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Purpose: Dementia is common among patients with primary open angle glaucoma (POAG) and neovascular age-related macular degeneration (nAMD). This study compares visit frequency, diagnostic test utilization, and treatment patterns for POAG and nAMD among persons with vs. without dementia., Methods: Optum's de-identified Clinformatics ® Data Mart Database (January 1, 2000-June 30, 2022) was used for this study. Two cohorts were created from newly diagnosed POAG or nAMD patients. Within each cohort, an exposure cohort was created of newly diagnosed dementia patients. The primary outcome was the number of visits to an eye care provider. Secondary analyses for the POAG cohort assessed the number of visual field tests, optical coherence tomography (OCT), and glaucoma medication prescription coverage. The secondary analysis for the nAMD cohort included the number of injections performed. Poisson regression was used to determine the relative rates of outcomes., Results: POAG patients with dementia had reduced rates of eye care visits (RR 0.76, 95% CI: 0.75-0.77), lower rates of testing utilization for visual fields (RR 0.66, 95% CI: 0.63-0.68) and OCT (RR 0.67, 95% CI: 0.64-0.69), and a lower rate of glaucoma prescription medication coverage (RR 0.83, 95% CI: 0.83-0.83). nAMD patients with dementia had reduced rates of eye care visits (RR 0.74, 95% CI: 0.70-0.79) and received fewer intravitreal injections (RR 0.64, 95% CI: 0.58-0.69) than those without dementia., Conclusions: POAG and nAMD patients with dementia obtained less eye care and less monitoring and treatment of their disease. These findings suggest that this population may be vulnerable to gaps in ophthalmic care., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of Pennsylvania Institutional Review Board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s).)

Objectives: This study aimed to establish normative health utility data in Thai patients with diabetic retinopathy, wet age-related macular degeneration, and cataract; evaluate the sensitivity of different utility instruments to visual impairment; explore the relationship among these health utility values with the vision-specific quality of life (QoL); and assess the association of baseline characteristics and visual acuity level with health utility values and vision-specific QoL., Methods: This multicenter cross-sectional survey included 309 patients from tertiary eye centers. We used health utility instruments (time trade-off [TTO], EuroQol five-dimension [EQ-5D-5L], and Health Utility Index 3 [HUI3]) and vision-specific QoL instrument (National Eye Institute Visual Function Questionnaire) for face-to-face interviews. Demographic data and Early Treatment Diabetic Retinopathy Study visual acuity were recorded during the participants ophthalmic visits. Univariable and multivariable mixed-effect models were used to evaluate factors associated with the utility scores. Health utility scores among each type of eye disease were compared., Results: The overall mean utility values from the TTO, EQ-5D-5L, and HUI3 were 0.84 ± 0.25, 0.70 ± 0.19, and 0.68 ± 0.26, respectively. The health utility scores obtained from TTO and HUI3 showed a significant response to severe visual impairment or worse. Health utility scores from HUI3 (r = 0.54; P < .01) and EQ-5D-5L (r = 0.43; P < .01) displayed a moderate correlation with the National Eye Institute Visual Function Questionnaire score. There were no significant differences in health utility value among the 3 diseases upon adjusting for the visual acuity level and demographics., Conclusions: Visual acuity level has a greater impact on a patient's QoL than the type of eye disease. HUI3 and EQ-5D-5L and TTO are suitable for measuring health utility in leading causes of blindness., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Purpose: The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown., Methods: In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti-thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti-VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group., Results: We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow-up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10-1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13-1.34; p < 0.001) were both associated with the development of exudative AMD. The age-stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population., Conclusion: This is the first longitudinal nationwide study showing that both hypo- and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The objective of this study is to evaluate the relationship of psoriasis and neovascular age-related macular degeneration (nAMD) in a population with diabetic mellitus (DM)., Design: Nationwide, population-based, retrospective cohort study., Methods: Records of patients over 40 years of age who had been diagnosed with type 2 diabetes mellitus from January 2009 to December 2012 were analyzed. The incidence of nAMD was observed from the index year to December 2018 in all subjects. The incidence rate of nAMD was compared between the psoriasis group and control group. Covariates include age, sex, body mass index, income level, smoking status, drinking status, regular exercise habits, hypertension, dyslipidemia, end-stage renal disease, diabetic retinopathy, glucose level, prescription of more than 3 oral hypoglycemic agents, and a history of diabetes mellitus exceeding 5 years., Results: Of 2,245,358 patients with type 2 DM, 20,853 patients were classified in the psoriasis group and the other 2,224,505 in the control group. A total of 105 nAMD cases were observed in the psoriasis group and 7459 cases in the control group. According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly higher risk for nAMD compared to controls (hazard ratio = 1.329, 95% CI = 1.096-1.612) after adjustments for covariates., Conclusions: This study demonstrated that psoriasis was an independent risk factor for developing nAMD in DM patients. Therefore, physicians should be alert to the development of nAMD in DM patients who also have psoriasis., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To determine the incidence of blepharoptosis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and compare the rates of blepharoptosis between patients injected with an eyelid speculum and those injected without a speculum., Design: Retrospective cohort study., Methods: International Classification of Diseases, Tenth Revision (ICD-10), codes were used to identify patients with exudative age-related macular degeneration (AMD) and those who developed ptosis after intravitreal injections. Patients with nonexudative AMD who did not receive intravitreal injections served as controls. The outcomes were the incidence of ptosis in the injection group compared to the noninjection group and incidence of ptosis in patients whose injections were performed with an eyelid speculum as compared to those whose injections were performed without a speculum., Results: We recruited 1100 exudative AMD patients who received at least 1 intravitreal anti-VEGF injection and 2258 nonexudative AMD patients who had not received an injection. In the injection group, 18 of 1100 patients (1.6%) developed ptosis, compared with 52 of 2258 patients (2.3%) in the noninjection group (P = .25). Within the injection group, ptosis was mostly bilateral, diagnosed on average 22.4 months after the initial injection, and after more than a 1-year injection-free period. Eleven of 537 patients (2.0%) injected without a speculum developed ptosis, compared with 8 of 444 patients (1.8%) injected with a speculum (P = .82)., Conclusions: No statistically significant differences in incidence rates of ptosis were observed. In this analysis, neither intravitreal anti-VEGF injections nor speculum use during injections appears to increase the risk of ptosis., (Copyright © 2024. Published by Elsevier Inc.)

Background/objectives: To assess the prevalence and correlates of impaired activities of daily living (ADLs) in patients with neovascular age-related macular degeneration (nAMD) who present for anti-vascular endothelial growth factor (VEGF) therapy., Methods: In a clinic-based cohort of 437 patients with nAMD who presented for anti-VEGF therapy, the Older American Resources and Services Scale (OARS) was administered to assess for impairments in basic, instrumental and total ADL. Logistic regression analyses were conducted to determine odds ratios (OR) and 95% confidence intervals (CI) for factors associated with ADL impairment., Results: The prevalence of impaired basic, instrumental and total ADL was 37.76%, 67.82% and 39.59%, respectively. In multivariate-adjusted models, moderate visual impairment [OR 5.65, 95% CI (2.31-13.83) and blindness [OR 5.43, 95% CI (2.09-14.12)] were associated with greater odds of impaired total ADL. Depressive symptoms [OR 2.08, 95% CI (1.08-4.00)], the presence of any disability [OR 3.16, 95% CI (1.64-0.07)] and never driving [OR 4.00, 95% CI (1.60-10.00)] were also positively associated with total ADL impairment. Better vision-related quality of life (QoL) was inversely associated with impaired instrumental ADL whilst higher health-related QoL scores were associated with decreased odds of total ADL impairment., Conclusions: There is a high prevalence rate of ADL impairment among nAMD patients presenting for therapy. Visual impairment, never driving, poor physical and mental health increased the odds of experiencing ADL impairment whilst better VRQoL and HRQoL reduced the odds of impairment., (© 2024. The Author(s).)

