234–239. doi: 10.1097/ICB.0000000000000470. Full text in Research Archive
• Schippert, Ana Carla Soares Portugal; Jelin, Elma; Moe, Morten Carsten; Heiberg, Turid & Grov, Ellen Karine (2018). The impact of age-related macular degeneration on quality of life and its association with demographic data. Results from the NEI VFQ-25 questionnaire in a Norwegian population. Gerontology and geriatric medicine. 4, p. 1–9. doi: 10.1177/2333721418801601. Full text in Research Archive Show summary

  Objective: To describe vision-related quality of life (VRQoL) in a Norwegian population of patients with newly diagnosed neovascular age-related macular degeneration (nAMD), and to evaluate the association with demographic data of age, gender, and civil status (married, cohabitants/unmarried, not cohabitants). Method: The Norwegian version of the National Eye Institute Visual Functioning Questionnaire–25 (NEI VFQ-25) questionnaire was administered to 145 patients recently diagnosed with nAMD. We used descriptive statistics and bivariate analysis to determine the distribution of demographic parameters and a possible association between demographic parameters and NEI VFQ-25 scores. Spearman correlation was employed to analyze the NEI VFQ-25 items and subscales scores. Results: Mean (SD) VFQ-25 total score was 78.5 (14.7). The scores per subscales varied from 64.7 to 89.7. No significant difference was revealed between demographic parameters and the NEI VFQ-25 items, except for one item (being with others) when comparing paired and nonpaired participants. Conclusion: In a Norwegian population with newly diagnosed nAMD, VRQoL is reported at a high baseline level. This is an important information for the health care personnel when discussing expectations during treatment with the patient. Age, gender, and civil status did not affect VRQoL.

• Szabó, Dóra Júlia; Nagymihály, Richárd; Veréb, Zoltán; Josifovska, Natasha; Noer, Agate & Liskova, Petra [Show all 9 contributors for this article] (2018). Ex vivo 3D human corneal stroma model for schnyder corneal dystrophy - Role of autophagy in its pathogenesis and resolution. Histology and Histopathology. ISSN 0213-3911. 33(5), p. 455–462. doi: 10.14670/HH-11-928. Full text in Research Archive
• Sivertsen, Magne S.; Jørstad, Øystein Kalsnes; Grevys, Algirdas; Foss, Stian; Moe, Morten Carsten & Andersen, Jan Terje (2018). Pharmaceutical compounding of aflibercept in prefilled syringes does not affect structural integrity, stability or VEGF and Fc binding properties. Scientific Reports. 8(1). doi: 10.1038/s41598-018-20525-8. Full text in Research Archive Show summary

  Macular edema due to neovascular age-related macular degeneration, diabetes or retinal vein occlusion can cause central vision loss. Intravitreal treatment with antibody-based biopharmaceutical compounds designed to neutralize vascular endothelial growth factor (VEGF) has proven to be an efficient strategy to ameliorate macular edema and restore visual acuity. At the same time, the use of anti-VEGF drugs places an economic burden on the health care system; the drugs are expensive, and repeated injections are usually required to maintain the therapeutic effect. Thus, there is an unmet need for more cost-effective procedures. We here describe how the most recently approved anti-VEGF drug, aflibercept, can be compounded into prefilled sterile syringes and stored for up to 4 weeks without compromising its quality, stability or functional properties, including VEGF and neonatal Fc receptor (FcRn) binding. The novel compounding method for repackaging of aflibercept in sterile plastic syringes can greatly reduce both cost and time spent per patient in the injection room.

