Macular lesions associated with age-related macular degeneration in pachydrusen eyes.

BACKGROUND: To investigate the prevalence of macular lesions associated with age-related macular degeneration (AMD) in eyes with pachydrusen. METHODS: Clinical records and multimodal imaging data of patients over 50 years old with drusen or drusenoid deposits were retrospectively assessed, and eyes with pachydrusen were included in this study. The presence of AMD features, including drusen or drusenoid deposits, macular pigmentary abnormalities, geographic atrophy (GA), and macular neovascularization (MNV), were evaluated. RESULTS: Out of 967 eyes of 494 patients with drusen or drusenoid deposits, 330 eyes of 183 patients had pachydrusen (34.1%). The mean age was 66.1 ± 9.3 years, and the subfoveal choroidal thickness (SFCT) was 292.7 ± 100.1 µm. The mean number of pachydrusen per eye was 2.22 ± 1.73. The majority of eyes with pachydrusen had no other drusen or drusenoid deposits (95.2%). Only 16 eyes (4.8%) had other deposits, including soft drusen (10 eyes, 3.0%), cuticular drusen (3 eyes, 0.9%), and reticular pseudodrusen (RPD; 3 eyes, 0.9%). Macular pigmentary abnormalities accompanied pachydrusen in 68 eyes (27.4%). None of the eyes had GA, and 82 eyes (24.8%) had MNV. The majority of MNV was polypoidal choroidal vasculopathy (PCV; 65 eyes, 19.7%), followed by type 1 (10 eyes, 3.0%), type 2 (5 eyes, 1.5%), and type 3 MNV (2 eyes, 0.6%). CONCLUSIONS: Eyes with pachydrusen in Korean population have several characteristic AMD lesions in low frequencies. These findings indicate that pachydrusen might have diagnostic and prognostic values that are different from those of other drusen or drusenoid deposits.

Dry age-related macular degeneration in the Japanese population.

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.

GEOGRAPHIC ATROPHY INCIDENCE AND PROGRESSION AFTER INTRAVITREAL INJECTIONS OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS FOR AGE-RELATED MACULAR DEGENERATION: A Meta-Analysis.

PURPOSE: Geographic atrophy (GA) is a complication of advanced neovascular age-related macular degeneration that can lead to permanent vision loss. We sought to estimate the incidence and progression of GA after intravitreal injections of antivascular endothelial growth factor agents in eyes with neovascular age-related macular degeneration. METHODS: Ovid MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to May 2020. Included studies reported on the progression or development of GA in eyes with neovascular age-related macular degeneration after antivascular endothelial growth factor therapy. RESULTS: Thirty-one articles and 4,609 study eyes (4,501 patients) were included. Eyes received a mean of 17.7 injections over 35.2 months. The prevalence of GA at baseline was 9.7%. The pooled incidence of GA was 30.5% at the end of follow-up. There was a positive, moderate linear correlation between the mean total number of injections and GA incidence at the final follow-up (R2 = 0.30; P = 0.01). Monthly treatment was associated with a significantly higher risk for GA development relative to pro re nata (relative risk = 1.40, 95% confidence interval = [1.21-1.61], P < 0.001). Risk factors for GA development included GA in the fellow eye, retinal angiomatous proliferation, drusen, and reticular pseudodrusen. CONCLUSION: We found an association between the frequency and number of treatments with antivascular endothelial growth factor agents and the development of GA in neovascular age-related macular degeneration. Future studies should clarify risk factors, population characteristics, and relative contributions of treatment and disease progression on GA development in this context.

SYSTEMIC MEDICATION USE AND THE INCIDENCE AND GROWTH OF GEOGRAPHIC ATROPHY IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENTS TRIALS.