Purpose: To evaluate the impact of the changes in treatment patterns before, during and after the COVID-19 pandemic on best-corrected visual acuity (BCVA) in previously treated neovascular age-related macular degeneration (nAMD) patients., Methods: A multi-centre, retrospective, observational study of consecutive nAMD patients during 2019-2021. Data collected included demographics, BCVA, dates of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and clinic visits., Results: A total of 1652 eyes of 1652 nAMD patients were included, out of which 850 eyes were assessed in 2019 (pre-COVID-19), 630 eyes were assessed in 2020 (COVID-19) and 974 eyes were assessed in 2021 (post-COVID-19). During the COVID-19 period, the mean number of anti-VEGF injections was significantly lower than the corresponding pre-COVID-19 and post-COVID-19 periods (5.55 compared to 6.13 and 6.60, respectively p < 0.01). A constant lower ratio of injections per patient/month was observed during COVID-19 compared to previous and following years, with a notable decline during March-April, reaching a ratio of 0.4 in 2020 versus 0.65 in 2019 and 0.62 in 2021 (p < 0.01). Baseline BCVA (0.825, p < 0.001), number of injections (-0.007, p < 0.001), gender (-0.027, p = 0.037) and age (0.004, p < 0.001) were shown to be significant predictors of final BCVA., Conclusion: During the COVID-19 period, patients were treated with significantly less intravitreal anti-VEGF injection compared to the previous year with compensation in the following year. These changes in treatment patterns did not have a significant impact on BCVA outcomes. Age, gender, baseline BCVA and number of injections are predictors of final visual outcomes., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Aims: To investigate the incidence of macular neovascularisation (MNV) subtypes of neovascular age-related macular degeneration (nAMD) and summarise these subtypes' clinical features in the Chinese population using multimodal imaging., Methods: We retrospectively analysed 506 consecutive treatment-naïve nAMD patients (582 eyes). Incidence of MNV subtypes and clinical features were recorded based on their multimodal images. The classification of MNV subtypes in nAMD patients were referred to Consensus on Neovascular Age-related Macular Degeneration Nonmenclature (CONAN) study group classifications., Results: 460 eyes of 389 nAMD patients were included in our study. 68.5% (315/460) of nAMD eyes were from male. According to CONAN, we identified type 1 macular neovascularisation (MNV) in 61.1% of eyes (281/460), type 2 MNV in 16.3% of eyes (75/460), type 3 MNV in 2.0% of eyes (9/460), mixed type 1 and type 2 MNV in 20.6% of eyes (95/460). 58% of eyes (267/460) were diagnosed as polypoidal choroidal vasculopathy lesions (PCV). 45.2% of eyes (208/460) with PCV lesions were type 1 MNV and 12.8% of eyes (59/460) with PCV lesions were co-occurred with type 2 MNV., Conclusion: Based on the consensus anatomical classification system developed by the CONAN Study Group, we updated the incidence of MNV subtypes and found that PCV was the most common subtype and type 3 MNV was the least common subtype among Chinese nAMD patients. In addition, the co-occurrence of PCV and type 2 MNV was typically observed, and its frequency was reported in our study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We investigate the impact of COVID-19 and lockdowns on anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (AMD) in Victoria (Australian state with highest burden of COVID-19 in 2020) and Australia, by examining anti-VEGF prescriptions supplied for AMD treatment between 2018 and 2020., Methods: We performed a retrospective, population-based analysis of aflibercept and ranibizumab prescriptions supplied for the treatment of AMD in Victoria and Australia between 1 January 2018 and 31 December 2020, as recorded by the Pharmaceutical Benefits Scheme (PBS) and Repatriation PBS, the Australian Government program subsidising medication costs for Australian residents and veterans. Poisson models and univariate regression were used to descriptively examine trends in monthly anti-VEGF prescription rates with time and changes in monthly prescription rates (prescription rate ratios [RR])., Results: In 2020, anti-VEGF AMD prescription rates in Victoria decreased by 18% during the nationwide lockdown between March and May (RR 0.82, 95% CI: 0.80-0.85, p < .001), and by 24% during the Victorian-specific lockdown between July and October (RR 0.76, 95% CI: 0.73-0.78, p < .001). In Australia, prescription rates tended to decrease between January and October 2020, reducing by 25% (RR 0.75, 95% CI: 0.74-0.77, p < .001) between these months, including between March and April (RR 0.94, 95% CI: 0.92-0.95, p < .001) but not April and May (RR 1.10, 95% CI: 1.09-1.12, p < .001)., Conclusion: In 2020, anti-VEGF prescriptions for AMD treatment decreased modestly in Victoria during both lockdowns and in Australia during the year. Decreases may represent reduced treatment because of COVID-19, including public health orders, patients' self-limiting care, and ophthalmologists treating-and-extending to maximum intervals.

Purpose: To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD)., Methods: This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched control subjects using the Merative Marketscan Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic control subjects was also performed., Results: Metformin use was associated with reduced odds ratio of developing nAMD (odds ratio 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy-an effect that persisted after Bonferroni correction. In the diabetic cohort without diabetic retinopathy, reduced odds ratio was observed at 24-month cumulative doses of 1 to 300 g, 301 to 630 g, and 631 to 1,080 g., Conclusion: Metformin use was associated with reduced odds ratio of nAMD, particularly in patients without diabetic retinopathy. The protective effect was noted for 24-month cumulative doses below 1,080 g. Metformin may be a novel preventive strategy for nAMD.

Background: The purpose of the study was to compare the real-world aflibercept treatment and visual outcomes, and to examine the adherence to pandemic guidelines in two groups of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) before and during the first year of the COVID-19 pandemic in Sweden up to the 1-year follow-up., Methods: This is a retrospective observational study including 2915 treatment naïve eyes with nAMD. Using data from the Swedish Macula Register (SMR), 1597 eyes initiating treatment between 1 July 2018 and 31 January 2019 (pre-pandemic group) were compared with 1318 eyes starting treatment between 1 February and 31 August 2020 (pandemic group). The eyes were then followed for 1 year ± 2 months, hence the first group was unaffected by the pandemic while the second group was affected. The focus was on baseline characteristics, visual acuity (VA) change from baseline, number of injections, treatment regimen, number of appointments and the frequency and length of appointment delays. The Wilcoxon Signed-Rank Test was used to compare baseline VA to follow-up VA within the respective groups. The Mann-Whitney U-test and Fisher's exact test were used to compare outcomes between the groups., Results: Baseline characteristics were similar between the two groups. The percentage of eyes with an available follow-up VA after 1 year was 58% in the pre-pandemic group vs. 44% in the pandemic group. VA in the pre-pandemic group had increased significantly after 1 year, from 62.2 ± 14.1 letters to 64.8 ± 16.1 letters (n = 921); p < 0.0001. In the pandemic group, VA increased from 61.1 ± 15.8 to 64.9 ± 16.9 (n = 575); p < 0.0001. There was no significant difference in mean VA change between the groups; p = 0.1734. The pre-pandemic group had significantly more delays than the pandemic group, 45% vs. 36%; p < 0.0001., Conclusions: The pre-pandemic and pandemic groups had similar VA gains at 1-year follow-up, but with a reduced number of available VA in the pandemic group. Clinics were able to implement and prioritize injection visits excluding VA measurements, helping to reduce delays and maintain VA gains during the COVID-19 pandemic., (© 2024. The Author(s).)

Importance: Age-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older people and is expected to affect approximately 288 million people worldwide by 2040., Observations: Older age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD. AMD occurs when extracellular deposits accumulate in the outer retina, ultimately leading to photoreceptor degeneration and loss of central vision. The late stages of AMD are characterized by outer retinal atrophy, termed geographic atrophy, or neovascularization associated with subretinal and/or intraretinal exudation, termed exudative neovascular AMD. The annual incidence of AMD ranges from 0.3 per 1000 in people who are aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older. The estimated heritability of late-stage AMD is approximately 71% (95% CI, 18%-88%). Long-term prospective cohort studies show a significantly higher AMD incidence in people who smoke more than 20 cigarettes per day compared with people who never smoked. AMD is diagnosed primarily with clinical examination that includes a special lens that focuses light of the slit lamp through the pupil. Exudative neovascular AMD is best identified using angiography and by optical coherence tomography. Individuals with AMD who take nutritional supplements consisting of high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability to progress to late-stage AMD at 5 years vs a 28% probability for those taking a placebo. In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections experience less than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving sham treatment., Conclusions and Relevance: The prevalence of AMD is anticipated to increase worldwide to 288 million individuals by 2040. Intravitreally administered anti-VEGF treatment is first-line therapy for exudative neovascular AMD.

Purpose: To prevent vision loss, it is important to monitor patients with age-related macular degeneration (AMD) for the development of choroidal neovascularization. The coronavirus disease 2019 (COVID-19) pandemic caused many patients to miss or delay visits. To offset those gaps in care, providers utilized telehealth (TH) to evaluate patients for symptoms of disease progression and provide health education on the importance of continuous monitoring., Methods: This study evaluates the impact of TH encounters on the rate of return for recommended in-person examinations for 1103 patients with non-neovascular (dry) AMD seen in an outpatient ophthalmology clinic in 2019 and due for return evaluation after the outbreak of COVID-19 in 2020. Logistic regression analysis was used to identify demographic, clinical, and sociomedical factors associated with TH utilization and in-person return., Results: 422 patients (38%) utilized TH during the study period. Patients who completed a TH encounter were more likely to return for an in-person examination as compared with those who did not receive TH (OR: 1.8, CI 95%: 1.4-2.3, P < 0.001). Completing a TH visit was associated with the detection of new wet AMD (OR: 3.3, 95% CI 1.04-10.6, P = 0.043), as well as with an earlier return for those patients who were found to have disease progression (62 ± 54 days vs. 100 ± 57 days, P = 0.049)., Conclusion: Completing a TH visit increased the rate at which patients with dry AMD returned for recommended in-person eye examinations. In many cases, this permitted the earlier detection of wet AMD, which is linked with achieving better outcomes., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) are at risk of developing macular neovascularisation (MNV). These eyes may first develop subclinical non-exudative MNV (neMNV) before they leak to form exudative MNV (eMNV). The EYE NEON study is a 2-year study aimed at estimating the prevalence and incidence of neMNV and evaluating its role as a predictor for conversion to neovascular AMD., Methods: EYE NEON is a multicentre study that will run in retinal clinics across 25 National Health Service with the aim to recruit 800 patients with new onset nAMD in the first eye. The fellow-eye with no evidence of nAMD at baseline will be the study eye. All study eyes will have OCT and OCTA done at first and second year following first anti-VEGF treatment to the first eye (non-study eye), with new onset nAMD. We will estimate the prevalence and incidence of neMNV over 2 years, rate of conversion from neMNV to eMNV and numbers initiated on treatment for neovascular AMD in the study eye will be reported. Predictive models of conversion including neMNV with other demographic and imaging parameters will be developed., Conclusion: The study design with proposed target sample size is sufficient to evaluate the retinal imaging characteristics of the study eyes with and without neMNV and develop predictive models to inform risk of conversion to nAMD., (© 2023. The Author(s).)