• Jørstad, Øystein Kalsnes; Faber, Rowan Thomas & Moe, Morten Carsten (2017). Two-year functional and anatomical results after converting treatment resistant eyes with exudative age-related macular degeneration to aflibercept in accordance with a treat and extend protocol. Acta Ophthalmologica. ISSN 1755-375X. 95(5), p. 460–463. doi: 10.1111/aos.13480. Full text in Research Archive Show summary

  Purpose: To study the effects of converting to aflibercept in accordance with a treat and extend (T&E) strategy in eyes with treatment resistant exudative agerelated macular degeneration (AMD). Methods: Two-year prospective study of eyes with exudative AMD and persistent macular fluid despite monthly treatment with ranibizumab or bevacizumab. Eyes were converted to 2.0 mg aflibercept in accordance with a T&E protocol. Results: Fifty eyes from 47 patients were included. At baseline, the mean central retinal thickness (CRT) was 273 lm and mean best-corrected visual acuity (BCVA) 0.25 logarithm of the minimal angle of resolution (logMAR). The mean number of aflibercept injections the first year was 9.2. After 1 year, there was a reduction in mean CRT to 228 lm (p < 0.001); 22 eyes (44%) had a dry macula; and the mean BCVA was 0.24 logMAR (p = 0.531). The mean number of aflibercept injections the second year was 8.0 (p = 0.013 compared to first year). After 2 years, 24 eyes (48%) received treatment more frequently than every eighth week. The mean CRT was 225 lm (p < 0.001 compared to baseline); 31 eyes (62%) had a dry macula; and mean BCVA was 0.32 logMAR (p = 0.005 compared to baseline). Five eyes did not complete 2 years of aflibercept treatment after failing to improve. Conclusion: A majority of eyes showed improved anatomic outcomes. There was a small decrease in mean BCVA after the second year of treatment. About half of the eyes required treatment. This research has been published in Acta Ophtalmologica. © 2017 Wiley

• Johnsen, Erik Otter; Frøen, Rebecca Cathrine; Olstad, Ole Kristoffer; Nicolaissen, Bjørn; Petrovski, Goran & Moe, Morten Carsten [Show all 7 contributors for this article] (2017). Proliferative cells isolated from the adult human peripheral retina only transiently upregulate key retinal markers upon induced differentiation. Current Eye Research. ISSN 0271-3683. 43(3), p. 340–349. doi: 10.1080/02713683.2017.1403630. Full text in Research Archive
• Josifovska, Natasha; Szabó, Dóra Júlia; Nagymihály, Richárd; Veréb, Zoltán; Facskó, Andrea & Eriksen, Ketil [Show all 8 contributors for this article] (2017). Cultivation and characterization of pterygium as an ex vivo study model for disease and therapy. Contact lens & anterior eye. ISSN 1367-0484. 40(5), p. 283–292. doi: 10.1016/j.clae.2017.04.002. Full text in Research Archive
• Nagymihály, Richárd; Veréb, Zoltán; Facskó, Andrea; Moe, Morten Carsten & Petrovski, Goran (2017). Effect of isolation technique and location on the phenotype of human corneal stroma-derived cells. Stem Cells International. ISSN 1687-966X. 2017:9275248, p. 1–12. doi: 10.1155/2017/9275248. Full text in Research Archive
• Ness, Charlotte Larsen; Garred, Øystein; Eide, Nils; Kumar, Neena Theresa; Olstad, Ole Kristoffer & Bærland, Thomas Pedersen [Show all 9 contributors for this article] (2017). Multicellular tumor spheroids of human uveal melanoma induce genes associated with anoikis resistance, lipogenesis, and ssxs. Molecular Vision. 23, p. 680–694. Full text in Research Archive
• Eszes, Dóra J; Szabó, Dóra Júlia; Russell, Greg; Kirby, Phil; Paulik, Edit & Nagymajtenyi, Laszlo [Show all 9 contributors for this article] (2016). Diabetic Retinopathy Screening Using Telemedicine Tools: Pilot Study in Hungary. Journal of Diabetes Research. ISSN 2314-6745. 2016. doi: 10.1155/2016/4529824. Full text in Research Archive
• Skjellegrind, Håvard Kjesbu; Fayzullin, Artem; Johnsen, Erik Otter; Eide, Lars; Langmoen, Iver Arne & Moe, Morten Carsten [Show all 7 contributors for this article] (2016). Short-Term Differentiation of Glioblastoma Stem Cells Induces Hypoxia Tolerance. Neurochemical Research. ISSN 0364-3190. 41(7), p. 1545–1558. doi: 10.1007/s11064-016-1868-2. Full text in Research Archive Show summary

