ABCA4-Related Retinopathy - a model to investigate the effect of altered retinal pigment epithelium and geographic atrophy on the choroid

Abstract

 

Purpose

 

To investigate choroidal structure and thickness in ABCA4-related retinopathy, the phenotypic features of which include characteristically altered and/or atrophic retinal pigment epithelium (RPE).

 

Methods

 

In this monocenter cross-sectional case series, diagnosis of ABCA4-related retinopathy was based on ophthalmologic examination, retinal imaging and genetic analysis. Eyes were subdivided into 3 groups: Bulls-eye like foveal alterations (Group 1); yellow-white flecks surrounding the fovea and/or exceeding the vascular arcades (Group 2); and panretinal disease manifestations (Group 3). Choroidal thickness was measured using enhanced depth imaging optical coherence tomography (Spectralis, Heidelberg Engineering, Germany). Mean choroidal thickness (MCT; calculated along the horizontal and vertical OCT-scan through the fovea with a 500 µm interval between measures) and subfoveal choroidal thickness (SCT) were compared. Sixty-five eyes of 65 normal subjects served as controls.

 

Results

 

Forty eyes of 40 patients with ABCA4-related retinopathy (age 37.9±2.6 years; range 9-77 years) were included in this study. Two mutations in ABCA4 were identified in 35 patients, and only 1 mutation was found in 5 patients. Compared to controls, SCT and MCT were significantly reduced in patients with ABCA4-related retinopathy (both, p<0.01), mainly due to choroidal thinning in groups 2 and 3 (mean_SCT±SEM and mean_MCT±SEM]; group 1: 333±12 µm and 304±11 µm; group 2: 276±22 µm and 251±18 µm; group 3: 274±18 µm and 250±12 µm). Presence of any geographic atrophy (GA) >300 µm² was associated with a thinner choroid (mean_SCT±SEM and mean_MCT±SEM]; GA: 277±17 and 225±13; no GA: 341±16 and 313±13; both, p ≤ 0.001). Choroidal thinning was not focal within areas of GA, but was generalized and widespread. Structural changes in eyes with choroidal thinning included apparent loss of small choroidal vessels. Patients and controls revealed a similar negative and positive association of choroidal thickness with age and spherical equivalent, respectively.

 

Conclusions

 

The results indicate that ABCA4-related retinopathy can be associated with choroidal alterations, which are most pronounced in eyes with widespread disease manifestation and those with GA. The absence of focal choroidal thinning within areas of GA is suggestive for a diffusible factor from the RPE sustaining the choroidal structure.