Rheumatic fever and long-term use of benzathine penicillin as possible risk factors for extensive macular atrophy with pseudodrusen in a Brazilian cohort.

BACKGROUND: Although there has been a large increase in the number of extensive macular atrophy with pseudodrusen (EMAP) cases, the basic aspects of this disease remain unknown. Brazilian patients have a common past history of rheumatic fever (RF) and/or benzathine penicillin (BP) treatment possibly related to the disease. We analyzed how RF and BP might be correlated with EMAP in Brazilian patients. DESIGN: Observational, retrospective, case-control study. METHODS: The databases of three private eye clinics in Brazil were searched for patients with an EMAP-like appearance. Each patient was asked about a previous history of RF and/or long-term use of BP. Patients underwent best-corrected visual acuity (BCVA) measurement, color fundus imaging, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT) imaging, and electroretinography (ERG). The following characteristics were analyzed: subretinal drusenoid deposits (SDD), pigment mottling, retinal pigment epithelial/basement membrane (RPE/BM) separation, outer retinal or RPE atrophy, and identification of a paving stone-like appearance. The choroidal thickness was measured using enhanced depth imaging OCT. The central atrophic area was measured manually on ultra-wide-field FAF. RESULTS: A total of 154 eyes of 77 patients (women, 66.2%; mean age, 58.6 years) with EMAP were included; 90.9% of patients were diagnosed with RF; 94.8% had been treated with BP and treatment was started at an average age of 7.3 years (mean duration, 11.8 years). The treatment duration was significant for the area of atrophy (P = 0.027) in which each 1-year increase in treatment duration led to an average reduction of 6.91 mm2 in area. The age at diagnosis of RF was significant (P = 0.026) for SDD. The increase of 1 year in the diagnosis of RF (late disease) led to a reduction of 24% in the chance of central SDD being present. On OCT, 65.5% eyes had SDD and more than 70% had a split RPE/BM and outer retinal or RPE atrophy. The choroidal thickness in patients with EMAP was significantly (P < 0.001) thinner than the control group. The ERG was abnormal in all eyes. CONCLUSION: These findings may suggest a relation between RF and EMAP in Brazilian patients. Patients with EMAP should be questioned about a history of RF.

Prevalence of age-related macular degeneration and retinal pseudodrusen in an elderly population. The ural very old study.

PURPOSE: To assess the prevalence of age-related macular degeneration (AMD) and reticular pseudodrusen (RPD) in very old individuals. METHODS: The population-based Ural Very Old Study consisted of 1526 (81.1%) out of 1882 eligible individuals aged 85 + years. All individuals living in the study regions and having an age of 85 + years were eligible for the study. The presence of AMD and RPDs was assessed on color fundus photographs, red-free fundus images, and optical coherence tomographic images. RESULTS: The study included 932 (61.1% of 1526) individuals (age:88.6 ± 2.7 years) with available fundus images. Prevalence of any, early, intermediate and late AMD was 439/932 (47.1%; 95%CI:44.0,50.0), 126/932 (13.5%; 95% CI:11.0,16.0), 185/932 (19.8%; 95% CI:17.3,22.3) and 128/932 (13.7%; 95% CI:11.7,15.7), respectively. Neovascular AMD was present in 63 eyes (6.8%;95%CI:5.3,8.3) and geographic atrophy in 65 eyes (7.0%;95%CI:5.0,9.0). Higher prevalence of any AMD and late AMD was significantly correlated with urban region of habitation (OR:3.34; 95% CI:2.37,4.71; P < 0.001), and with older age (OR:1.12; 95% CI:1.04,1.19; P = 0.001), female sex (OR:1.63; 95%CI:1.02,2.60; P = 0.04), and urban region of habitation (OR:2.89; 95% CI:1.59,5.26; P < 0.001), respectively. RPDs (assessed in 889 (58.3%) study participants) were present in 220/889 participants (24.7%; 95%CI:21.7,27.7). Higher RPD prevalence was associated (multivariable analysis) with higher serum concentration of the rheumatoid factor (OR:1.15; 95% CI:1.04,1.28; P = 0.008), shorter axial length (OR:0.84;95%CI:0.71,0.00;P = 0.04), and higher degree of nuclear cataract (OR:1.06; 95% CI:1.01,1.12; P = 0.02). AMD was the main cause for vision impairment in 230 (24.7%) participants, for moderate-to-severe vision impairment in 75 (8.0%; 95% CI: 6.4, 10.0) individuals, and for blindness in 15 (1.6%; 95%CI: 0.8, 2.5) persons respectively. CONCLUSIONS: In this ethnically mixed, very old population, AMD prevalence (any AMD:47.1%;late AMD:13.7%) was statistically independent of most systemic and ocular parameters. Higher RPD prevalence correlated with shorter axial length. KEY MESSAGES: What is known The prevalence of age-related macular degeneration (AMD) has been explored in many studies and societies. Information is missing about its prevalence and associations in very old individuals. The same holds true for reticular pseudodrusen of the macula. What is new In an ethnically mixed, very old population in Bashkortostan / Russia, the prevalence of AMD (any AMD: 47.1%; late AMD:13.7%) was statistically independent of most systemic and ocular parameters. Higher prevalence of reticular pseudodrusen correlated with shorter axial length.

