Abstract
Purpose :
L-ORD is an autosomal dominantly inherited condition that causes devasting visual loss and currently without a cure. It is caused by variants in C1QTNF5, a member of the complement family that encodes a membrane-bound protein secreted by the RPE. Pathogenic mutations lead to accumulation of sub RPE deposits, which result in overlying photoreceptor dysfunction and subsequent nightblindness, visual field constriction and eventual macular pathology. Identification of robust clinical markers for early disease is required to maximise the therapeutic window for emerging treatments.
Methods :
20 LORD patients (mean age 63 years , range 34-75 years) harbouring the founder variant in C1QTNF5 (c.489C>G) were examined clinically. They underwent best-corrected distance visual acuity, low luminance visual acuity (LLVA) testing with a 2 log unit neutral density filter using Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Pelli-Robson contrast sensitivity, Bailey Lovie near acuity chart, mesopic and scotopic microperimetry were also performed (S-MAIA, iCare). Vision related quality of life were assessed by visual function questionnaires including VFQ-25/39 and low luminance questionnaire.
Results :
A low luminance deficit (LLD; ie a difference between standard VA and LLVA of greater than 13 letters) was observed early in LORD disease. Further, a LLD correlated with a reduction in VFQ/LLQ scores. Microperimetry testing found that mean retinal sensitivity loss correlated with an LLD (scotopic v mesopic).
Conclusions :
Our results show that LLDs and are a robust marker of early LORD disease. Further, LORD patients score poorly on VFQs in more advanced stages resulting in poor vision-related quality of life. These tests correlate with loss of mean retinal sensitivity on microperimetry testing. LLVA and VFQs, therefore, offer a cheap, readily available clinical assessment to identify early functional decline in LORD and, therefore, the earliest possible window for any emerging therapies. In addition they serve as valuable, tools in screening and monitoring for progression.
Funding:
LifeArc Philanthropic Fund "Towards a therapy for L-ORD"
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.