Rapid resolution of severe exudation in uveal effusion syndrome with anti-vascular endothelial growth factor alone in a case of bilateral nanophthalmos: a case report.

BACKGROUND: Uveal effusion syndrome is a rare disease characterized by exudative detachments of the choroid, ciliary body, and retina. Various surgical procedures and nonsurgical strategies have been described to treat uveal effusion syndrome with limited success. The treatment for uveal effusion syndrome remains a serious challenge for clinicians. To the best of our knowledge, no previous report has described a severe uveal effusion syndrome patient with nanophthalmos treated by using an anti-vascular endothelial growth factor agent alone. We report here one such case with unexpected positive results. CASE PRESENTATION: A 30-year-old Chinese male patient presented with painless vision loss in both eyes that had persisted for 2 months. Examination of the right eye revealed a best corrected visual acuity of 0.03; the best corrected visual acuity of the left eye was finger count/20 cm. The intraocular pressure was normal on both eyes. A-scan revealed an right eye axial length of 15.88 mm and a left eye axial length of 16.21 mm. In the right eye, half of the peripheral choroid and nearly three-fourths of the retina were detached. The left fundus was not visible because of the total retinal detachment located just behind the lens, which could be clearly observed directly with a slit lamp. Considering all the possibilities and available treatments as well as the patient's intentions after discussion, we first administered an intravitreal injection of ranibizumab 0.5 ml into both eyes. The patient's visual perception improved 3 days after the injection. One month later, most of the effusion under the choroid and retina was absorbed. Visual acuity improved from finger count to 0.05 in both eyes, and vision quality was remarkably improved. Encouraged by this good result, the patient opted to undergo a second injection 1 month later. Choroidal and retinal detachment completely vanished 30 days after the second injection. CONCLUSIONS: Using an anti-vascular endothelial growth factor agent alone may be a potentially effective and safe method for managing some types of uveal effusion syndrome, such as in nanophthalmos. The injection may be administered before considering more aggressive procedures in some uveal effusion syndrome patients.

Observation of retinal neovascularization using optical coherence tomography angiography after panretinal photocoagulation for proliferative diabetic retinopathy.

BACKGROUND: To describe the longitudinal changes in retinal neovascularization elsewhere (NVE) as observed on optical coherence tomography angiography (OCTA) in proliferative diabetic retinopathy (PDR) treated by panretinal photocoagulation (PRP). METHODS: Each patient included in this prospective clinical study was newly diagnosed with PDR and NVE confirmed by both fundus fluorescein angiography (FFA) and OCTA. They received four sessions of PRP using a multiwavelength laser. Best-corrected visual acuity (BCVA) and OCTA images of the NVE were obtained before each PRP session and at 1 month, 3 months, and 6 months after the PRP treatment. Generalized estimating equations (GEE) was used to investigate the differences between the BCVA and NVE areas before and after PRP. RESULTS: Thirty-two eyes of 32 patients with a mean age of 50.56 ± 7.05 years were included. We found a statistically significant reduction in the NVE area at all time points compared with the baseline except at 6 months (all P < 0.05). Further analysis demonstrated no statistically significant change in the NVE area between two adjacent timepoints except from baseline to post-1st PRP (P < 0.05). BCVA at 3 months showed a statistically significant improvement compared with baseline (P < 0.05), but no significant changes in BCVA were observed during the other visits. CONCLUSIONS: We found an overall regression in the NVE area following PRP starting as early as 1 week after the 1st session and lasting up to 3 months. OCTA provides quantitative information on vascular changes and could be a practical method for the longitudinal evaluation of neovascularization.

Two different treatment regimens of ranibizumab 0.5 mg for neovascular age-related macular degeneration with or without polypoidal choroidal vasculopathy in Chinese patients: results from the Phase IV, randomized, DRAGON study.

