In the developed world, age-related macular degeneration (AMD) is the most common cause of permanent vision loss1 and has two different advanced forms: neovascular (wet) and atrophic (dry) geographic atrophy (GA). A pigment epithelium detachment (PED) is currently a poorly understood finding, both as it relates to disease pathophysiology and vision prognosis. There are three different kinds of PEDs: neovascular, serous, and drusenoid.
Although more research into the pathophysiologic mechanisms underlying the development of PEDs is needed, it is thought that they may be the result of a variety of degenerative and other processes.2 Previous research has suggested that serous PEDs may be caused by the prevention of diffusion of fluid from the retinal pigment epithelium to choriocapillaris due to the formation of an age-related hydrophobic barrier in Bruch membrane.3 However, there are other pathologic mechanisms that may be involved as well. It has been demonstrated that soft drusen are primarily composed of lipoprotein particles secreted by the retinal pigment epithelium and then not properly recycled, leading to the formation/expansion of drusen, retinal pigment epithelium migration, druse collapse, and atrophy.1 Drusenoid PEDs, however, are thought to be the aggregate of large drusen, and because of the hydrophobic nature of the drusen, a similar barrier in Bruch membrane is created as with serous PEDs and causes the accumulation of fluid.1
With new therapies emerging for the intermediate stages of AMD, the ability to accurately and repeatedly assess the efficacy of treatments is critical. Currently, best-corrected visual acuity (BCVA) is the most common measure of visual function; however, it is insufficient for assessing disease severity in intermediate AMD because BCVA is not affected until later stages of the disease.
Low luminance visual acuity (LLVA) is measured by placing a 2.0 log unit neutral density filter over best-corrected vision and reading a normally illuminated Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Low luminance visual acuity has been found to be significantly reduced in eyes with non-foveal GA, despite BCVA being good, and predicted subsequent loss of vision.4 In addition, low luminance deficit, the difference between the ETDRS letter score under photopic and low luminance conditions, is a strong predictor for AMD progression.
In this case report, spontaneous optical coherence tomography (OCT)-based improvement of a drusenoid PED with the return of a foveal contour and the absence of either GA or choroidal neovascularization was demonstrated. Furthermore, although there was loss of LLVA, a spontaneous improvement of 13 letters was observed after the resolution of the PED by this functional assessment and continued to improve over the 24-month follow-up period to a total gain of 35 letters. These results indicate the anatomic and functional vision improvement possible in PEDs associated with intermediate AMD and denote the degree of amelioration that is possible in this disease.
A 73-year-old white man presented with a history of AMD. The subject's personal, family, and systemic history were unremarkable. Baseline BCVA was 76 ETDRS letters (20/32 +1) and LLVA was 59 letters (20/63 −1) (Figure 1). Slit-lamp exam revealed trace nuclear sclerosis cataracts OU. Spectral domain OCT (Heidelberg, Heidelberg, Germany) showed a drusenoid PED central to the fovea, vitreomacular adhesion without foveal distortion, and an absence of fluid or choroidal neovascularization (Figure 2). Fundus autofluorescence (Heidelberg) showed intraretinal hyperfluorescence areas around the fovea (Figure 3).
During the first 17 months, extensive intraretinal hyperreflective foci appeared over the PED (Figure 2), BCVA remained stable at 80 letters (20/25), and LLVA decreased from baseline over Months 6, 16, and 17, with letter scores to 60 (20/63), 50 (20/100), and 39 (20/160 −1) respectively (Figure 1). However, at Month 19, LLVA improved to 52 (20/100 +2) letters with BCVA holding at 75 letters (20/32) (Figure 1). By Month 21, anatomical resolution of the drusenoid PED by OCT was seen (Figure 2) and LLVA had improved to 60 letters (20/63). Hyperfluorescence areas around the fovea, as shown in fundus autofluorescence images, decreased after PED improvement at Month 21 (Figure 3). A vitelliform lesion was present at the apex of the drusenoid PED at baseline and Month 17 (Figure 2). At Months 21 and 41 no evidence of GA or choroidal neovascularization, confirmed by fundus photography (Canon CF-1, Canon U.S.A, Melville, NY) was seen. At Month 41, OCT-Angiography was conducted with a Zeiss Plex Elite 9000 (Carl Zeiss, Jena, Germany) and showed no evidence of choroidal neovascularization. Interestingly LLVA continued to improve to 73 (20/40 +2) and 74 (20/32 −2) letters at Months 24 and 41 respectively.
Although BCVA may remain unchanged, LLVA has been shown to be significantly reduced in early AMD5 and has been demonstrated to be highly repeatable6 with 6.5 letter variation.4 In this case report, the patient's LLVA decreased to an ETDRS letter score of 39 (20/160 −1) from a baseline of 59 letters (20/63 −1), then improved by 35 letters after resolution of the drusenoid PED. Anatomical improvements, as shown by the spectral domain OCT, are aligned with the LLVA improvements (Figure 3). This suggests that LLVA may be a sensitive approach to structure/function analysis.
Certain features on the patient's baseline OCT were indicators of a risk of the development of subsequent GA, such as the height of the drusenoid PED and hyperreflective foci.7 Through natural history studies, it is known that the prognosis of a drusenoid PED is not favorable. The Age-Related Eye Disease study found that of the 282 eyes observed with a drusenoid PED, 42% progressed to advanced AMD, with 45% of those patients developing GA and the other 55% developing neovascular AMD.2 In addition, in this case, numerous intraretinal hyperreflective foci were noted at baseline (Figure 2). Hyperreflective foci have also been associated with an increased risk in developing atrophy at their location,8 and as the number of hyperreflective foci increases, the risk of atrophy at that location also increases.9
As this case demonstrated, the use of LLVA outcome has implications when considering different functional measures as intermediate AMD clinical trial endpoints. Not only can spontaneous improvement in large drusenoid PEDs occur, but increases in functional outcomes, such as LLVA, can occur well beyond the limits of variability. This needs to be taken into account both when designing clinical trials and when considering the potential extent of future therapeutic interventions.
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