PURPOSE: To determine associations of systemic medications with the incidence and growth of geographic atrophy (GA) in participants of the comparison of age-related macular degeneration treatments trials. METHODS: Participants of comparison of age-related macular degeneration treatments trials with new untreated choroidal neovascularization in the study eye (one study eye per participant) were randomized to receive treatment with bevacizumab or ranibizumab. Participants were released from clinical trial treatment at 2 years and examined at approximately 5 years. Color fundus photographs and fluorescein angiograms taken at baseline, Years 1, 2, and 5 were assessed for the presence and size of GA by two masked graders. Participants were interviewed about systemic medication use at baseline. Systemic medications previously reported to be associated with age-related macular degeneration were evaluated for associations with GA incidence in study eye using univariable and multivariable Cox models and for association with the GA growth using linear mixed effects models. RESULTS: In multivariable analysis of 1,011 study eyes without baseline GA, systemic medications, including cholinesterase inhibitors, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, diuretics, aspirin, steroids, statins, hormone replacement therapy, antacids, and drugs targeting G protein-coupled receptors, were not associated with GA incidence in the study eye (all adjusted hazard ratios ≤1.86, P ≥ 0.18). In multivariable analysis of 214 study eyes with longitudinal GA size measurements, calcium channel blockers were associated with a higher GA growth rate (0.40 vs. 0.30 mm/year, P = 0.02). CONCLUSION: None of the systemic medications analyzed were associated with GA incidence. However, calcium channel blockers were associated with a higher growth rate of GA in the study eye.

Central geographic atrophy vs. neovascular age-related macular degeneration: differences in longitudinal vision-related quality of life.

OBJECTIVE: Prior studies of vision-related quality of life (VRQoL) have examined advanced age-related macular degeneration (AMD) as a single group or focused on neovascular AMD (nAMD), even though advanced AMD can refer to either central geographic atrophy (GA) or nAMD. We compared the natural progression of VRQoL in central GA versus nAMD. METHODS: We included Age-Related Eye Disease Study (AREDS) participants with central GA (n = 206) or nAMD (n = 198) who completed the National Eye Institute Visual Function Questionnaire (NEI-VFQ) between 1997 and 2005. The rate of change of VRQoL was calculated as the slopes of linear models fit to longitudinal individual-level NEI-VFQ scores. Multivariable regressions identified factors associated with experiencing a decline in VRQoL during the study period and cross-sectional VRQoL score. RESULTS: There was a minor decline in VRQoL prior to the development of nAMD but a significantly steeper decline after progression to nAMD (0.49 ± 2.91 vs. 3.30 ± 5.58 NEI-VFQ units/year; p < 0.001). The rates of VRQoL decline were similar before and after the development of central GA (1.99 ± 4.97 vs. 1.68 ± 4.65 NEI-VFQ units/year; p = 0.66). Prior to the development of advanced AMD, the rate of VRQoL decline was greater for participants destined to develop central GA versus nAMD (p = 0.007), while postprogression to advanced disease, the rate was greater in nAMD compared with central GA (p = 0.012). Female gender (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.38-5.06; p = 0.003) and higher baseline VRQoL score (OR 1.03, 95% CI 1.01-1.06; p = 0.006) were independently associated with experiencing a longitudinal decline in VRQoL. CONCLUSION: The natural progression of VRQoL differed in central GA versus nAMD, both before and after the development of advanced disease, suggesting that future studies should consider separating these phenotypes. Females and those with a higher baseline VRQoL were more likely to experience a longitudinal decline in VRQoL following progression to advanced AMD.

Macular Atrophy Incidence and Progression in Eyes with Neovascular Age-Related Macular Degeneration Treated with Vascular Endothelial Growth Factor Inhibitors Using a Treat-and-Extend or a Pro Re Nata Regimen: Four-Year Results of the MANEX Study.

PURPOSE: To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro re nata (PRN) regimen over 4 years in a real-world setting. DESIGN: Four-year, multicenter, retrospective comparative study. PARTICIPANTS: Two hundred sixty-four patients with treatment-naive nAMD. METHODS: Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n = 163) or PRN (n = 101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had undergone annual fundus autofluorescence (FAF) and OCT imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. MAIN OUTCOMES MEASURES: Macular atrophy incidence and progression over 4 years, association between treatment strategies, and number of injections. RESULTS: At baseline, MA was present in 24% and 20% of study eyes in T&E and PRN groups, respectively (P = 0.45). At year 4, 27% (34/124) and 25% (20/81) of eyes without baseline MA showed detectable MA in the T&E and PRN groups, respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4 ± 0.2 mm/year and 0.4 ± 0.1 mm/year in the T&E and PRN groups, respectively (P = 0.23). Multivariate analysis for baseline predictors of MA growth demonstrated that older age, poorer baseline visual acuity, and presence of retinal angiomatous proliferation had a higher risk of greater MA progression (P = 0.03). Regression analysis demonstrated no association between T&E and PRN treatment strategies with the risk of new MA developing during the 4 years of follow-up or the progression of pre-existing MA at year 4 (P = 0.692). CONCLUSIONS: Over 4 years, neither incidence nor progression of MA in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and achieved better visual outcomes compared with those treated with a PRN approach.