Extensive macular atrophy with pseudodrusen-like appearance: comprehensive review of the literature.

PURPOSE: This review focuses on extensive macular atrophy with pseudodrusen-like appearance (EMAP), a recently described maculopathy presenting with pseudodrusen-like lesions and chorioretinal atrophy more pronounced in the vertical axis. METHODS: Narrative review of the literature published until May 2024. RESULTS: The early onset age of EMAP (50-55 years) and its distinctive natural history, which includes night blindness followed by severe vision loss, differentiate it from atrophic age-related macular degeneration (AMD). A clear pathogenesis has not been determined, but risk factors include female gender and complement system abnormalities (altered levels of C3 and CH50). Moreover, lifelong exposure to pesticides has been suggested as risk factor for direct neuronal degeneration involving rods and cones. In the early phase of the disease, reticular pseudodrusen-like lesions appear in the superior perifovea and tend to coalescence horizontally into a flat, continuous, reflective material localized between the retinal pigmented epithelium and Bruch's membrane. Over time, EMAP causes profound RPE and outer retinal atrophy in the macular area, with a recent classification reporting a 3-stages evolution pattern. Blue autofluorescence showed rapidly evolving atrophy with either hyperautofluorescent or isoautofluorescent borders. Significant similarities between the diffuse-trickling phenotype of geographic atrophy and EMAP have been reported. Macular neovascularization is a possible complication. CONCLUSION: EMAP is specific form of early-onset atrophic macular degeneration with rapid evolution and no treatment. Further studies are needed to assess the best management.

Reticular Pseudodrusen: Impact of Their Presence and Extent on Local Rod Function in Age-Related Macular Degeneration.

Purpose: To understand the spatial relationship between local rod-mediated visual function and reticular pseudodrusen (RPD) in eyes with large drusen. Design: Retrospective cross-sectional study. Participants: One eye with large drusen (>125 µm) each from 91 individuals with intermediate age-related macular degeneration, with and without RPD. Methods: All participants underwent dark adaptation testing using a dark-adapted chromatic perimeter, where visual sensitivities were measured over 30 minutes of dark adaptation after photobleach. The rod intercept time (RIT; a measure of dynamic rod function) and pointwise sensitivity difference (PWSD; a relative measure of rod- compared with cone-mediated function) was determined at multiple retinal locations, and their association with the overall (central 20° × 20° region) and local (2° diameter region centered on the location tested) extent of RPD and drusen (quantified using multimodal imaging) was examined. Main Outcome Measures: Association between overall and local extent of RPD and drusen with RIT and PWSD at each retinal location tested. Results: In a multivariable analysis, delayed RIT was associated with an increasing overall (P < 0.001), but not local (P = 0.884), extent of RPD. In contrast, the increasing local (P < 0.001), but not overall (P = 0.475), extent of drusen was associated with delayed RIT. Furthermore, only an increasing overall extent of RPD (P < 0.001) was associated with reduced PWSD (or worse rod compared with cone function), but not the local extent of RPD and drusen, or overall extent of drusen (P ≥ 0.344). Conclusions: Local rod-mediated function was associated with the overall, rather than local, extent of RPD in eyes with large drusen, suggesting that there may be widespread pathologic changes in eyes with RPD that account for this. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Geographic Atrophy-associated Intraretinal Neovascularization (GAIN): A novel clinical entity.

