Methods

The spectral-domain optical coherence tomography (SD OCT) database was reviewed to identify patients with a diagnosis of X-linked retinoschisis who underwent SD OCT imaging. This retrospective study was approved by the Institutional Review Board at the University of Illinois Medical Center. The diagnosis of X-linked retinoschisis was based on clinical criteria including fundoscopy, electroretinogram results, and OCT findings. Age-similar controls with low refractive error, no visual impairment, and no known retinal conditions were identified in the database as a comparison group. BCVA was determined from the patient records. All OCT scans were obtained using the MM5 protocol consisting of a 5 mm by 5 mm grid of horizontal and vertical scans through the macula on an Optovue RTVue SD OCT system (Optovue Inc, Fremont, California, USA). The automated scans were reviewed and inaccurate segmentation boundaries were corrected manually. The inner retina was defined as retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer for the purposes of this study. Full-thickness, inner and outer retina thickness, and volume measurements in 15 regions of the macula were automatically generated by the Optovue software and were recorded from thickness maps. These measurement regions and inner retinal segmentation boundaries are illustrated in Figure 1 . For thickness and volume measurements, evaluated regions include temporal, superior, nasal, inferior, superior hemisphere, and inferior hemisphere areas of the parafoveal and perifoveal regions, as well as the central foveal zone.

Retinal thickness measurements in X-linked retinoschisis patients by optical coherence tomography. (Top) Representative map of macular regions used for thickness and volume measurements. (Bottom) Optical coherence tomography scan of the right macula in a 44-year-old male subject with X-linked retinoschisis demonstrating automated segmentation of the retina (white lines represent the boundaries of the inner retina).

Two-tailed t tests were performed to compare means between the groups. Multiple linear regression analysis was performed to correlate OCT measurements with BCVA. Condition indices less than 15 were considered acceptable collinearity measures. Pearson correlation analysis was generated for patient age in relation to OCT measurements. A P value less than .05 was considered statistically significant.

Results

Sixty-three eyes of 33 male patients identified with X-linked retinoschisis were analyzed. Figure 2 presents the OCT image and corresponding thickness map for a retinoschisis patient with typical schisis cavities. Forty-one eyes of 21 patients served as age-similar controls. The mean age of retinoschisis patients was 26.4 years (range 7–58 years). The mean age of the age-similar controls was 30.0 years (range 11–56 years). There was no statistical difference in age distribution between the cases and controls ( P = .350). The mean logMAR BCVA for the eyes of the cases was 0.5, corresponding to a Snellen acuity of approximately 20/65. Foveal schisis was observed on OCT in 81% of the retinoschisis patient eyes. The mean age of patients without foveal schisis was 40.9 years, which was significantly older than patients with foveal schisis (22.3 years; P < .0001). Five patients required manual re-segmentation. In 2 eyes, automated or manual segmentation was deemed inaccurate owing to severe foveal schisis, and these measurements were excluded from the corresponding statistical analysis.

Optical coherence tomography scan of the left macula with accompanying thickness maps and measurements in a 14-year old male subject with X-linked retinoschisis demonstrating macular schisis and subtle thinning of the inner retina.

Figure 3 illustrates the full-thickness retinal measurements for cases and controls. Figure 4 depicts the thickness and volume measurements of the outer retina. Figure 5 summarizes the thickness and volume measurements of the inner retina. Although most of the full-thickness retinal measurements did not differ between the 2 groups, a few select full-thickness measurements, namely foveal thickness, temporal parafoveal thickness, and foveal volume, were greater in the retinoschisis group. In contrast, all of the segmented outer retina and inner retina thickness and volume measurements differed between the case and control groups. The outer retinal thicknesses and volumes were statistically increased in the X-linked retinoschisis group compared to the control group in all instances. The inner foveal thickness and volume measurements were greater in the X-linked retinoschisis patients than in the controls, while the inner retinal measurements in the perifoveal and parafoveal areas were decreased in the retinoschisis patients compared to controls.

Mean full-thickness retinal volume (mm ³ ) and thickness (μm) measurements in X-linked retinoschisis and control patients, based on the key in Figure 1 . Symbols denote regions that are statistically significant between the cases and controls (∗ P < .001, ⁺ P < .05).

Mean outer retinal volume (mm ³ ) and thickness (μm) measurements in X-linked retinoschisis and control patients, based on the key in Figure 1 . Symbols denote regions that are statistically significant between the cases and controls (∗ P < .001, ⁺ P < .05).