Purpose: To investigate whether a seasonal distribution of the frequency of exudative age-related macular degeneration (wet AMD) recurrences exists., Methods: In total, 129 eyes with 171 recurrences in patients suffering from wet AMD were included in the study. All the patients had been treated with intravitreal anti-VEGF injections according to Pro Re Nata treatment regimen. Recurrence was defined as the re-detection of sub-retinal fluid, intraretinal fluid, and/or sub-macular hemorrhage in optical coherence tomography scans, after at least two consecutive monthly examinations with a "dry" macula. The year was divided in three 4-month periods (zone A: June-September, zone B: October-January, and zone C: February-May) based on the weather conditions prevailing in each period. Mean temperature and hours of sunlight exposure were the main weather markers recorded., Results: Eighty-two recurrences (48%) occurred during the period June-September, 50 (29.2%) during the period October-January, and 39 (22.8%) during the period February-May (Chi-square = 17.5, p < 0.001). Among the groups, neither patients' age (78 ± 8 years A, 76 ± 7 years B, and 79 ± 8 years C, p = 0.15) nor gender status (40% men A, 36% men B, and 51% men C, p = 0.35) differed significantly. Mean temperature was 27.6 ± 1.8 °C, 15.1 ± 4.6 °C, and 16.5 ± 4.4 °C in zones A, B, and C, respectively. Hours (h) of sunlight exposure (average hours/month) were 344 ± 34 h, 188 ± 42 h, and 223 ± 57 h in zones A, B, and C., Conclusion: We demonstrated that the frequency of wet AMD recurrences is significantly elevated during the warmer months, possibly due to the higher levels of UV radiation and mean temperature. Further research is necessary to validate our findings., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To report the incidence and risk factors for fibrosis at 10 years in a large cohort of persons with neovascular age-related macular degeneration (nAMD)., Design: Retrospective, multicenter, cohort study., Methods: We included 225 naive nAMD eyes that underwent intravitreal anti-vascular endothelial growth factor treatment over 10 years of follow-up at two Italian referral centers. Demographic and clinical data were reviewed at baseline and on an annual basis. Onset of fibrosis was defined by clinically assessing photographs, fundus descriptions, or fluorescein angiograms. Optical coherence tomography (OCT) scans of fibrosis were inspected by an external reading center and graded as subretinal pigment epithelium (RPE), mixed, or subretinal., Results: The mean age at baseline was of 72.1 ± 6.9 years. The incidence rate of fibrosis was estimated to be 8.9 per 100 person-years, with a cumulative incidence of 62.7% at 10 years. Fibrotic lesions were sub-RPE in 46.1%, mixed in 29.8%, and subretinal in 22.7%. Independent factors associated with fibrosis included the following: larger central subfield thickness variation (P < .001), submacular hemorrhages (P = .008), higher number of injections (P = .01), and worse baseline visual acuity (VA) (P = .03). Type 2 macular neovascularization was significantly associated with mixed and subretinal fibrosis. VA significantly declined over 10 years (-16.4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), particularly in eyes with mixed and subretinal fibrosis (P < .001)., Conclusions: We identified a 62.7% cumulative incidence of fibrosis in a large nAMD cohort at 10 years. Fibrosis was more common with frequent reactivations and lower baseline VA; its onset had a significant impact on final VA. This supports the hypothesis that nAMD patients should be promptly treated with proactive regimens., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To assess the impact of the measures taken during the lockdown period from March 17 to May 11, 2020 on the management of patients with exudative age related macular degeneration treated by intravitreal anti-VEGF injections at the University Hospital of Tours., Methods: In this retrospective study, patients were included after analysis of the computerized medical records of patients with age related macular degeneration. Those who were treated for exudative age related macular degeneration who received at least 1 intravitreal injection in the 12 months prior and at least one consultation in the 6 months prior to the lockdown period, were included. The initial and final mean visual acuity were compared with a 5 letter non-inferiority margin. A subgroup analysis was performed according to outcomes. The visual acuities immediately after this period were also recorded., Results: In all, 595 eyes of 493 patients were included. The mean initial visual acuity was 59.6 letters, vs. 58.5 for the final visual acuity, i.e. a difference of -1.13 letters with a lower limit of the confidence interval of less than 5. The visual acuity on release from lockdown was comparable to the other 2 measurements. Initial visual acuity and the number of missed treatments were the main factors associated with functional loss., Conclusion: Patients' visual acuity during the lockdown period was able to be maintained despite the restrictive measures and limitation of care access in France. The most common cause of substantial visual decline was missed intravitreal injections., (Copyright © 2023. Published by Elsevier Masson SAS.)

Aim: The risk of dry and wet age-related macular degeneration (AMD) based on fasting glucose levels and disease duration of type 2 diabetes was investigated., Methods: Using a health insurance claims database and the results of health examinations in South Korea, we conducted a retrospective, population-based cohort study of 2,103,604 adults ≥ 45 years of age who were AMD-free based on health checkups in 2009 and observed from January 1, 2011, to December 31, 2018. Glycemic status was classified into five groups: normal, impaired fasting glucose, new-onset diabetes (fasting glucose level ≥ 126 mg/dl but no diabetes diagnosis or diabetes medication), diabetes diagnosis < 5 years, and diabetes ≥ 5 years. According to the presence and absence of choroidal neovascularization, AMD was classified as wet AMD and dry AMD, respectively. Adjusted hazard ratios (HRs) of AMD occurrence were estimated in each category., Results: For dry AMD (n = 36,271, 1.72%), the HR was 1.192 (1.141-1.245) among subjects with diabetes < 5 years and 1.294 (1.242-1.349) among subjects with diabetes ≥ 5 years compared with subjects with normal glycemic status after adjusting for age, sex, body mass index, lifestyle, and medical history. For wet AMD (n = 12,912, 0.61%), the HR was 1.103 (1.011-1.203) among subjects with new-onset diabetes, 1.252 (1.167-1.344) among subjects with diabetes < 5 years, and 1.506 (1.413-1.605) among subjects with diabetes ≥ 5 years. The HR of AMD was significantly increased among participants ≤ 65 years old and those who did not have hypertension., Conclusions: The incidence of dry and wet AMD increased among diabetes patients compared to the normal glycemic status group. These risks increased when the duration of diabetes was 5 years or more. The risk of wet AMD was increased among new-onset diabetes patients. These results suggest that high blood glucose levels without treatment might induce the vision-threatening condition of wet AMD, emphasizing the importance of early blood glucose management., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: To examine the risk for retinal-vein-occlusion (RVO) in patients with neovascular age-related-macular-degeneration (AMD) as compared to age- and sex-matched controls., Method: This is a population-based, cohort study. The study encompassed 24,578 consecutive patients with neovascular AMD and 66,129 control subjects. Multivariate cox regression analysis was utilized to detect the risk of RVO among patients with neovascular AMD. Predictors of RVO in patients with neovascular AMD were identified using multivariate logistic regression analysis. Mortality of patients was assessed using Kaplan-Meier method., Results: The incidence rate of RVO was estimated at 1.25 (95% CI, 1.06-1.45) per 1000 person-years among patients with neovascular AMD and 0.25 (95% CI, 0.20-0.31) per 1000 person-years among controls. Patients with neovascular AMD were associated with an increased risk of RVO (adjusted HR, 4.35; 95% CI, 3.34-5.66; P < 0.001). Among patients with neovascular AMD, older age (≥79.0 years) was associated with a decreased risk of RVO (adjusted OR, 0.50; 95% CI, 0.37-0.70; P < 0.001), whilst a history of glaucoma increased the likelihood of RVO (adjusted OR, 2.66; 95% CI, 1.94-3.65; P < 0.001). Patients with neovascular AMD and comorbid RVO had a comparable risk of all-cause mortality relative to other patients with neovascular AMD (HR, 0.90; 95% CI, 0.67-1.22; P = 0.500) CONCLUSIONS: An increased risk of RVO was found among patients with neovascular AMD. Younger age and glaucoma predicted the development of RVO in patients with neovascular AMD. Awareness of this comorbidity is of benefit for clinicians as patients with neovascular AMD might be carefully examined for RVO signs and complications., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD)., Study Design: Retrospective multicenter case series., Methods: We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis., Results: In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001)., Conclusion: The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age., (© 2023. Japanese Ophthalmological Society.)

