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.

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.

Electrophysiological findings in extensive macular atrophy with pseudodrusen.

PURPOSE: To present electroretinogram findings in extensive macular atrophy with pseudodrusen (EMAP) and describe associated systemic factors. DESIGN: Retrospective case series. METHODS: Data on medical history, visual symptoms, multimodal imaging findings, and visual field were collected from the medical records of patients with extensive macular atrophy with pseudodrusen who attended a visual electrophysiology laboratory. Electrophysiological tests, including full-field electroretinogram, multifocal electroretinogram and photopic negative response, were performed. RESULTS: Eighteen patients (10 [56%] females, age 49-66 years) were included. Of these, 17 (94%) had a history of rheumatic fever in childhood and/or adolescence, 7 (39%) had cardiovascular disease, 4 (22%) had autoimmune disease, and 10 (56%) had inflammatory conditions. The primary visual complaints were nyctalopia (95%), followed by visual field loss (67%) and dyschromatopsia (67%). The key retinal findings included retinal pigmented epithelium atrophy in the macular region and subretinal drusenoid deposits. Regarding electrophysiological results, 100% of patients had abnormalities on multifocal electroretinogram, 94% displayed alterations in photopic negative response, and 78% showed changes in the full-field electroretinogram. CONCLUSIONS: In this cohort, electrophysiologic evaluation demonstrated diffuse retinal dysfunction affecting all layers of the retina in patients with EMAP. The disease is associated with immune-mediated systemic conditions, chiefly rheumatic fever.

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).

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.

Extensive macular atrophy with pseudodrusen-like: Case series and review.

PURPOSE: To describe the clinical characteristics of two patients affected by extensive macular atrophy with pseudodrusen-like (EMAP). METHODS: Two patients affected by EMAP underwent multimodal imaging, including fundus autofluorescence and optical coherence tomography. RESULTS: The patients showed the typical clinical appearance with macular atrophy with larger vertical axis surrounded by pseudodrusen-like deposits involving the midperiphery, associated with paving stone lesions in the retinal periphery. CONCLUSION: EMAP is a complex condition sharing clinical characteristics of age-related macular degeneration. Further studies are warranted to identify the early biomarker of the disease.

Peripheral Retinal Involvement in Extensive Macular Atrophy with Pseudodrusen-Like Deposits.

PURPOSE: To describe the alterations of the peripheral retina in extensive macular atrophy with pseudodrusen-like deposits (EMAP) by means of ultrawidefield fundus photography (UWFFP) and ultrawidefield fundus autofluorescence (UWF-FAF). STUDY DESIGN: Prospective, observational case series. PARTICIPANTS: Twenty-three patients affected by EMAP. METHODS: Each patient underwent best-corrected visual acuity (BCVA) measurement, UWFFP, and UWF-FAF. The area of macular atrophy, as well as the pseudodrusen-like deposits and peripheral degeneration, were assessed using UWF images, at baseline and over the follow-up. MAIN OUTCOME MEASURES: The assessment of the clinical patterns of both pseudodrusen-like deposits and peripheral retinal degeneration. Secondary outcomes included assessing macular atrophy by means of UWFFP and UWF-FAF, and tracking progression over the follow-up. RESULTS: Twenty-three patients (46 eyes) were included, of whom 14 (60%) were female. Mean age was 59.0 ± 5 years. Mean BCVA at baseline was 0.4 ± 0.4, declining at a mean rate of 0.13 ± 0.21 logarithm of the minimum angle of resolution/year. Macular atrophy at baseline was 18.8 ± 14.2 mm2 on UWF-FAF, enlarging at a rate of 0.46 ± 0.28 mm/year, after the square root transformation. Pseudodrusen-like deposits were present in all cases at baseline, and their detection decreased over the follow-up. Three main types of peripheral degeneration were identified: retinal pigment epithelium alterations, pavingstone-like changes, and pigmented chorioretinal atrophy. Peripheral degeneration progressed in 29 eyes (63.0%), at a median rate of 0.7 (interquartile range, 0.4-1.2) sectors/year. CONCLUSIONS: Extensive macular atrophy with pseudodrusen-like deposits is a complex disease involving not only the macula, but also the midperiphery and the periphery of the retina. 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 in a Japanese Patient Evaluated by Wide-Field OCTA.