Mean inner retinal volume (mm ³ ) and thickness (μm) measurements in X-linked retinoschisis and control patients, based on the key in Figure 1 . Symbols denote regions that are statistically significant between the cases and controls (∗ P < .001, ⁺ P < .05).

Multiple linear regression analysis was performed with logMAR BCVA as the dependent variable and all retinal thickness and volume measurements as the independent variables. The generated regression model (R = 0.552, R ² = 0.305, adjusted R ² = 0.279) yielded volume of the inner retina at the fovea (beta = 0.446; P < .0001) and volume of the temporal perifoveal inner retina (beta = −0.551; P < .0001) as statistically significant variables. The standardized beta coefficient suggests an inverse relationship for temporal perifoveal inner retinal volume and visual acuity, suggesting that visual acuity declines as the inner temporal perifoveal retina thins.

Pearson correlation coefficients were calculated to assess the relationship between patient age and retinal thickness or volume measurements. The Table summarizes the statistically significant correlations. In general, full-thickness retinal thicknesses and volumes decreased with age. Several outer retinal perifoveal thicknesses and volumes also declined with age. Overall, the strongest Pearson correlations were for inner retinal thickness and volume measurements, which also diminished with age ( Figure 6 ).

Table

Statistically Significant Pearson Correlations for Retinal Measurements and Patient Age in X-Linked Retinoschisis Patients

Variable	Pearson Correlation	P Value
Full-thickness parafoveal inferior hemisphere thickness	−0.332	.008
Full-thickness parafoveal nasal thickness	−0.304	.015
Full-thickness parafoveal inferior thickness	−0.274	.029
Full-thickness perifoveal thickness	−0.258	.041
Full-thickness perifoveal inferior hemisphere thickness	−0.376	.002
Full-thickness perifoveal nasal thickness	−0.473	<.001
Full-thickness perifoveal inferior thickness	−0.384	.002
Full-thickness parafoveal inferior hemisphere volume	−0.268	.034
Full-thickness parafoveal nasal volume	−0.305	.015
Full-thickness parafoveal inferior volume	−0.270	.033
Full-thickness perifoveal volume	−0.347	.005
Full-thickness perifoveal superior hemisphere volume	−0.251	.048
Full-thickness perifoveal inferior hemisphere volume	−0.428	<.001
Full-thickness perifoveal nasal volume	−0.500	<.001
Full-thickness perifoveal inferior volume	−0.435	<.001
Outer retina perifoveal inferior hemisphere thickness	−0.264	.036
Outer retina perifoveal nasal thickness	−0.410	.001
Outer retina perifoveal inferior thickness	−0.292	.020
Outer retina perifoveal inferior hemisphere volume	−0.264	.036
Outer retina perifoveal nasal volume	−0.411	.001
Outer retina perifoveal inferior volume	−0.290	.021
Inner retina parafoveal thickness	−0.459	<.001
Inner retina parafoveal superior hemisphere thickness	−0.405	.001
Inner retina parafoveal inferior hemisphere thickness	−0.483	<.001
Inner retina parafoveal temporal thickness	−0.471	<.001
Inner retina parafoveal superior thickness	−0.291	.020
Inner retina parafoveal nasal thickness	−0.471	<.001
Inner retina parafoveal inferior thickness	−0.452	<.001
Inner retina perifoveal thickness	−0.555	<.001
Inner retina perifoveal superior hemisphere thickness	−0.489	<.001
Inner retina perifoveal inferior hemisphere thickness	−0.564	<.001
Inner retina perifoveal temporal thickness	−0.536	<.001
Inner retina perifoveal superior thickness	−0.421	.001
Inner retina perifoveal nasal thickness	−0.447	<.001
Inner retina perifoveal inferior thickness	−0.527	<.001
Inner retina parafoveal volume	−0.460	<.001
Inner retina parafoveal superior hemisphere volume	−0.404	.001
Inner retina parafoveal inferior hemisphere volume	−0.481	<.001
Inner retina parafoveal temporal volume	−0.471	<.001
Inner retina parafoveal superior volume	−0.293	.020
Inner retina parafoveal nasal volume	−0.470	<.001
Inner retina parafoveal inferior volume	−0.450	<.001
Inner retina perifoveal volume	−0.554	<.001

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