Purpose: Alzheimer disease (AD), a common form of dementia, shares several clinical and pathologic features with age-related macular degeneration (AMD). Epidemiologic reports on the association of AMD with subsequent dementia or AD are inconsistent., Design: Systematic review and meta-analysis., Methods: The Meta-analysis of Observational Studies in Epidemiology reporting guidelines were applied. The Newcastle-Ottawa Scale was used to evaluate the risk of bias in the included cohort studies that examined the association of AMD with subsequent dementia or AD. We estimated the pooled hazard ratios (HRs) of dementia or AD using random effects model meta-analysis and subgroup analysis on different follow-up periods, AMD subtype, gender, age, study design, and methods to ascertain dementia or AD., Results: A total of 8 223 581 participants were included in 8 studies published during 2000-2021. The meta-analysis showed that AMD was significantly associated with subsequent dementia (pooled HR 1.22, 95% CI 1.01-1.47) or AD (pooled HR 1.21, 95% CI 1.03-1.43). Our secondary analysis revealed that the association was more noticeable in dry AMD than wet AMD., Conclusions: Patients with AMD have higher risks of developing dementia or AD, and therefore identifying related comorbidities and retinal biomarkers is much warranted for older adults with AMD in ophthalmologic practice., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: The aim of this study was to evaluate the impact of adherence to French coronavirus disease 2019 (COVID 19)-related guidelines for intravitreal injection (IVI) practice on the visual outcomes of patients treated with anti-vascular endothelial growth factor (VEGF) agents for macular diseases during the first lockdown period., Methods: Observational multicentre study including all patients from 18 centres with an IVI initially planned during the lockdown. Visual acuity (VA, ETDRS) was recorded at 1 and 4 months after lockdown. French COVID 19-related guidelines recommended maintaining IVI practice. We defined three groups of patients: A, adherent to guidelines; NA+, non-adherent with delayed IVIs; and NA-, non-adherent without IVIs performed during the lockdown. Risk factors for non-adherence and visual loss were studied., Results: A total of 3020 eyes of 3020 patients, aged 77.8 ± 11.6 years, 59.8% women, were included. 59.3% were non-adherent(46.7% NA+, 12.6% NA-). A smaller decrease in VA at 4 months was observed in the A group than the NA+ and NA- group (-0.2 ± 6.7, -0.3 ± 6.9 and -1.5 ± 6.9, respectively [p < 0.001]). Factors associated with non-adherence were in multivariable analysis, older age, hospital practice, low-density population areas, high viral incidence areas, longer intervals between injection and treat and extent protocol. Factors associated with visual loss at 4 months in multivariable analysis were, being in the NA- group, older age, T&E and fixed regimens., Conclusion: Strict adherence to guidelines was associated with better visual outcome, although most of our patients did not attend as planned. Identification of patients at risk could help in the future in case of a new pandemic lockdown., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objective: Predicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2., Methods and Analysis: This retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238)., Results: At our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%-7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%-7.8%) after 12 months without treatment., Conclusions: Here, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments., Trial Registration Number: NCT00056836., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To report the diagnosis and definitions, epidemiology, risk factors, and visual outcomes of fibrosis in neovascular age-related macular degeneration (nAMD)., Design: Systematic review and meta-analysis., Methods: The review was performed using the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies and randomized controlled trials were included., Results: Identification of fibrosis is challenging. Optical coherence tomography angiography and polarization-sensitive optical coherence tomography represent novel options in multimodal imaging. The prevalence of fibrosis at baseline, 12, 24, and 60 months was 13%, 32%, 36%, and 56%, respectively. Approximately 60% of the fibrosis burden in nAMD at 5 years was present in the first year of treatment. Fibrosis development was highest in the first 12 months and slowed down over time. The risk factors of fibrosis included classic choroidal neovascularization (CNV), intra-retinal fluid, hemorrhage, hyperreflective material, CNV lesion size, and retinal thickness. Sub-retinal fluid and pigment epithelial detachment may be protective. Treatment-associated factors included disease activity and time to diagnosis. At baseline, the best corrected visual acuity in eyes with fibrosis was poorer than in eyes without fibrosis (-18.50 letters); this difference became larger at 12 months despite treatment (-26.86 letters)., Conclusions: There is a need to identify effective treatment strategies for fibrosis and to closely monitor at-risk patients. More studies involving multimodal imaging are required to clarify the definitions and grading criteria for fibrosis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To assess 5-year cumulative incidence and risk factors of fellow eye involvement in Asian neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy., Methods: In a prospective cohort study of Asian nAMD and polypoidal choroidal vasculopathy, the fellow eyes were evaluated for exudation. The 5-year incidence of exudation was compared between nAMD and polypoidal choroidal vasculopathy., Results: A total of 488 patients were studied. The 5-year incidence of exudation in fellow eyes was 16.2% (95% confidence interval: 12.0-20.2). Polypoidal choroidal vasculopathy compared with nAMD in the first eye was associated with lower fellow eye progression (9.8% [95% confidence interval: 5.1-14.3]) vs. 22.9% [95% confidence interval: 15.8-29.3], P < 0.01). Drusen (hazards ratio 2.11 [95% confidence interval: 1.10-4.06]), shallow irregular retinal pigment epithelium elevation (2.86 [1.58-5.18]), and pigment epithelial detachment (3.01 [1.27-7.17]) were associated with greater progression. A combination of soft drusens and subretinal drusenoid deposits, and specific pigment epithelial detachment subtypes (multilobular, and sharp peaked) were associated with progression. Pigment epithelial detachment, shallow irregular retinal pigment epithelium elevation, and new subretinal hyperreflective material occurred at 10.4 ± 4.2 months, 11.1 ± 6.0 months, and 6.9 ± 4.3 months, respectively, before exudation., Conclusion: The 5-year incidence of fellow eye involvement in Asian nAMD is lower than among Caucasians because of a higher polypoidal choroidal vasculopathy prevalence. Drusens, shallow irregular retinal pigment epithelium elevation, and pigment epithelial detachment are risk factors for fellow eye progression.