  Glioblastoma is the most common and malignant brain cancer. In spite of surgical removal, radiation and chemotherapy, this cancer recurs within short time and median survival after diagnosis is less than a year. Glioblastoma stem cells (GSCs) left in the brain after surgery is thought to explain the inevitable recurrence of the tumor. Although hypoxia is a prime factor contributing to treatment resistance in many cancers, its effect on GSC has been little studied. Especially how differentiation influences the tolerance to acute hypoxia in GSCs is not well explored. We cultured GSCs from three patient biopsies and exposed these and their differentiated (1- and 4-weeks) progeny to acute hypoxia while monitoring intracellular calcium and mitochondrial membrane potential (ΔΨm). Undifferentiated GSCs were not hypoxia tolerant, showing both calcium overload and mitochondrial depolarization. One week differentiated cells were the most tolerant to hypoxia, preserving intracellular calcium stability and ΔΨm during 15 min of acute hypoxia. After 4 weeks of differentiation, mitochondrial mass was significantly reduced. In these cells calcium homeostasis was maintained during hypoxia, although the mitochondria were depolarized, suggesting a reduced mitochondrial dependency. Basal metabolic rate increased by differentiation, however, low oxygen consumption and high ΔΨm in undifferentiated GSCs did not provide hypoxia tolerance. The results suggest that undifferentiated GSCs are oxygen dependent, and that limited differentiation induces relative hypoxia tolerance. Hypoxia tolerance may be a factor involved in high-grade malignancy. This warrants a careful approach to differentiation as a glioblastoma treatment strategy.

• RINGEN, ØYVIND; Haug, Kristiane; Moe, Morten Carsten; Zetterström, Charlotta; Røger, Magnus & Nicolaissen, Bjørn (2016). Cell death pattern in lens epithelium of cataract patients. Acta Ophthalmologica. ISSN 1755-375X. 94(5), p. 514–520. doi: 10.1111/aos.13009. Full text in Research Archive

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• Grory, Brian Mac; Preterre, Cécile; Lebranchu, Pierre; Ryan, Stephen James; Jørstad, Øystein Kalsnes & Moe, Morten Carstens [Show all 16 contributors for this article] (2026). Intravenous thrombolysis for acute central retinal artery occlusion: Protocol for a systematic review and individual participant data meta-analysis of randomized controlled trials. doi: 10.1371/journal.pone.0342739. Full text in Research Archive
• Jørstad, Øystein Kalsnes; Meling, Eva Ødegaard & Moe, Morten Carstens (2025). Transition to high-dose aflibercept and intraocular pressure risk: A two-step approach to injection volume at Oslo University Hospital. Acta Ophthalmologica. ISSN 1755-375X. doi: 10.1111/aos.17571. Full text in Research Archive
• Ryan, Stephen James; Jørstad, Øystein Kalsnes; Skjelland, Mona; Simonsen, Claus Z; Bek, Toke & Blauenfeldt, Rolf Ankerlund [Show all 65 contributors for this article] (2025). Tenecteplase in Central Retinal Artery Occlusion Study (TenCRAOS): Protocol for a randomized-controlled trial. doi: 10.1177/23969873251344199. Full text in Research Archive Show summary