KEY MESSAGES     : WHAT IS KNOWN : Geographic atrophy could be associated with MNV or other vascular alterations. Intraretinal fluid could be present in GA also without neovascularization. WHAT IS NEW : GAIN is a novel clinical entity characterized by GA and an intraretinal neovascular network. GAIN could be exudative or non-exudative.

Pachy-Reticular Pseudodrusen.

PURPOSE: To characterize the features of a peculiar association between reticular pseudodrusen (RPD) and pachychoroid (pachy-RPD) and to compare them with eyes affected by RPD and normal/leptochoroid. DESIGN: Observational, retrospective, case-control study. PARTICIPANTS: Among a cohort of patients with intermediate age-related macular degeneration (AMD), we selected eyes with RPD and pachychoroid (i.e., choroidal thickness of >50 µm). A control group of RPD eyes but without pachychoroid (i.e., a choroidal thickness of <250 µm) was included. METHODS: Number and stages of RPD were evaluated in each ETDRS subfield. Furthermore, choroidal perfusion was investigated using the choroidal vascularity index (CVI), and choriocapillaris perfusion density (PD) on structural OCT and OCT angiography. MAIN OUTCOME MEASURES: Description of the multimodal imaging features of pachy-RPD and differences with RPD associated with normal/leptochoroid. RESULTS: Among 111 RPD eyes, 37 were included in the pachy-RPD group and 74 in the control group. Patients with pachy-RPD were significantly younger than patients with RPD and normal/leptochoroid (mean age, 75 ± 16 and 82 ± 7 years, respectively; P = 0.002). Total RPD number was comparable between the 2 groups (P = 0.220). However, pachy-RPD eyes showed a significantly higher number of stage 1 RPD in comparison to the controls (P < 0.001), and a lower number of stage 3 (P < 0.001) and stage 4 RPD (P = 0.052). The CVI and choriocapillaris PD were greater in pachy-RPD than in the control group (P < 0.001 and P= 0.010, respectively). CONCLUSIONS: Pachy-RPD are characterized by a different distribution of RPD stages (i.e., more early stages and fewer advanced stages) in comparison to RPD with normal/leptochoroid. Furthermore, pachy-RPD eyes showed greater perfusion indices of the choroid. These features suggest that the presence of pachychoroid could be a protective factor in the RPD evolution to the advanced AMD forms. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Extensive Macular Atrophy with Pseudodrusen-like appearance: Progression Kinetics and Late-Stage Findings.