Purpose: To analyse the development of neovascular age-related macular degeneration (nAMD) in the fellow eye in patients initially presenting with unilateral nAMD, using data from the Swedish Macula Register., Methods: This observational study included data on treatment-naïve patients who initially underwent unilateral treatment for nAMD, and then required bilateral treatment, between 2010 and 2018, according to the Swedish Macula Register (SMR). The data were also stratified according into three time periods (2010-2013; 2014-2016; 2017-2018). Treatment duration, best-corrected visual acuity (BCVA) in the first and second eye, number of injections in the first eye before falling ill in the second, and the time between the last injection in the first eye and the start of treatment of the fellow eye were analysed., Results: 5216 out of 28 670 (18%) patients treated for nAMD subsequently required bilateral treatment. The mean age was 77.7 ± 7.3 years, and 69% were female. The mean duration of treatment of the first eye before nAMD was diagnosed in the fellow eye was 1.58 years, and the mean number of injections in the first eye was 8.9 ± 8.6. Best-corrected visual acuity, according to the ETDRS chart, was higher in the second eye at the time when treatment started in that eye compared to treatment start in the first eye: 62.8 (14.7) versus 57.6 (15.5); p < 0.001, and was higher in the 66% whose first eye was still undergoing treatment: 63.6 ± 14.5 versus 61.0 ± 14.8; p = 0.001., Conclusions: The mean duration of treatment of the first eye before treatment started in the fellow eye was 19 months, and treatment of the second eye had started within 2 years in 61% of the patients. Best-corrected visual acuity was higher in the second eye than in the first eye at the start of treatment of that eye and was higher in the second eye at the start of treatment of that eye when the first eye was still being treated., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To examine the risk, prevalence, and progression of glaucoma development in age-related macular degeneration (AMD) eyes receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections compared to controls., Design: Retrospective clinical cohort study., Methods: Retrospective review of eyes receiving intravitreal anti-VEGF injections from January 1, 2004, to December 31, 2013, for exudative AMD. Age- and sex-matched control groups of eyes included eyes with nonexudative AMD (NEAMD) and no AMD. Eyes with a diagnosis of glaucoma or glaucoma suspect were reviewed for injection details, type and date of glaucoma diagnosis, glaucoma treatments, standard automated perimetry (SAP), and spectral domain optical coherence tomography (SD-OCT). Qualitative progression was determined by indication of glaucoma progression in provider notes. Quantitative progression was assessed based on change in mean deviation (MD) on SAP, retinal nerve fiber layer thickness on SD-OCT, and intraocular pressure (IOP)., Results: There were 707 eyes of 504 patients treated with anti-VEGF injections and 1008 eyes in the NEAMD and no-AMD cohorts. There was no difference in glaucoma or suspect prevalence at initial presentation between eyes treated with injections and NEAMD (6.9% vs 9.7%, P = .22) or no-AMD controls (vs 8.5%, P = .55). There was no difference in cumulative 5-year probability of new glaucoma diagnosis after anti-VEGF injections compared to NEAMD (1.9% vs 1.0%, P = .69) or no-AMD controls (vs 1.6%, P = .88). There was no difference in qualitative progression of glaucoma in the injection cohort vs NEAMD (P = .19) or no-AMD controls (P = .61). The rate of MD change in injection eyes was similar to NEAMD eyes (P = .74) but greater than no-AMD eyes (P = .02). Eyes receiving injections required more topical glaucoma medications compared with NEAMD (P = .03) and more glaucoma laser treatments compared with no-AMD controls (P = .009). Eyes receiving injections did not require more frequent incisional glaucoma surgery compared with NEAMD (21.0% vs 15.0%, P = .95) or no-AMD controls (vs 10.0%, P = .10)., Conclusion: Eyes treated with intravitreal anti-VEGF injections for exudative AMD did not have increased risk of developing glaucoma compared with controls. Of those with a glaucoma diagnosis, exudative AMD eyes receiving injections required a greater number of topical glaucoma medications compared with NEAMD eyes and had a greater rate of MD loss than no-AMD controls., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objective: Macular atrophy (MA) contributes to declining vision during prolonged anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (nAMD) so greater understanding of its incidence, evolution, and impact on visual acuity is merited., Materials and Methods: This is a retrospective review of nAMD patients receiving anti-VEGF therapy for ≥ 5 years. Near-infrared reflectance images and vision data were extracted every 6 months. MA lesion areas were measured using ImageJ., Results: Vision showed a mean decline of -1.2 letters/year. Eyes with MA showed a greater decrease of -1.6 letters/year compared to eyes without MA (-0.7 letters/year). Cumulative incidence of MA was 38% at 5 years. MA was significantly associated with declining vision, showing a -0.7 letter decrease for every 1 mm 2 increase in lesion size., Conclusion: Over a 5-year course of nAMD treatment, MA affected most eyes, and MA progression was significantly associated with vision decline. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:546-552.] .

Purpose: Antivascular endothelial growth factor (anti-VEGF) agents are routinely intravitreously injected to treat neovascular age-related macular degeneration (AMD). Postoperative endophthalmitis, a side effect after intravitreal anti-VEGF injection, has been reported to have a low incidence but may threaten vision. In this study, we aimed to analyze the incidence of acute endophthalmitis after intravitreal anti-VEGF injection and associated risk factors in patients with neovascular AMD in South Korea., Methods: Using the health claims data recorded in the Korean National Health Insurance System database, we identified newly developed neovascular AMD cases from 2010 through 2019. Acute endophthalmitis was defined as a case of invasive treatment for accompanying symptoms. All statistical analyses were performed with a significance level p < 0.05. To find risk factors, we used univariate and multivariable Poisson regression., Results: The overall incidence of acute endophthalmitis was 0.019% (p = 0.21) during the 10-year period: 0.025% for aflibercept injection and 0.014% for ranibizumab injection. The incidence was higher in metropolitan city residents than in Seoul (incidence rate ratio [IRR], 1.96; 95% confidence interval [CI], 1.02-3.79; p = 0.04) and was higher for aflibercept injections than for ranibizumab injections (IRR, 1.82; 95% CI, 1.17-2.82; p = 0.01). However, in multivariate analysis, only aflibercept injections showed a significant effect on the incidence of acute endophthalmitis (IRR, 1.80; 95% CI, 1.16-2.79; p = 0.01)., Conclusions: The incidence of acute endophthalmitis after intravitreal anti-VEGF injections was generally low, and aflibercept was revealed as a significant risk factor.

Objectives: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the gold standard treatment for wet age-related macular degeneration (wet AMD). Coronavirus disease 2019 (COVID-19) has led to the cancellation of many scheduled intravitreal anti-VEGF injection visits. We compared the functional and structural visual outcomes of wet AMD patients who did not adhere to their planned intervals (group 1) with those who did (group 2)., Methods: Wet AMD patients of Swiss Visio Montchoisi and RétinElysée were included. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) changes between their first visit after the end of the first national lockdown in Switzerland (27 April 2020, first post-lockdown visit) and their last visit before the beginning of the first national lockdown in Switzerland (13 March 2020, last pre-lockdown visit) were assessed. The BCVA outcome was defined as unfavorable when there was a loss of≥5 ETDRS letters in the first post-lockdown visit compared to the BCVA at last pre-lockdown visit. The OCT outcome was defined as unfavorable when there was an increase in at least one of the parameters, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment (PED), at the first post-lockdown visit compared to the last pre-lockdown visit., Main Results: Group 1 (89 patients, 109 eyes) had a 13.41% greater rate of unfavorable BCVA outcomes and a 38.27% greater rate of unfavorable OCT outcomes than group 2 (96 patients, 122 eyes) (P=0.04, P<0.0001, respectively). Multivariate analysis showed that the more the patients deviated from their programmed injections and the higher the BCVA pre-lockdown, the higher the rate of unfavorable BCVA outcomes (P=0.03 and P=0.02, respectively). OCT outcomes were not a predictive factor for an unfavorable BCVA outcome., Conclusions: The cancellation of many intravitreal anti-VEGF injection appointments resulted in worse functional and structural outcomes in wet AMD patients. The COVID-19 pandemic led many patients to refrain from their routine intravitreal anti-VEGF injection appointments, allowing us to analyze the role of designated intervals in the treatment of wet AMD. During any future lockdown due to COVID-19 or similar circumstances, continuity of care for wet AMD patients should be maintained., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background/purpose: To report the rate of delayed follow-up visits (DFU), to identify risk factors of DFU, and to assess the impact of DFU on outcomes in neovascular age-related macular degeneration., Methods: This retrospective study included all patients with neovascular age-related macular degeneration (n = 1,291) treated with antivascular endothelial growth factor injections between January 2013 and December 2020 in 2 centers in Quebec, Canada. A DFU was defined as a delay of ≥4 weeks than scheduled. Visual outcomes, especially ≥15 letters loss, were reported., Results: A total of 351 patients (27.2%) experienced ≥1 DFU. Odds were greater among older patients ( P = 0.005), patients treated at the hospital rather than the clinic ( P < 0.001), and patients with worse initial visual acuity ( P = 0.024). A DFU was associated with a mean visual acuity loss of 4.2 ± 13.4 letters ( P < 0.001) and an increased incidence of intraretinal fluid and subretinal fluid ( P = 0.001, P = 0.005) at 6 months despite resumption of injections. Central foveal thickness increased after DFU but returned to pre-DFU visit at 6 months., Conclusion: The DFU rate in patients with neovascular age-related macular degeneration treated under a universal health care system was around 27%. Delayed follow-up visits caused significant decreases in visual acuity and increases in intraretinal fluid and subretinal fluid on optical coherence tomography that did not recover after injections resumption despite normalization of central foveal thickness.