Incidence and Progression of Nongeographic Atrophy in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) Clinical Trial.

Importance: Retinal hypopigmentation and hyperpigmentation are precursors of geographic atrophy (GA). Incidence and progression to GA in eyes treated with anti-vascular endothelial growth factor for neovascular age-related macular degeneration (nAMD) have not been investigated. Objective: To determine the incidence and progression of non-GA (NGA) and associated risk factors. Design, Setting, and Participants: This study is a post hoc analysis of a cohort study within the Comparison of Age-Related Treatments Trials (CATT) clinical trial. Participants were recruited February 20, 2008, through December 9, 2009; released from protocol follow-up and treatment after 2 years; and recalled from March 14, 2014, through March 31, 2015. Data analyses were conducted from January 11, 2019, through November 27, 2019. Interventions: Participants were randomized to ranibizumab or bevacizumab for (1) 2 years of monthly or as-needed injections or (2) monthly injections for 1 year and as-needed injections the following year. Participants were treated according to best medical judgement thereafter. Main Outcomes and Measures: Incidence of nAMD-associated NGA (hypopigmentation and hyperpigmentation in color images) and progression; adjusted risk ratios (aRR) for baseline characteristics. Results: Among 1107 participants, risk of NGA was 35% (391 eyes), 59% (246 eyes), and 81% (122 eyes) at 1, 2, and 5 years, respectively. Risk factors for NGA included worse visual acuity (20/200-20/320: aRR, 1.74 [95% CI, 1.24-2.43], compared with ≤20/40; P = .006), larger neovascularization area (>4 disc areas: aRR, 1.31 [95% CI, 1.01-1.71], compared with ≤1 disc areas; P = .007), switched drug regimen (aRR, 1.28 [95% CI, 1.06-1.54], compared with as-needed injections; P = .02), and single-nucleotide variants Age-Related Maculopathy Susceptibility 2 (ARMS2) (TT variant: relative risk [RR], 1.53 [95% CI, 1.22-1.93]; P = .001) and HtrA Serine Peptidase 1 (HTRA1) (AG variant: RR, 1.23 [95% CI, 1.01-1.48]; AA variant: RR, 1.51 [95% CI, 1.20-1.91]; P = .002). Sub-retinal pigment epithelium thickness was protective (>275 µm: aRR, 0.59 [95% CI, 0.46-0.75], compared with ≤75 µm; P < .001). Among 389 eyes with NGA by 2 years and subsequent color images, risk of progression to GA was 29%, 43%, and 50% at 1, 3, and 4 years, respectively. Risk factors for progression to GA included worse visual acuity (20/200-20/320: aRR, 2.75 [95% CI, 1.54-4.93], compared with ≤20/40; P < .001), worse fellow-eye visual acuity (<20/40: aRR, 1.77 [95% CI, 1.12-2.79], compared with ≥20/40; P = .01), fellow-eye GA (aRR, 1.71 [95% CI, 1.06-2.75]; P = .03), and pseudodrusen in either eye (aRR, 1.65 [95% CI, 1.17-2.34]; P = .005). Subretinal fluid was associated with a decreased risk of progression (aRR, 0.42 [95% CI, 0.28-0.63]; P < .001). Conclusions and Relevance: In this study, after 2 years of protocol-guided anti-vascular endothelial growth factor treatment for nAMD, more than half of the eyes in the study developed NGA in the location of nAMD. After 3 additional years of regular care, half of them progressed to GA. Trial Registration: ClinicalTrials.gov Identifier: NCT00593450.

Prevalence and characteristics of macular atrophy in eyes with neovascular age-related macular degeneration. A study from a long-term observational dataset: the Fight Retinal Blindness! project.

