Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.

Highly efficient capture approach for the identification of diverse inherited retinal disorders.

Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay's effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher's syndrome, Leber's congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.

Efficacy and safety profile of intravitreal dexamethasone implant versus antivascular endothelial growth factor treatment in diabetic macular edema: a systematic review and meta-analysis.

To better understand the efficacy of intravitreal dexamethasone implant (Ozurdex) versus antivascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). A systematic review and meta-analysis. The study included randomized control trials (RCTs) and non-randomized control trials (Non-RCTs) before December 2021 that compare the efficacy of Ozurdex-related therapyand anti-VEGF therapy. We searched PubMed, Cochrane Library, and EMBASE. The quality of the included studies was assessed carefully. 30 studies were included. Regarding BCVA change, the overall result revealed no significant differences between Ozurdex and anti-VEGF therapies in patients with nonresistant DME, but Ozurdex group had significantly more VA improvement than anti-VEGF therapies in patients with resistant DME (MD 0.12, 95% CI 0.02-0.21). In terms of central retinal thickness (CRT) decrease, there was a significant difference between Ozurdex therapy and anti-VEGF therapy in patients with nonresistant DME (MD 48.10, 95% CI 19.06-77.13) and resistant DME (MD 65.37, 95% CI 3.62-127.13). Overall, Ozurdex therapy resulted in significantly greater VA improvement and CRT decrease than anti-VEGF therapy in resistant DME patients. Ozurdex therapy was not inferior to anti-VEGF therapy in patients with nonresistant DME.

Ophthalmic characteristics and retinal vasculature changes in Williams syndrome, and its association with systemic diseases.

BACKGROUND: We aim to characterise the ophthalmic findings and retinal vasculature changes in patients with WS, and to analyse the correlation between ophthalmic manifestations and the associated systemic diseases. METHODS: This retrospective case-control study included 27 WS patients and 28 age-matched healthy participants. Stellate pattern of iris, central macular thickness (CMT), foveal width, retinal vessel diameter, superficial vascular density (SVD) of macula and foveal avascular zone (FAZ) were compared between WS patients and healthy participants. RESULTS: Twenty-five patients (93%) had the classic stellate iris presentation. Compared with healthy controls, WS patients had decreased CMT, increased foveal width and a lower SVD of macula (all P < 0.001). Significantly decreased mean retinal arterial (117.9 ± 9.9 µm vs. 133.0 ± 6.7 µm in WS and controls, respectively; p < 0.001) and venous (158.9 ± 11.2 µm vs. 174.0 ± 8.0 µm in WS and controls, respectively; p < 0.001) outer diameters, as well as mean arterial wall thickness (11.2 ± 1.3 µm vs. 12.2 ± 0.8 µm in WS and controls, respectively; p < 0.01) were found in WS. Stellate iris grading was significantly associated with CMT, foveal width, retinal vessel diameter (all p < 0.05), and a significant increase in the odds of having hypertension (Odds ratio (OR), 5.63; P < 0.05). The severity of stellate iris in WS seemed to have the trend of increasing risk of having pulmonary stenosis, tricuspid regurgitation and mitral regurgitation. CONCLUSIONS: This study provides the first in vivo evidence reflecting current knowledge on vessel morphology in WS patients that deficient circumferential growth is the predominant pathophysiologic changes resulting from elastin deficiency. The ophthalmic characteristics may serve as a complementary tool to diagnose and follow-up patients suffering from WS.

Bleb-related infection after primary trabeculectomy: medical chart reviews from 1993 to 2021.

BACKGROUND: To investigate the incidence of and risk factors for bleb-related infection (BRI) in patients who underwent mitomycin C-augmented primary trabeculectomy. METHODS: We reviewed the medical charts of consecutive patients who had received primary trabeculectomy in Taipei Veterans General Hospital. We recorded the demographic and clinical characteristics of patients before, during and after surgery. Furthermore, we recorded the time interval between surgery and infection onset, clinical manifestations and visual outcomes of patients with BRI. The cumulative incidence of BRI was estimated using the Kaplan-Meier method. A Cox proportional hazards model was used to explore factors associated with BRI. RESULTS: In total, 1663 eyes were postoperatively followed up for 94.57±65.23 months. The cumulative incidence of BRI was 1.86 per 1000 person-years during the 28-year follow-up period: 24 (1.44%) patients developed BRI and 6 (0.36%) patients additionally developed endophthalmitis. A multivariate analysis revealed a significant association of BRI with wound manipulation, high myopia and hyperlipidaemia. Patients younger than 60 years were more likely to receive wound manipulation than their elderly counterparts (<0.001). One year after BRI, the best corrected visual acuity of the eyes with blebitis did not change significantly, whereas that of the eyes with endophthalmitis worsened significantly. CONCLUSION: Risk factors for BRI after trabeculectomy include wound manipulation, high myopia and hyperlipidaemia. Considering myopia is highly prevalent throughout the world and is a risk factor for glaucoma, the lifelong risk of BRI after trabeculectomy in eyes with high myopia warrants the attention of ophthalmologists.