Purpose: To examine whether systemic medications are associated with the subsequent development of wet age-related macular degeneration (AMD)., Methods: A retrospective study of 259 562 individuals based on registry data, from January 1, 2001, to December 31, 2017. End-point event was the International Classification of Diseases (ICD)-10 diagnosis for wet AMD. Association between use of systemic medication covering 85 generic drugs categorized according to Anatomical Therapeutic Chemical (ATC) codes and the incidence of wet AMD was evaluated using multivariate Poisson regression model (adjusted for age, sex, diabetes, cancer and socioeconomic group) and nested case-control design., Results: The mean length of follow-up was 9.84 years. The number of cases with wet AMD was 2947 and incidence rate was 1.15 per 1000 person-years. After adjustment, we observed an increased risk for the development of wet AMD for patients exposed to amlodipine (IRR 1.33, 95% CI 1.16-1.53), or felodipine (1.24, 95% CI 1.02-1.50). Similarly, an increased risk of wet AMD was associated with the use of bicalutamide (2.14, 95% CI 1.14-4.02), estradiol (1.20, 95% CI 1.03-1.40) and atorvastatin (1.22, 95% CI 1.05-1.43). Of note, digoxin (0.72, 95% CI 0.57-0.91), and ramipril (0.80, 95% CI 0.65-0.99) users had a lower incidence of wet AMD., Conclusions: Our findings suggest that the use of second-generation calcium channel blockers could be associated with an increased risk for wet AMD development. Of note, the incidence of wet AMD seemed to be lower in patients using ramipril and digoxin. More studies are needed to elucidate the associations further., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Medical services are still developing in Bhutan. There is no published national report on age-related macular degeneration (AMD). We therefore aim to determine the demographic characteristics and severity of AMD at first presentation among Bhutanese patients attending their recently inaugurated vitreoretinal (VR) clinics over a 3-year national survey, and to inform national health policy to develop suitable health program to prevent AMD-related blindness and visual impairment., Methods: A retrospective cross-sectional consecutive case series study was conducted on all new AMD cases in Bhutan. If a patient presented with asymmetrical AMD, the eye with more severe AMD was considered. If both the eyes had the same severity one eye was chosen randomly. Collection of demographic data and clinical details including diagnostic testing (fundus photography, OCT and fluorescent angiography) and clinical staging were performed., Results: Of 521 new AMD patients aged 71.9 ± 11.3 years, 306/521 (58.7%) were males (p = 0.005). At their first presentation, 234/521 patients (44.9%) already had late-stage AMD. Importantly, 69/234 patients (29.5%), that is half of total neovascular AMD (nAMD) patients, had disciform scars (DS) which were beyond treatment, and 7/234 patients (3.0%) had geographic atrophy (GA). Seven patients had retinal pigment epithelium tear at presentation. Fourteen of nineteen polypoidal choroidal vasculopathy (PCV) patients were younger than 50 years., Conclusions: Half of nAMD cases presented as DS not amenable to the treatment. Many potentially treatable nAMD patients had already lost central vision and were legally blind. Young people with PCV losing vision early in life with longer morbidity-affected life and socio-economic burden was concerning. GA and DS cases need visual rehabilitation to improve their QoL. Incorporating a screening program for AMD with effective health education, and maintaining a national AMD Registry, would potentially lower AMD-related blindness and visual impairment., (© 2022. The Author(s).)

Background: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic in 2020 outpatient care of neovascular age-related macular degeneration (nAMD) patients was severely reduced due to lockdown. Missed visits are known to be detrimental to patients in need of continued anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVIs). The purpose of the study was to assess the effect of a month-long pause of regular visits and anti-VEGF IVIs in nAMD patients., Methods: A retrospective study was performed. Patients were treated in a pro re nata ("as needed") scheme. Distance (logMAR) and near (logRAD) visual acuity (VA), optical coherence tomography, delay between planned and actual visit date and the indication for IVI were assessed for 3 continous visits in the 6 months before lockdown (V-3, -2, -1) and the 2 visits after lockdown (V0, V + 1). For analysis of long-term impact, records for visits 1 years before and after lockdown (V-3, V + 2) were gathered., Results: We included 166 patients (120 female, 46 male) with a median (range) age of 80.88 (59.8-99.36) years. Compared to V-1, distance VA was significantly worse at both V0 (0.27 ± 0.21 vs 0.31 ± 0.23 logMAR, p < 0.001) and V + 1 (0.27 ± 0.21 vs 0.30 ± 0.23 logMAR, p = 0.021). Near VA was significantly worse at both V0 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.037) and V + 1 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.02). Visit delay (VD) at V0 was significantly longer than at V + 1 (30.81 ± 20.44 vs 2.02 ± 6.79 days, p < 0.0001). Linear regression analysis showed a significant association between visit delay and a reduction of near VA between V-1 and V + 1 (p = 0.0223). There was a significant loss of distance VA (p = 0.02) in the year after the lockdown period (n = 125) compared to the year before. Loss of reading acuity was not significantly increased (p = 0.3). One year post lockdown, there was no correlation between VA change and visit delay after lockdown (p > 0.05)., Conclusions: In nAMD patients whose visits and treatment were paused for a month during the first wave of the COVID-19 pandemic, we found a loss of VA immediately after lockdown, which persisted during follow-up despite re-established anti-VEGF treatment. In the short term, length of delay was predictive for loss of reading VA. The comparison of development of VA during the year before and after the lockdown showed a progression of nAMD related VA loss which may have been accelerated by the disruption of regular visits and treatment., Trial Registration: This article does not report the outcome of a health care intervention. This retrospective study was therefore not registered in a clinical trials database., (© 2022. The Author(s).)

Purpose: To investigate the ophthalmic risk factors related to neovascular change and the subtype-wise incidence of progression from intermediate to neovascular age-related macular degeneration (AMD)., Methods: In this retrospective cohort study, 632 eyes with intermediate AMD from 418 patients (older than 50 years) were enrolled. The systemic factors and ophthalmic factors were statistically analysed with respect to neovascular change., Results: The 5-year cumulative incidence of progression to neovascular AMD (nAMD) from intermediate AMD was 17.8% and 17.0% in eyes with soft drusen and pachydrusen (p = 0.316). Older age (p = 0.025), preexisting nAMD in the fellow eye (p < 0.001), and reticular pseudodrusen (RPD; p = 0.007) were associated with the risk of progression to nAMD. In reference to soft drusen, pachydrusen was associated with progression to polypoidal choroidal vasculopathy (PCV; p < 0.001) and not to typical nAMD (p = 0.064)., Conclusions: The ophthalmic risk factors related to the progression of nAMD from intermediate AMD were found to be preexisting nAMD in the fellow eye and RPD. Pachydrusen showed a similar incidence of neovascular change with soft drusen, and was associated with the progression to PCV but not to typical nAMD., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To explore the relationship between single-nucleotide polymorphisms (SNPs) in complement factor I ( CFI ), interleukin-8 ( IL-8 ), transferrin ( TF ), and transferrin receptor 2 ( TFR2 ) and age-related macular degeneration (AMD) in a northeastern Chinese population. Methods: A total of 400 AMD patients (200 wet AMD and 200 dry AMD) and 200 controls were enrolled in this study, and genetic polymorphisms in the above genes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The χ 2 test was used to compare differences in allele frequencies in each group, and the associations of genotype frequencies with AMD were determined by multivariate logistic regression analysis. Results: Our research shows that CFI rs141853578, IL-8 rs2227543, TF rs8177178 and TFR2 rs2075674 are associated with the incidence of AMD. In wet AMD, allele T of CFI rs141853578, IL-8 rs2227543 and TFR2 rs2075674 may be a risk factor. Allele A of TF rs8177178 may increase the risk of dry AMD. Conclusions: CFI rs141853578, IL-8 rs2227543, TF rs8177178 and TFR2 rs2075674 genetic polymorphisms are associated with the occurrence of AMD in a northeastern Chinese population, especially wet AMD.

Objectives: To report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at 1 year., Design: Retrospective clinical audit and simulation model., Setting: Multiple UK National Health Service (NHS) ophthalmology centres., Participants: Data on the reduction in new nAMD referrals were obtained from four NHS Trusts comparing April 2020 with April 2019. To estimate the potential impact on 1-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20 825 nAMD eyes from 27 NHS Trusts., Main Outcome Measures: Simulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at 1 year under four hypothetical scenarios: 0-month, 3-month, 6-month and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at 1 year nationally., Results: The number of nAMD referrals dropped on average by 72% (range 65%-87%). Simulated 1-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2%-17.9%) to 23.3% (20.7%-25.9%), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1%-38.1%) to 26.4% (23.8%-29.2%). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level for 1 month nationally, these simulated results suggest an additional 186-365 eyes with vision ≤6/60 at 1 year., Conclusions: We report a large decrease in nAMD referrals during the COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at 1 year., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the risk of developing late age-related macular degeneration (AMD) after incident cataract surgery., Design: A prospective cohort study within a randomized controlled clinical trial of oral supplementation for the treatment of AMD, the Age-Related Eye Disease Study 2 (AREDS2)., Participants: AREDS2 participants aged 50 to 85 years with bilateral large drusen or unilateral late AMD., Methods: In eyes free of cataract surgery and late AMD at baseline, 2 groups were compared for incident late AMD: (1) eyes that received cataract surgery after the baseline visit and before any evidence of late AMD and (2) eyes that remained phakic until study completion. Eyes with at least 2 years of follow-up after cataract surgery were included in the analysis. We used Cox regression models, matched-pairs analysis, and logistic regression models that were adjusted for age, sex, smoking, education, study treatment group, and AMD severity., Main Outcome Measures: Late AMD was defined as the presence of geographic atrophy or neovascular AMD detected on annual stereoscopic fundus photographs or as documented by medical records, including intravitreous injections of anti-vascular endothelial growth factor medication., Results: A total of 1767 eligible eyes (1195 participants) received cataract surgery; 1981 eyes (1524 participants) developed late AMD during a mean (range) follow-up of 9 (1-12) years. The Cox regression model showed no increased risk of developing late AMD after cataract surgery: hazard ratio, 0.96; 95% confidence interval (CI), 0.81-1.13 (P = 0.60) for right eyes and hazard ratio, 1.05; 95% CI, 0.89-1.25 (P = 0.56) for left eyes. Of the matched pairs, late AMD was identified in 408 eyes that received cataract surgery and in 429 phakic controls: odds ratio (OR) 0.92 (95% CI, 0.77-1.10; P = 0.34). The risk of late AMD after cataract surgery from the logistic regression model was not statistically significant (risk ratio, 0.92; 95% CI, 0.56-1.49; P = 0.73)., Conclusions: Cataract surgery did not increase the risk of developing late AMD among AREDS2 participants with up to 10 years of follow-up. This study provides data for counseling AMD patients who might benefit from cataract surgery., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The phenotypes of neovascular age-related macular degeneration (nAMD) are recognized as differing between Caucasian and Asian patients. Pachychoroid is thought to be more prevalent in Asians than in Caucasians, and may be involved in the development of nAMD in Asian patients. Therefore, we investigated the clinical characteristics and pachychoroid incidence in Japanese patients with nAMD. We retrospectively analyzed 385 eyes of 370 consecutive Japanese patients with treatment naïve nAMD. According to the nAMD nomenclature, type 1 macular neovascularization (MNV) was observed in 132 eyes (34.3%), polypoidal choroidal vasculopathy (PCV) in 137 (35.6%), mixed type 1 and type 2 MNV in 32 (8.3%), type 2 MNV in 43 (11.2%), and type 3 MNV in 41 (10.6%). Pachychoroid was seen in 58.3% of type 1 MNV, 75.2% of PCV, 34.4% of mixed type 1 and type 2 MNV, 14.0% of type 2 MNV, and 0% of type 3 MNV. Compared to nAMD patients without pachychoroid (188 eyes), those who had nAMD with pachychoroid (197 eyes) were significantly younger, had a higher proportion of males, greater central choroidal thickness, and a higher frequency of macular vortex vein anastomoses (all P < 0.001). Furthermore, drusen subtypes differed significantly between the two groups (P < 0.001). These results suggest that most Japanese nAMD patients might have type 1 MNV or PCV. Moreover, in approximately half of patients, nAMD might be associated with pachychoroid, and choroidal congestion may be involved in the development of MNV in these cases., (© 2022. The Author(s).)