  Rationale: Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that, without prompt reperfusion, is associated with a high risk of permanent blindness. There is currently no evidence-based, effective treatment for CRAO. Methods and design: TenCRAOS is an investigator-initiated, international, multicenter, randomized controlled, double-dummy, double-blind, phase III trial testing tenecteplase (TNK) 0.25 mg/kg + placebo versus acetylsalicylic acid (ASA) 300 mg + placebo. The target population is patients diagnosed with CRAO and a best-corrected visual acuity (BCVA) of ⩾1.0 logarithm of the minimum angle of resolution (logMAR), corresponding to a decimal BCVA of ⩽0.1 or a fraction BCVA of ⩽6/60, who can be treated within 4.5 h. Sample size: Assuming a difference in proportion of participants reaching the primary endpoint of 20% in the placebo/ASA treatment group versus 50% in the TNK/placebo group, we need 78 participants to reach 80% power to detect the difference on a 5% significance level. Outcomes: The primary outcome is the proportion of participants with BCVA of ⩽0.7 logMAR in the affected eye at 30-day follow-up, corresponding to a decimal BCVA of ⩾0.2 or fraction BCVA of ⩾6/30, representing a clinically relevant improvement of BCVA of ⩾0.3 logMAR (or 15 letters). Secondary efficacy outcomes include proportion of participants with BCVA of ⩽0.5 logMAR, corresponding to a decimal BCVA of ⩾0.32 or fraction BCVA of ⩾ 6/19, self-reported vision-targeted health status, quality of life, and modified Rankin Score at 30 and 90 days. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding, and mortality. Exploratory analyses include assessment with optical coherence tomography with angiography and transorbital ultrasound. Discussion: TenCRAOS intends to assess the efficacy and safety of systemic TNK within 4.5 h of CRAO onset.

• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Show all 30 contributors for this article] (2023). A novel non-invasive FcRn-targeted mucosal vaccine strategy. Full text in Research Archive
• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Show all 30 contributors for this article] (2023). A non-invasive subunit vaccine technology targeting FcRn induces protective mucosal and systemic antibody immunity in mouse models. Full text in Research Archive
• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Show all 30 contributors for this article] (2023). A novel non-invasive FcRn-targeted mucosal vaccine strategy. Full text in Research Archive
• Nilsen, Henning Yu; Jørstad, Anna-Katharina; Ryan, Stephen James; Moe, Morten Carsten; Grimstad, Kristoffer & Aamodt, Anne Hege [Show all 8 contributors for this article] (2023). En kvinne i 60-årene som ikke lenger gjenkjente det hun så. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(16), p. 1419–1423. doi: 10.4045/tidsskr.23.0198. Full text in Research Archive
• Anthi, Aina Karen; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa; Tjärnhage, Elias & Lode, Heidrun Elisabeth [Show all 29 contributors for this article] (2023). A non-invasive subunit vaccine technology targeting FcRn induces protective mucosal and systemic antibody immunity in mouse models. Full text in Research Archive
• Faraj, Sayed; Bathen, Marianne Etzelmüller; Galeckas, Augustinas; Myrold, Andreas; Stene-Johansen, Ingar & Jørstad, Øystein Kalsnes [Show all 7 contributors for this article] (2022). Retinal injuries in seven teenage boys from the same handheld laser. American Journal of Ophthalmology Case Reports. 27. doi: 10.1016/j.ajoc.2022.101596. Full text in Research Archive Show summary

  This paper presents retinal injuries in 10 eyes of seven teenagers who had been playing with a handheld laser. They reported different degrees of visual symptoms in the form of central scotomas. Clinical examination revealed light burns in the maculae and disruption of the retinal layers on OCT. One patient developed secondary choroidal neovascularization (CNV), which was successfully treated with intravitreal ranibizumab. For some of the patients, the injuries led to permanent visual sequela. This devastating case series emphasizes the need for awareness among minors, parents and communities about the danger of playing with handheld lasers.