PURPOSE: To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP). DESIGN: Retrospective cohort study. PARTICIPANTS: Seventy-eight patients (156 eyes) affected by EMAP. METHODS: We collected data on best-corrected visual acuity, kinetic perimetry, OCT, short-wavelength autofluorescence, and near-infrared autofluorescence findings. Genetic testing for the TIMP3 and C1QTNF5 genes was performed via Sanger sequencing for 58 patients, with no pathogenic variants identified. MAIN OUTCOME MEASURES: The primary outcomes were best-corrected visual acuity at the last examination, visual field at the last examination, and incidence rates and time-to-event curves for blindness with the United States Social Security Administration and World Health Organization (WHO) criteria, foveal involvement, and atrophy enlargement beyond the 30° and 55° field of view. Imaging findings at the last examination were secondary outcomes. RESULTS: At the most recent visit, mean age was 70.9 ± 5.2 years. Using United States criteria, 58.1% of the patients were blind, and 25.8% were blind according to WHO criteria. All eyes showed large central scotomas, which were associated with visual field constriction in 22.2% of eyes. We detected focal openings or large dehiscences of Bruch's membrane (BM) in 25.4% of eyes. Near-infrared autofluorescence showed increased visibility of the choroidal vessels beyond the atrophy in 87.2% of eyes. The incidence rates for blindness were 3.95 per 100 patient-years with United States criteria and 1.54 per 100 patient-years according to WHO criteria. The incidence rates were 22.8 per 100 eye-years for foveal involvement, 12.0 per 100 eye-years for atrophy enlargement beyond 30°, and 6.6 per 100 eye-years for atrophy enlargement beyond 55°. The estimates were not influenced by the age at onset. CONCLUSIONS: We identified characteristic imaging findings, including BM ruptures, in elder patients with EMAP and calculated incidence rates for different functional and anatomic outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Structural OCT and OCT angiography biomarkers associated with the development and progression of geographic atrophy in AMD.

BACKGROUND: Geographic atrophy (GA) is an advanced, irreversible, and progressive form of age-related macular degeneration (AMD). Structural optical coherence tomography (OCT) and OCT angiography (OCTA) have been largely used to characterize this stage of AMD and, more importantly, to define biomarkers associated with the development and progression of GA in AMD. METHODS: Articles pertaining to OCT and OCTA biomarkers related to the development and progression of GA with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility. RESULTS: Previous reports have highlighted various OCT and OCTA biomarkers linked to the onset and advancement of GA. These biomarkers encompass characteristics such as the size, volume, and subtype of drusen, the presence of hyperreflective foci, basal laminar deposits, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), persistent choroidal hypertransmission defects, and the existence of subretinal drusenoid deposits (also referred to as reticular pseudodrusen). Moreover, biomarkers associated with the progression of GA include thinning of the outer retina, photoreceptor degradation, the distance between retinal pigment epithelium and Bruch's membrane, and choriocapillaris loss. CONCLUSION: The advent of novel treatment strategies for GA underscores the heightened need for prompt diagnosis and precise monitoring of individuals with this condition. The utilization of structural OCT and OCTA becomes essential for identifying distinct biomarkers associated with the initiation and progression of GA.

An Updated Simplified Severity Scale for Age-Related Macular Degeneration Incorporating Reticular Pseudodrusen: Age-Related Eye Disease Study Report Number 42.

PURPOSE: To update the Age-Related Eye Disease Study (AREDS) simplified severity scale for risk of late age-related macular degeneration (AMD), including incorporation of reticular pseudodrusen (RPD), and to perform external validation on the Age-Related Eye Disease Study 2 (AREDS2). DESIGN: Post hoc analysis of 2 clinical trial cohorts: AREDS and AREDS2. PARTICIPANTS: Participants with no late AMD in either eye at baseline in AREDS (n = 2719) and AREDS2 (n = 1472). METHODS: Five-year rates of progression to late AMD were calculated according to levels 0 to 4 on the simplified severity scale after 2 updates: (1) noncentral geographic atrophy (GA) considered part of the outcome, rather than a risk feature, and (2) scale separation according to RPD status (determined by validated deep learning grading of color fundus photographs). MAIN OUTCOME MEASURES: Five-year rate of progression to late AMD (defined as neovascular AMD or any GA). RESULTS: In the AREDS, after the first scale update, the 5-year rates of progression to late AMD for levels 0 to 4 were 0.3%, 4.5%, 12.9%, 32.2%, and 55.6%, respectively. As the final simplified severity scale, the 5-year progression rates for levels 0 to 4 were 0.3%, 4.3%, 11.6%, 26.7%, and 50.0%, respectively, for participants without RPD at baseline and 2.8%, 8.0%, 29.0%, 58.7%, and 72.2%, respectively, for participants with RPD at baseline. In external validation on the AREDS2, for levels 2 to 4, the progression rates were similar: 15.0%, 27.7%, and 45.7% (RPD absent) and 26.2%, 46.0%, and 73.0% (RPD present), respectively. CONCLUSIONS: The AREDS AMD simplified severity scale has been modernized with 2 important updates. The new scale for individuals without RPD has 5-year progression rates of approximately 0.5%, 4%, 12%, 25%, and 50%, such that the rates on the original scale remain accurate. The new scale for individuals with RPD has 5-year progression rates of approximately 3%, 8%, 30%, 60%, and 70%, that is, approximately double for most levels. This scale fits updated definitions of late AMD, has increased prognostic accuracy, seems generalizable to similar populations, but remains simple for broad risk categorization. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Macular Neovascularization Secondary to Subclinical Angioid Streaks in Age-Related Macular Degeneration: Treatment Response to Anti-VEGF at 2-Year Follow-up.