BACKGROUND: To assess the prevalence and characteristics associated with macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors. METHODS: This was a retrospective, cross-sectional study of nAMD eyes that commenced anti-VEGF between January 2006 and August 2016. MA (absent/extrafoveal/subfoveal) was graded by treating practitioners based on multimodal imaging from April 2016. The prevalence of MA over time and risk factors of MA were assessed. RESULTS: The prevalence of MA in a cohort of 1689 eyes was 9.9% (22/222) in eyes within 1 year of starting treatment, 41.5% (71/171) after 5 years and 48.4% (30/62) after 9 years of treatment. Risk factors for subfoveal MA included the proportion of visits at which the lesion was graded as inactive ((adjusted OR (AOR) 3.72 for the highest vs lowest the quartile of frequency of inactive gradings (95% CI 2.33 to 6.07)), age (AOR 1.05 per year (95% CI 1.02 to 1.07)), baseline visual acuity (AOR 3.9 for ≤35 letters vs ≥70 letters (95% CI 2.4 to 6.4)) and the number of injections received (AOR 1.20 every 10 injections (95% CI 1.08 to 1.33)). Similar associations were observed with extrafoveal MA. CONCLUSIONS: The risk of MA appeared to drop in eyes that had not developed it within 5 years. Low choroidal neovascularisation activity was by far the strongest predictor. We could not determine whether the increased prevalence of MA with time was due to anti-VEGF treatment or the natural history of the condition.

Prevalence and Phenotypes of Age-Related Macular Degeneration in Eyes With High Myopia.

Purpose: To analyze the frequency and phenotypic variation of AMD in subjects with high myopia (HM), and to describe the clinical course and response to treatment of neovascularization (NV). Methods: Patients with HM were identified at five retina tertiary referral centers. Inclusion criteria were myopic patients aged 55 years or more with axial lengths equal or greater than 25.5 mm. Results: A total of 874 eyes from 442 HM subjects older than 55 years were identified and 104 eyes of 54 patients (72 ± 11 years) were included in the study and followed up for 23.5 ± 19.5 months. The estimated AMD frequency in HM subjects over 55 years was 11.9% (95% confidence interval; 9.8%-14.0%). A total of 34 of 104 eyes were diagnosed with drusen, 22 with reticular pseudodrusen (RPD), 28 with both drusen and RPD, and 20 with geographic atrophy. Neovascularization was detected in 52 eyes (50%), and type 1 was the most frequent form (39 eyes, 75%). Overall, NV was treated with 4.6 ± 2.6 anti-VEGF injections. Eyes with treatment-naïve NV at baseline (n = 34) required 3.8 ± 1.5 anti-VEGF injections during the first year of treatment. This exceeded the injection number in the purely myopic population (1.8 to 3.6 injections for the first year). Conclusions: This study provides evidence to suggest that older patients with HM are at a significant risk of the dry and neovascular forms of AMD. NV in eyes with HM and AMD required more injections in the first year compared to NV in HM eyes without AMD.

Development and Course of Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials.

PURPOSE: To describe risk factors for scar formation and changes to fibrotic scar through 5 years in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). DESIGN: Multicenter, prospective cohort study. PARTICIPANTS: A total of 1061 subjects in CATT. METHODS: Color photographic and fluorescein angiographic images from baseline and 1, 2, and 5 years were evaluated. Incidence of scar formation was estimated with Kaplan-Meier curves. Risk factors were assessed with Cox regression models. MAIN OUTCOME MEASURES: Scar formation, fibrotic scar area, and macular atrophy associated with fibrotic scar ("atrophy"). RESULTS: Cumulative proportion of eyes with scar was 32%, 46%, and 56% at years 1, 2, and 5, respectively. Baseline factors associated with increased risk (adjusted hazards ratio [aHR] and 95% confidence interval [CI]) were classic choroidal neovascularization (CNV) (aHR, 4.49; 95% CI, 3.34-6.04) versus occult, hemorrhage >1 disc area (DA) (aHR, 2.28; 95% CI, 1.49-3.47) versus no hemorrhage, retinal thickness >212 µm (aHR, 2.58; 95% CI, 1.69-3.94) versus <120 µm, subretinal tissue complex thickness >275 µm (aHR, 2.64; 95% CI, 1.81-3.84) versus ≤75 µm, subretinal fluid thickness >25 µm (aHR, 1.31; 95% CI, 0.97-1.75) versus no fluid, visual acuity (VA) in fellow eye 20/20 (aHR, 1.72; 95% CI, 1.25-2.36) versus 20/50 or worse, retinal pigment epithelium elevation absence (aHR, 1.71; 95% CI, 1.21-2.41), and subretinal hyperreflective material (aHR, 1.72; 95% CI, 1.25-2.36). Among 68 eyes that developed fibrotic scar at year 1, VA decreased by a mean of additional 13 letters between years 1 and 5. Mean scar area was 1.2, 1.2, and 1.9 DA at 1, 2, and 5 years, respectively. Atrophy was present in 18%, 24%, and 54% of these eyes at years 1, 2, and 5, respectively; the mean areas were 1.6, 2.0, and 3.1 DA, respectively. Atrophy replaced fibrotic scar in 8 eyes at year 5. There was no significant correlation between scar growth and atrophy growth. The rate of growth for both was similar between the clinical trial and observation periods. CONCLUSIONS: Several morphologic features, including classic CNV and large hemorrhage, are associated with scar formation. Rate of new scar formation declined after 2 years. Most fibrotic scars and accompanying macular atrophy expanded over time, reducing VA.

