Microcatheter-Assisted Circumferential Trabeculotomy After Failed Glaucoma Surgeries in Childhood Glaucoma.

PURPOSE: To evaluate the outcomes of microcatheter-assisted trabeculotomy (MAT) in childhood glaucoma (primary congenital glaucoma [PCG], juvenile open-angle glaucoma [JOAG], and secondary childhood glaucoma [SCG]) after failed glaucoma surgery. DESIGN: Retrospective interventional case series. METHODS: Patients with childhood glaucoma who underwent MAT after failed glaucoma surgery with at least 12 months of follow-up were evaluated. Pre- and postoperative intraocular pressure (IOP) and the number of glaucoma medications were recorded and compared. Success was defined as an IOP ≤21 mm Hg with or without glaucoma medication. Analysis of variance was used to compare the glaucoma subgroups. RESULTS: Forty-five eyes (42 patients) with a median follow-up period of 19 months were included. The median age at the time of MAT was 10 (range, 0.8-33) years. The mean number of previous surgeries was 1.3 ± 0.5. The IOP had significantly reduced from baseline in all PCG, JOAG, and SCG patients (27.9 ± 4.5 vs 16.3 ± 8.0 mm Hg, P = .001; and 30.8 ± 9.4 vs 13.5 ± 3.0 mm Hg, P < .001; and 31.5 ± 7.1 vs 16.5 ± 5.3 mm Hg, P = .001, respectively). Fewer glaucoma medications were needed after MAT in all 3 groups (each P < .001). At the last visit, the total success rates in PCG, JOAG, and SCG were 93.8%, 100%, and 88.9%, respectively. No severe complications were observed. CONCLUSION: MAT can effectively manage PCG, JOAG, and SCG after failed surgeries, providing successful outcomes and no serious complications. Following failed glaucoma surgeries, MAT may offer these patients with childhood glaucoma an excellent opportunity to achieve IOP control.

INVERSE SOURCE PROBLEM FOR ACOUSTICALLY-MODULATED ELECTROMAGNETIC WAVES.

We propose a method to reconstruct the electrical current density from acoustically-modulated boundary measurements of time-harmonic electromagnetic fields. We show that the current can be uniquely reconstructed with Lipschitz stability. We also report numerical simulations to illustrate the analytical results.

Use of ultrasound biomicroscopy to predict the outcome of anterior segment reconstruction in congenital fibrovascular pupillary membrane with secondary glaucoma.

AIMS: To evaluate the efficacy and safety of anterior segment reconstruction (ASR) in congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG) basing ultrasound biomicroscopy (UBM) classification. METHODS: This ambispective cohort study enrolled patients with CFPMSG who underwent ASR between January 2014 and September 2020. Comprehensive ophthalmic examinations and UBM were performed before surgery and postoperatively. The patients were classified into three types according to the UBM configurations. Anterior chamber recovery (ACR) was defined as deepening in anterior chamber (≥1.5 mm all through final follow-up (FFU), while success following ASR was defined as ACR and intraocular pressure (IOP)≤21 mm Hg. RESULTS: 25 eyes of 25 patients underwent ASR (average age at operation 5.8±5.0 months, 48% girls) with FFU 15.8±16.9 months. Enrolled subjects were classified into type Ⅰ (11 eyes), type Ⅱ (11 eyes) and type Ⅲ (3 eyes). After ASR, 23 eyes (92%) achieved ACR, and the mean ACD increased in all groups (p=0.006, <0.001 and 0.003, respectively). Eyes with types Ⅰ and Ⅱ demonstrated a reduction of IOP (p=0.009 and 0.002, respectively). ASR success rate was highest in type Ⅰ (72.9%) compared with types Ⅱ and Ⅲ (18.2% and 0%, respectively; p=0.011). ASR led to decreased number of antiglaucoma medications for type Ⅰ CFPMSG at FFU (p=0.016). No vision-threatening postoperative complications occurred. CONCLUSIONS: ASR for CFPMSG results in increased ACD and improvement in IOP. Postoperative IOP control was best in type Ⅰ CFPMSG but not as effective in types Ⅱ and Ⅲ. UBM-based classification helps to predict the surgical outcome of ASR in CFPMSG.