INTRODUCTION: To characterize the response to antivascular endothelial growth factor (VEGF) treatment of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) with subclinical angioid streaks (AS) during a 2-year follow-up. METHODS: Retrospective, longitudinal, case-control, and multicentric study. Among a cohort of neovascular AMD population, we selected patients with subclinical AS and treatment-naïve MNV treated with anti-VEGF for a 2-year follow-up. An age- and sex-matched control group with treatment-naïve MNV secondary to AMD without subclinical AS was selected. Demographics and differences in treatment response (i.e., number of injections needed, anatomical and functional outcomes) between the two groups were analyzed. RESULTS: Among 102 eyes of 102 patients with neovascular AMD, 34 eyes of 34 patients (82 ± 6 years old) were included in the subclinical AS group, whereas 68 eyes of 68 patients (81 ± 6 years old, p = 0.342) in the control group. All eyes with subclinical AS presented RPD compared to 56% of eyes without subclinical AS (p < 0.001). During the 2-year follow-up, eyes with subclinical AS needed more injections (10.6 ± 3.2 vs 8.3 ± 3.1 injections for eyes with and without subclinical AS, respectively, p < 0.001). Visual acuity (VA) decreased during the treatment (from 0.53 ± 0.37 at the baseline to 0.69 ± 0.45 LogMAR at 2-year follow-up, p = 0.044) in eyes with subclinical AS; no VA changes were observed in the control group (p = 0.798). RPE atrophy at the end of the 2-year follow-up affected 74% of cases with subclinical AS and 29% of cases of the control group (p < 0.001). CONCLUSIONS: MNVs secondary to AMD with subclinical AS are characterized by worse functional and anatomical outcomes after 2-year anti-VEGF treatment compared to MNV secondary to AMD without subclinical AS, supporting the different pathophysiological mechanisms involved in this recently described AMD phenotype.

In vivo cone-photoreceptor density comparison between eyes with subretinal drusenoid deposits and healthy eyes using high magnification imaging.

PURPOSE: To compare photoreceptor density automated quantification in eyes with subretinal drusenoid deposits (SDD) and healthy controls using Heidelberg Spectralis High Magnification Module (HMM) imaging. METHODS: Twelve eyes of 6 patients with intermediate AMD, presenting with SDD were included, as well as twelve eyes of healthy controls. Individual dot SDD within the central 30° retina were examined with infrared confocal laser ophthalmoscopy, HMM, and spectral-domain optical coherence tomography (SD-OCT). Photoreceptor density analysis was performed on the best-quality image using the ImageJ Foci Picker plugin, after the removal of SDD from the HMM image. Correlations were made between the HMM quantified photoreceptor density, SD-OCT characteristics, stage, and number of SDD. RESULTS: Mean age was 75.17 ± 2.51 years in the SDD group (3 males, 3 females) versus 73.17 ± 3.15 years in the healthy control group (p = 0.2). Defects in the overlying ellipsoid zone were present on SD-OCT in 8/12 (66.66%) eyes. The mean ± standard deviation foci detected (i.e., cone photoreceptors) was 7123.75 ± 3683.32 foci/mm2 in the SDD group versus 13,253 ± 3331.00 foci/mm2 in the healthy control group (p = 0.0003). The number of SDD was associated with a reduction in foci density, p = 0.0055, r = - 0.7622. CONCLUSION: The decreased cone density in eyes with SDD may correlate with a decrease in retinal function in intermediate AMD eyes independent of neovascular complications or outer retinal pigment epithelial atrophy.