PURPOSE: To evaluate the efficacy and safety of monthly and pro re nata (PRN, guided by visual acuity stabilization and disease activity criteria) ranibizumab regimens in Chinese patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This double-masked study randomized nAMD patients (1:1) to ranibizumab monthly from baseline to Month (M) 11 to a PRN regimen from M12 to M23 (monthly group, n = 167) versus ranibizumab three monthly doses followed by a PRN regimen up to M23 (PRN group, n = 166). Subgroups were assessed based on the presence/absence of PCV (indicated by indocyanine green angiography). RESULTS: Of 334 randomized patients, 41.7% had PCV at baseline. Mean average best-corrected visual acuity (BCVA) change from M3 to M4 through M12 was 3.3 letters with monthly and 1.7 letters with PRN (mean difference: 1.6; 95% CI: -2.95, -0.20, primary end-point). Mean change in BCVA from baseline (monthly/PRN, 53.8/53.7) to M12 and M24 was 12.3 and 11.3 letters in monthly and 9.6 and 9.3 letters in PRN group. Corresponding values for patients with PCV/without PCV were 12.7/12.1 letters (M12) and 12.3/10.6 letters (M24) in monthly and 9.4/9.4 letters (M12) and 9.7/8.7 letters (M24) in PRN groups. The mean number of injections was 11.4 (monthly) and 8.2 (PRN) from Day 1 to M11 and 4.8 (monthly) and 5.0 (PRN) from M12 to M23. No new safety findings were reported. CONCLUSIONS: The study results support the use of either ranibizumab monthly or PRN regimens in Chinese patients with nAMD, regardless of presence of PCV.

PHENOTYPIC VARIABILITY OF RECESSIVE RDH12-ASSOCIATED RETINAL DYSTROPHY.

PURPOSE: To characterize the phenotypic variability and report the genetic defects in a cohort of Chinese patients with biallelic variants of the retinol dehydrogenase 12 (RDH12) gene. METHODS: The study included 38 patients from 38 unrelated families with biallelic pathogenic RDH12 variants. Systematic next-generation sequencing data analysis, Sanger sequencing validation, and segregation analysis were used to identify the pathogenic mutations. Detailed ophthalmic examinations, including electroretinogram, fundus photography, fundus autofluorescence and optical coherence tomography, and statistical analysis were performed to evaluate phenotype variability. RESULTS: Twenty-five different mutations of RDH12 were identified in the 38 families. Six of these variants were novel. Val146Asp was observed at the highest frequency (23.7%), and it was followed by Arg62Ter (14.5%) and Thr49Met (9.2%). Twenty-three probands were diagnosed with early-onset severe retinal dystrophy, 6 with Leber congenital amaurosis, 7 with autosomal recessive retinitis pigmentosa, and 2 with cone-rod dystrophy. Self-reported nyctalopia occurred in about a half of patients (55.3%) and was significantly more common among older patients (P < 0.01). Nyctalopia was not significantly associated with best-corrected visual acuity (P = 0.72), but older patients had significantly greater best-corrected visual acuity loss (P < 0.01). Only 15.8% of the patients had nystagmus, which was significantly more likely to occur among 36.8% of the patients with hyperopia >3D (P < 0.01) and/or in cases of reduced best-corrected visual acuity (P = 0.01), but was not associated with age (P = 0.87). CONCLUSION: Several high-frequency RDH12 variants were identified in patients with inherited retinal dystrophies, most of which were missense mutations. Variable but characteristic phenotypes of a progressive nature was observed. Overall, the findings indicated that biallelic RDH12 mutations are a common cause of early-onset retinal dystrophy and a rare cause of cone-rod dystrophy.

Efficacy and Safety of Intravitreal Conbercept, Ranibizumab, and Triamcinolone on 23-Gauge Vitrectomy for Patients with Proliferative Diabetic Retinopathy.

INTRODUCTION: To compare the effect and safety of intravitreal conbercept (IVC), intravitreal ranibizumab (IVR), or intravitreal triamcinolone acetonide (IVTA) injection on 23-gauge (23-G) pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). METHODS: Fifty patients (60 eyes) of varying degrees of PDR were randomly grouped into 3 groups (1 : 1 : 1) (n = 20 in each group). The 23-G PPV was performed with intravitreal conbercept or ranibizumab injection 3-7 days before surgery or intravitreal TA injection during surgery. The experiment was randomized controlled, with a noninferiority limit of five letters. Main outcome measures included BCVA, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, and silicone oil tamponade. RESULTS: At 6 months after surgery, there were no significant differences of BCVA improvements, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, silicone oil tamponade, vitreous clear-up time, and the incidence of intraoperative bleeding between the IVC and IVR groups (all P values ≥ 0.05), but they were significantly different from the IVTA group (all P values < 0.05). IOP increases did not show significant differences between the IVC and IVR groups, but both were significantly different with the IVTA group. More patients had higher postoperative IOP in the IVTA group. CONCLUSIONS: The intravitreal injection of conbercept, ranibizumab, or TA for PDR had a significant different effect on outcomes of 23-G PPV surgery. Conbercept and ranibizumab can reduce difficulty of the operation, improve the success rate of PPV surgery, and decrease the incidence of postoperative complications.