Extensive macular atrophy with pseudodrusen (EMAP) is a relatively newly proposed clinical entity that was first reported in 2009. Although no definitive diagnostic criteria have been defined, characteristic findings can distinguish it from other diseases, especially dry age-related macular dystrophy (AMD). Herein, we present the case of a patient with EMAP who underwent a comprehensive ophthalmic examination and whole-exome sequencing (WES). A 72-year-old Japanese man complained of progressive visual impairment in his right eye and nyctalopia. Ophthalmic examination revealed that the best-corrected visual acuity (BCVA) in decimal units was 0.08 on the right and 0.8 on the left. Fundoscopy and fundus autofluorescence (FAF) revealed well-demarcated symmetrical macular atrophy, with a vertical axis larger than the horizontal axis, which reached the vascular arcade inferiorly and exceeded it superiorly. Pseudodrusen were widespread throughout the retina in both eyes. Paving-stone degeneration was not observed in the extreme periphery of either eye. Seven months later, his left BCVA decreased to 0.3 without major changes on multimodal imaging. Based on the above findings, we diagnosed EMAP. Wide-field optical coherence tomography angiography (OCTA) showed no significant changes in the retinal vessels, but the density of choroidal vessels was reduced in the degenerated areas. We thought that this finding suggests that EMAP originates between the deep retina and choroid. WES did not reveal any candidate mutations in known pathogenic genes. To the best of our knowledge, this is the first report of a Japanese patient with EMAP, and no data for analysis of wide-field OCTA or equatorial OCT images of EMAP cases have been found in previous reports. EMAP is not well recognized in Asia and may be incorrectly diagnosed as dry-type AMD. EMAP should be included in the differential diagnosis of dry AMD, and this may lead to more Asians being diagnosed with EMAP in the future.

Progression of Atrophy and Visual Outcomes in Extensive Macular Atrophy with Pseudodrusen-like Appearance.

Purpose: To report visual outcomes and rate of retinal pigment epithelium (RPE) atrophy progression in patients with extensive macular atrophy with pseudodrusen-like appearance (EMAP). Design: Retrospective, observational study. Participants: Patients with EMAP and symptom onset before 55 years of age, at least 12 months of follow-up using Spectralis blue-light fundus autofluorescence (BAF) and OCT and with no other ocular or systemic conditions. Methods: Best-corrected visual acuity (BCVA), BAF, and OCT images were reviewed at baseline and at each annual visit until the last available follow-up. Atrophy was measured by 2 graders using the region finder software on Heidelberg Explorer and confirmed using OCT scans covering the entire atrophic lesion. The following imaging biomarkers were analyzed at each visit: foveal atrophy, vitreomacular traction, outer retinal tubulations, choroidal caverns and subfoveal choroidal thickness, border autofluorescence pattern (hyper-autofluorescent or iso-autofluorescent), and border irregularity as expressed by circularity index (CI). Main Outcome Measures: Primary outcomes were annual rate of atrophy enlargement and BCVA loss in EMAP patients. Secondary outcomes included the assessment of potential factors able to predict disease progression. Results: Thirty-six eyes from 18 patients with EMAP (6 men [33%]; mean age at symptom onset, 48.1 ± 1.7 years) were included. Mean follow-up lasted 32.8 ± 14.3 months. RPE atrophy increased from 10.8 ± 6.3 mm2 at baseline to 18.1 ± 8.3 mm2 at the end of follow-up, with a rate of 2.91 ± 1.09 mm2/year. Faster progression was associated with smaller CI at baseline (P = 0.02) and with iso-autofluorescent lesion borders (P = 0.01). Visual acuity declined progressively at a rate of 7.4 ± 5.8 letters per year, with 57% of eyes showing vision of 20/200 Snellen or worse at the 4-year follow-up. Worse visual outcomes were observed in patients with early foveal involvement at baseline (P = 0.02). Conclusions: Patients affected by EMAP present a rapid expansion of RPE atrophy that is comparable with the diffuse-trickling form of geographic atrophy. More irregular and iso-autofluorescent lesion borders seem to predict faster progression. Our findings may provide relevant information for patient counseling and future interventional approaches to select the best candidates and proper clinical outcomes.