Incidence and Growth of Geographic Atrophy during 5 Years of Comparison of Age-Related Macular Degeneration Treatments Trials.

PURPOSE: To estimate the incidence, size, and growth rate of geographic atrophy (GA) during 5 years of follow-up among participants in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). DESIGN: Cohort within a clinical trial. PARTICIPANTS: Participants included in CATT. METHODS: A total of 1185 CATT participants were randomly assigned to ranibizumab or bevacizumab treatment and to 3 treatment regimens. Participants were released from protocol treatment at 2 years and examined at approximately 5 years (N = 647). Two masked graders assessed the presence and size of GA in digital color photographs (CPs) and fluorescein angiograms (FAs) taken at baseline and years 1, 2, and 5. Cox proportional hazard models were used to identify risk factors for incidence of GA. Annual change in the square root of the total area of GA was the measure of growth. Multivariate linear mixed models including baseline demographic, treatment, and ocular characteristics on CP/FA and optical coherence tomography (OCT) as candidate risk factors were used to estimate adjusted growth rates, standard errors (SEs), and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: Geographic atrophy incidence and growth rate. RESULTS: Among the 1011 participants who did not have GA at baseline and had follow-up images gradable for GA, the cumulative incidence was 12% at 1 year, 17% at 2 years, and 38% at 5 years. At baseline, older age, hypercholesterolemia, worse visual acuity, larger choroidal neovascularization (CNV) area, retinal angiomatous proliferation (RAP) lesion, GA in the fellow eye, and intraretinal fluid were associated with a higher risk of incident GA. Thicker subretinal tissue complex and presence of subretinal fluid were associated with less GA development. The overall GA growth rate was 0.33 mm/year (SE, 0.02 mm/year). Eyes treated with ranibizumab in the first 2 years of the clinical trial had a higher growth rate than eyes treated with bevacizumab (adjusted growth rate, 0.38 vs. 0.28 mm/year; P = 0.009). Geographic atrophy in the fellow eye, hemorrhage, and absence of sub-retinal pigment epithelium fluid at baseline were associated with a higher growth rate. CONCLUSIONS: Development of GA is common 5 years after initiating therapy. Several risk factors identified at 2 years of follow-up persist at 5 years of follow-up.

Implications of the anatomical classification of the neovascular form of age-related macular degeneration. / Implicaciones de la clasificación anatómica de la forma neovascular de la degeneración macular asociada a la edad.

OBJECTIVE: To present the clinical relevance of the anatomical classification of the neovascular form of Age-Related Macular Degeneration (AMD). METHODS: Critical analysis of the current situation in the management of patients with neovascular AMD, by reviewing the available scientific evidence with regards to the classification of the types of neovascular lesion by angiography and optical coherence tomography (OCT). RESULTS: The classification of the neovascular lesion type secondary to AMD by OCT in type 1 lesions (under the pigment epithelium), type 2 (subretinal), and type 3 (retinal angiomatous proliferation), provides an added value in allowing to establish a long-term visual prognosis, an estimate of the number of treatments that a certain case may require, and a stratification of the risk for secondary geographic atrophy. CONCLUSIONS: Incorporating OCT to the initial qualitative analysis of cases with neovascular AMD offers an added value superior to that provided by the angiography, with the relevant clinical implications.

Prevalence and quantification of geographic atrophy associated with newly diagnosed and treatment-naïve exudative age-related macular degeneration.