Clinical and genetic features of eight Chinese autosomal-dominant optic atrophy pedigrees with six novel OPA1 pathogenic variants.

BACKGROUND: Autosomal-dominant optic atrophy (ADOA) is one of the most common types of inherited optic atrophy. We identify OPA1 pathogenic variants and assess the clinical features of a cohort of Chinese ADOA patients Materials and Methods: Detailed clinical evaluations were performed and genomic DNA was extracted from peripheral blood for all the participants. Sanger sequencing was used to analyze all exons and exon/intron junctions of OPA1 for eight pedigrees. Target exome capture plus next-generation sequencing (NGS) were applied for one atypical family with photophobia. Reverse transcription polymerase chain reaction was carried out to further characterize the mRNA change of selected splicing alteration. RESULTS: All 17 patients had impaired vision and optic-disk pallor; however, the clinical severity varied markedly. Two patients complicated with hearing loss. Six novel and two reported pathogenic variants in OPA1 (GenBank Accession No. NM_130837.2) were identified including four nonsynonymous variants (c.2400T > G, c.1468T > C, c.1567A > G and c.1466T > C), two splicing variants (c.2984-1_2986delGAGA and c.2983 + 5G > A), one small deletion (c.2960_2968delGCGTTCAAC), and one small insertion (c.3009_3010insA). RNA analysis revealed the splicing variant c.2984-1_2986delGAGA caused small deletion of mRNA (r.2983_2988del). CONCLUSIONS: ADOA patients presented variable clinical manifestations. Novel OPA1 pathogenic variants are the main genetic defect for Chinese ADOA cases. NGS may be a useful molecular testing tool for atypical ADOA.

Longitudinal observation of subretinal fibrosis in Vogt-Koyanagi-Harada disease.

BACKGROUND: Subretinal fibrosis (SRF) is a vision-threatening complication of Vogt-Koyanagi-Harada disease (VKH). It has long been recognized as a sequela of chronic inflammation. The developmental process of SRF, however, has not been described. The purpose of this study is to provide longitudinal observations of SRF in VKH. METHODS: Retrospective chart review of 10 VKH patients referred to our group between January 2008 and September 2015 at acute uveitic stage with SRF at presentation or who developed SRF during follow up. RESULTS: Ten patients (6 males and 4 females) with a median age of 39.0 (range, 23 to 58) years old were included. The median disease duration at presentation and median duration of follow up were 25.5 (range 5 to 60) days and 32.5 (range 13 to 61) months respectively. At presentation, all patients except one had been inappropriately treated with glucocorticosteroid (insufficiently dosed or tapered too fast) for longer than 2 weeks. Despite large dose oral glucocorticosteroid (1 mg/kg/d prednisone or equivalent) with slow tapering in combination with at least one immunomodulatory agent (cyclosporin A, cyclophosphamide or azathioprine) after presentation, all patients developed bilateral SRF within the first 4 months of disease course and 7 patients within the first 2 months. In 8 patients, shape-change/migration and progressive proliferation/pigmentation of SRF was observed over a period of several months after its formation, and then became quiescent but may further underwent depigmentation or pigmentation. SRF involved macula in 12 eyes (7 patients) and caused treatment resistant macular detachment and severe visual impairment in 6 eyes (4 patients). At the last visit, eyes with macular involvement were more common to had worse final best corrected visual acuity (≤20/50) than those without (9/12 vs. 0/8, p = 0.001). CONCLUSIONS: SRF usually develop early in the disease course in VKH patients who are not adequately controlled; it usually undergoes a highly dynamic process within the subretinal space and may involve the macula and resulted in poor final visual outcome.

Intraocular Detection of Herpes viruses by xTAG Liquid Chip Technology in Patients with Acute Retinal Necrosis.

PURPOSE: To evaluate the performance of the xTAG liquid chip technology (xTAG-LCT) for etiological diagnosis of acute retinal necrosis (ARN). METHODS: Fifteen vitreous and 3 aqueous samples from 18 ARN patients were analyzed by xTAG-LCT and multiplex PCR (mPCR)/quantitative PCR (qPCR). RESULTS: xTAG-LCT revealed positive results in 17 of the 18 samples: 10 for Varicella Zoster Virus (VZV) alone; 5 for VZV and Epstein-Barr virus (EBV); 1 for herpes simplex viruses type 1 (HSV-1) and EBV; 1 for VZV, HSV-1 and EBV. While mPCR revealed the same results as xTAG-LCT for VZV and HSV-1 in all samples, only 2 of the 7 samples positive for EBV on xTAG-LCT were confirmed by qPCR. None of the 28 control vitreous samples from 8 non-ARN patients and 10 pair of cadaveric eyes was positive for any of the tested viruses. CONCLUSIONS: xTAG-LCT could be a useful alternative for etiological diagnosis of ARN.