Background: Wet age-related macular degeneration (AMD) and age-related cataract are often coexisting causes of visual impairment. Yet, the timing of cataract surgery in wet AMD patients is controversial., Methods: One hundred and eleven eyes of 111 patients with wet AMD underwent cataract surgery at Helsinki University Hospital in Finland during 2014-2018. Best-corrected visual acuity and central subfield macular thickness (CSMT) were analysed at the time of wet AMD diagnosis, at the last recording prior to cataract surgery and at the first recording and at 1 year after surgery. The cumulative number of antivascular endothelial growth factor (anti-VEGF) injections at surgery, systemic and topical medication and postoperative anti-VEGF burden were recorded., Results: Mean age was 78.9 ± 5.6 years at the time of surgery. Central subfield macular thickness (CSMT) significantly decreased (280.1 ± 75.0 µm preoperatively to 268.6 ± 67.6 µm at the first postoperative recording, p = 0.001, and to 265.9 ± 67.9 µm at 1 year, p = 0.003), visual acuity improved (0.70 ± 0.46 logMAR units preoperatively to 0.39 ± 0.40 at the first postoperative recording, and to 0.33 ± 0.34 at 1 year, p < 0.001 for both) and anti-VEGF treatment intervals lengthened despite the surgery (6.53 ± 2.08 weeks prior to surgery to 7.03 ± 2.23 weeks at 1 year, p = 0.246, and to 7.05 ± 2.57 weeks at the last documented visit, p = 0.035). A CSMT increase of over 30% from the preoperative values was seen in only one case (1 out of 111 eyes, 0.9%). Macular status at surgery, wet AMD subtype, comorbidity of type II diabetes, systemic drugs and topical anti-inflammatory medication were not associated with macular changes nor with treatment intervals after surgery. The cumulative number of anti-VEGF injections correlated neither with CSMT change postoperatively (r = -0.051, p = 0.619) nor with CSMT change at 1 year (r = 0.091, p = 0.426)., Conclusion: Satisfactory visual outcomes and controlled disease activity were seen in patients with wet AMD undergoing cataract surgery. We found no evidence to support delaying surgery in patients who require it., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To elucidate the clinical characteristics of eyes with dry age-related macular degeneration (AMD) in Japan., Study Design: Retrospective., Methods: We performed a nationwide survey of dry AMD. A questionnaire on dry AMD was sent to 3,801 major hospitals and eye clinics nationwide. Whenever both eyes met the diagnostic criteria, only the eye with more advanced geographic atrophy was included., Results: In the current survey, 81 patients (81 eyes) with dry AMD were included. Of the 81 patients, 56 (69.1%) were men, and the mean age of the patients was 76.6 ± 8.4 (range, 54-94) years. Twenty-four patients (29.6%) had a history of smoking. The decimal best corrected-visual acuity (BCVA) was equal to or better than 0.7 in 25 eyes (30.9%), but worse than 0.1 in 17 eyes (21.0%). The mean BCVA was 0.62 ± 0.59 in logarithm of the minimum angle of resolution. Lesion size (the greatest linear dimension of the largest geographic atrophy) was ≥ 2 disc diameter in 33 eyes (40.7%) and < 1 disc diameter in 21 eyes (25.9%). Soft drusen was observed in 27 eyes (33.3%), and reticular pseudodrusen was observed in 31 eyes (38.3%). Of the 81 patients, the other eye was diagnosed as dry AMD in 26 eyes (32.1%), neovascular AMD in 16 eyes (19.8%), and intermediate AMD in 18 eyes (22.2%)., Conclusion: Dry AMD in the Japanese population has characteristics of male predominance, older age, high prevalence of reticular pseudodrusen, and high bilaterality., (© 2021. Japanese Ophthalmological Society.)

Purpose: The number of patients receiving anti-VEGF therapy has increased rapidly since its introduction in Denmark in 2007, placing an enormous pressure on the public healthcare system. In this study, we attempt to describe this growth and identify the factors driving it., Methods: Data on treatment of the entire population of neovascular AMD patients in the Capital Region of Denmark between 2007 and 2019 was retrieved. The age and sex standardized incidences of first time treatment and changes in duration of treatment were analysed., Results: The number of patients in active treatment increased from 576 in 2007 to 3684 in 2019. The growth was initially driven by accumulation of patients continuing anti-VEGF therapy for extended periods of time (259 patients/year). As larger numbers of patients began to be discharged, the increase slowed to 181 patients/year in late 2010s, with demographic change becoming the main growth driving factor. The incidence of first treatment increased slightly during the study period, mainly for individuals over 85 years. For patients under 85 years, treatment incidences closely followed neovascular AMD incidences from population studies. The likelihood of remaining in anti-VEGF treatment after the initial injection followed exponential decay curve (t 1/2  = 3.6 years). Based on this observation, a model was created to describe the number of patients in active treatment, which accurately described historical data (R 2  = 0.999), and forecast a linear growth of 138 patients/year until 2030., Conclusion: Treatment incidences and modelling reported in this study might facilitate a more informed and accurate planning of future ophthalmology services., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the association between female reproductive factors and the incidence of exudative age-related macular degeneration (AMD)., Methods: A total of 1,297,388 postmenopausal women over 50 years of age who participated in both national health screening and cancer screening in 2009 were identified using the Korea National Health Insurance System database. Data on female reproductive factors were collected using a self-administered questionnaire. Patients were followed up until 2018, and the incident cases of exudative AMD were identified. The hazard ratios and 95% confidence intervals for exudative AMD were estimated using the multivariable-adjusted Cox proportional hazard model., Results: During a mean follow-up of 7.27 years, 4,086 patients were newly diagnosed with exudative AMD. The hazard ratio (95% confidence intervals) for exudative AMD was 1.14 (1.01-1.31) for a reproductive period ≥40 years compared with a reproductive period <30 years, 1.72 (1.48-2.00) for patients with ≥5 years of hormone replacement therapy, and 1.29 (1.09-1.52) for those with 2 to 5 years of hormone replacement therapy compared with those who never underwent hormone replacement therapy., Conclusion: Female reproductive factors were associated with the risk of exudative AMD. Greater lifetime exposure to endogenous and exogenous estrogen was associated with a higher incidence of exudative AMD.