Candidate Modifier Genes for the Penetrance of Leber's Hereditary Optic Neuropathy.

Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease caused by mitochondria DNA (mtDNA) mutation. It is characterized by acute and subacute visual loss predominantly affecting young men. The mtDNA mutation is transmitted to all maternal lineages. However, only approximately 50% of men and 10% of women harboring a pathogenic mtDNA mutation develop optic neuropathy, reflecting both the incomplete penetrance and its unexplained male prevalence, where over 80% of patients are male. Nuclear modifier genes have been presumed to affect the penetrance of LHON. With conventional genetic methods, prior studies have failed to solve the underlying pathogenesis. Whole exome sequencing (WES) is a new molecular technique for sequencing the protein-coding region of all genes in a whole genome. We performed WES from five families with 17 members. These samples were divided into the proband group (probands with acute onset of LHON, n = 7) and control group (carriers including mother and relative carriers with mtDNSA 11778 mutation, without clinical manifestation of LHON, n = 10). Through whole exome analysis, we found that many mitochondria related (MT-related) nuclear genes have high percentage of variants in either the proband group or control group. The MT genes with a difference over 0.3 of mutation percentage between the proband and control groups include AK4, NSUN4, RDH13, COQ3, and FAHD1. In addition, the pathway analysis revealed that these genes were associated with cofactor metabolism pathways. Family-based analysis showed that several candidate MT genes including METAP1D (c.41G > T), ACACB (c.1029del), ME3 (c.972G > C), NIPSNAP3B (c.280G > C, c.476C > G), and NSUN4 (c.4A > G) were involved in the penetrance of LHON. A GWAS (genome wide association study) was performed, which found that ADGRG5 (Chr16:575620A:G), POLE4 (Chr2:7495872T:G), ERMAP (Chr1:4283044A:G), PIGR (Chr1:2069357C:T;2069358G:A), CDC42BPB (Chr14:102949A:G), PROK1 (Chr1:1104562A:G), BCAN (Chr 1:1566582C:T), and NES (Chr1:1566698A:G,1566705T:C, 1566707T:C) may be involved. The incomplete penetrance and male prevalence are still the major unexplained issues in LHON. Through whole exome analysis, we found several MT genes with a high percentage of variants were involved in a family-based analysis. Pathway analysis suggested a difference in the mutation burden of MT genes underlining the biosynthesis and metabolism pathways. In addition, the GWAS analysis also revealed several candidate nuclear modifier genes. The new technology of WES contributes to provide a highly efficient candidate gene screening function in molecular genetics.

Leber Hereditary Optic Neuropathy: Molecular Pathophysiology and Updates on Gene Therapy.

Molecular pathophysiology of LHON was reviewed and the current status of gene therapy for LHON is updated.

Comparison of Efficacy between Non-Steroidal Anti-Inflammatory Drugs and Anti-Vascular Endothelial Growth Factor in Preventing Macular Edema after Cataract Surgery in Diabetic Patients.

(1) Background: There is no consensus regarding the optimal strategy to prevent macular edema after cataract surgery in diabetic patients. The purpose of study is to compare the efficacy of topical nonsteroidal anti-inflammatory agents (NSAIDs) and intravitreal injections of anti-VEGFs for the prevention of macular edema after cataract surgery in diabetic patients without pre-existing macular edema. (2) Methods: A literature search of the MEDLINE, PUBMED, and EMBASE databases was conducted in July 2021. Studies involving either topical NSAIDs or intravitreal injections of anti-VEGF arms that reported either the occurrence of macular edema or changes in best corrected visual acuity (BCVA) were included. Weighted mean differences and risk ratios were calculated along with 95% confidence intervals. (3) Results: Intravitreal injection of anti-VEGFs provided short-term structural protection for one month in patients receiving cataract surgery, but the protective effect ceased to exist after three months. The structural protection of topical NSAIDs, however, can last for at least three months. Meanwhile, neither anti-VEGFs nor NSAIDs provided significant visual improvement. (4) Conclusions: Our study suggested that topical NSAIDs eye drops is an effective prevention strategy for macular edema after cataract surgery in diabetic patients.

Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry.

Glaucoma is a progressive and irreversible blindness-causing disease. However, the underlying genetic factors and molecular mechanisms remain poorly understood. Previous genome-wide association studies (GWAS) have made tremendous progress on the SNP-based disease association and characterization. However, most of them were conducted for Europeans. Since differential genetic characteristics among ethnic groups were evident in glaucoma, it is worthwhile to complete its genetic landscape from the larger cohorts of Asian individuals. Here, we present a GWAS based on the Taiwan Biobank. Among 1013 glaucoma patients and 36,562 controls, we identified a total of 138 independent glaucoma-associated SNPs at the significance level of p < 1 × 10-5. After clumping genetically linked SNPs (LD clumping), 134 independent SNPs with p < 10-4 were recruited to construct a Polygenic Risk Score (PRS). The model achieved an area under the receiver operating characteristic curve (AUC) of 0.8387 (95% CI = [0.8269-0.8506]), and those within the top PRS quantile had a 45.48-fold increased risk of glaucoma compared with those within the lowest quantile. The PRS model was validated with an independent cohort that achieved an AUC of 0.7283, thereby showing the effectiveness of our polygenic risk score in predicting individuals in the Han Chinese population with higher glaucoma risks.

To measure the amount of ocular deviation in strabismus patients with an eye-tracking virtual reality headset.

PURPOSE: To investigate the accuracy of a newly developed, eye-tracking virtual reality (VR)-based ocular deviation measurement system in strabismus patients. METHODS: A VR-based ocular deviation measurement system was designed to simulate the alternative prism cover test (APCT). A fixation target was made to alternate between two screens, one in front of each eye, to simulate the steps of a normal prism cover test. Patient's eye movements were recorded by built-in eye tracking. The angle of ocular deviation was compared between the APCT and the VR-based system. RESULTS: This study included 38 patients with strabismus. The angle of ocular deviation measured by the VR-based system and the APCT showed good to excellent correlation (intraclass correlation coefficient, ICC = 0.897 (range: 0.810-0.945)). The 95% limits of agreement was 11.32 PD. Subgroup analysis revealed a significant difference between esotropia and exotropia (p < 0.001). In the esotropia group, the amount of ocular deviation measured by the VR-based system was greater than that measured by the APCT (mean = 4.65 PD), while in the exotropia group, the amount of ocular deviation measured by the VR-based system was less than that of the APCT (mean = - 3.01 PD). The ICC was 0.962 (range: 0.902-0.986) in the esotropia group and 0.862 (range: 0.651-0.950) in the exotropia group. The 95% limits of agreement were 6.62 PD and 11.25 PD in the esotropia and exotropia groups, respectively. CONCLUSIONS: This study reports the first application of a consumer-grade and commercial-grade VR-based device for assessing angle of ocular deviation in strabismus patients. This device could provide measurements with near excellent correlation with the APCT. The system also provides the first step to digitize the strabismus examination, as well as the possibility for its application in telemedicine.

Systematic review with network meta-analysis of antivascular endothelial growth factor use in managing polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is a vision-threatening disease common in Asian populations. However, the optimal treatment for PCV remains under debate. We searched the databases with optimal searching strategy. The study included randomized clinical trials and prospective studies that recruited patients with active PCV who had received interventions, including PDT, anti-VEGF, or a combination of PDT and anti-VEGF. The Grading of Recommendations Assessment, Development, and Evaluation methodology was used for rating the quality of evidence. Our study included 11 studies involving 1277 patients. The network meta-analysis of RCTs revealed the anti-VEGF group, early combination group, and late combination group had significant BCVA changes compared with the PDT group. Early combination therapy led to a significant decrease in CRT compared with PDT, anti-VEGF, and late combination therapy. Additionally, the early combination group had a significantly higher complete polyp regression rate than the anti-VEGF group. No significant differences were detected in the analysis of the number of anti-VEGF injections and safety profile. This network meta-analysis revealed that early combination therapy exhibited better efficacy related to anatomical outcomes than other therapies. Nonetheless, no significant differences related to BCVA change could be detected between anti-VEGF and late combination therapy.

An Updated Systematic Review With Meta-Analysis Of Randomized Trials On Topical Cyclosporin A For Dry-Eye Disease.

BACKGROUND/AIMS: To evaluate the effects of topical cyclosporin A (CsA) and artificial tears (ATs) for treating patients with dry-eye disease (DED). METHODS: On January 25, 2019, five electronic databases and reference lists were searched for randomized clinical trials (RCTs) comparing CsA with ATs among patients with DED. The search strategy had no restriction on language or time. Two authors extracted surgery, mean age, anesthesia for Schirmer's test, tear-breakup time, Schirmer's test score, fluorescein-staining score, ocular surface-disease index, and adverse events. Mean differences (MDs) were calculated for continuous outcomes and Peto ORs for dichotomous data with zero cells. Results were analyzed with 95% CIs in a random-effect model. RESULTS: Eleven RCTs recruiting 1,085 cases with DED were included. Pooled results showed that CsA had better tear-breakup time (MD 0.94, 95% CI 0.08-1.80), fluorescein-staining score (standardized MD -0.72, 95% CI -1.28 to -0.16), and ocular surface-disease index (MD -4.75, 95% CI -6.31 to -3.18) when compared to ATs. Although CsA had more adverse events than ATs (Peto OR 7.70, 95% CI 3.17-18.68), no serious adverse events were reported. CONCLUSION: Overall, CsA is an effective option for treating patients with DED, yet our evidence indicated decreasing effects when CsA was combined with ATs. CsA may be worth suggesting to relatively older patients with DED. We anticipate further RCTs to explore the effects of treatment duration, optimal dosage, and efficacy of CsA in different DED etiology.

Selective laser trabeculoplasty versus medication for open-angle glaucoma: systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: The only widely accepted, effective treatment for open-angle glaucoma (OAG) is to reduce the intraocular pressure (IOP), with medical therapy being the typical first-line therapy. Notably, an alternative therapy is selective laser trabeculoplasty (SLT), which is safe and effective in lowering the IOP. Nonetheless, whether SLT could replace medication as the first-line therapy for OAG is still under debate. METHODS: Studies involving randomised controlled trials conducted before August 2019 that compared the efficacy of SLT-related and medication-only treatments for OAG were selected from PubMed, Embase, Cochrane Library and Web of Science. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology was employed to rate the quality of the body of evidence. RESULTS: 1229 patients in eight trials were included. The overall results revealed no significant differences between SLT-related and medication-only treatments regarding the IOP reduction (mean difference (MD): 0.18, 95% CI -0.72 to 1.07, p=0.70, I2=73%) and the success rate of IOP control (risk ratio: 1.02, 95% CI 0.99 to 1.04, p=0.74, I2=0%). The SLT-related therapy group required significantly fewer medications compared with the medication-only group (MD: -1.06, 95% CI -1.16 to -0.96, p<0.0000, I2=5%). A quantitative analysis was not performed concerning adverse events and quality of life because of the limited data available. CONCLUSION: SLT is safe and has a lower incidence of ocular side effects. SLT can be the choice of first-line therapy for OAG. However, clinicians should consider the cost-effectiveness, as well as the patient's characteristics, before deciding on the therapeutic option.