Current Perspectives on Type 3 Macular Neovascularization due to Age-Related Macular Degeneration.

BACKGROUND: The aim of this review was to systematically summarize the current knowledge on type 3 macular neovascularization (MNV3) in age-related macular degeneration (AMD). SUMMARY: Recent histopathologic and multimodal imaging findings led to the consensus definition of the new term "type 3 macular neovascularization" in AMD. MNV3 originates in the deep vascular plexus as a neovascular process without connection with the retinal pigment epithelium in the initial stages. This type has numerous clinical and pathomorphologic features that separate it from the other two types of MNV in AMD. Besides, its frequency appears to be higher than previously thought. In optical coherence tomography (OCT), MNV3 can be classified into stages 1-3. Hyperreflective foci in the outer retina possibly represent a precursor lesion. In addition, MNV3 is characterized by a strong association with reticular pseudodrusen, a high rate of bilaterality, close associations with advanced age and arterial hypertension, decreased choroidal thickness, and decreased choriocapillaris flow signals. Data from latest anti-vascular endothelial growth factor studies in MNV3 suggest that the OCT biomarkers in intraretinal and subretinal fluids should be interpreted differently than in the other types. Additionally, data from MNV3 eyes should be analyzed separately, allowing optimal type-specific treatment strategies in the future. KEY MESSAGES: This review highlights the need for accurate characterization of neovascular AMD lesions and an MNV type-specific approach, particularly for MNV3.

Local and Global Associations of Reticular Pseudodrusen in Age-Related Macular Degeneration.

PURPOSE: To investigate the spatial distribution of reticular pseudodrusen (RPD) in eyes with age-related macular degeneration (AMD) and their correlation with functional measures, retinal thickness, and changes over time. DESIGN: Longitudinal, cohort study. PARTICIPANTS: Thirty-five participants with RPD and spectrum of AMD severity (including no AMD). METHODS: Multimodal imaging was graded by a reading center, including evaluation of color fundus imaging to assess AMD severity scores. Reticular pseudodrusen presence on OCT volumes was confirmed on en face imaging and the RPD extent was contoured on infrared images. One study eye per participant underwent rod-mediated dark adaptation, measuring rod intercept time (RIT) at 5° and, if needed, 12° superior to the fovea. MAIN OUTCOME MEASURES: The primary outcome was RIT and OCT thickness measures which were correlated with RPD area. RESULTS: A total of 51 eyes had ≥ 1 visit with RPD detected (mean follow-up, 2.19 ± 2.04 years; range, 0-5 years), totaling 169 eye-based visits with RPD. Of the 51 eyes with RPD, 5 (9.8%) developed geographic atrophy and 17 (33.3%) progressed to neovascular AMD. Larger RPD areas were detected more frequently in AMD severity scores 6-7. Reticular pseudodrusen area within an eye generally increased over time. The lesion distribution showed a predilection for the superior retina, especially the outer superior subfield of the ETDRS grid, with the central subfield having least involvement. Reticular pseudodrusen area was inversely correlated with central subfield thickness and positively correlated with RIT at 5° (P = 0.001; r2 = 0.01) and 12° (P = 0.004; r2 = 0.01). Rod-mediated dark adaptation at 5° reached the test ceiling in > 85% of visits, irrespective of RPD lesion presence/absence at the test location. Retinal thickness decreased monotonically, with the central subfield demonstrating the greatest percentage change over 5 years (Δ = -5.47%). CONCLUSIONS: In AMD, RPD involve predominantly the superior retina but can involve all ETDRS subfields and evolve over time. Eyes with RPD exhibit structural and functional impairments that can be measured beyond the boundaries of the RPD lesions, suggesting changes associated with RPD are associated with both local changes and a more widespread process. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Fundus autofluorescence of retinal atrophy progression between fundus flavimaculatus and extensive macular atrophy with pseudo-drusen.

