Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial.

MERTK is an essential component of the signaling network that controls phagocytosis in retinal pigment epithelium (RPE), the loss of which results in photoreceptor degeneration. Previous proof-of-concept studies have demonstrated the efficacy of gene therapy using human MERTK (hMERTK) packaged into adeno-associated virus (AAV2) in treating RCS rats and mice with MERTK deficiency. The purpose of this study was to assess the safety of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK in subjects with MERTK-associated retinitis pigmentosa (RP). After a preclinical phase confirming the safety of the study vector in monkeys, six patients (aged 14 to 54, mean 33.3 years) with MERTK-related RP and baseline visual acuity (VA) ranging from 20/50 to <20/6400 were entered in a phase I open-label, dose-escalation trial. One eye of each patient (the worse-seeing eye in five subjects) received a submacular injection of the viral vector, first at a dose of 150 µl (5.96 × 10(10)vg; 2 patients) and then 450 µl (17.88 × 10(10)vg; 4 patients). Patients were followed daily for 10 days at 30, 60, 90, 180, 270, 365, 540, and 730 days post-injection. Collected data included (1) full ophthalmologic examination including best-corrected VA, intraocular pressure, color fundus photographs, macular spectral domain optical coherence tomography and full-field stimulus threshold test (FST) in both the study and fellow eyes; (2) systemic safety data including CBC, liver and kidney function tests, coagulation profiles, urine analysis, AAV antibody titers, peripheral blood PCR and ASR measurement; and (3) listing of ophthalmological or systemic adverse effects. All patients completed the 2-year follow-up. Subretinal injection of rAAV2-VMD2-hMERTK was associated with acceptable ocular and systemic safety profiles based on 2-year follow-up. None of the patients developed complications that could be attributed to the gene vector with certainty. Postoperatively, one patient developed filamentary keratitis, and two patients developed progressive cataract. Of these two patients, one also developed transient subfoveal fluid after the injection as well as monocular oscillopsia. Two patients developed a rise in AAV antibodies, but neither patient was positive for rAAV vector genomes via PCR. Three patients also displayed measurable improved visual acuity in the treated eye following surgery, although the improvement was lost by 2 years in two of these patients. Gene therapy for MERTK-related RP using careful subretinal injection of rAAV2-VMD2-hMERTK is not associated with major side effects and may result in clinical improvement in a subset of patients.

Effectiveness of 0.15% hylan A eye drops in ameliorating symptoms of severe dry eye patients in Saudi Arabia.

PURPOSE: The aim of the HYLAN A study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) in Saudi Arabia can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. METHODS: The HYLAN M study, a multicenter prospective randomized open-label study, was performed in 11 centers in eight countries. Patients suffering from severe DED were electronically randomized in two parallel arms. patients with symptoms of at least ocular surface disease index (OSDI) 33 and corneal fluorescein staining (CFS) of at least Oxford grade 3 were included . The patients in the control group continued with their individual optimized therapy as by the time of inclusion. The patients in the hylan A group replaced their individual lubricant eye drops by preservative-free eye drops containing 0.15% hylan A. The total OSDI scores as well as the OSDI subscores for pain and for visual disturbances of each patient at baseline, at 4 weeks, and at 8 weeks of treatment was used to analyse the improvement of symptoms. We focus and report the results obtained at the two study centers in Riyadh ,Saudi Arabia (King Khaled Eye Specialist Hospital and Riyadh Military Hospital). RESULTS: A total of 13 patients were included in the study. The majority of the study participants were middle aged (40-65 years). Overall, female patients accounted for 76.9% of all study participants. At the initiation of the study, both hylan A and control groups had relatively similar total OSDI scores together with pain and vision subscores. At 4-week follow-up, both groups demonstrated a noticeable decrease in all study variables. Nevertheless, the OSDI scores improved significantly in the group of patients treated with hylan A eye drops at 8 weeks, whereas the scores increased in the control group. CONCLUSION: Saudi Arabia has a very high prevalence of patients with severe dry eye disease. Ethnicity, climate, and a high incidence of diabetes mellitus may contribute to this situation. Lubricant eye drops frequently do not provide adequate relief from ocular pain and instable vision in severe chronic ocular surface disease. High molecular weight hyaluronan (HMWHA) eye drops provide superior relief of symptoms of patients suffering from severe DED. This includes ocular pain as well as unstable vision.

Refractive error of Saudi children enrolled in primary school and kindergarten measured with a spot screener.

AIMS: To evaluate the refractive status of young Saudi schoolchildren with a "Spot Screener." SUBJECTS AND METHODS: This cross-sectional study was conducted from January to July 2016 in Riyadh, Saudi Arabia. Children of kindergarten (3-5 years) and grades 1 and 2 (6-7 years) were screened for refractive error (RE) using the handheld Spot Screener (Welch Allyn, Skaneateles Falls, NY, USA). Data were collected on age, gender, and spectacle use. The pass/fail notation from the Spot Screener and the RE were documented. Children with a "fail" were re-tested with an autorefractor (AR). The rate of agreement was evaluated for the spherical equivalent (SE) from the Spot Screener and AR. RESULTS: We examined 300 schoolchildren and 114 preschool children. The prevalence of RE was 22% in schoolchildren and 25% in preschoolers. There were 183 (61%) hyperopes, 110 (36.7%) myopes, 6 (2%) emmetropes, and 29 (9.7%) astigmats (>2 D cylinder) in grade 1 and 2. There were 85 (74.6%) hyperopes, 22 (19.3%) myopes, 7 (6.1%) emmetropes, and 10 (8.8%) astigmats among preschoolers. The SE differed between the AR and the Spot Screener in 17 (28%) children of 61 failed Spot Screener tests. Accommodation (9, 53%) and high astigmatism (8, 47%) were the main underlying causes of the difference. The Spot Screener could identify RE for the first time in 51 (17%) schoolchildren and 26 (22%) preschoolers. End-users suggested that Spot Screener was child-friendly and quick to test RE. CONCLUSIONS: The Spot Screener could be a good initial screening tool for RE in young schoolchildren.