Purpose: To compare treatment outcomes of treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) with bevacizumab as the first-line treatment, according to the guidelines of the Dutch Ophthalmological Society, with those treated first with either ranibizumab or aflibercept, as used in many other countries, all treated using a treat-and-extend strategy., Methods: Data were obtained from the prospectively designed Fight Retinal Blindness! outcomes registry. The primary outcome was the mean change from baseline in visual acuity of all treated eyes, after 12, 24 and 36 months of treatment. Secondary outcomes were the number of injections, the number of visits and the rate of switching to a second anti-VEGF drug., Results: The study included 703 treatment-naïve eyes with nAMD with 12 months follow-up, 373 eyes with 24 months follow-up, and 171 eyes with 36 months follow-up in the Netherlands, and 1131, 652, and 303 treatment-naïve eyes with respectively 12, 24, and 36 months of follow-up in all other countries. The change in visual acuity from baseline did not differ between the Netherlands and the other countries at any follow-up time. The median number of injections, visits and the proportion of eyes switching treatment was significantly higher in the Netherlands than in the other countries., Conclusion: Starting anti-VEGF treatment for nAMD with bevacizumab, as is mandatory in the Netherlands, delivers outcomes similar to those starting treatment with either ranibizumab or aflibercept, but at a cost of more frequent injections, and visits, and more frequent switching treatment to a second drug., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: To evaluate natural history of drusen ooze and its role as a predictor for progression of dry age-related macular degeneration (AMD) longitudinally., Methods: Multi-centric retrospective observational case series of 72 eyes (72 patients) with dry AMD with a minimum follow-up of 4 years. Drusen types were identified on volume scans on optical coherence tomography (OCT) and were characterized for occurrence of drusen ooze at baseline until last visit. Drusen ooze was defined as hyperreflective dots overlying a collapsing drusen or pseudodrusen, or hyperreflective RPE above drusen or isoreflective dots at the level of outer nuclear layer. The consequent incidence of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), complete retinal pigment epithelium and outer retinal atrophy (cRORA), and neovascular AMD (nAMD) were evaluated statistically., Results: In total, 72 eyes with a mean follow-up of 68.89 (± 25.57 months) were studied. At presentation, 11 eyes (15.3%) had a single drusen type, whereas 61 eyes (84.7%) had mixed drusen. Reticular pseudodrusen were most common (84.7%) followed by soft drusen (66.6%). Drusen ooze was seen in 47 eyes (65.2%) at presentation. The presence of drusen ooze at baseline (p < 0.01) and baseline best corrected visual acuity (BCVA) (p = 0.04) significantly correlated with development of iRORA and cRORA. In total, 14 eyes progressed from iRORA to cRORA over a mean follow up of 29.14 (± 24.33) months. Odds of progression to iRORA or cRORA were 20.3 times greater for eyes with drusen ooze at baseline (95% C.I., 4.4-94.2)., Conclusions: In dry AMD, drusen ooze is a useful sign for predicting progression to iRORA and cRORA over time., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Choosing a first-line treatment to optimize long-term outcomes is a major challenge for treating patients with neovascular age-related macular degeneration (AMD). The development of several new molecules makes it critical to identify the relevant factors to consider so as to provide an optimal risk-benefit ratio when initiating a treatment in naïve patients with neovascular AMD. This paper proposes a consensus established with the Delphi method (which includes a gradation in a consensus based on an analysis of the convergence rate of answers) to provide criteria that guide the ophthalmologist's decision for treatment initiation and follow-up in neovascular AMD patients. Fourteen questions were submitted to 93 French retina experts. Thirteen (93%) of the questions reached a consensus (≥50% of answers consensual). The criteria recommended to take into account were both efficacy and onset of action of the molecules, their safety, and the ability to decrease injection frequency. The primary criterion of expected efficacy of a molecule is a combination of the gain in visual acuity and resorption of retinal fluid. With regard to safety, experts recommend tighter follow-up for molecules currently in development, and at every scheduled visit, patients should be screened to identify early any potential adverse effects such as intraocular inflammation, retinal vasculitis or vascular occlusion. Experts also emphasize the importance of the packaging of the biological, with a preference toward prefilled syringes. Injection frequency is a key factor, and the authors recommended aiming for a maximal injection interval of 12 to 16 weeks. The stability of that maximum interval is also an important factor to consider in treatment selection., (Copyright © 2021. Published by Elsevier Masson SAS.)

Purpose: To evaluate the difference in the treatment burden among different types of neovascular age-related macular degeneration (AMD)., Methods: This retrospective, observational study included 431 patients who were diagnosed with neovascular AMD. Patients were divided into three groups: type 1 or 2 neovascularization group (n = 167), type 3 neovascularization group (n = 50), and polypoidal choroidal vasculopathy (PCV) group (n = 214). The number of hospital visits per year and the number of anti-vascular endothelial growth factor (VEGF) injections per year were compared among these groups. Furthermore, the incidence of bilateral involvement during the follow-up period was compared among the groups., Results: The mean follow-up period was 50.6 ± 11.3 months. The number of hospital visits per year was significantly higher in the type 1 or 2 neovascularization group (mean: 6.1 ± 1.5) and type 3 neovascularization (6.6 ± 1.6) than in the PCV group (6.0 ± 1.5) (P < 0.001). The number of anti-VEGF injections per year was significantly higher in type 3 neovascularization group (3.1 ± 1.7) than in the type 1 or 2 neovascularization group (2.3 ± 1.5) or the PCV group (2.3 ± 1.2) (P = 0.042). There was a significant difference in the incidence of bilateral involvement among patients in type 1 or 2 neovascularization group (20.4%), type 3 neovascularization group (46.0%), and the PCV group (15.4%) (P < 0.001)., Conclusions: The high frequency of hospital visits and that of anti-VEGF injections in patients with type 3 neovascularization suggests high treatment burden in these patients. The high incidence of bilateral involvement could be one of the primary reasons for high treatment burden in patients with type 3 neovascularization., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To analyze the association between glucosamine (GlcN) use and the risk of age-related macular degeneration (AMD) using claims data from the National Health Insurance Research Database (NHIRD)., Methods: A retrospective, population-based study was conducted with NHIRD data from a 14-year period (2000-2013). Chi-squared and Student's t-tests were used to evaluate differences between the study and comparison cohorts for categorical and continuous variables, respectively. Risk factors for disease development were examined by the adjusted hazard ratio (aHR) with 95% confidence interval. Kaplan-Meier analysis was performed to compare the cumulative risk of AMD between the two cohorts., Results: In total, 1,344 patients with GlcN treatment were enrolled in the study cohort and 5,376 patients without GlcN use were enrolled in the comparison cohort. The incidence rate of AMD was lower with GlcN use (3.65%) than without GlcN use (5.26%) (P = 0.014). GlcN use was associated with a lower risk of developing AMD among patients with hyperlipidemia, coronary artery disease, chronic obstructive pulmonary disease, stroke, other neurological disorders, or degenerative arthritis. Although the incidence of wet type AMD did not significantly differ (P = 0.91), the incidence of dry type AMD was lower in patients with GlcN use (2.9%) than those without GlcN use (4.84%) (P = 0.003). Kaplan-Meier analysis similarly revealed a lower rate of dry type AMD in patients with GlcN use compared to those without GlcN use (log-rank P = 0.004)., Conclusions: GlcN treatment can decrease the risk of developing dry type AMD. Further prospective controlled studies are needed to determine the effectiveness of GlcN treatment in patients with AMD and the associated mechanism., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The objective of this study was to analyze the reproducibility or variability of the time period to exudative recurrences in patients who were treated with intravitreal injections (IVT) of anti-VEGF (ranibizumab, aflibercept) for exudative age-related macular degeneration (AMD). The data studied included the number of recurrences per year, the time between the last IVT and the recurrence, fluctuation over time in the same patient, and changes in the therapeutic management of these exudative recurrences with regard to repeat induction therapy of three IVT, changes in monitoring protocols, and switches in anti-VEGF molecules., Materials and Methods: We conducted a retrospective, single center, "real-life" study at the Nantes University Hospital, including 33 patients (42 eyes) between March 2012 and March 2017. These were IVT-naive patients, in whom anti-VEGF IVT treatment was initiated for management of exudative AMD, with a follow-up period of at least two consecutive years. The main outcome was the fluctuation in recurrences times for the same patient., Results: Of the 33 patients included, 9 had bilateral involvement, for a total of 42 eyes. Twenty were women (60.6 %), the median age at inclusion was 78.5 years with a follow-up period of 3.7 years. The average time to recurrence was 11.6 weeks after the last IVT. The first recurrence occurred within 9.8 weeks after the last IVT. 12.3% of the eyes had consisent recurrence times, with fluctuations of less than 2 weeks between the various relapses over the two years of follow-up. a total of 7.1% of the eyes had no exudative recurrences during follow-up. The first exudative recurrence occurred at a mean of 38.2 weeks after diagnosis of the disease, or 37.2 weeks after the first IVT. 14.3% of the recurrences led to the administration of a repeat induction of three intravitreal anti-VEGF injections, 8.6% led to a change in anti-VEGF molecule, and 7.1% to a modification of the treatment protocol., Discussion: The goal of this study was to analyze the variability of the time to exudative recurrence in patients treated with anti-VEGF IVT in the context of exudative AMD, because, since the advent of anti-VEGF IVT in 2007, few data have been available on long-term follow-up and fluctuations in recurrence times in patients who will receive treatment for several years., Conclusion: Recurrences times are not reproducible over follow-up, particularly in patients experience their first exudative recurrence beyond 8 weeks and in patients with multiple exudative recurrences., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)