Effect of Combined Surgery in Patients with Complex Nanophthalmos.

(1) Background: To evaluate the efficacy and safety of combined surgery (limited pars plana vitrectomy, anterior-chamber stabilized phacoemulsification, IOL implantation and posterior capsulotomy, LPPV + ACSP + IOL + PC) in complex nanophthalmos. (2) Methods: Patients with complex nanophthalmos were recruited to undergo LPPV + ACSP + IOL + PC from January 2017 to February 2021. Preoperative and post-operative intraocular pressure (IOP), best corrected visual acuity (BCVA), anterior chamber depth (ACD), and number of glaucoma medications were compared using the paired t-test or Wilcoxon signed rank sum tests. Surgical success rate was evaluated. Surgery-associated complications were documented. (3) Results: Forty-five eyes of 37 patients with complex nanophthalmos were enrolled. The mean follow-up period was 21.7 ± 10.6 months after surgery. Mean IOP decreased from 32.7 ± 8.7 mmHg before surgery to 16.9 ± 4.5 mmHg (p < 0.001) at the final follow-up visit, mean logMAR BCVA improved from 1.28 ± 0.64 to 0.96 ± 0.44 (p < 0.001), mean ACD significantly increased from 1.14 ± 0.51 mm to 3.07 ± 0.66 mm (p < 0.001), and the median number of glaucoma medications dropped from 3 (1, 4) to 2 (0, 4) (p < 0.001). The success rate was 88.9% (40 eyes) at the final follow-up visit. Two eyes had localized choroidal detachments which resolved with medical treatment. (4) Conclusions: LPPV + ACSP + IOL + PC is a safe and effective surgical procedure, which can decrease IOP, improve BCVA, deepen the anterior chamber, and reduce the number of glaucoma medications in patients with complex nanophthalmos. It can be considered as one of the first treatment in nanophthalmic eyes with complex conditions.

Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell Inner Plexiform Layer in Progressive Myopia and Glaucoma Among Adolescents.

Purpose: This study aimed to investigate the differences in longitudinal changes in the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) caused by progressive myopia and glaucoma among adolescents. Design: This was a retrospective observational study. Methods: A total of forty-seven and 25 eyes of 47 and 25 adolescents with myopia progression (MP) and glaucoma progression (GP), respectively, who were followed up at the Zhongshan Ophthalmic Center for at least 3 years, were included in the study. The pRNFL and GCIPL that measured at the initial and last visits were analyzed. Results: The median follow-up period was 5 years for both two groups. During follow-up, the whole, superior, and inferior pRNFL decreased in both the MP and GP groups, (p < 0.001). Nasal pRNFL decreased in the MP group (p < 0.001) but had no significant difference in the GP group (p = 0.19). Temporal pRNFL was increased in the MP group (p < 0.001) but decreased in the GP group (p < 0.001). The average and sectoral GCIPL decreased in both groups (p < 0.001). The annual change rate of temporal pRNFL and pRNFL at 10-, 8-, 9-, and 7-clock-hour sectors and the inferotemporal GCIPL has better diagnostic value to differentiate glaucoma from myopia (the area under the receiver operating characteristic curve, AUC > 0.85). Conclusion: Glaucoma and MP could cause loss of the pRNFL and GCIPL in adolescents; however, the loss patterns were different between the two groups. The temporal quadrant and 7-, 8-, 9-, and 10-clock-hour sector pRNFL and the inferotemporal GCIPL can help distinguish pRNFL and GCIPL loss caused by glaucoma or MP.

Long-Term Visual Outcomes of Primary Congenital Glaucoma in China.