OBJECTIVE: To identify and quantify geographic atrophy (GA) associated with neovascular age-related macular degeneration (AMD) at initial presentation using a fundus autofluorescence (FAF) semi-automated software and to correlate the results with demographic and clinical data. DESIGN: Retrospective, observational study. METHODS: The study population consisted of treatment-naïve patients with newly diagnosed neovascular AMD. Best-corrected visual acuity, fundus photographs, infrared reflectance, FAF and spectral-domain optical coherence tomography were performed, associated with fluorescein and indocyanine green angiographies. Identification of GA was independently performed by three readers. Quantification of atrophy areas was done using RegionFinder Software (RFA), a semi-automated software embedded in Spectralis device (Heidelberg Engineering, Germany). RESULTS: We included 206 eyes of 173 consecutive patients (72% female, mean age: 79.7±9.1 years). Type I choroidal neovascularisation (CNV) was observed in 44.2% of eyes, type II CNV was observed in 20.9% and mixed CNV lesion was observed in 11.7%. Polypoidal choroidal vasculopathy was diagnosed in 7.7% and type III CNV was diagnosed in 15.5%. Analysis of FAF frames showed that GA was associated with nAMD in 46/206 eyes (22.3%). Taking into account data both from Region Finder and multimodal imaging, our results suggest that GA was present in 24.3% of eyes newly diagnosed with exudative AMD. Mean size of GA was 1.23±1.76 mm2 (range 0.03-7.39). CONCLUSION: GA is associated with nAMD in 1/4 of cases at initial presentation. Combined imaging, including RFA is an effective tool to identify and quantify GA at diagnosis.

Clinical Characteristics and Risk Factors of Extensive Macular Atrophy with Pseudodrusen: The EMAP Case-Control National Clinical Trial.

PURPOSE: To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years. DESIGN: A national matched case-control study. PARTICIPANTS: Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers. All 115 patients with EMAP had symptoms before the age of 55 years due to bilateral extensive macular atrophy with a larger vertical axis and diffuse pseudodrusen. Three controls without age-related macular degeneration (AMD) or retinal disease at fundus examination were matched for each patient with EMAP by gender, age, and geographic area (in total 415). METHODS: Subjects and controls underwent an eye examination including color, red-free autofluorescent fundus photographs and spectral-domain optical coherence tomography with macular analysis. The interviews collected demographic, lifestyle, family and personal medical history, medications, and biological data. Associations of risk factors were estimated using conditional logistic regression. MAIN OUTCOME MEASURES: Extensive macular atrophy with pseudodrusen status (cases vs. controls). RESULTS: Extensive macular atrophy with pseudodrusen most frequently affected women (70 women, 45 men). After multivariate adjustment, family history of glaucoma or AMD was strongly associated with EMAP (odds ratio [OR], 2.3, P = 0.008 and OR, 1.5, P = 0.01, respectively). No association was found with cardiac diseases or their risk factors. Mild and moderate kidney disease and higher neutrophil rate were associated with a reduced risk of EMAP (OR, 0.58, P = 0.04; OR, 0.34, P = 0.01; and OR, 0.59, P = 0.003, respectively). On the contrary, eosinophilia (OR, 1.6; P = 0.0002), lymphocytosis (OR, 1.84; P = 0.0002), increased erythrocyte sedimentation rate (OR, 6.5; P = 0.0005), decreased CH50 (P = 0.001), and high plasma C3 level (P = 0.023) were significantly associated with a higher risk of EMAP. CONCLUSIONS: This study documents an association between EMAP and family history of AMD and glaucoma, a clear female predominance, and a systemic inflammatory profile. The reduced CH50 and increased C3 plasma values could reflect a more severe complement pathway dysfunction than in AMD, leading to early pseudodrusen and rapid development of geographic atrophy. There is no association of EMAP with AMD cardiac diseases or cardiac risks, including cigarette smoking.

Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials.

