Study finds MLSDT reliable in advanced retinitis pigmentosa

A newly published observational study suggests that the Multi-luminance Shape Discrimination Test (MLSDT) may offer a reliable and clinically meaningful way to assess functional vision in patients with advanced retinitis pigmentosa, a population in whom conventional visual acuity testing often fails to capture real-world visual performance. The findings, published in Documenta Ophthalmologica, come as interest grows in alternative endpoints for inherited retinal diseases, particularly in the context of emerging therapies targeting patients with profound photoreceptor loss.

The prospective observational study enrolled 35 participants, including 25 individuals with severe vision loss due to retinitis pigmentosa, defined as visual acuity ≥1.6 LogMAR, and 10 participants with normal vision. The MLSDT evaluates functional vision by requiring participants to identify and grasp objects of varying shapes under different luminance conditions, generating quantifiable performance scores.

Test–retest reliability for the MLSDT exceeded 0.50, meeting commonly accepted thresholds for moderate reliability in early-stage validation studies. Investigators also reported strong correlations between MLSDT performance and standard visual acuity measures, with correlation coefficients greater than −0.7. A clinically interpretable relationship was observed: a 0.3 LogMAR difference in visual acuity corresponded to an approximately 2-level difference in MLSDT score.

In addition, MLSDT scores demonstrated moderate to strong correlations with visual field measures and patient-reported outcomes, supporting convergent validity. Performance improved with higher luminance levels, underscoring the test’s ability to capture functional vision changes under varying environmental conditions.

Retinitis pigmentosa comprises a heterogeneous group of inherited retinal degenerations characterized by progressive photoreceptor loss, leading to nyctalopia, visual field constriction, and eventual central vision impairment. While best-corrected visual acuity remains a regulatory standard endpoint, it may remain relatively preserved until late disease stages and does not fully reflect mobility, object recognition, or daily visual function.

The MLSDT has also been incorporated as a secondary endpoint in the phase 2b/3 RESTORE trial evaluating MCO-010, an investigational optogenetic therapy designed to confer light sensitivity to bipolar retinal cells. The sponsor has reported improvements of at least two luminance levels in MLSDT performance among treated patients at 52 weeks.

The current study provides preliminary evidence supporting the reliability and validity of MLSDT as a functional vision endpoint. However, the sample size was small and the study design was observational, limiting generalizability and precluding assessment of responsiveness to treatment over time. Further validation in larger, multicenter cohorts is needed.