Purpose: The purpose of this study was to describe the mutational landscape, clinical characteristics, and natural history of PCARE-associated retinopathy.
Methods: Retrospective cohort study including 28 patients (56 eyes) affected by an inherited retinal disease related to PCARE variants. The main outcome measures were best-corrected visual acuity (BCVA) and degree of vision impairment, kinetic visual field (KVF) area delimited with the V4e target, area of macular atrophy (MA) with definitely decreased autofluorescence (DDAF) on short-wavelength autofluorescence, total macular volume (TMV) and foveal sparing (FS) on optical coherence tomography.
Results: The median age at first examination was 40.7 years (Interquartile range [IQR] = 28.8-49.6), whereas the median follow-up time was 5.7 years (IQR = 3.6-7.1). The retinal phenotype was consistent with a severe generalized photoreceptor dystrophy with MA in all patients. DDAF lesions were observed in 85% of the eyes. Loss of FS (occurring at a median age of 45 years) was associated with a mean BCVA (logMAR) worsening by 1.1 (95% confidence interval [CI] = 0.6 to 1.5, P < 0.001). Low vision and blindness in the better-seeing eye occurred at median ages of 50 and 57 years, respectively. Longitudinal analysis revealed the following mean slopes of change: BCVA (logMAR) worsened by 0.06/year (95% CI = 0.03 to 0.09, P < 0.001), KVF area decreased by -23%/year (95% CI = -35% to -12%, P = 0.004), square root-transformed DDAF area expanded by 0.20 mm/year (95% CI = 0.16 to 0.23, P < 0.001), and TMV declined by -0.015 mm3/year (95% CI = -0.023 to -0.007, P = 0.003). Eleven novel PCARE variants were identified.
Conclusions: PCARE-associated retinopathy is a severe generalized photoreceptor dystrophy with MA. Although visual field loss occurs early, useful central vision is often retained into late adulthood because of FS. Based on the age of onset of legal blindness, the optimal therapeutic window appears to be before the fifth decade of life.