Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Keratoconus in Asians: demographics, clinical characteristics and visual function in a hospital-based population.

BACKGROUND: To describe the demographics, clinical characteristics and visual function of Asian patients with keratoconus managed in a tertiary eye centre. DESIGN: Prospective cross-sectional study. PARTICIPANTS: 116 patients with clinically evident or suspected keratoconus (on videokeratography) recruited over 11 months. METHODS: A standardised interview, full ophthalmic examination, refraction and corneal topography were performed. Visual function was assessed with the VF-14 questionnaire. MAIN OUTCOME MEASURES: Demographics, clinical characteristics and visual function. RESULTS: Mean age of our patients was 29.5 ± 9.40 years on enrolment, 62.9% were male, and the ethnic distribution was 60.3% Chinese, 13.8% Malays and 9.5% Indians. Clinically evident keratoconus was present bilaterally in 65 patients (56.0%) and unilateral keratoconus in five patients (4.3%). Five patients (4.3%) had a family history of keratoconus. The majority of patients were managed with contact lenses (60.8%) or glasses (24.5%). Eye rubbing was common (68%) as were asthma (26.3%) and eczema (18.4%). Conical protrusion was the commonest sign (75.3%). The mean cylinder was higher in keratoconus eyes compared with keratoconus suspect eyes (-4.01 vs. -1.27, P < 0.001), and best-corrected visual acuity was poorer (0.19 vs. 0.05, P < 0.001). Unaided visual acuity was significantly worse with increasing age (P = 0.016). On the VF-14, 32% scored 90 or less (out of 100), reflecting difficulties with vision-related daily activities. CONCLUSIONS: Our Asian patients with keratoconus had similar demographic and clinical characteristics to patients in Western populations. Even with apparently good visual acuity, some patients still experience substantial impairment in vision-related activities.