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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.

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.

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. Keywords: Angiotensin receptor blocker, Aortic aneurysm, Beta blocker, Losartan, Marfan

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 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.

BackgroundThe 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.MethodsStudies 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.Results1229 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, p2=5%). A quantitative analysis was not performed concerning adverse events and quality of life because of the limited data available.ConclusionSLT 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.

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&rsquo, 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 &lt, 0.001), osmolarity (MD = &minus, 15.95, 0.001), and OSDI scores (MD = &minus, 10.19, 0.001) than those who received placebo treatment. However, the effects of PUFAs on TBUT (p &lt, 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.

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 (β = .526, p < .001) was completely mediated by psychomotor help (β = .399, p < .001) and affective help (β = .413, p < .001) to overall helps in FC. The affective help (β = .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.