Natural history of drusenoid pigment epithelial detachment in age-related macular degeneration: Age-Related Eye Disease Study Report No. 28

Abstract

Objective: To describe the natural history of eyes with drusenoid pigment epithelial detachments (DPEDs) associated with age-related macular degeneration (AMD).

Design: Multicenter, clinic-based, prospective cohort study.

Participants: Among 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), 255 were identified as having DPED in at least 1 eye and having 5 or more years of follow-up after the initial detection of the DPED.

Methods: Baseline and annual fundus photographs were evaluated for the evolution of the fundus features and the development of advanced AMD in the forms of central geographic atrophy (CGA) or neovascular (NV) AMD. Kaplan-Meier analyses of progression to advanced AMD and of moderate vision loss (> or =15 letters compared with baseline) were performed.

Main outcome measures: Rate of progression to advanced AMD and change in visual acuity from baseline (in terms of mean letters lost and proportion losing > or =15 letters).

Results: A total of 311 eyes (from 255 participants) with DPED were followed for a median follow-up time of 8 years subsequent to the initial detection of a DPED. Of the 282 eyes that did not have advanced AMD at baseline, advanced AMD developed within 5 years in 119 eyes (42%) (19% progressing to CGA and 23% progressing to NV-AMD). In the remaining eyes that did not develop advanced AMD (n=163), progressive fundus changes, typified by the development of calcified drusen and pigmentary changes, were detected. Visual decline was prominent among study eyes, with approximately 40% of all eyes decreasing in visual acuity by > or =15 letters at 5 years follow-up. Mean visual acuity decreased from 76 letters ( approximately 20/30) at baseline to 61 letters ( approximately 20/60) at 5 years. Five-year decreases in mean visual acuity averaged 26 letters for eyes progressing to advanced AMD and 8 letters for non-progressing eyes.

Conclusions: The natural history of eyes containing DPED is characterized by a high rate of progression to both CGA and NV-AMD. Among eyes not progressing to advanced AMD, progressive development of pigmentary changes and calcified drusen were observed. Decline of visual acuity is a common outcome, with or without progression to advanced forms of AMD.

Figure 1

Progression of study eyes with drusenoid pigment epithelial detachments (DPED) to advanced forms of age-related macular degeneration (AMD). A. Proportions of eyes (n = 311) with DPED with concurrent central geographic atrophy (CGA), neovascular (NV) AMD, both NV AMD and CGA, and without any advanced forms of AMD at DPED baseline (left) and at 5 years following baseline (right). B. Cumulative percentage of eyes (n = 282 eyes; eyes with no evidence of advanced AMD at baseline) progressing to either CGA or NV AMD in the first 5 years of follow-up. C. Kaplan-Meier analysis of the cumulative percentage of eyes progressing to either CGA or NV AMD up to 10 years after baseline. The cumulative percentage of eyes progressing to CGA was estimated to exceed that progressing to NV AMD at year 7.

Figure 2

Natural history of fundus changes in eyes with drusenoid pigment epithelial detachments (DPEDs) not progressing to advanced forms of age-related macular degeneration (AMD) by 5 years (n = 163). Prevalences of the presence of each fundus finding at year 0, 1, 2, 3, 4, 5 following baseline are plotted. A. Percentage of eyes with hyperpigmentary changes. B. Percentage of eyes with hypopigmentary changes. C. Percentage of eyes with calcified drusen. D. Percentage of eyes with geographic atrophy (GA) not involving the center of the fovea (i.e. non-central GA). E. The total drusen area in each eye was estimated and classified in one of the following categories: smaller than area of grading circle O2 (circle diameter = 660 microns), from area of circle O2 to ½ disk area (DA), from ½ DA to 1 DA, and greater than 1 DA. The proportions of eyes in each area category are shown for each year of follow-up. The total numbers of eyes for each time point are as follow: 163 eyes at year 0, 87 eyes at year 1, 156 eyes at year 2, 155 eyes at year 3, 149 eyes at year 4, 152 eyes at year 5).

Figure 3

Case 1: Fundus changes occurring in the left eye of a 73 year-old woman with a drusenoid pigment epithelial detachment (DPED) at baseline. A. Fundus at year 0 (baseline): A centrally located DPED is seen with scattered large drusen in the inferior macula. B. At year 4, new calcified, refractile drusen emerge in the temporal macula (black arrow). Central DPED is decreased in height and area. C. At year 7, new hyperpigmentary changes appear at the fovea (black arrowhead). Large drusen in the inferior macula enlarge in size and coalesce to form a new DPED (white arrows). D. At year 8, DPEDs in both the central and inferior macula have disappeared. Calcified drusen are increased in number and an area of hypopigmentation has appeared in the nasal macula (white arrowhead). Central hyperpigmentary changes have also decreased as areas of hypopigmentation have increased. This natural history illustrates the dynamic changes in fundus features over a 8-year period, involving the appearance and disappearance of DPEDs, hyper- and hypopigmentary changes and calcified drusen, without overt progression to advanced forms of age-related macular degeneration.

Figure 4

Case 2: Fundus changes occurring in the left eye of a 73-year old man with a drusenoid pigment epithelial detachment (DPED) that progressed to central geographic atrophy (CGA) during the course of the study. A. Fundus at year 0: A centrally located DPED is present with hyperpigmentary changes. B. At year 2, most of the DPED has disappeared and a new area of hypopigmentation has emerged (black arrow). C. At year 4, an additional area of hypopigmentation has arisen (black arrows). In the meantime, the hyperpigmentary changes seen earlier have decreased. D. At year 7, areas of geographic atrophy have emerged from earlier patches of hypopigmentation that have enlarged and coalesced.

Figure 5

Case 3: Fundus changes occurring in the left eye of a 72 year-old woman with a drusenoid pigment epithelial detachment (DPED) that progressed to neovascular age-related macular degeneration (NV AMD) during follow-up. A. Fundus at year 0: A DPED with associated hyperpigmentary changes is located in the temporal perifovea (black arrowhead). B. At year 4, additional hyperpigmentary changes have emerged (black arrow) overlying the DPED. C. At year 9, new onset retinal edema, subretinal lipid exudate emerged in the region of the DPED. D. Three months after the onset of retinal edema, subretinal hemorrhage, indicative of NV AMD is seen in the same location.

Figure 6

Change in best corrected visual acuity over time in eyes with drusenoid pigment epithelial detachments (DPED). A. Proportions of eyes in each visual acuity range at baseline and at 5 years. All eyes with DPEDs (n = 311) were included. B. Change in mean best corrected visual acuity (BCVA) as measured in letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart over the first 5 years after DPED baseline for all eyes with DPED (n = 311), eyes progressing to advanced age-related macular degeneration (AMD) by year 5 (either central geographic atrophy (CGA) or neovascular (NV) AMD) (n = 148), and eyes not progressing to advanced AMD (n = 163) over this time period. C. Percentage of eyes losing ≥15 letters of best corrected visual acuity (BCVA) from DPED baseline for all eyes, and also separately for eyes progressing to advanced AMD, and eyes not progressing to advanced AMD. D. Kaplan-Meier analysis of the percentage of all eyes losing ≥15 letters of BCVA up to 12 years after DPED baseline.