Purpose: The first ocular gene augmentation therapy, voretigene neparvovec (Luxturna®), has been approved for clinical use in an increasing number of countries (FDA USA 2017, EMA Europe 2018, MoHAP United Arab Emirates 2019, SFDA Saudi Arabia 2019, Swiss Medic Switzerland 2020, TGA Australia 2020, BFR Brazil 2020). Among the EVICR.net clinical centers, we conducted the first multinational survey to understand distribution, diagnostic work-up, and management of inherited retinal degenerations (IRD) cases in Europe with a special focus on RPE65 mutation-associated IRDs. Methods: An electronic survey questionnaire including 35 questions specifically addressing RPE65 mutation-associated IRDs was developed and sent to the 101 EVICR.net clinical centers. Results: The overall response rate was 49%. Forty-two centers see IRD patients, and 22/42 follow patients with confirmed biallelic RPE65 mutations. Fifteen of the 22 centers (68%) and 3/22 (14%) follow 1-5 and 6-10 patients with homozygous RPE65 mutations, respectively. Additionally, 15/22 (68%) and 3/22 (14%) follow 1-5 and >20 patients with compound heterozygous RPE65 mutations, respectively. Fifty-nine percent of mutations were ACMG Class 4 and 5 (at least one allele), 82.8% reported previously and 17.2% novel. Referral diagnoses (mean per center) were Leber Congenital Amaurosis (38.2%), Early-onset severe retinal degeneration (16.8%), Rod-Cone-Dystrophy/Retinitis pigmentosa (RP) (28.1%), and unclassified visual impairment (17.0%). Twenty-five percent of the centers changed the referral diagnosis in > 47.5% of cases; 32% follow a specific referral process for RPE65 mutation-associated IRD patients. Annual follow-up visits are done in 55% of the centers, and biannual visits in 23%. In 32%, other centers also follow the patients. Kinetic perimetry is done in 82%, static perimetry in 45%, microperimetry in 18% of the centers. Full-field Light Stimulus Threshold Testing (FST) with blue and red stimuli to quantify rod and cone function is used in 6/22 centers (27%). A mobility course is available in one center (5%). Conclusion: This first multinational survey on management of patients with RPE65 mutationassociated IRDs in Europe shows that about half of the responding EVICR.net centers have such patients under care. There is heterogeneity in diagnoses and management practices. At the start of clinical practice experience with voretigene neparvovec, these data provide a useful baseline and highlight the need for consensus/guidelines to inform standard of care in this new era of gene therapy.
|Publication status||E-pub ahead of print - 8 Mar 2021|