Surgical Treatment of Subretinal Fibrosis Caused Macular Detachment in Vogt-Koyanagi-Harada Disease: A Pioneer Study.

PURPOSE: To describe surgical outcomes of macular detachment caused by subretinal fibrosis (SRF) in Vogt-Koyanagi-Harada disease (VKH). METHODS: Retrospective review of VKH patients who underwent SRF removal surgery. RESULTS: Seven eyes of six VKH patients with preoperative BCVA ranging from light perception to 20/250 were included. Six eyes underwent uncomplicated SRF removal with C3F8 or silicone oil (SO) tamponade and the following optional primary or subsequent procedures: intravitreal injection of triamcinolone acetonide, SO removal, lensectomy, or phacoemulsification with intraocular lens (IOL) implantation. All six eyes had attached macula and improved BCVA at the last visit (ranging from 20/2000 to 20/67) compared to baseline; the other eye, however, showed no light perception after surgery due to optic nerve injury. CONCLUSIONS: In VKH patients, macular detachment caused by SRF can be treated with surgery with generally favorable outcomes. Extreme caution should be taken to avoid optic nerve injury.

Characteristics of the Choriocapillaris Layer in Optical Coherence Tomography Angiography of Acute Central Serous Chorioretinopathy.

BACKGROUND AND OBJECTIVE: To describe the vascular characteristics of the choriocapillaris layer in acute central serous chorioretinopathy (CSC) imaged by optical coherence tomography angiography (OCTA), and to analyze the vascular density. PATIENTS AND METHODS: Retrospective, observational case series. In the study, 20 eyes of patients with acute CSC and 20 normal individuals were selected. All underwent OCTA, and 3 mm × 3 mm scanning mode was chosen for analyzing vascular density and morphological characteristics on the choriocapillaris layer. RESULTS: A dark region with some hyperreflective signal spots on the choriocapillaris layer was found in all affected eyes' OCTA images. The choroidal vascular density (CVD) in the affected eyes was significantly lower than in the normal eyes (P = .000 vs. P < .05). Additionally, the density of affected eyes was much smaller in comparison with the fellow eyes, which was statistically significant (P = .000 vs. P < .05). Fellow eyes' density was also lower than in normal eyes (P = .009 vs. P < .05). CONCLUSION: OCTA could offer a new approach to help understand the mechanisms of changes in the choriocapillary with imaging and provide quantitative analysis, as well. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:1000-1005.].

Sphere-Induced Rejuvenation of Swine and Human Müller Glia Is Primarily Caused by Telomere Elongation.

Müller cells are the major supportive and protective glial cells in the retina with important functions in histogenesis and synaptogenesis during development, and in maintenance of mature neurons as they show to secrete various cytokines and manifest potentials of self-renewal and transdifferentiation into retinal neurons following injury in the vertebrate retinas. The swine retina has a visual streak structure similar to the human macular where cone photoreceptors are highly concentrated, thereby can serve as a better model for studying retinal diseases and for formulating cell-based therapeutics than the rodent retinas. Like most differentiated somatic mammalian cells, the isolated swine and human Müller glia become senescent over passages in culture, which restricts their potential application in basic and clinic researches. Here, we demonstrate that the senescence of swine and human Müller cells is caused by telomere attrition upon multiplications in vitro; and the senescent cells can be rejuvenated by sphere suspension culture. We also provide evidence that sphere-induced extension of telomeres in swine and human Müller glia is achieved by alternative lengthening of telomeres or/and by telomerase activation. Stem Cells 2017;35:1579-1591.

Internal limiting membrane transplantation for unclosed and large macular holes.