INTRODUCTION: The aim of this study was to investigate the long-term visual outcomes and factors associated with vision loss in Chinese patients with primary congenital glaucoma (PCG) after successful intraocular pressure (IOP) control (IOP ≤21 mm Hg). METHODS: PCG patients with IOP control who were examined in the glaucoma clinic at Zhongshan Ophthalmic Center from 2019 to 2020 were enrolled. The final visual outcome was evaluated by the best corrected visual acuity (VA). Univariate and multivariate analyses were used to investigate the associations of visual impairment with potential risk factors. The causes for decreased VA (<20/50) were also analyzed. RESULTS: Fifty-nine patients (95 eyes) were included in the cohort, with a mean age of 8.7 years. The mean logMAR VA was 0.62 ± 0.64. The VAs of eyes treated for PCG were good (≥20/50) in 56%, fair (20/60-20/200) in 30%, and poor (<20/200) in 14%. The most common cause of decreased VA was amblyopia (64.3%). Multivariate logistic regression analysis showed that undergoing multiple surgeries (OR: 4.86, 95% CI: 1.11-21.16, p = 0.035) was significantly associated with visual impairment. CONCLUSION: The results showed that good VA was attainable in approximately half of PCG eyes under IOP control. Prompt and effective treatment of PCG, management of amblyopia and ocular comorbidities may be potential steps toward achieving good visual outcomes in PCG patients.

Medication Adherence and Common Barriers for Caregivers of Preschool Children with Pediatric Glaucoma.

Purpose: To investigate the medication adherence among caregivers of preschool children with pediatric glaucoma and to elucidate common barriers leading to poor adherence. Methods: A cross-sectional study. Caregivers of preschool children with pediatric glaucoma completed a questionnaire on demographic information of caregivers, demographic and disease characteristics of children, caregivers-reported medication adherence (by an adapted Morisky Adherence Scale), and possible 13 barriers. Results: Overall 132 questionnaires were considered valid. Thirty-six percent of all reported poor medication adherence. Caregivers' age and self-evaluated knowledge about pediatric glaucoma showed a significant difference between the adherent and nonadherent groups (P < 0.05). Nineteen percent of all reported only one barrier as important, 65% cited multiple barriers, and 16% cited no barriers. Anxiety and depression were cited as important by most caregivers in both groups. Univariate logistic regression analysis demonstrated that difficulty with the acquisition of medications (OR, 2.5; 95% CI, 1.1-5.7; P=0.025), difficulty with medication schedule (OR, 2.3; 95% CI, 1.0-5.0; P=0.043), and high expenses for medications (OR, 4.8; 95% CI, 1.4-15.9; P=0.011) were significantly associated with higher odds of poor adherence. Conclusions: Over one-third of caregivers of preschool children with pediatric glaucoma were in poor medication adherence. Nearly two-thirds of caregivers cited multiple barriers simultaneously as important hindrances to medication usage. Anxiety and depression, difficulty with the acquisition of medications, difficulty with the medication schedule, and high expenses for medications were prominent barriers. Individualized solutions should be provided according to reported barriers by each caregiver and the other most common barriers.

Clinical and Ultrasound Biomicroscopic Characteristics of Congenital Fibrovascular Pupillary Membrane-Induced Secondary Glaucoma.

