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

Abstract

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.

Keywords: AMD, age-related macular degeneration; BAF, blue-light fundus autofluorescence; BCVA, best-corrected visual acuity; CI, circularity index; EMAP; EMAP, extensive macular atrophy with pseudodrusen-like appearance; ETDRS, Early Treatment Diabetic Retinopathy Study; Extensive macular atrophy with pseudodrusen-like appearance; Multimodal imaging; Progression of atrophy; RPE, retinal pigment epithelium; Visual outcomes.

Figure 1

Measurement of macular atrophy (MA) in a patient affected by extensive macular atrophy with pseudodrusen-like appearance from baseline (A–A2) to the last available follow-up at 36 months (D–D2). A–D, The first row shows the annual progression of MA using blue-light fundus autofluorescence, whereas the second row (A1–D1) displays the corresponding OCT passing through the fovea. Of note, the pseudodrusen-like material lying above the Bruch’s membrane disappeared progressively with follow-up, leaving space for MA characterized by thinning of outer retinal layers and choroidal signal hypertransmission. The use of the expert modus of Region Finder software (Heidelberg Engineering) is depicted in the bottom row (A2–D2); the measured area is yellow, whereas constraints are outlined in red. In this specific patient, visual acuity dropped from 20/50 to 20/320 Snellen equivalent.

Figure 2

Imaging features investigated for possible association with faster disease progression. The blue-light fundus autofluorescence characteristics analyzed are shown in the left column, whereas OCT findings are presented in the right column.

Figure 3

A representative case of extensive macular atrophy with pseudodrusen-like appearance using multimodal imaging. A, Color fundus photography showing a large macular atrophic area with a predominant vertical axis surrounded by pseudodrusen-like deposits. B, OCT scan showing collapse of the perifoveal outer retinal layers with choroidal hypertransmission, whereas the fovea appears unaffected, as evidenced by the preserved central vision (20/32 Snellen). C–E, The extension of the atrophic lesion can be appreciated on (C) near-infrared reflectance, (D) blue-light fundus autofluorescence, and (E) green autofluorescence. F–K, The corresponding (F–H) fluorescein angiography and (I–K) indocyanine green angiography appearance of extensive macular atrophy with pseudodrusen is depicted at 40 seconds and 3 and 10 minutes.

Figure 4

Scatterplot showing retinal pigment epithelium (RPE) atrophy progression and visual acuity variation. The visual loss mirrors the enlargement of RPE atrophy during the entire follow-up. BCVA = best-corrected visual acuity; ETDRS = Early Treatment Diabetic Retinopathy Study.