OBJECTIVE: To analyze the progression of macular atrophy in Fundus Flavimaculatus (FFM) versus Extensive Macular Atrophy with Pseudo-drusen (EMAP), using Spectralis® RegionFinder™ tool. METHODS: Retrospective review of patients diagnosed with FFM and EMAP. Ophthalmic imaging features were reviewed by retina specialists for each patient in both eyes. The atrophic zones were measured on fundus autofluorescence acquisitions using the RegionFinder™ tool. RESULTS: FFM group included 16 eyes of 8 patients, whose mean age was 61.42 ± 10.76 years, with a mean 4.54 ± 2.73 years of follow-up. EMAP group contained 16 eyes of 8 patients, whose mean age was 67.81 ± 3.03 years (p = 0.12), with a mean 3.62 ± 2.49 years of follow-up (P = 0.63). The atrophy progression rates were 3.73 ± 6.75 and 0.70 ± 0.98 mm2/year, for EMAP and FFM respectively. The yearly rate of progression of the atrophic areas in EMAP was 5.3 times higher than in FFM (mm2/year) (p = 0.03). CONCLUSION: The progression of the atrophy in eyes with Extensive Macular Atrophy with Pseudo-drusen (EMAP) is significantly more rapid than in eyes with Fundus Flavimaculatus (FFM).

An incipient late-onset retinal degeneration with a C1QTNF5 mutation: a case report with an 11-year follow-up.

PURPOSE: The purpose of this study was to describe and diagnose the difficulty in a long-term follow-up (eleven years) patient with a very early presentation of late-onset retinal degeneration (L-ORD) and the significance of electrophysiological examinations and follow-up in assessing undiagnosed inherited retinal diseases. METHODS: This is an observational case report of a 56-year-old woman, with scattered multiple yellow-white retinal dots firstly diagnosed as fundus albipunctatus. Ten years after presentation, a deterioration in rod and cone responses in ff-ERG was detected, which allowed us to discard the first diagnostic hypothesis and proceed with a genetic testing. RESULTS: Ten years after presentation, she presented a clear progression of the abnormal photoreceptor response with a cone and rod involvement in ff-ERG, which was not compatible with the previous suspicion of fundus albipunctatus. Six months later, genetic testing results together with the typical progression of atrophic patchy lesions in multimodal imaging allowed a certain diagnosis of L-ORD, caused by an already reported pathogenic variant in the C1QTNF5 gene (c.563C > T; p. Pro188 Leu). CONCLUSIONS: We demonstrate the importance of the ff-ERG examination and the follow-up (or ERG and imaging repetition) in the differential diagnosis of an incipient L-ORD, which can be easily misdiagnosed in the early stages, before the appearance of the characteristic chorioretinal atrophy seen with the progression of this rare disease.

Epidemiology of geographic atrophy and its precursor features of intermediate age-related macular degeneration.

Globally age-related macular degeneration (AMD) is a leading cause of blindness with a significant impact on quality of life. Geographic atrophy (GA) is the atrophic late form of AMD and its prevalence increases markedly with age with around 1 in 5 persons aged 85 and above having GA in at least one eye. Bilateral GA leads to severe visual impairment thus posing a significant burden on patients, careers and health providers. The incidence and prevalence of GA varies across different geographic regions, with the highest rates in those of European ancestry. Although heterogeneity in definitions of GA and reporting strategy can explain some of the discrepancies, the data overall are consistent in showing a lower prevalence in other ethnicities such as those of Asian heritage. This is at present unexplained but thought to be due to the existence of protective factors such as differences in eye pigmentation, diet, environmental exposures and genetic variability. This review covers key aspects of the prevalence and incidence of the ocular precursor features of GA (large drusen, pigmentary abnormalities and reticular pseudo-drusen), the late stage of GA and factors that have been known to be associated with modifying risk including systemic, demographic, environment, genetic and ocular. Understanding the global epidemiology scenario is crucial for the prevention of and management of patients with GA.