BACKGROUND: To present the surgical technique and clinical outcomes of transplantation of autologous internal limiting membrane (ILM) for large macular holes (MHs) after failed surgeries with ILM removal. METHODS: Thirteen eyes of 13 consecutive patients with MHs larger than 500 µm after failed surgeries with ILM removal underwent vitrectomy with transplantation of autologous ILM. In the ILM transplantation technique, a small piece of the ILM was peeled off and transplanted inside the macular hole. Fluid-air exchange was then performed. The air was then replaced with 10 % perfluoropropane (C3F8) gas. Comprehensive ophthalmologic examinations and spectral-domain optical coherence tomography were performed preoperatively and postoperatively. The main outcome measures were best-corrected Snellen visual acuity (BCVA) and MH closure rate. RESULTS: The preoperative mean base diameter of the MHs was 1637.6 + 412.7 µm (range, 814-2092 µm). The preoperative mean minimum diameter was 814.4 + 255.0 µm (range, 546 µm-1485 µm). Complete MH sealing was achieved in 12 eyes after transplantation of the ILM flap. The mean BCVA was 1.15 + 0.21 (range, 1.0-1.6) before surgery and 0.99 + 0.17 (range, 0.7-1.3) at 12 months postoperatively. There was a significant difference in BCVA before versus after the surgery (t = 3.825, P = 0.0002, paired t- test). CONCLUSIONS: Transplantation of autologous ILM is an effective addition to the surgical options for large macular holes after failed surgeries with ILM removal.

[Clinical study of vitrectomy with epiretinal membrane peeling for idiopathic macular epiretinal membrane].

OBJECTIVE: To investigate the result of vitrectomy with epiretinal membrane (ERM) peeling for idiopathic macular epiretinal membrane (IMEM). METHODS: Clinical data of 51 patients (51 eyes) of IMEM who underwent vitrectomy with ERM peeling were retrospectively investigated. All the patients were examined by visual acuity, slit lamp, fundus under mydriasis, optical coherence tomography (OCT) before and after the surgery. The 3-18 months follow-up were included, mean (5.8±3.2) months. All the macular ERM were removed successfully. Paired-sample t test was used to study the visual acuity and macular foveal thickness before and after surgery. The Pearson correlation analysis was used to study the correlation between visual acuity and macular foveal thickness. RESULTS: In the 51 patients, the best visual acuity improved from 4.25±0.34 to 4.65±0.23 postoperatively. The difference was statistically significant (t=-9.012, P=0.000), and the mean foveomacular thickness decreased from (432.7 ± 91.7) to (333.3 ± 66.1)µm postoperatively, the difference was statistically significant (t=10.565, P=0.000). There was negative correlation between visual acuity and mean foveomacular thickness (r=- 0.452, P=0.001), and it was obvious postoperatively (r=-0.602, P=0.000). The increase of visual acuity was strongly correlated with the decline of mean foveomacular thickness (r=0.382, P=0.006). Twelve eyes have developed cataract in 3 to 6 months after vitrectomy which affect the visual acuity. All of them went phacoemulsification and intraocular lenses(IOL) implantation and visual acuity after surgery had an obviously improvement. CONCLUSIONS: Vitrectomy with ERM peeling can improve visual acuity and ease macular edema. And it is a safe and effective therapy to treat patients of IMEM.

The Influence of Age and Central Foveal Thickness on Foveal Zone Size in Healthy People.

BACKGROUND AND OBJECTIVE: To investigate the influence of age and central foveal thickness (CFT) on the foveal avascular zone (FAZ) size in healthy people using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: A cross-section study. One hundred thirty-two healthy subjects (224 eyes) were included. All participants underwent examination with OCTA. CFT and FAZ size, including vertical radius (VR), horizontal radius (HR), and area, were measured. RESULTS: Linear regression analysis showed a positive correlation between age and FAZ size. The HR, VR, and area had an increase of 0.001 mm (P = .002), 0.001 mm (P = .001), and 0.001 mm(2) (P = .000) each year, respectively. There was a negative correlation between CFT and FAZ size. When the CFT increased per 1 µm, the HR, VR, and area decreased by 0.002 mm (P = .000), 0.001 mm (P = .000), and 0.003 mm(2) (P = .000), respectively. CONCLUSIONS: FAZ size increases with age and decreases with CFT. OCTA is a novel method to study the FAZ in healthy people.

Comprehensive Molecular Diagnosis of a Large Chinese Leber Congenital Amaurosis Cohort.