PURPOSE: To evaluate the association between pseudodrusen and incidence of late age-related macular degeneration (AMD) in fellow eyes of patients with unilateral neovascular AMD (nAMD). DESIGN: Cohort study within the Comparison of AMD Treatments Trials (CATT). PARTICIPANTS: Patients with neither nAMD nor geographic atrophy (GA) in the fellow eye at baseline. METHODS: Presence and type (dot, reticular, or confluent) of baseline pseudodrusen were assessed using digital color fundus photography (CFP) viewed under full color, green channel, and blue channel; red-free images; and fluorescein angiography (FA). Incidence of nAMD was based on monthly clinical examination and reading center evaluation of images at years 1 and 2. Incidence of GA was based on reading center evaluation of CFP and FA images at years 1 and 2. Associations of baseline pseudodrusen with incident nAMD and GA were summarized with adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs) from multivariate Cox models, with adjustment of covariates identified through backward stepwise selection. MAIN OUTCOME MEASURES: Incident nAMD and GA. RESULTS: Among 620 fellow eyes, 176 (28.4%) had baseline pseudodrusen (55% dot, 82% reticular, 35% confluent). Within 2 years, nAMD occurred in 54 eyes (30.7%) with pseudodrusen and in 72 eyes (16.2%) without pseudodrusen (aRR, 2.05; 95% CI, 1.43-2.93); GA occurred in 27 eyes (15.3%) with pseudodrusen and in 37 eyes (8.3%) without pseudodrusen (aRR, 1.89; 95% CI, 1.13-3.17); late AMD occurred in 73 eyes (41.5%) with pseudodrusen and in 101 eyes (22.8%) without pseudodrusen (aRR, 2.07; 95% CI, 1.51-2.83). Dot pseudodrusen were associated independently with nAMD (aRR, 2.53; 95% CI, 1.60-4.00), whereas confluent pseudodrusen were associated independently with GA (aRR, 4.35; 95% CI, 1.69-11.2). Eyes with pseudodrusen had increased incidence of late AMD regardless of whether the Age-Related Eye Diseases Study (AREDS) severity score was 2 (28.7% vs. 10.3%), 3 (34.9% vs. 13.7%), or 4 (50.5% vs. 32.0%). CONCLUSIONS: In fellow eyes of CATT participants, pseudodrusen were associated independently with a higher incidence of both nAMD and GA. Dot pseudodrusen were associated with nAMD, whereas confluent pseudodrusen were associated with GA. Pseudodrusen should be considered along with the AREDS severity score for predicting late AMD.

Prevalence and Genetic Characteristics of Geographic Atrophy among Elderly Japanese with Age-Related Macular Degeneration.

OBJECTIVE: To investigate the prevalence and genetic characteristics of geographic atrophy (GA) among elderly Japanese with advanced age-related macular degeneration (AMD) in a clinic-based study. METHODS: Two-hundred and ninety consecutive patients with advanced AMD were classified into typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP) or geographic atrophy (GA). Genetic variants of ARMS2 A69S (rs10490924) and CFH I62V (rs800292) were genotyped using TaqMan Genotyping Assays. The clinical and genetic characteristics were compared between patients with and without GA. RESULTS: The number of patients diagnosed as having typical neovascular AMD, PCV, RAP and GA were 98 (33.8%), 151 (52.1%), 22 (7.5%) and 19 (6.6%), respectively. Of 19 patients with GA, 13 patients (68.4%) had unilateral GA with exudative AMD in the contralateral eye. Patients with GA were significantly older, with a higher prevalence of reticular pseudodrusen, bilateral involvement of advanced AMD and T-allele frequency of ARMS2 A69S compared with those with typical AMD and PCV; although there were no differences in the genetic and clinical characteristics among patients with GA and RAP. CONCLUSIONS: The prevalence of GA was 6.6% among elderly Japanese with AMD. Patients with GA and RAP exhibited genetic and clinical similarities.

Geographic Atrophy and Choroidal Neovascularization in the Same Eye: A Review.

Geographic atrophy (GA) and choroidal neovascularization (CNV), the two late forms of age-related macular degeneration, are generally considered two distinct entities. However, GA and CNV can occur simultaneously in the same eye, with GA usually occurring first. The prevalence of this combined entity is higher in histological studies than in clinical studies. No distinct systemic or genetic risk characteristics are associated with the combined GA/CNV entity, although on clinical examination and retinal imaging it can feature drusen or subretinal drusenoid deposits. GA and CNV may exist within the spectrum of a single disease, or they may be two very different diseases. Therapy with antivascular endothelial growth factor (anti-VEGF) is often successful for CNV, but some evidence suggests increased rates of GA development in eyes treated with anti-VEGF. In this article, we review the current literature regarding the epidemiology, clinical presentation, and treatment options for patients with the combined GA/CNV entity.

Age-related macular degeneration in Portugal: prevalence and risk factors in a coastal and an inland town. The Coimbra Eye Study - Report 2.

