X-linked juvenile retinoschisis is a progressive bilateral disease that is probably present at birth and has been documented as early as 7 weeks of age.1 It was first reported by Haas in 18982 and has recently become better understood as a mutation of the XLRS1 gene on the short arm of the X chromosome (Xp22).3 This mutation results in an abnormal retinal protein that participates in intercellular spaces.3 Cystoid changes arranged in a stellate pattern with radial striae projecting from the fovea are seen in all patients, along with a peripheral schisis in 50% of cases, and variable findings are well described by Gass4 and others. In this study, we used optical coherence tomography (OCT) (Stratus OCT; Carl Zeiss Meditec AG, Jena, Germany) to examine the foveal areas in 2 patients with juvenile retinoschisis. Our OCT findings suggest that the foveal schisis is probably located in the outer plexiform layer, not in the nerve fiber layer (NFL), as described previously in peripheral retinoschisis.5,6
A 19-year-old African-American man had had poor vision in both eyes since early childhood. Family history was significant for 1 male sibling with poor vision and 2 blind male cousins. On examination, best-corrected Snellen visual acuity was 20/100− OD and 20/300 OS. Pupils were normal with no relative afferent pupillary defect. The anterior segments were unremarkable. Fundus examination showed typical stellate cystoid changes at the central macula in both eyes (Figure 1). In the right eye, the stellate change did not start in the central fovea, where a 400-μm area of the retina looked flat. The radial stellate change was apparent outside of this flat zone (Figure 1A). In the left eye, the stellate change started from the central fovea (Figure 1B). At the inferior temporal periphery, retinoschisis cavities with inner-layer holes were noticed in both eyes.
Fundus photographs of the macula in a 19-year-old man with X-linked juvenile retinoschisis. A, Right eye. There is a 400-μm round zone in the foveal center where the retina appears flat. Prominent stellate cystoid changes are visualized surrounding this zone. Visual acuity is 20/100−. B, Left eye. There is a small depigmented spot in the foveal center where the stellate cystoid changes originate. Visual acuity is 20/300.
The OCT scans showed that in the right fovea (Figure 2A), the inner nuclear layer and ganglion cell layer were condensed into a single layer. The outer nuclear layer was not of uniform thickness and showed atrophic change. The outer plexiform layer appeared as an uneven slit between the outer nuclear layer and the inner retina. The retinal pigment epithelium showed focal atrophic changes (Figure 2A). In the left fovea (Figure 2B), large foveal cystoid spaces were noticed that were localized between the inner and outer retina, specifically in the outer plexiform layer. These cystoid spaces were of relatively uniform thickness, and there were multiple bridging strands crossing in the cystoid spaces. These strands were vertically oriented and, in some areas, very evenly spaced, resembling a ladder resting on its side. In other areas, a “rung” was missing, suggesting the possible coalescence of smaller uniform spaces. There were also small areas of early retinal pigment epithelial atrophy. The most notable finding, however, was that the cystoid pockets appeared to be located deeper in the retina than the highly reflective NFL. They were localized in the outer plexiform layer, as seen in typical pseudophakic cystoid macular edema.4
Optical coherence tomography of the fovea of a 19-year-old patient. A, Right eye. The inner nuclear layer and ganglion cell layer are condensed into a single layer. The outer nuclear layer shows atrophic change. The outer plexiform layer appears as an uneven layer. The retinal pigment epithelium shows focal atrophic changes. B, Left eye. Large foveal cystoid spaces are localized in the outer plexiform layer. There are multiple bridging strands crossing in the cystoid spaces. In other areas, a strand is missing, suggesting the possible coalescence of smaller spaces.
The patient’s 12-year-old brother was also examined, and his visual acuity was counting fingers at 3 ft OD and 20/60 OS. The fundus photographs of the right eye were nearly identical to those of his 19-year-old brother’s left eye: prominent stellate change present in the foveal center. His left eye showed no stellate change but only atrophic retinal pigment epithelial mottling (photograph not shown). The OCT of the 12-year-old showed that in the right fovea, cystoid spaces were already formed in the foveal center, where the foveal pit was still recognizable (Figure 3A). In the parafoveal area, small cystoid changes were noticed as well. These cystoid spaces were clearly localized in the outer plexiform layer. Occasional tiny pockets of cystoid changes were seen in the inner retina, probably in the inner plexiform layer. In the left eye, small cystoid changes had begun to develop on the temporal side of the fovea (Figure 3B) but not on the nasal side. The foveal pit was easily identified. Thus, retinoschisis appeared to start in the foveal center and spread toward the parafoveal area.
Optical coherence tomography of the fovea of the patient’s 12-year-old brother with X-linked juvenile retinoschisis. A, Right eye. The foveal pit is recognizable. Cystoid changes are visible in the foveal area and are clearly localized in the outer plexiform layer. Occasional tiny cystoid changes are noticed in the inner plexiform layer. B, In the left eye, small cystoid changes have started to develop on the temporal side of the fovea. The foveal pit is easily identified.
Yanoff et al5 and Manschot6 described the retinoschisis in this disease as occurring in the NFL based on histopathologic findings, further postulating that the primary defect might then involve the Müller cells. The OCT findings in our cases suggest that the foveal cystoid separation is not located in the NFL, as described in peripheral retinoschisis,5,6 but is in the outer plexiform layer. Trese and Foos7 reported a series of premature infants with infantile cystoid maculopathy resembling X-linked juvenile retinoschisis, in whom gross examination showed cystoid pockets at various retinal layers including deep to the NFL. Azzolini et al8 reported OCT findings in 3 cases of X-linked juvenile retinoschisis showing a macular cleavage plane in the outer retinal layers as well as in the NFL. Optical coherence tomography provides an in vivo correlation to previous investigations of the histopathologic features of the disease. The OCT findings in this report suggest that the primary abnormality of the fovea in patients with juvenile retinoschisis is actually in the outer retina, specifically in the outer plexiform layer, unlike the peripheral retina, where the schisis is located in the NFL. These findings suggest different developmental mechanisms of retinoschisis in the fovea and peripheral retina. A larger series of OCT imaging in this interesting disease is desirable.
Correspondence: Dr Gao, Department of Ophthalmology, Indiana University School of Medicine, 702 Rotary Cir, Indianapolis, IN 46202 (firstname.lastname@example.org).
Financial Disclosure: None.
Funding/Support: This study was supported by the Research to Prevent Blindness Foundation, New York, NY.
Gao H, Kusumi R, Yung C. Optical Coherence Tomographic Findings in X-linked Juvenile Retinoschisis. Arch Ophthalmol. 2005;123(7):1006-1008. doi:10.1001/archopht.123.7.1006