Kwak JJ, et al. Yonsei Med J. 2022 Jul;63(7):701-705. https://doi.org/10.3349/ymj.2022.63.7.701

Autosomal recessive bestrophinopathy (ARB) is a rare subtype of bestrophinopathy caused by biallelic mutations of the BEST1 gene. ARB is characterized by multifocal subretinal deposits accompanied by macular edema or subretinal fluid, hyperopia, co-existing narrow angle, and a marked decrease in electrooculogram. However, little is known about the genetic variants and specific clinical features of ARB. This is an observational case series of patients with a clinical and genetic diagnosis of ARB who underwent multimodal imaging. We describe ten patients from nine unrelated families with six known variants and three novel missense variants: c.236C→T, p.(Ser79Phe); C.452C→T, p.(Leu151Pro); and c.650C→T, p.(Trp217Met). The most common variant was c.584C→T, p.(Ala195Val), observed in six patients, without correlation to the severity of the phenotype. All patients manifested bilateral multifocal subretinal deposits and subretinal fluid throughout the follow-up period, while intraretinal fluid was found in approximately half of the eyes. The extent or chronicity of the fluid collection did not correlate with visual acuity. Angle-closure glaucoma was present in five eyes. Three patients had a genetically confirmed family history of ARB, and one patient had a clinically suspected family history. This study reveals novel mutations in the BEST1 gene and adds to the spectrum of clinical presentations of ARB.

Background/Objectives: Vogt–Koyanagi–Harada (VKH) disease is a bilateral granulomatous panuveitis that can progress to a chronic, relapsing phase. Patients refractory or intolerant to systemic corticosteroids and conventional immunomodulatory therapy pose a major therapeutic challenge, as persistent inflammation can lead to cumulative ocular damage and permanent vision loss. This study assessed the efficacy of tumor necrosis factor-α (TNF-α) inhibitor adalimumab in chronic recurrent VKH disease. Methods: We retrospectively reviewed 16 eyes from 8 patients with chronic recurrent VKH disease who had persistent inflammation despite treatment with corticosteroids and conventional immunomodulatory therapy, and subsequently received adalimumab. Primary outcomes were changes in subfoveal choroidal thickness (SFCT) and systemic corticosteroid dose reduction. Secondary outcomes included visual acuity, inflammatory parameters (anterior chamber cell, flare, and vitreous haze), and central macular thickness (CMT). All outcomes were compared between baseline and 6 months after adalimumab initiation using the Wilcoxon signed-rank test. Results: Mean patient age was 47.6 years and mean follow-up was 31.8 months. SFCT decreased from 326.7 ± 129.1 µm to 231.6 ± 72.9 µm at 6 months (p < 0.001). Systemic steroid dose decreased from 14.7 ± 14.0 mg to 4.1 ± 3.8 mg (p = 0.027). Mean annualized relapse rate decreased from 3.61 to 0.08 episodes/year (p = 0.012). Anterior chamber cell grade decreased from 0.81 ± 0.66 to 0.09 ± 0.20 (p < 0.001). Visual acuity, flare, vitreous haze, and CMT showed no significant change. No serious adverse events occurred. Conclusions: TNF-α inhibition with adalimumab appears effective as steroid-sparing therapy for controlling recurrent inflammation and reducing steroid dependence in patients with chronic recurrent VKH disease refractory to conventional treatment.