Purpose: The purpose of this study was to describe and summarize the clinical features of congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG). Design: Cross-sectional case series. Methods: Eyes of 32 patients with CFPMSG were enrolled. Demographic data, including gender, laterality, age at presentation, and age at onset of glaucoma were collected. Patients underwent comprehensive ophthalmic examinations and ultrasound biomicroscopy (UBM). CFPMSG eyes were classified into three groups based on UBM findings and intergroup analysis was performed using ANOVA. Results: The average age at presentation was 2.4 ± 4.6 months (mean ± SD) and at glaucoma onset was 3.8 ± 4.5 months. Compared to normal fellow eyes, all affected eyes had increased intraocular pressure (IOP), axial length, corneal diameter, and central corneal thickness, and decreased anterior chamber depth (ACD) (all P ≤ 0.001). Twenty-two affected eyes (68.8%) had evidence of glaucomatous optic neuropathy. Based on iris configuration on UBM, eyes were classified as 53% type I ("U" shape), 34% type II ("Y" shape), and 13% type III (no anterior chamber). IOP in types II (33.8 ± 5.9 mmHg) and III (35.2 ± 5.9 mmHg) was significantly higher than in type I eyes (26.5 ± 5.1 mmHg). The ACD was shallower in type II compared to type I (P = 0.045). Conclusion: Congenital fibrovascular pupillary membrane-induced secondary glaucoma is characterized by ocular hypertension, corneal enlargement and edema, axial length elongation, and glaucomatous optic neuropathy. Glaucoma in this condition is secondary to pupillary block and angle-closure. UBM provides important information for the diagnosis and classification of CFPMSG. This novel classification system demonstrated varying levels of severity and may guide on management of this disease.

Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG.

Primary open angle glaucoma (POAG) is the leading cause of irreversible blindness. Dysfunction of the trabecular meshwork (TM), resulting in decreased outflow of aqueous humor and increased intraocular pressure (IOP), plays an important role in the pathogenesis of POAG. However, the underlying mechanisms still remain unclear. In this study, we demonstrated that the eIF2-α/ATF4/CHOP branch of unfolded protein response (UPR) was activated in human trabecular meshwork cells (HTMCs) upon tert-butyl hydroperoxide (TBHP) exposure. Inhibition of ATF4 ameliorated TBHP-induced apoptosis and inflammatory cytokine production, while ectopic expression of ATF4 increased the expression of endothelial leukocyte adhesion molecule (ELAM)-1 and IL-8 in HTMCs. Furthermore, we found that ATF4 inhibition reduced tunicamycin-induced caspase-3 activation, ROS production, ELAM-1 expression, and HTMCs phagocytosis impairment. By an in vivo study in mice, we showed that overexpression of ATF4 in the TM induced C/EBP homologous protein (CHOP) expression and TM cells apoptosis, contributing to inflammatory cytokine production, and probably IOP elevation. More importantly, upregulation of ATF4 and CHOP, and colocalization of ATF4 with ELAM-1 were found in the TM of POAG patients. These results suggest that ATF4 is a critical mediator of oxidative stress and ER stress-induced TM cell dysfunction and apoptosis in POAG.

Surgical outcomes of Ahmed glaucoma valve implantation in patients with glaucoma secondary to iridocorneal endothelial syndrome.

OBJECTIVES: To evaluate the long-term outcome of patients with iridocorneal endothelial (ICE) syndrome who underwent Ahmed glaucoma valve implantation surgery for uncontrolled glaucoma. METHODS: Eighteen patients who suffered from unilateral ICE syndrome with uncontrolled glaucoma and subsequently underwent Ahmed aqueous shunt surgery at Zhongshan Ophthalmic Center between January 2008 and December 2016 were reviewed. Outcome measures included intraocular pressure (IOP), the use of glaucoma medications, visual acuity, further surgical interventions, and surgical complications. RESULTS: The mean IOP was reduced from 34.8 ± 10.6 mmHg on 3.6 ± 0.5 medications to 17.4 ± 4.9 mmHg (t = 6.791, P = 0.000) on 1.6 ± 1.1 medications (Z = -3.545, P = 0.000) at the last follow-up (42.0 ± 19.3 months). Five eyes (27.8%) achieved complete success, nine (50.0%) achieved qualified success, and the remaining four (22.2%) were considered failures. Survival was 94.4% at 1 year, 88.1% at 2 years, and 73.5% at 3 years. Four cases displayed a flat anterior chamber and were treated with a single anterior chamber reformation surgery with no recurrence. No other complications related to the glaucoma drainage implants occurred in this series. CONCLUSIONS: Ahmed glaucoma valve implantation appears to be a safe and effective method for treating glaucoma secondary to ICE syndrome. Postoperative shallow anterior chamber and hypotony may occur but responds well to the treatment. Early consideration may be given to aqueous shunt surgery in patients with glaucoma secondary to ICE syndrome when trabeculectomy fails.