PURPOSE: Leber congenital amaurosis (LCA) is an inherited retinal disease that causes early-onset severe visual impairment. To evaluate the mutation spectrum in the Chinese population, we performed a mutation screen in 145 Chinese LCA families. METHODS: First, we performed direct Sanger sequencing of 7 LCA disease genes in 81 LCA families. Next, we developed a capture panel that enriches the entire coding exons and splicing sites of 163 known retinal disease genes and other candidate retinal disease genes. The capture panel allowed us to quickly identify disease-causing mutations in a large number of genes at a relatively low cost. Thus, this method was applied to the 53 LCA families that were unsolved by direct Sanger sequencing of 7 LCA disease genes and an additional 64 LCA families. Systematic next-generation sequencing (NGS) data analysis, Sanger sequencing validation, and segregation analysis were used to identify pathogenic mutations. RESULTS: Homozygous or compound heterozygous mutations were identified in 107 families, heterozygous autosomal dominant mutations were identified in 3 families and an X-linked mutation was found in 1 family, for a combined solving rate of 76.6%. In total, 136 novel pathogenic mutations were found in this study. In combination with two previous studies carried out in Chinese LCA patients, we concluded that the mutation spectrum in the Chinese population is distinct compared to that in the European population. After revisiting, we also refined the clinical diagnosis of 10 families based on their molecular diagnosis. CONCLUSIONS: Our results highlight the importance of a molecular diagnosis as an integral part of the clinical diagnostic process.

Systemic lupus erythematosus and antiphospholipid syndrome related retinal vasculitis mimicking ocular cysticercosis: a case report.

Making accurate and timely diagnosis is often challenging when patients with a systemic disease first present with ocular manifestations. The possibility that vasculitis associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) can be misdiagnosed as cysticercosis has not been discussed in the literatures.

Natural course of vitreomacular traction syndrome observed by spectral-domain optical coherence tomography.

OBJECTIVE: Our study aimed to characterize the natural course of vitreomacular traction (VMT) syndrome, on which discrepancies have been reported in previous publications, by spectral-domain optical coherence tomography (SD-OCT). DESIGN: Retrospective chart review. PARTICIPANTS: A total of 23 eyes of 23 patients with idiopathic symptomatic VMT syndrome diagnosed and followed up in Peking Union Medical College Hospital from 2008 to 2013. METHODS: Clinical records of all patients who underwent SD-OCT examination and were diagnosed and followed up as idiopathic VMT syndrome were reviewed. Those who had at least 2 visits were included. The median observation period of the patients was 8.2 ± 7.9 months. RESULTS: The 23 eyes were categorized into 3 groups based on the follow-up results of SD-OCT: the posterior vitreous detachment (PVD) group comprised 4 eyes that developed complete PVD, the full-thickness macular hole (FMH) group included 4 eyes that formed FMH, and the persisted VMT (PVMT) group comprised the other 15 eyes with PVMT. Epiretinal membrane (ERM) persisted in all 5 eyes in the PVMT group. FMH occurred in 3 of 7 eyes with outer lamellar macular hole (LMH) at the first visit. CONCLUSIONS: Spontaneous development of complete PVD in VMT syndrome during follow-up appeared to be more common in our study than in previous reports without SD-OCT. Persistence of ERM might be an unfavourable prognostic factor in the natural course of VMT syndrome. The outer LMH might be a risk factor for FMH formation.

Novel CNGA3 mutations in Chinese patients with achromatopsia.

OBJECTIVE: To study the clinical features and to identify the pathogenic mutations in Chinese patients with achromatopsia (ACHM). DESIGN: Fifteen patients from 10 unrelated families were included in this study. Detailed ocular examinations were performed for the affected subjects, including best-corrected visual acuity (BCVA), colour vision, slit lamp, fundus, electroretinography, perimetry, and spectral domain optical coherent topography (SD-OCT). Peripheral blood samples were obtained from all of the patients and their family members for genomic DNA extraction. All exons of CNGA3, CNGB3, GNAT2, PDE6C and PDE6H were amplified by a PCR and screened for mutation by direct Sanger sequencing. The sequences were analysed using the Blat tool and then compared with the gene transcript. A segregation test was conducted in the patients' parents if they were available. The variants were compared with the database of the 1000 Genomes Project to exclude polymorphism. RESULTS: Nystagmus, photophobia, and impaired colour discrimination were observed in all patients. The BCVA of the affected subjects ranged from 0.05-0.2. Severely depressed and non-recordable cone electroretinograms were observed. Noticeable structural changes including disruption or loss of the macular inner/outer segments (IS/OS) junction of the photoreceptors were observed with SD-OCT. CNGA3 mutations were identified in 13 patients from eight families. Sequencing revealed seven novel missense mutations, three novel deletion mutations, and four previously reported mutations among those patients. CONCLUSIONS: CNGA3 mutation is the most frequent cause of ACHM in this cohort of patients. Ten novel mutations were identified in CNGA3. Genetic characterisation of patients with ACHM is important for genetic counselling and future gene therapies. This study reports the comprehensive clinical and genetic features of Chinese patients with ACHM.