Analysis of visual acuity and cyst volume measurements in a natural history study in X-Linked Retinoschisis (XLRS)

Abstract

 

Purpose

 

In preparation for upcoming Phase I/II gene therapy trials we have analyzed the initial data gathered from 45 participants with XLRS. The primary objective was to determine if visual acuity and cyst volume are useful measures of visual function. The secondary objective was to monitor maculoschisis during treatment with a topical carbonic anhydrase inhibitor (CAI) in a subset of participants.

 

Methods

 

Participants with XLRS were assessed from the retina and ophthalmic practices at Oregon Health & Science University Casey Eye Institute (OHSU CEI), Retina Foundation of the Southwest and University of Michigan Kellogg Eye Center. Subjects were evaluated with both standard and non-standard of care visual function and retinal structure tests. Our analysis focused on comparing Best Corrected Visual Acuity (BCVA) and cyst volume in these subjects. A subset of participants with maculoschisis were offered standard of care treatment with carbonic anhydrase inhibitors (CAIs) and macular cyst volume was quantified with SD-OCT using a custom algorithm.

 

Results

 

45 participants with genetically confirmed XLRS with mutations in RS1, ranging in age from 7 to 67 years were enrolled in the longitudinal study with 17 subjects in the carbonic anhydrase sub-study. Baseline vision ranged from 0.10 to 1.40 LogMar visual acuity, one subject was count fingers@3.5 feet in their right eye. There was no observed relationship of visual acuity with age (r²=0.0007.) Individual responses to CAIs were variable with some patients showing dramatic decreases in cyst volume, some demonstrating little change, and others exhibiting an increase in cyst volume. The effect was dynamic with the greatest change occurring within the first month of treatment and then tapering off with time. As a group there was a reduction in cyst volume over time, which weakly correlated with an improvement in visual acuity (Table 1.)

 

Conclusions

 

Measuring cyst volume in patients with XLRS might be a useful outcome measure for structural changes in these patients, but the correlation to visual acuity is weak. Correlation to other modalities such as visual fields and multifocal ERG is underway.