PURPOSE: To determine the age- and sex-specific prevalence of early and late age-related macular degeneration (AMD) in two Portuguese population-based samples and to identify its risk factors. POPULATION: A population of 6023 adults aged ≥55 years was recruited from two Portuguese primary healthcare units in the central region of Portugal - one from a coastal (n = 3000) and another from an inland town (n = 3023). METHODS: Cross-sectional population-based study. Participants were enrolled in the two locations between August 2009 and October 2013. Responders underwent standardized interviews and ophthalmologic examination, including digital fundus imaging. All fundus photographs were graded according to an International Classification and Grading System. The main outcome measures consisted of age- and sex-adjusted prevalence of early and late AMD. Potential epidemiologic risk factors were also evaluated using logistic regression analysis. RESULTS: Of the 6023 subjects enrolled, 5996 had gradable fundus images and were included in the analysis. The crude prevalence of early and late AMD was 6.99 and 0.67%, respectively, for the coastal town and 15.39 and 1.29% for the inland town. Age- and sex-adjusted prevalence of any AMD for the Portuguese population was 12.48% (95% CI: 11.61-13.33) with late AMD accounting for 1.16% (95% CI: 0.85-1.46). Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.55% (95% CI: 0.36-0.75) and 0.61% (95% CI: 0.37-0.84) of individuals, respectively. After adjusting for possible confounding factors, prevalence of early and late AMD increased with increasing age (OR = 1.35; 95% CI: 1.23-1.49 for early and OR = 3.01; 95% CI: 2.22-4.08 for late AMD, per each decade of age increase, p < 0.001). After adjustment for age, sex, family history, smoking history, hypertension, diabetes and BMI, subjects from the inland town presented a significantly higher OR of early and late AMD than subjects from the coastal town (OR = 2.57, 95% CI: 2.12-3.12, p < 0.001 for early and OR = 2.06, 95% CI: 1.07-3.95, p = 0.029 for late AMD). CONCLUSIONS: The prevalence of early and late AMD in this Portuguese population was similar to other large-scale population-based cohorts. After controlling for confounders, age and study site of inclusion were significant independent predictors for both early and late forms of the disease. Further analysis will be needed to completely unravel the underlying reasons for this difference regarding geographic location.

Reticular Pseudodrusen and Their Association with Age-Related Macular Degeneration: The Melbourne Collaborative Cohort Study.

PURPOSE: To determine the prevalence of reticular pseudodrusen (RPD) and its association with age-related macular degeneration (AMD) and AMD risk factors in a large sample. DESIGN: Community-based cohort study in Melbourne, Victoria, Australia. PARTICIPANTS: A total of 21,130 participants 48 to 86 years of age available for ophthalmic assessment at follow-up from 2003 through 2007. METHODS: Lifestyle, diet, and anthropometric measurements were obtained at baseline and follow-up. At follow-up, digital macular color photographs were graded for early, intermediate, and late AMD as well as the presence of RPD. Data were analyzed using multinomial logistic regression controlling for age, gender, smoking, country of birth, and diet. MAIN OUTCOME MEASURES: Detection of RPD based on color fundus photographs. RESULTS: Prevalence of RPD was 0.41% (87 of 21,130 participants), with 51% having bilateral RPD. Patients with RPD were older compared with patients with large drusen (>125 µm; 76±4 vs. 68±9 years; P < 0.001). Increasing age, female gender, being a current smoker, as well as focal pigmentary abnormalities and large drusen (>125 µm) were associated with a higher prevalence of RPD. Presence of geographic atrophy (GA) was associated with the highest odds of having RPD (odds ratio [OR], 153; 95% confidence interval [CI], 53-442), followed by choroidal neovascularization (CNV; OR, 90; 95% CI, 26-310), intermediate AMD (OR, 33; 95% CI, 14-77), and early AMD (OR, 12; 95% CI, 5-31) compared with those with no AMD. The ARMS2 single nucleotide polymorphism (SNP) rs10490924, HTRA1 SNPs rs11200638 and rs3793917, and CFH SNPs rs393955, rs1061170, and rs2274700 were associated with increased prevalence of RPD (all P < 0.05). CONCLUSIONS: Reticular pseudodrusen are highly concurrent with AMD and have similar associations with known AMD risk factors such as age, gender, smoking, and genetic risk factors. Reticular pseudodrusen are associated more strongly with GA than with CNV. Although RPD are not specific to AMD, they are likely to be a strong risk factor for progression to late-stage AMD, similar to focal pigmentary abnormalities and large drusen.

The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

PURPOSE: To evaluate the association of statin use with progression of age-related macular degeneration (AMD). DESIGN: Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. PARTICIPANTS: Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. METHODS: Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. MAIN OUTCOME MEASURES: Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). RESULTS: Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. CONCLUSIONS: Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the majority of previous studies. Statins have been demonstrated to reduce the risk of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression.