Ocular Biomarkers of Riboflavin Transporter Deficiency.

BACKGROUND: To describe the clinical presentation with a focus on ocular manifestations and response to riboflavin supplementation of 3 patients with riboflavin transporter deficiency (RTD) caused by mutations in SLC52A2 ( SLC52A2- RTD). METHODS: This is a retrospective review of records of 3 children (aged 18, n = 2 and age = 8, n = 1) with SLC52A2- RTD. Patients underwent comprehensive ophthalmic evaluations including color vision testing, pattern visual-evoked potentials (pVEPs, 1 patient) and spectral domain optical coherence tomography (SD-OCT) imaging. Patients received riboflavin supplements from the time of the molecular diagnosis of RTD. RESULTS: Two unrelated 18-year-old patients with SLC52A2- RTD had a symptomatic onset with sensorineural hearing loss and auditory neuropathy/dys-synchrony since age 3 and 11, respectively. On examination 7 years after symptomatic onset, they showed subnormal visual acuities (20/30 and 20/60, both eyes, respectively), preserved color vision, and a thin but measurable retinal ganglion cell layer (GCL) and nerve fiber (RNFL). The inner and outer nuclear layers were normal. The asymptomatic SLC52A2- positive brother of one of these patients started riboflavin supplementation right after the molecular diagnosis and had normal vision and SD-OCTs 7 years later. Onset of riboflavin supplementation in one of the 2 symptomatic cases resulted in acute improvement of the pattern visual-evoked potential and vision. CONCLUSIONS: Retinal ganglion cells and their axons are uniquely susceptible to RTD compared with other highly energy-dependent retinal neurons, such as photoreceptors, raising the possibility for alternative mechanisms of disease or protection. Riboflavin supplementation results in acute functional improvement of vision and long-term preservation of GCL and RNFL if initiated early.

Effectiveness of long-term infliximab use and impact of treatment adherence on disease control in refractory, non-infectious pediatric uveitis.

BACKGROUND: Refractory non-infectious uveitis is a serious condition that leads to ocular complications and vision loss and requires effective systemic treatment to control disease. The effectiveness of long-term infliximab [IFX] in refractory non-infectious childhood uveitis and the impact of treatment adherence on disease control were evaluated. METHODS: Retrospective, single-center study between December 2002 and April 2016 of 27 children with refractory non-infectious uveitis [17 with juvenile idiopathic arthritis, JIA] treated with long-term IFX [9+ months]. Disease activity was assessed prior to and while on IFX using the Standardization of Uveitis Nomenclature [SUN]. Number of visits per year with active uveitis was analyzed by repeated measures logistic regression analysis from 2 years prior to IFX initiation or from onset of uveitis until most recent visit on IFX. Incomplete treatment adherence was assessed for each visit and defined as any deviance in corticosteroid use, prescribed infusion frequency, and/or follow-up examination frequency. RESULTS: Primary outcomes were sustained uveitic and systemic disease control prior to and during IFX treatment and the impact of incomplete adherence on uveitic disease control while on IFX. Secondary outcomes included corticosteroid and glaucoma medication requirement, ocular complications and need for surgical intervention. Mean age at IFX initiation was 10.4 ± 4.5 years; initial mean dose was 6.6 ± 2.2 mg/kg [and given at weeks 0, 2, 4 and q4 weeks thereafter for 93%]. Median duration on IFX was 35 [range 9-128] months. Prior to IFX, 14/27 patients had failed adalimumab ± methotrexate [MTX]; 21/27 failed MTX. IFX led to uveitis control in 89% and arthritis control in 76% (13/17). The odds ratio of having controlled disease after IFX was 4.1 (2.6, 6.4) compared to pre-treatment visits. Topical corticosteroids and glaucoma medications were statistically decreased (p = 0.007 right eye [OD], 0.003 left eye [OS] and p = 0.001 OD, p = 0.028 OS respectively). Incomplete adherence to treatment showed 10.3 times greater odds (7.1, 15.0) of having disease activity than full adherence. CONCLUSIONS: This study adds significantly to the IFX literature by documenting outstanding uveitis control with long-term IFX treatment in non-infectious pediatric uveitis patients. Higher dosage and shorter interval were utilized without adverse effects. Importantly, this is the first study, to our knowledge, to document the significant impact of treatment adherence on uveitis control.