The importance of genome sequencing: unraveling SSBP1 variant missed by exome sequencing.

BACKGROUND: Single-stranded DNA-binding protein 1 (SSBP1) plays an essential role in mitochondrial DNA (mtDNA) replication and maintenance, as well as development of retina. Here, we describe the clinical findings and genetic basis of a family with two members affected with bilateral optic atrophy. MATERIALS AND METHODS: Clinical data were retrospectively collected from an electronic medical record system. Genetic results were obtained using exome sequencing (ES) and genome sequencing (GS). RESULTS: A 36-year-old man presented with low vision in both eyes since early childhood, with a best-corrected visual acuity of 20/500 in both eyes. He exhibited generalized optic atrophy and diffuse retinal nerve fiber layer thinning without retinal degeneration in both eyes. The family history was consistent with autosomal dominant traits. ES was performed; however, we did not identify any pathogenic variants in the known dominant optic atrophy genes. Subsequently, GS was performed, and it revealed a novel heterozygous c.364A>G p.(Lys122Glu) variant in SSBP1. In silico prediction supported it as deleterious, while segregation analysis detected it in his affected mother and his unaffected sister. No foveopathy or retinal degeneration was observed in the patient's family members. CONCLUSIONS: We report a novel pathogenic heterozygous SSBP1 variant in a family with autosomal dominant optic atrophy and incomplete penetrance. Furthermore, we demonstrated that GS is advantageous over ES even for the discovery of coding variants, providing uniform coverage. Therefore, GS should be emphasized to improve the molecular diagnostic rate of inherited optic neuropathy.

Therapeutic prognostic factors associated with retinal detachment and visual outcomes in acute retinal necrosis.

BACKGROUND: Acute retinal necrosis (ARN) is a fulminant necrotizing vaso-occlusive retinitis associated with a high incidence of vision loss. Prognostic factors associated with the treatment of ARN have not been comprehensively identified. This study aimed to determine therapeutic prognostic factors associated with long-term clinical outcomes in eyes with ARN. METHODS: This retrospective cohort study included patients with ARN who were treated between 2005 and 2019 in two tertiary ophthalmology departments in Seoul, Korea. Multiple logistic regression analysis was performed to investigate prognostic factors associated with late-onset retinal detachment (RD) and vision loss (<20/200). RESULTS: Sixty-one eyes with ARN with an average follow-up of 63.5 months were included. Surgical intervention of vitrectomy (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.004-0.47) and intraoperative prophylactic laser use (OR, 0.14; 95% CI, 0.02-0.81) were independently associated with a decreased risk of late RD. The factors independently associated with an increased risk of vision loss were worse initial visual acuity (OR, 3.28; 95% CI, 1.50-7.21), zone 1 involvement of necrotic retinitis (OR, 10.84; 95% CI, 1.62-72.41), and late-onset RD (OR, 5.38; 95% CI, 1.92-31.54). CONCLUSION: Vitrectomy and/or prophylactic intraoperative laser treatment may be effective treatment options in preventing delayed RD associated with an increased risk of vision loss in eyes with ARN.

Comparison of long-term surgical outcomes for scleral-fixated versus retropupillary iris-claw intraocular lens.

BACKGROUND: To compare the clinical features and long-term treatment outcomes of patients undergoing secondary intraocular lens (IOL) surgery with scleral-fixated (SFIOL) versus retropupillary iris-claw IOL (RPICIOL). METHODS: Consecutive patients treated between June 2014 and December 2019 at two tertiary centres were retrospectively reviewed. The primary outcome was the best-corrected visual acuity (BCVA). Secondary outcomes included factors associated with significant corneal endothelial injury and postoperative redislocation. RESULTS: This study included 395 eyes undergoing surgery with SFIOL (237 eyes, 60%) or RPICIOL (158 eyes, 40%), with no differences in baseline BCVA (p = 0.76) or endothelial cell density (ECD) (p = 0.39). Compared with the SFIOL group, the RPICIOL group had faster visual recovery (postoperative month 1, 20/37 vs. 20/46, p = 0.005) sustained to over 36 months (p = 0.034), favourable absolute prediction errors (within 0.5D, 67.3% vs. 54.9%, p = 0.027), and shorter operation times (52.7 vs. 60.9 min, p = 0.015). There was no difference in ECD after 12 months (P = 0.282). Over a mean follow-up duration of 33 months (152 cases >3 years, 38.5%), the SFIOL group experienced more cases of tilted/decentred IOLs (14 vs. 1, p = 0.006), suture exposure (7 vs. 0, p = 0.045), and redislocation (17.7% vs. 10.1%, p < 0.001). Multivariable regression showed that a final BCVA below 20/40 was associated with SFIOL (P = 0.007), older age (p = 0.001), intraoperative complications (p = 0.002), past history of vitrectomy/glaucoma surgery or uveitis (p = 0.046), and surgically induced astigmatism >1D (p = 0.029). CONCLUSIONS: RPICIOL appears to be a safe and effective surgical option for secondary IOL surgery over a long-term follow-up, comparing favourably against conventional SFIOL.

The Effect of Adalimumab in Korean Patients with Refractory Noninfectious Uveitis.

We sought to analyze the efficacy of adalimumab in active noninfectious uveitis, and evaluate its efficacy and safety for the management of refractory noninfectious uveitis in Korean patients. A retrospective observational study was conducted. A total of 23 eyes of 14 Korean patients with noninfectious uveitis refractory to conventional treatment, including corticosteroid and immunosuppressive agents, were treated with adalimumab between December 2017 and February 2020. The primary outcomes were vitreous haziness grades, anterior chamber cell grades, and central macular thickness measured prior to injection and at 1, 3, 6, and 12 months after the first adalimumab injection. Among the 23 eyes, 14 eyes (60.9%) were diagnosed with panuveitis and 9 eyes (39.1%) with posterior uveitis [mean follow-up period: 22.3 months (7-27)]. The most common etiologic diagnoses requiring adalimumab injection were Behçet's disease (9 eyes, 39.1%), followed by undifferentiated inflammation (6 eyes, 26.1%), Vogt-Koyanagi-Harada disease (3 eyes, 13.0%), psoriasis (2 eyes, 8.7%), serpiginous chorioretinopathy (2 eyes, 8.7%), and systemic lupus erythematosus (1 eye, 4.3%). At the 1-year follow-up after the first injection, anterior chamber cell grade decreased from 0.5±0.4 to 0.3±0.4, and vitreous haziness grade decreased from 1.1±1.1 to 0.3±0.5 (p<0.05). Central macular thickness improved from 347.2±98.1 µm to 264.3±61.1 µm (p<0.05). Adalimumab injection in patients with refractory noninfectious uveitis decreased the anterior chamber cell grade, vitreous haziness grade, and central macular thickness with no severe side effect. Overall, adalimumab injection may, therefore, be an effective and relatively safe treatment modality for noninfectious uveitis in Korean patients.