In vivo visualization of photoreceptor layer and lipofuscin accumulation in stargardt's disease and fundus flavimaculatus by high resolution spectral-domain optical coherence tomography

Abstract

Introduction: To assess photoreceptor (PR) layer morphology in patients with Stargardt's disease (STGD) and fundus flavimaculatus (FFM) using high resolution spectral domain optical coherence tomography (HD-OCT; OCT 4000 Cirrus, Humphrey-Zeiss, San Leandro, CA).

Methods: This was a prospective observational case series. Sixteen consecutive patients with STGD and FFM underwent a complete ophthalmologic examination. Optical coherence tomography examination was performed with HD-OCT, a high-speed (27,000 axial scans per second) OCT system using spectral/Fourier domain detection, with an axial image resolution of 5 mum.

Results: A total of 31 eyes were included in the study. Transverse loss of the PR layer in the foveal region was shown by HD-OCT. Twenty eyes with clinically evident central atrophy had a disruption of either the Verhoeff's membrane (VM) or the layer corresponding to the interface of inner segment (IS) and outer segment (OS) of PR in the foveal region. Among these eyes, 12/20 eyes had a loss of the PR layer (loss of both VM and IS-OS interface) in the foveal region. Eleven eyes (11/31) without clinically evident central atrophy had an intact interface of IS and OS of PR centrally. Moreover, we observed hyperreflective deposits: type 1 lesions located within the retinal pigment epithelium (RPE) layer and at the level of the outer segments of PR, and type 2 lesions located at the level of the outer nuclear layer and clearly separated from the RPE layer. Type 1 lesions alone were associated with absence of loss of the PR layer in the foveal region in all eyes; type 2 lesions were always associated with presence of type 1 lesions, and often (8/12 eyes) associated with loss of the PR layer within the foveal region. Mean best-corrected visual acuity (BCVA) was significantly correlated with loss of the PR layer in the foveal region (P < 0.001), as well as to presence of type 2 flecks (P = 0.03).

Conclusion: Type 2 deposits in STGD/FFM patients seem to represent a marker of the possible evolution towards foveal atrophy.

Keywords: fundus flavimaculatus; high definition optical coherence tomography; retinal dystrophy; stargardt’s disease.

Figure 1

Normal eye high definition spectral domain optical coherence tomography (HD-OCT). Abbreviations: ELM, external limiting membrane; is, inner segment layer; Os, outer segment layer; VM, Verhoeff‘s membrane; RPE, retinal pigment epithelium.

Figure 2

Case 4 fundus autofluorescence and high definition spectral domain optical coherence tomography (HD-OCT). Fundus autofluorescent frame of the left eye (20/25 best corrected visual acuity) shows mottled autofluorescence in the macular area and retinal flecks (thin arrows). HD-OCT scans (A and B) show disruption of either the layer between the retinal pigment epithelium (RPE) and the outer segment (OS) of the photoreceptors (PR) (enlarged view), either the layer corresponding to the interface of inner segment (IS) and OS of PR in the foveal region (enlarged view; asterisks), and a focal loss of the PR layer in the parafoveal region (open arrows).

Figure 3

Case 8 fundus autofluorescence and high definition spectral domain optical coherence tomography (HD-OCT). Fundus autofluorescent frame of the left eye (20/125 best corrected visual acuity) shows mottled autofluorescence in the macular area and clearly delineates the retinal flecks. HD-OCT scans (A, B, and C) show a diffuse loss of the photoreceptor layer (enlarged view) in the foveal region (B, open arrows), and small hyperreflective lesions presented as dome-shaped deposits located within the retinal pigment epithelium (A and C, thin arrows).

Figure 4

Case 2 fundus autofluorescence and high definition spectral domain optical coherence tomography (HD-OCT). Fundus autofluorescent frame of the right eye (20/20 best corrected visual acuity) shows mottled autofluorescence in the macular area and clearly delineates the retinal flecks. HD-OCT scans (A, B, and C) show an intact inner segment and outer segment interface of the photoreceptors (PR) centrally (enlarged view), but diffuse parafoveal loss of the PR layer (open arrows), and small hyperreflective lesions presented either as dome-shaped deposits within the retinal pigment epithelium (RPE) (B, thin arrow), or as small linear deposits located at the level of the outer nuclear layer and clearly separated from the RPE (A and C, arrowheads).

Figure 5

A) Case 5 fundus autofluorescence and high definition spectral domain optical coherence tomography (HD-OCT). Fundus autofluorescent frame of the right eye (20/25 best corrected visual acuity) shows mottled autofluorescence in the macular area and several diffuse retinal flecks. HD-OCT scans show disruption of either the layer between the retinal pigment epithelium (RPE) and the outer segment (OS) of the photoreceptors (PR), either the layer corresponding to the interface of inner segment (IS) and OS of PR in the foveal region (asterisk), and a focal loss of the PR layer in the parafoveal region (open arrows). Small, large and very large hyperreflective lesions presented as dome-shaped deposits located within the RPE and at the level of the outer segments of PR (thin arrows), and small linear deposits located at the level of the outer nuclear layer and clearly separated from the RPE layer (arrowhead), are visualized by HD-OCT scans. B) Case 1 fluorescein angiography and HD-OCT. Fluorescein angiography frame of the left eye (20/50 best corrected visual acuity) shows mottled fluorescence in the macular area and several diffuse retinal flecks. HD-OCT scans show a focal loss of the photoreceptor layer in the foveal region (open arrows), and very large hyperreflective lesions presented as dome-shaped deposits located within the retinal pigment epithelium (thin arrows).