Purpose: The aim of this study was to describe the genetic and clinical characteristics of Chinese patients with autosomal recessive bestrophinopathy (ARB). Methods: This study presents a retrospective observational case series. Twentyone ARB patients and 25 clinically healthy family members were recruited. The coding regions and adjacent intronic regions of BEST1 were analysed via Sanger sequencing. Clinical examinations, including ultrasound biomicroscopy, A-scan, optical coherence tomography, fundus autofluorescence, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and visual electrophysiology, were reviewed. Results: Six novel mutations (c.380C>T, p.T127M; c.397A>G, p.N133D; c.500A>G, p.E167G; c.817G>A, p.V273M; c.174_176del, p.Q58del; and c.950_955del, p.S318_L319) and 8 previously reported mutations were identified. The p.R255W mutation had the highest frequency in our cohort. Twenty patients had serous retinal detachment with multifocal subretinal vitelliform deposits in the posterior poles. One patient exhibited chorioretinal atrophy. FFA revealed peripheral vascular leakage in 10 patients, and ICGA revealed hyperfluorescent spots in 8 patients. Visual electrophysiology was abnormal in all patients. Fifteen patients with angle closure (AC) or angle-closure glaucoma (ACG) had shallower anterior chambers and shorter axial lengths than the patients with open angle, contributing to their risk of developing AC/ACG. One patient developed AC during the 7-year follow-up period. The misdiagnosis and missed rates were 35.3% and 58.8%, respectively. Conclusion: The six novel mutations and high frequency of p.R255W suggest ethnical differences in the BEST1 mutation spectrum among Chinese patients. BEST1 gene screening and detailed clinical examinations help establishing a diagnosis of ARB. Clinical evaluations of the risk of developing AC/ACG are recommended for ARB patients.

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Background/AimsThis study aims to assess the contribution of biallelic CPAMD8 variants in patients with different forms of glaucoma, especially primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), based on a systematic analysis of exome sequencing (ES).MethodsPotentially pathogenic CPAMD8 variants were selected from the ES data of 5307 subjects with various eye conditions through multiple bioinformatics analyses. Of the 5307 subjects, 1221 probands had different forms of primary glaucoma. The genotype–phenotype correlation was assessed by a systematic review of biallelic CPAMD8 variants that including our data and data from the literature. The expression profile of CPAMD8 in human tissues was determined at the mRNA and protein levels.ResultsBiallelic CPAMD8 variants, including one frameshift and six missense variants, were exclusively present and significantly enriched in patients with glaucoma (one with juvenile open-angle glaucoma (JOAG), two with POAG and two with PACG) compared with none of the 4086 probands with other eye conditions in this cohort (p=4.1E-07). The effect of variants in these patients is relatively mild compared with that reported in patients with anterior segment dysgenesis or primary congenital glaucoma. CPAMD8 mRNA was highly expressed in the optic nerve, ciliary body, retina and iris, whereas the CPAMD8 protein was mainly detected in the nonpigmented epithelium of the iris and ciliary process, determined by immunohistochemistry.ConclusionsThe data from this study not only provide further evidence to support the association of biallelic CPAMD8 variants with JOAG but also suggest that biallelic CPAMD8 variants might be associated with POAG and PACG.

IntroductionTrabeculotomy and combined trabeculotomy–trabeculectomy (CTT) are major surgical options for primary congenital glaucoma (PCG). However, it is unclear which of these two surgical procedures should be recommended as the optimum first-line treatment for PCG. This trial aims to determine whether the outcomes of trabeculotomy are non-inferior to those of CTT in moderate PCG with a horizontal corneal diameter (HCD) of 12–14 mm.Methods and analysisThis is a 3-year, non-inferiority, prospective, randomised controlled trial. We plan to recruite 248 participants (aged ≤3 years) with PCG with an HCD of 12–14 mm from the Department of Glaucoma, Zhongshan Ophthalmic Center, Guangzhou, China. One eye per participant will be randomly (1:1) assigned to receive trabeculotomy or CTT. The primary outcome is the 3-year postoperative success rate in lowering intraocular pressure (IOP), and the secondary clinical outcomes will include IOP reduction, visual acuity, HCD, central corneal thickness, axial length, cup–disc ratio, refractive error and postoperative complications. Data will be analysed by the intention-to-treat principle.Ethical approval and disseminationThe study protocol has been approved by the ethics committee of Zhongshan Ophthalmic Center (2014MEKY023) and the ‘5010 Plan’ evaluation committee at Sun Yat-Sen University, Guangzhou, China. The results will be disseminated in international academic meetings and published in peer-reviewed journals.Trial registration numberChinese Clinical Trial Registry, ChiCTR-IOR-14005588; Date registered: 20 November 2014.

Purpose: To compare the choroidal vasculature characteristics by using the choroidal vascularity index (CVI) in eyes with malignant glaucoma (MG), fellow eyes with non-MG, and eyes with uncomplicated primary angle-closure glaucoma (PACG) after trabeculectomy by spectral-domain optical coherence tomography (SD-OCT).Methods: This case–control study included 53 patients diagnosed with MG after trabeculectomy. Eyes with MG (n = 53) and the fellow eyes with non-MG (n = 50) were included. Eyes with PACG without MG after trabeculectomy (n = 60) were also enrolled as controls. The choroidal parameters, including CVI and the subfoveal choroidal thickness (SFCT), were measured by using SD-OCT images.Results: Eyes with MG and the fellow eyes showed a significantly lower CVI than eyes with PACG controls (p < 0.001). After adjusting for age, sex, axial length (AL), and intraocular pressure (IOP), eyes with the greater CVI [odds ratio (OR), 0.44] were significantly related to MG. The area under the receiver operating characteristic curve of the CVI was greater than that of the SFCT in the diagnosis of MG (0.911 vs. 0.840, p = 0.034).Conclusion: Eyes with MG showed a significantly lower macular CVI than eyes with PACG controls. A higher macular CVI was an associated factor of eyes with MG. The CVI serves as a more stable and sensitive indicator for MG than the SFCT in this group of patients with PACG.