RPE65-related retinal dystrophy: Mutational and phenotypic spectrum in 45 affected patients.

INTRODUCTION: Biallelic pathogenic RPE65 variants are related to a spectrum of clinically overlapping inherited retinal dystrophies (IRD). Most affected individuals progress to severe disease, with 50% of patients becoming legally blind by 20 years of age. Deeper knowledge of the mutational spectrum and the phenotype-genotype correlation in RPE65-related IRD is needed. PATIENTS AND METHODS: Forty-five affected subjects from 27 unrelated families with a clinical diagnosis of RPE65-related IRD were included. Clinical evaluation consisted of self-reported ophthalmological history and objective ophthalmological examination. Patients' genotype was classified according to variant class (truncating or missense) or to variant location at different protein domains. The main phenotypic outcome measure was age at onset (AAO) of symptomatic disease and a Kaplan-Meier analysis of disease symptom event-free survival was performed. RESULTS: Twenty-nine different RPE65 variants were identified in our cohort, 7 of them novel. Patients carrying two missense alleles showed a later disease onset than those with 1 or 2 truncating variants (log-rank test p <0.05). While 60% of patients carrying a missense/missense genotype presented symptoms before or during the first year of life, almost all patients with at least 1 truncating allele (91%) had an AAO ≤1 year (p <0.05). CONCLUSION: Our findings suggest an association between the type of RPE65 variant carried and AAO. These findings provide useful data on RPE65-associated IRD phenotypes and may help improve clinical and therapeutic management of these patients.

Spectrum of conjunctival tumours in a Spanish series: A review of 462 cases.

INTRODUCTION: To report the spectrum and frequency of conjunctiva tumours in an ocular oncology unit analysing the clinical profile of benign, precancerous and malignant conjunctival lesions. METHODS: A retrospective case series of 462 consecutive patients diagnosed at the Ocular Oncology Unit of the University Hospital of Valladolid from 1992 to 2017. RESULTS: Among 462 consecutive patients, the tumour was classified as melanocytic in 252 (54.5%) and non-melanocytic in 210 (45.5). Two hundred forty-eight males (mean age 51.63 (SD = 23.20)) and 214 females (mean age 48.27 (SD = 21.77)) were included. Mean patient age at diagnosis was 50.07 years (range = 1-92 years). The majority of tumours were benign (n = 307 (66.5%)) followed by precancerous (n = 103 (22.3%)) and finally by malignant ones (n = 52 (11.3%)). Benign lesions were predominantly found in younger individuals rather than premalignant (p < 0.05) and malignant ones (p < 0.05). Most of the melanocytic lesions were benign (88.5%), most epithelial ones were precancerous (61.4%) and most lymphoid lesions were malignant (56.3%). Tumours involving one or four quadrants of the ocular surface usually were benign, unlike tumours involving three quadrants that were malignant (16 (48.5%) p < 0.05). The majority of benign lesions were detected on females (n = 163 (53.1%)) by routine examination (n = 178 (86.4%)). However, main complaint in malignant tumours was the growth of the lesion (n = 39 (76.5%)). CONCLUSION: Most of the conjunctival tumours were melanocytic, mostly benign, closely followed by those of epithelial origin, with a predominance of precancerous lesions. Melanocytic, epithelial and lymphoid tumours accounted for over 90% of cases. A trend was identified with benign lesions being found in younger female patients on routine examination.