Different damage patterns of retinal nerve fiber layer and ganglion cell-inner plexiform layer between early glaucoma and non-glaucomatous optic neuropathy.

AIM: To compare the damage pattern of the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) between early glaucomatous and non-glaucomatous optic neuropathy (EGON and NGON). METHODS: It is a cross-sectional study. Thirty-eight healthy controls, 74 EGONs and 70 NGONs with comparable average pRNFL loss were included. The NGON group included 23 eyes of optic neuritis (ON), 13 eyes of hereditary optic neuropathy (HON), 19 eyes of toxic optic neuropathy (TON) and 15 eyes of compressive neuropathy (CON). The sectoral pRNFL and mGCIPL thickness obtained by high definition optical coherence tomography were analyzed. RESULTS: Compared to normal controls, the pRNFL thickness in all quadrants showed a decrease in both EGON and NGON group (P<0.001), but the average pRNFL thickness of EGON group was not different to that of NGON group (P=0.94). The inferior and superior pRNFL was thinner in EGON group compared to NGON group (P<0.001). The temporal pRNFL was thinner in NGON group compared to EGON group (P<0.001). No statistically significant difference was found in nasal pRNFL between EGON and NGON. While the nasal pRNFL was thinner in CON than other three types of NGON (P=0.01), no statistically significant difference was found in other three quadrantal pRNFL among the four types of NGON (P>0.05). The mGCIPL of EGON and NGON group were thinner than control group (P<0.001). In EGON group the severest sites of mGCIPL reduction was located at inferotemporal and inferior sectors. While, compared to EGON group, the average mGCIPL of NGON group were significantly thinner, especially in superonasal and inferonasal sectors (P<0.001). CONCLUSION: The damage pattern of pRNFL and mGCIPL caused by glaucoma is distinct from other NGON such as ON, TON, HON and CON, and this characteristic damage pattern is helpful in differentiating early glaucoma from other NGON.

Evaluation of the genetic association between early-onset primary angle-closure glaucoma and retinitis pigmentosa.

Primary angle-closure glaucoma (PACG) and retinitis pigmentosa (RP) can co-occur, but the mechanism of their association is not yet established. The purpose of this study was to investigate the differences in ocular biometry parameters and molecular genetics in patients with PACG with or without RP, and to determine the association between PACG and RP. Patients with early-onset PACG (age of onset <45 years) with or without RP were selected from the glaucoma outpatient department after full ocular examinations by the same glaucoma specialist (LX). Ocular biometry parameters were statistically analyzed. Blood samples were collected from the probands, and genomic DNA was sent out for whole exome sequencing. Variants in 326 selected genes, were extracted from the whole exome sequencing data and filtered using multiple bioinformatics analysis. The 326 genes included 10 PACG-associated genes from two genome wide association studies; 45 genes associated with anterior segment dysgenesis, microcornea, and microphthalmia; and 271 RetNet genes. Potential pathogenic variants (PPV) were obtained and underwent further genotype-phenotype analysis. As a result, a total of 32 probands with early-onset PACG were collected; nine had accompanying RP. No significant differences were noted for ocular biometry parameters between patients with PACG with RP and with PACG alone. Systematic analysis of the variants revealed that 16 of 32 probands (50%) carried PPV in 15 of 326 genes, including 14 RetNet genes and one anterior segment dysgenesis-associated gene. Of these 16 probands with PPV, five (55.56%) were from the group of nine probands with both had PACG and RP and 11 (47.83%) were from the group of 23 probands with PACG alone. Of the 15 genes, five genes, CRB1, COL2A1, RHO, RP1L1, and PAX6, were reported to cause phenotypes including glaucoma. The variants in RetNet genes appeared to be associated with a significant proportion of PACG, especially in probands with both PACG and RP. These findings enrich the phenotype spectrum of RetNet genes and provide clues for genetic screening for glaucoma. Our study suggests a genetic association between PACG and RP, although the cause-effect relationship between them needs further validation.

Multimodal Imaging Features of Bilateral Choroidal Ganglioneuroma.

PURPOSE: Bilateral choroidal ganglioneuroma is extremely rare, and no cases have been described in the literature. Multimodal images are crucial for its diagnosis. Here, we evaluated multimodal images in the early stage of choroidal ganglioneuroma. METHODS: A 6-year-old boy was recruited who had experienced gradually progressive vision loss and rapidly progressive myopia in both eyes over the past 2 years. His eyes were comprehensively evaluated via slit-lamp microscopy, ultrasound biomicroscopy, swept-source optical coherence tomography (SS-OCT), fundoscopy, fundus fluorescein angiography, indocyanine green angiography (ICGA), ultrasound B scanning, and magnetic resonance imaging. Electrophysiological examinations included electrooculography and electroretinography. Choroid biopsy and pathological examination were performed. RESULTS: Over the past 2 years, the patient's best-corrected visual acuity had gradually decreased to hand motions at 10 cm in the right eye and 20/63 in the left, with axial length growth to 25.89 mm in the right and 28.99 mm in the left. Diffuse thickening in bilateral eyewalls was depicted in B scanning and magnetic resonance imaging. Secondary exudative retinal detachment was evident in SS-OCT and B scanning. SS-OCT depicted low optical reflections in the choroidal layer, revealing a lack of choroidal vasculature. Diffuse hypofluorescence in ICGA photography confirmed extensive loss of choroidal vasculature. In electrophysiological function investigations, electrooculography revealed remarkable bilateral low Arden ratios, with almost extinguished electroretinogram in the right eye. Right-eye choroid biopsy was performed, resulting in a histological diagnosis of choroidal ganglioneuroma. CONCLUSION: Choroidal ganglioneuroma is rare. To our knowledge, no bilateral cases have been described in the literature. Major clinical features include a rapid increase in axial length, diffuse choroidal thickening, hyper-reflectivity in the choroid on optical coherence tomography, and loss of choroidal vasculature on ICGA. The current report provides multimodal imaging of choroidal ganglioneuroma for the first time and can be valuable for early diagnosis.

Trabeculotomy versus combined trabeculotomy-trabeculectomy for primary congenital glaucoma: study protocol of a randomised controlled trial.

INTRODUCTION: Trabeculotomy 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 ANALYSIS: This 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 DISSEMINATION: The 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 NUMBER: Chinese Clinical Trial Registry, ChiCTR-IOR-14005588; Date registered: 20 November 2014.

Reproducibility of Foveal Avascular Zone and Superficial Macular Retinal Vasculature Measurements in Healthy Eyes Determined by Two Different Scanning Protocols of Optical Coherence Tomography Angiography.

PURPOSE: To assess the reproducibility of quantitative measurements of the foveal avascular zone (FAZ) and retinal vasculature determined by different scanning protocols of optical coherence tomography angiography (OCTA) in healthy volunteers. METHOD: All participants were scanned by two trained operators using an AngioPlex OCTA. Both angiography protocols (6 × 6 mm and 3 × 3 mm) were performed three times on the same eye by operator A and one additional time by operator B. The FAZ area and perimeter, retinal vessel length density (VLD) and perfusion density (PD) of different regions were analysed. RESULTS: Fifty-two eyes from 52 subjects were recruited for this study. The repeated measurements of FAZ, VLD, and PD parameters obtained by the same operator, as well as by different operators, were not significantly different when the same protocol was used (p > 0.05). The intra- and inter-operator intraclass correlation coefficients (ICCs) of the FAZ and central VLD and PD parameters (range, 0.99-0.95) were better than the intra- and inter-operator ICCs of VLD and PD in the inner and outer rings (range, 0.86-0.90). The FAZ area, perimeter, and VLDs obtained by the 3 × 3 mm protocol were larger than those obtained by the 6 × 6 mm protocol (p < 0.01), but the PDs obtained by the 3 × 3 mm protocol were smaller than those obtained by the 6 × 6 mm protocol (p < 0.001). All of the corresponding parameters obtained by the two protocols were positively correlated (r = 0.64-0.99, p < 0.001). CONCLUSION: Both the 6 × 6 and 3 × 3 mm protocols of the AngioPlex OCTA provide good reproducibility for assessing the FAZ and superficial retinal vasculature. However, the values obtained by these different protocols cannot be compared directly.

