A prospective study of reticular macular disease

Abstract

Purpose: To determine the risk of progression to advanced age-related macular degeneration (AMD) conferred by reticular pseudodrusen (RPD), an imaging presentation of reticular macular disease (RMD), in high-risk fellow eyes of subjects with AMD and unilateral choroidal neovascularization (CNV) in a large, prospective study.

Design: Cohort study.

Participants: Two hundred seventy-one subjects with AMD; 94 with RPD and 177 without RPD.

Methods: Images from a cohort of 271 subjects with AMD in the Nutritional AMD treatment phase II (NAT 2) Study, a 3-year prospective study of subjects with unilateral CNV and large soft drusen in the fellow eye, were studied. The fellow eye, at high risk for advanced AMD developing, was the study eye. There were 5 visits per subject. Imaging at each visit consisted of color, red-free, and blue-light photography and fluorescein angiography. The images were analyzed for the presence of RPD, following disease progression throughout the 3-year study.

Main outcome measures: The development of advanced AMD (CNV or geographic atrophy).

Results: For the 271 subjects who completed the full 3-year study, there was a significantly higher rate of advanced AMD (56% or 53/94) in fellow eyes with RPD at any visit compared with eyes without RPD (32% or 56/177; P < 0.0001, chi-square test; relative risk [RR], 1.8; 95% confidence interval [CI], 1.4-2.4). The chance of developing advanced AMD in the fellow eye in women with RPD (66%) was more than double that of women without RPD (30%; P < 0.00001; RR, 2.2; 95% CI, 1.6-3.1).

Conclusions: To the authors' knowledge, this is the first comprehensive prospective study of RMD, a distinct clinical phenotype of AMD that includes RPD. It provides strong confirmation that RMD, a disease entity with stereotypical presentations across imaging methods, is associated with a high risk of progression to advanced AMD, perhaps on an inflammatory or vascular basis. Reticular macular disease deserves wider recognition and consideration by clinicians caring for patients with AMD.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Figure 1. Identifying and tracking progression of reticular pseudodrusen (RPD)

RPD are yellow or light interlacing networks ranging from 125 to 250 µm in width in color, red free, and blue light fundus photos; lesions are relatively low contrast and occur in regular patterns with well-defined domains. This study eye showed a reticular pattern in all 3 imaging modalities: contrast-enhanced color (top row), red free (middle row), and blue light (bottom row) photos, all of which were precisely registered to each other and cropped. The fellow eye (not shown) had choroidal neovascularization. (Column 1) Initial images, visit 1. (Column 2) Our user-interactive drusen segmentation tool applied in the 6000-µm region. The reticular pattern is displayed in green. (Columns 3, 4) Follow-up images after 3 years document the progression of RPD without conversion to advanced age-related macular degeneration (AMD).

Figure 2. Reticular pseudodrusen (RPD) fading with development of choroidal neovascularization (CNV)

(Top row) A. Original color photo with RPD inapparent. B. The contrast-enhanced color fundus (CF) photo shows a reticular pattern in 2 quadrants, outlined in green, with noticeable large soft drusen and pigment. The red free (RF) photo (C) and the blue light photo (D), registered to the CF photo, show a reticular pattern in 3 quadrants, outlined in blue and magenta, respectively. (Bottom row) Follow-up images were obtained from visit 5 (after 3 years), during which time occult CNV was detected on fluorescein angiography (FA). E. The FA image showing CNV. The reticular patterns in the enhanced CF photo (F), RF photo (G), and blue light photo (H) are faint, even in the areas not involved by exudation.

Figure 3. Reticular pseudodrusen with development of geographic atrophy (GA)

(Top row) This study eye initially showed large soft drusen and pigment (early age-related macular degeneration [AMD]) in the color photo and a faint reticular pattern superiorly in the red free and blue light images. The fluorescein angiogram (FA) showed late staining of coalescent soft drusen. (Bottom row) By visit 5, the reticular pattern was more prominent in the enhanced color, red free, and blue light images and surrounded multiple lobules of GA coalescing centrally. The FA shows sharply defined, scalloped lesions with baring of large choroidal vessels characteristic of GA, and the multilobular character of the GA lesions is apparent.