Multimodal Imaging of Reticular Pseudodrusen in Turkish Patients.

Objectives: To investigate the presence and prevalence of reticular pseudodrusen (RPD) in patients with age-related macular degeneration using multiple imaging modalities and to compare the sensitivity and specificity of these modalities in the detection of RPD. Materials and Methods: Images from a total of 198 consecutive patients were analyzed prospectively. Color fundus photography, red-free imaging, spectral domain optical coherence tomography (SD-OCT), infrared and blue reflectance (BR) imaging, fundus autofluorescence (FAF), enhanced-depth imaging OCT (EDI-OCT), fundus fluorescein angiography (FFA) and indocyanine green angiography were performed. RPD was diagnosed in the presence of relevant findings in at least two of the imaging methods used. Results: RPD were detected in 149 eyes (37.6%). In the detection of RPD, color fundus photography, red-free photography, SD-OCT, infrared, FAF, BR, and FFA imaging had sensitivity values of 50%, 57.7%, 91.6%, 95%, 74.6%, 65.7%, and 28.2% and specificity values of 99.6%, 100%, 98.4%, 94.6%, 100%, 99.6%, and 69.8%, respectively. Conclusion: Infrared imaging had the highest sensitivity. SD-OCT combined with infrared imaging was the most sensitive imaging technique for detecting RPD. The high specificity of FAF, red-free, and BR imaging may be useful to confirm a diagnosis of RPD.

Reticular Pseudodrusen Voids after Rhegmatogenous Retinal Detachment.

We present a case of reticular pseudodrusen (RPD) regression on multimodal retinal imaging following a rhegmatogenous retinal detachment. Two mechanisms of action can be postulated. The subretinal deposits dissolve due to voluminous subretinal fluid during retinal separation from the retinal pigment epithelium and are in turn mechanically cleared during retinal re-attachment surgery. Alternatively, an RPD clearance is facilitated by enhanced phagocytic activity of macrophages and microglial cells as a response to acute retinal stress.

A semi-automated pipeline for quantifying drusen-like deposits in human induced pluripotent stem cell-derived retinal pigment epithelium cells.

Age-Related Macular Degeneration (AMD) is a highly prevalent form of retinal disease amongst Western communities over 50 years of age. A hallmark of AMD pathogenesis is the accumulation of drusen underneath the retinal pigment epithelium (RPE), a biological process also observable in vitro. The accumulation of drusen has been shown to predict the progression to advanced AMD, making accurate characterisation of drusen in vitro models valuable in disease modelling and drug development. More recently, deposits above the RPE in the subretinal space, called reticular pseudodrusen (RPD) have been recognized as a sub-phenotype of AMD. While in vitro imaging techniques allow for the immunostaining of drusen-like deposits, quantification of these deposits often requires slow, low throughput manual counting of images. This further lends itself to issues including sampling biases, while ignoring critical data parameters including volume and precise localization. To overcome these issues, we developed a semi-automated pipeline for quantifying the presence of drusen-like deposits in vitro, using RPE cultures derived from patient-specific induced pluripotent stem cells (iPSCs). Using high-throughput confocal microscopy, together with three-dimensional reconstruction, we developed an imaging and analysis pipeline that quantifies the number of drusen-like deposits, and accurately and reproducibly provides the location and composition of these deposits. Extending its utility, this pipeline can determine whether the drusen-like deposits locate to the apical or basal surface of RPE cells. Here, we validate the utility of this pipeline in the quantification of drusen-like deposits in six iPSCs lines derived from patients with AMD, following their differentiation into RPE cells. This pipeline provides a valuable tool for the in vitro modelling of AMD and other retinal disease, and is amenable to mid and high throughput screenings.