Multimodal Imaging Analysis of Cone Photoreceptors Mosaic in Human Juvenile X-linked Retinoschisis

Abstract

Purpose : Juvenile X-linked retinoschisis (XLRS) is characterized by the formation of schitic cavities within the retinal layers. XLRS is a monogenic disease caused by mutation in the RS1 gene. Retinoschisin (RS) is an extracellular binding protein secreted from retinal cells as a disulphide-linked octamer. Although most classes of adult retinal neurons express RS, it is most abundant in photoreceptors. One putative mechanism in XLRS is the failure of RS to cross the photoreceptor membrane to the extracellular space, causing it to accumulate in photoreceptors which become swollen and sick. We studied the cone mosaic in adaptive optics (AO) scanning light ophthalmographic (SLO) images of XLRS retinae.

Methods : A 17 year old boy with a Trp96Arg missense mutation in the RS1 gene and a 12 year old boy with an unspecified mutation were studied. Following a standard clinical examination, images of the macula from 2°-10° eccentric along the horizontal meridian were obtained using our multimodal adaptive optics retinal imager (MAORI). Cones were identified in these images using a semi-automated routine. The diameter of every identified cone was measured by calculating the number of pixels at the half-height of the intensity distribution of the cone 2(pixels/π)^½. To convert pixels to degrees to microns, the ‘angular subtense’ of 1° of retina was estimated using the parameters of Gullstrand’s Schematic Eye No. 2.

Results : The 17 year old XLRS subject presented with Snellen visual acuity 20/38 (1.91 minutes of arc) in the imaged eye. His spherical equivalent was -0.75 D. Central macular thickness was 296 µm; the AO-SLO also showed apparent swelling of the inner segments. Patchy views of the photoreceptors were obtained, between the schitic cavities, in the AO-SLO. Cone diameter was 4.2 µm. In the 12 year old subject, Snellen acuity was 20/100 (5.01 minutes of arc); spherical equivalent was 1.13 D, central macular thickness was 335 µm and cone diameter was 3.5 µm. In contrast, in control subjects (n=7), cone diameter is 3.1±0.45 µm.

Conclusions : The diameters of the cones displayed in AO-SLOs were larger in XLRS than normal subjects, consistent with putative swelling. Conceivably the abnormal protein is trapped in the inner segment. However, poor fixation XLRS subjects may have led to more eccentric scans, or, perhaps, only the largest and brightest cones were visible due to disease.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.