Inner retinal abnormalities in X-linked retinitis pigmentosa with RPGR mutations

Abstract

Purpose: To investigate in vivo the retinal microstructure in X-linked retinitis pigmentosa (XLRP) caused by RPGR mutations as a prelude to treatment initiatives for this common form of RP.

Methods: Patients with RPGR-XLRP (n = 12; age range, 10-56 years) were studied by optical coherence tomography (OCT) in a wide region of central retina. Overall retinal thickness and outer nuclear layer (ONL) and inner retinal parameters across horizontal and vertical meridians were analyzed and compared.

Results: Retinal architecture of all patients with RPGR mutations was abnormal. At the fovea in younger patients, the ONL could be normal; but, at increasing eccentricities, there was a loss of photoreceptor laminar structure, even at the youngest ages studied. At later ages and advanced disease stages, the ONL was thin and reduced in extent. Inner retinal thickness, in contrast, was normal or hyperthick. Inner retinal thickening was detectable at all ages studied and was strongly associated with ONL loss.

Conclusions: Inner retinal laminar abnormalities in RPGR-XLRP are likely to reflect a neuronal-glial retinal remodeling response to photoreceptor loss and are detectable relatively early in the disease course. These results should be factored into emerging therapeutic strategies for this form of RP.

Figure 1

Retinal thickness topography of RPGR-XLRP. Topographical maps of retinal thickness (left), ONL thickness (middle), and inner retinal thickness (right) in a normal 22-year-old man (A) and three patients with RPGR-XLRP (P1, P8, and P12) of different ages and disease stages (B–D). Traces of major blood vessels and location of optic nerve head are overlaid on each map (depicted as right eyes). Note that pseudocolor scales (shown beneath the normal maps) for (A) and (C) are the same but the scale for (B) is different. T, temporal; N, nasal; S, superior; I, inferior.

Figure 2

Retinal laminar architecture in RPGR-XLRP (A, B). Cross-sectional scans along the horizontal (left) and vertical (right) meridians in a normal subject (A) and a 15-year-old patient (B). Brackets defining ONL and inner retina are labeled (left) and a bracket showing total retinal thickness is at the right. Nuclear layers are colored (ONL, blue; inner nuclear layer, purple). OCTs are in grayscale with lowest reflectivity as black and highest reflectivity as white. Insets: schematic location of the scans. (C–E) Thickness of the retina (C), ONL (D), and inner retina (E) along the horizontal and vertical meridians in the 12 patients, identified by symbols and grouped by age. Vertical axes in (D) and (E) start at the axial resolution of the OCT system. Shaded areas: normal limits; mean ± 2 SD; (C), n = 27; (D), n = 26; (E), n = 14. T, temporal; S, superior.

Figure 3

Relationship of outer and inner laminar features in RPGR-mutant retina. Inner retinal thickness as a function of ONL thickness at extrafoveal (>2 mm of eccentricity; 0.15 mm bins) retinal locations in patients with RPGR-XLRP and normal subjects. Both inner retinal and ONL thicknesses are specified as change from the mean normal value calculated at each retinal location. Vertical dashed line: lower normal limit (−2 SD from normal mean) for ONL thickness; horizontal dashed line: upper normal limit (+2 SD from normal mean) for inner retinal thickness.