Age-Related Macular Degeneration: A Review.

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.

ASSOCIATION OF METFORMIN USE WITH RISK OF NEWLY ONSET NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEVELOPMENT.

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.

The impact of COVID-19 on aflibercept treatment of neovascular AMD in Sweden - data from the Swedish Macula Register.

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.

Incidence and multimodal imaging characteristics of macular neovascularisation subtypes in Chinese neovascular age-related macular degeneration patients.

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.

Intravitreal Injection Rates for Neovascular Age-Related Macular Degeneration in Australia During the 2020 COVID-19 Lockdowns.

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.

Treatment patterns and visual acuity change of AMD patients, before, during and after the COVID-19 pandemic lockdowns: A large cohort.

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.

Telehealth improves follow-up and monitoring of age-related macular degeneration during the COVID-19 pandemic.

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.

Is there any association between the frequency of wet age-related macular degeneration recurrences and the seasons of the year?

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.

[Impact of the French 2020 COVID-19 lockdown on the treatment and follow-up of patients with exudative age-related macular degeneration]. / Impact du confinement français en 2020 sur la prise en charge des patients atteints de dégénérescence maculaire liée à l'âge exsudative.

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.

Ten-Year Incidence of Fibrosis and Risk Factors for Its Development in Neovascular Age-Related Macular Degeneration.

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.

Study protocol on prevalence of non-exudative macular neovascularisation and its contribution to prediction of exudation in fellow eyes with unilateral exudative AMD (EYE-NEON).

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.

Subtype prevalence and baseline visual acuity by age in Japanese patients with neovascular age-related macular degeneration.

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.

Association between glycemic status and age-related macular degeneration: A nationwide population-based cohort study.

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.

FIVE-YEAR INCIDENCE OF FELLOW EYE NEOVASCULAR INVOLVEMENT IN AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY IN AN ASIAN POPULATION.

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.

Risk of Subsequent Dementia or Alzheimer Disease Among Patients With Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

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.

IMPACT study: Impact of adherence to anti-VEGF intravitreal injections for macular disease during COVID 19-related confinement in France.

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.

The risk of retinal vein occlusion among patients with neovascular age related macular degeneration: a large-scale cohort study.

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.

Predicting the immediate impact of national lockdown on neovascular age-related macular degeneration and associated visual morbidity: an INSIGHT Health Data Research Hub for Eye Health report.

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.

Review of Fibrosis in Neovascular Age-Related Macular Degeneration.

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.

Macular Atrophy Incidence, Progression, and Visual Acuity Effects in 5-Year Treatment of Neovascular Age-Related Macular Degeneration.

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 mm2 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.].