The effects of losartan versus beta-blockers on cardiovascular protection in marfan syndrome: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Variable effects of beta-blockers (BB) and/or angiotensin receptor blockers (ARB) were reported to retard aortic root growth in Marfan syndrome (MFS). This study aimed to compare the effects of BB therapy and ARB-related therapies on cardiovascular protection in MFS. METHODS: Studies of randomized control trials comparing the efficacy of only-BB and ARB-related (only-ARB or ARB-plus-BB) therapies for MFS published before July 31, 2018 in PubMed, Embase, and the Cochrane Library were selected. The outcomes included changes in aortic growth and cardiovascular events. RESULTS: Eight trials involving 1381 patients were included. Patients received only-BB and ARB-related therapies did not differ significantly in changes in aortic growth (aortic root diameter: standardized mean difference [SMD] = 0.04, 95% confidence interval [CI]: -0.11-0.19, p = 0.63) or cardiovascular events (aortic dissection: Peto odds ratio [OR] = 1.67, 95% CI: 0.42-6.72, p = 0.47; aortic surgery: risk ratio = 0.97, 95% CI: 0.66-1.41, p = 0.86; death: Peto OR = 2.78, 95% CI: 0.39-19.82, p = 0.31). Subgroup analysis revealed that ARB-plus-BB therapy exhibited nonsignificantly better outcomes than only-BB therapy (aortic root diameter: SMD = 0.11, 95% CI: -0.22-0.45, p = 0.52; ascending aorta diameter: SMD = 0.10, 95% CI: -0.07-0.27, p = 0.26; aortic surgery: Peto OR = 1.10, 95% CI: 0.75-1.61, p = 0.62). CONCLUSION: For cardiovascular protection in MFS, only-ARB therapy is not inferior to only-BB therapy. Moreover, the outcomes of ARB-plus-BB therapy seemed to be favourable to those of only-BB therapy.

Effects of Polyunsaturated Fatty Acids on Nonspecific Typical Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

To investigate the effects of polyunsaturated fatty acids (PUFAs) in patients with dry eye disease (DED), a multifactorial inflammatory disorder, we searched Cochrane Library, EMBASE, PubMed, and Web of Science for randomized clinical trials (RCTs) investigating the effect of PUFAs in patients with DED before March 2019. Two reviewers independently abstracted data of tear breakup time (TBUT), Schirmer's test, osmolarity, and ocular surface disease index (OSDI). We conducted pairwise meta-analysis using means and standard deviations (SDs) in a random-effects model for continuous outcomes. Thirteen eligible RCTs with 1782 patients with nonspecific typical DED were included. Patients who received PUFA treatment without other eye medications exhibited greater improvements in TBUT (MD = 1.80; p = 0.001), Schirmer test scores (MD = 0.50; p < 0.001), osmolarity (MD = -15.95; p < 0.001), and OSDI scores (MD = -10.19; p < 0.001) than those who received placebo treatment. However, the effects of PUFAs on TBUT (p < 0.001) and OSDI scores (p = 0.03) weakened with treatment duration. PUFAs are effective in treating nonspecific typical DED, particularly as a short-term treatment, with relatively few adverse events. Therefore, in real-world clinical practice, PUFA supplements are worth being suggested to patients with nonspecific typical DED who are not concurrently using other topical or systematic eye medications.

Helps from flipped classroom in learning suturing skill: The medical students' perspective.

BACKGROUND: Today, flipped classroom (FC) has been widely used in medical education. However, the effectiveness of FC remains controversial. The variation may cause by different subjects or different course design. Moreover, those studies did not explain how the association among different domains of learning objective was in FCs. The purpose of this study was to explore the help of learning domains from a FC of suturing skill in year-5 medical students. DESIGN: This study determined sample size according to statistical power. A minimum number of 77 participants for regression analysis are needed. Therefore, this study enrolled 78 medical students in a 2-hour suturing course, which consisted of pre-class video and in-class instruction. Both simple and mattress suturing were taught. The students received an anonymous survey with questionnaire of Help from Instruction Questionnaire for Clinical Skills (HIQ-CS) after the course. The HIQ-CS was developed by medical education team according to Bloom's taxonomy, and its reliability was favorable (Cronbach's ^l = 0.839). Factor loadings among all items in the HIQ-CS was also favorable (0.790 to 0.849). This study determined consensus of students' perspective by median (Me) and interquartile range (IQR), and tested mediation among different learning domains by regression. RESULTS: The results showed medical students agreed FC can help them in learning suturing (Me = 4, IQR = 1). The cognitive help (ß = .526, p < .001) was completely mediated by psychomotor help (ß = .399, p < .001) and affective help (ß = .413, p < .001) to overall helps in FC. The affective help (ß = .617, p < .001) was partially mediated by psychomotor help to overall helps in FC. CONCLUSIONS: FC may help students in learning suturing skill in different domains. Our model explains the cognitive help from FC provides an important foundation for the helps of other domains. Although the model should be examined by different curricula and measurements in future, the model of help from instruction in our study provided an innovated concept and framework in medical education.