Abstract
Purpose :
LORD is an autosomal dominant retinal degeneration resulting from heterozygous mutations in the C1QTNF5 gene. LORD primarily affects retinal pigment epithelium, resulting in a characteristic scalloped atrophy. We aimed to characterise the natural history of LORD to assess the suitability of fundus autofluorescence (FAF) for disease monitoring.
Methods :
Patients with a confirmed molecular diagnosis of C1QTNF5-LORD were retrospectively identified from Moorfields Eye Hospital (UK). Short-wavelength FAF and best-corrected visual acuity (BCVA) were collected. Area of atrophy (AA) was manually drawn in FAF images by one experienced clinician. AA within 6mm and 14mm diameter circles centred on the fovea were extracted at all visits. Age-related changes of clinical parameters were tested with linear mixed models. AA measures were square root transformed.
Results :
Sixteen patients from 10 unrelated families were identified. Most patients (n=12, 75%) had the founder missense mutation c.489C>G (p.Ser163Arg). There were 26 eyes from 13 patients with usable FAF (median baseline age: 65.2, IQR: 58.5-66.2), and 23 had 2 or more visits (median follow-up: 4 years, IQR: 1.5-6.1). At baseline, median AA was 71.1mm2 (IQR: 0-106.2) and 19.7mm2 (IQR: 0-27.6) within 14mm and 6mm diameter circles, and median BCVA was 0.35 LogMAR (IQR: 0-2.6). FAF atrophic changes were absent until age 50, and started to progress rapidly from age 53.9 (95%CI: 45.9-61.8) and age 56.3 (95%CI: 52.5-60.1), for 14mm and 6mm diameter circles, respectively. Progression rates for square root AA were 0.53mm/year (95%CI: 0.45-0.62, R2=0.774, p<0.0001) and 0.24mm/year (95%CI: 0.18-0.29, R2=0.657, p<0.0001). Square root AA showed strong inter-ocular correlation (r: 0.90-0.97, both p<0.0001) but poor correlation with BCVA (r: 0.30-0.34, both p<0.05). Findings from patients with early FAF changes at baseline showed atrophy to often appear first in the temporal retina, and then progress to the posterior pole.
Conclusions :
LORD patients remained asymptomatic until age 50, and symptom onset was consistent with initial FAF atrophy. FAF atrophic changes often originate temporally. AA measures also capturing temporal retina may be preferable, as they are capable of detecting earlier changes and monitoring patients for a longer time. AA may be a suitable outcome measure in future clinical trials.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.