Parents' perceptions of diagnostic genetic testing for children with inherited retinal disease in China.

BACKGROUND: In this study, we aim to investigate the awareness of, attitudes toward, and experiences with diagnostic genetic testing among parents of children suspected of having inherited retinal disease (IRDs) in China. METHODS: Semistructured, face-to-face, and in-depth interviews were carried out with parents of children with suspected IRDs in this qualitative study. Inductive content analysis was used for data processing. RESULTS: Forty-six parents participated in our interviews, and 47.8% of them supported genetic testing for following four main reasons: to help in making informed reproductive health decisions, to prepare for novel potential treatment, to identify the underlying causes of IRDs, and to satisfy curiosity about the heredity of IRDs. Among them, 19.6% were opposed to the testing for four main reasons, namely lack of therapeutic benefit, difficulty in affording the testing cost, doubt in the accuracy of clinical diagnosis, and the presence of concerns about the limitations of genetic testing. 47.8% of the parents expressed concerns that the genetic findings might lead to potential psychological stress. CONCLUSION: In this study, we showed that nearly half of the parents supported genetic testing mainly for family planning, and a fifth of the parents were opposed to the testing mainly for lack of therapeutic benefit. Moreover, half of the parents expressed concern that a positive genetic result may create potential psychological burden to the parents and children.

Novel BEST1 mutations and special clinical characteristics of autosomal recessive bestrophinopathy in Chinese patients.

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. Twenty-one 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.

Age related changes of the central lamina cribrosa thickness, depth and prelaminar tissue in healthy Chinese subjects.

AIM: To investigate the variation in the central lamina cribrosa thickness (cLCT), and the central anterior lamina cribrosa surface depth (cALCSD), as well as the central prelaminar tissue thickness (cPLTT) related to age in healthy Chinese subjects. METHODS: A total of 96 eyes from 96 Chinese healthy subjects were recruited. According to age, the 96 cases were divided into three groups: the young group (YG, 18-39y), middle-age group (MG, 40-59y) and older-age group (OG, 60y and above). Lamina cribrosa images were obtained from all participants using radial linear protocol by enhanced depth imaging spectral-domain optical coherence tomography. The cLCT, cALCSD and cPLTT were calculated from the average value of the lamina cribrosa thickness, anterior lamina cribrosa surface depth and prelaminar tissue thickness in the optic nerve head (ONH) centre point and paracentral points (150 µm from the centre point in the horizontal and vertical directions). RESULTS: For the total subjects, the mean cLCT, cALCSD and cPLTT were 235.18±41.27, 358.02±93.80 and 182.02±92.11 µm, respectively. No statistically significant differences in cLCT, cALCSD or cPLTT were found between gender and different eyes (P=0.27-0.92). The cLCT of the OG was the thickest among the three groups, while the cPLTT of the YG was the thickest among the three groups (P<0.05). Age was positively correlated with cLCT (r=0.42, P<0.001), and negatively correlated with cPLTT (r=-0.24, P=0.02). No significant correlation was found between the age and cALCSD (r=-0.06, P=0.55). And no correlation has been found between axial length and cLCT, cALCSD and cPLTT (P=0.11-0.81). CONCLUSION: The impact of age on the cLCT and the cPLLTT should be taken into account when analysing glaucoma and other diseases related to lamina cribrosa.

