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.

Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents.

Sympathetic ophthalmia (SO) is a bilateral diffuse granulomatous intraocular inflammation that occurs in most cases within days or months after surgery or penetrating trauma to one eye. The incidence of SO ranges from 0.2 to 0.5% after penetrating ocular injuries and 0.01% after intraocular surgery. Vitreoretinal surgery and cyclodestructive procedures are considered risk factors. The time from ocular injury to onset of SO varies greatly, ranging from a few days to decades, with 80% of the cases occurring within 3 months after injury to the exciting eye and 90% within 1 year. The diagnosis is based on clinical findings rather than on serological testing or pathological studies. It presents as a bilateral diffuse uveitis. Patients report an insidious onset of blurry vision, pain, epiphora, and photophobia in the sympathizing, non-injured eye. Classically this is accompanied by conjunctival injection and a granulomatous anterior chamber reaction with mutton-fat keratic precipitates (KPs) on the corneal endothelium. In the posterior segment, the extent of inflammation can vary. Systemic corticosteroids are the first line therapy for SO. If patients are non-responsive to steroid therapy or have clinically significant side effects, cyclosporine, azathioprine or other immunosuppressive agents can be used for long-term immunomodulatory therapy.

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; for the FAST Research Group IMPORTANCE Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. OBJECTIVE To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. DESIGN, SETTING, AND PARTICIPANTS The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the

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This study provides a comprehensive description of choroidal involvement in TBU. Patients with SLC and ampiginous choroiditis may have better clinical outcomes.