• Blom, Kathrine; Bragadottir, Ragnheidur; Sivertsen, Magne S.; Moe, Morten Carsten & Jørstad, Øystein Kalsnes (2022). Re: Writing committee for the Post-Injection Endophthalmitis Study Group, et al.: The influence of universal face mask use on endophthalmitis risk after intravitreal anti-vascular endothelial growth factor injections (Ophthalmology. 2021;128:1620–1626). Ophthalmology (Rochester, Minn.). ISSN 0161-6420. 129(5), p. 1620–1626. doi: 10.1016/j.ophtha.2022.01.017. Full text in Research Archive
• Ryan, Stephen J; Falkenberg, Helle Kristine; Moe, Morten Carsten; Jørstad, Anna-Katharina; Jørstad, Øystein Kalsnes & Aamodt, Anne Hege (2022). StrokeVis – The Oslo study of visual impairment after Stroke. Full text in Research Archive
• Blom, Kathrine; Bragadóttir, Ragnheiður; Sivertsen, Magne S.; Moe, Morten Carsten & Jørstad, Øystein Kalsnes (2021). Mask use by patients in the context of COVID-19 can increase the risk of postinjection endophthalmitis. Acta Ophthalmologica. ISSN 1755-375X. doi: 10.1111/aos.14945. Full text in Research Archive
• Blom, Kathrine; Bragadottir, Ragnheidur; Sivertsen, Magne S.; Moe, Morten Carsten & Jørstad, Øystein Kalsnes (2021). Mask use by patients in the context of COVID-19 can increase the risk of postinjection endophthalmitis. Acta Ophthalmologica. ISSN 1755-375X. Full text in Research Archive
• Jørstad, Øystein Kalsnes; Kongsrud, Anne; KINGE, BETTINA; Fossen, Kristian; Basit, Samy & Forsaa, Vegard Asgeir [Show all 8 contributors for this article] (2021). Choosing Wisely: recommendations from the Norwegian Ophthalmological Society. Acta Ophthalmologica. ISSN 1755-375X. 99. doi: 10.1111/aos.15080. Full text in Research Archive
• Jørstad, Øystein Kalsnes; Sivertsen, Magne S.; Andersen, Jan Terje & Moe, Morten Carsten (2020). Kan ampullene med covid-19-vaksine utnyttes bedre? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 20.1039. doi: 10.4045/tidsskr.20.1039. Full text in Research Archive
• Jørstad, Øystein Kalsnes; Moe, Morten Carsten; Eriksen, Ketil; Petrovski, Goran & Bragadottir, Ragnheidur (2020). Coronavirus disease 2019 (COVID-19) outbreak at the Department of Ophthalmology, Oslo University Hospital, Norway. Acta Ophthalmologica. ISSN 1755-375X. 98(3), p. e388–e389. doi: 10.1111/aos.14426. Full text in Research Archive
• Jørstad, Øystein Kalsnes; Wigers, Andreas Reidar; Marthinsen, Pål Bache; Evang, Johan Arild & Moe, Morten Carsten (2019). Could optical coherence tomography add to the history of the pituitary incidentaloma? Acta Ophthalmologica. ISSN 1755-375X. 97(8), p. e1157–e1158. doi: 10.1111/aos.14151. Full text in Research Archive
• Landsend, Erlend Christoffer Sommer; Utheim, Øygunn Aass; Pedersen, Hilde Røgeberg; Baraas, Rigmor C.; Lagali, Neil S. & Bragadottir, Ragnheidur [Show all 8 contributors for this article] (2018). Fundus Autofluorescence in Congenital Aniridia. Investigative Ophthalmology and Visual Science. ISSN 0146-0404. 59(9), p. 1514–1514. Full text in Research Archive
• Jelin, Elma; Heiberg, Turid; Moe, Morten Carsten & Wisløff, Torbjørn (2018). Patient Reported Outcome measures in neovascular Age-Related Macular Degeneration. Full text in Research Archive
• Jelin, Elma; Moe, Morten Carsten; Wisløff, Torbjørn & Heiberg, Turid (2018). Psychometric properties of the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) tested in observational longitudinal study of patients with neovascular Age-related Macular Degeneration (Norwegian cohort). Full text in Research Archive
• Jelin, Elma; Heiberg, Turid; Moe, Morten Carsten & Wisløff, Torbjørn (2017). The development and psychometric performance of a new patient derived tool to measure important Dimensions In Treatment of Age-related Macular Degeneration (DITAMD). Full text in Research Archive
• Jelin, Elma; Heiberg, Turid; Moe, Morten Carsten & Wisløff, Torbjørn (2017). The development and psychometric performance of a new patient derived tool to measure important Dimensions In Treatment of Age-related Macular Degeneration (DITAMD). Acta Ophthalmologica. ISSN 1755-375X. Full text in Research Archive

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