Regulation of Nrf2 by X Box-Binding Protein 1 in Retinal Pigment Epithelium.

Normal function of the retinal pigment epithelium (RPE) is essential for maintaining the structural integrity of retinal photoreceptors and the visual process. Sustained oxidative damage of the RPE due to aging and other risk factors contributes to the development of age-related macular degeneration (AMD). The transcription factor NF-E2-related factor 2 (Nrf2) is a central regulator of cellular antioxidant and detoxification responses. Enhancing Nrf2 function protects RPE cells from oxidation-related apoptosis and cell death. Previously, we demonstrated that Nrf2 activation can be induced by endoplasmic reticulum (ER) stress; however, the mechanisms are not fully understood. In the present study, we examined the role of X box-binding protein 1 (XBP1), an ER stress-inducible transcription factor, in regulation of Nrf2 in the RPE. We found that RPE-specific XBP1 conditional knockout (cKO) mice exhibit a significant reduction in Nrf2 mRNA and protein levels, along with decreased expression of major Nrf2 target genes, in the RPE/choroid complex. Using primary RPE cells isolated from XBP1 cKO mice and human ARPE-19 cell line, we confirmed that loss of XBP1 gene or pharmacological inhibition of XBP1 splicing drastically reduces Nrf2 levels in the RPE. Conversely, overexpression of spliced XBP1 results in a modest but significant increase in cytosolic and nuclear Nrf2 protein levels without affecting the transcription of Nrf2 gene. Moreover, induction of ER stress by tunicamycin and thapsigargin markedly increases Nrf2 expression, which is abolished in cells pretreated with XBP1 splicing inhibitors 4µ8C and quinotrierixin. Mechanistic studies indicate that quinotrierixin reduces Nrf2 expression likely through inhibition of protein translation. Finally, we demonstrate that overexpression of Nrf2 protected RPE cells against oxidative injury but appeared to be insufficient to rescue from XBP1 deficiency-induced cell death. Taken together, our results indicate that XBP1 modulates Nrf2 activity in RPE cells and that XBP1 deficiency contributes to oxidative injury of the RPE.

Comparison between flipped classroom and lecture-based classroom in ophthalmology clerkship.

BACKGROUND: In recent years, the flipped classroom method of teaching has received much attention in health sciences education. However, the application of flipped classrooms in ophthalmology education has not been well investigated. OBJECTIVE: The goal of this study was to investigate the effectiveness and acceptability of the flipped classroom approach to teaching ophthalmology at the clerkship level. DESIGN: Ninety-five fourth year medical students in an ophthalmology clerkship were randomly divided into two groups. An ocular trauma module was chosen for the content of this study. One group (FG (flipped group), n = 48) participated in flipped classroom instruction and was asked to watch a recorded lecture video and to read study materials before a face-to-face class meeting. They used the in-class time for discussion. The other group (TG (traditional group), n = 47) was assigned to traditional lecture-based instruction. These students attended a didactic lecture and completed assigned homework after the lecture. Feedback questionnaires were collected to compare students' perspectives on the teaching approach they experienced and to evaluate students' self-perceived competence and interest in ocular trauma. Pre- and post-tests were performed to assess student learning of the course materials. RESULTS: More students in the FG agreed that the classroom helped to promote their learning motivation, improve their understanding of the course materials, and enhance their communication skill and clinical thinking. However, students in the FG did not show a preference for this method of teaching, and also reported more burden and pressure than those from the TG. Students from the FG performed better on the post test over the ocular trauma-related questions when compared to those from the TG. CONCLUSIONS: The flipped classroom approach shows promise in ophthalmology clerkship teaching. However, it has some drawbacks. Further evaluation and modifications are required before it can be widely accepted and implemented. Abbreviations FG: Flipped classroom group; TG: Traditional lecture-based classroom group; TBL: Team-based learning; PBL: Problem-based learning; ZOC: Zhongshan Ophthalmic Center.