Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study.

PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel2). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients undergoing surgery for MacTel2-associated full-thickness macular hole (MTMH). METHODS: Standardized data collection sheet distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH. RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% female, 72% White, 21% East or South Asian, 2% African American, and 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peeling, preoperative visual acuity (VA) was 0.667 ± 0.423 logarithm of the minimum angle of resolution (logMAR). Minimum hole diameter (MHD) was 305.5 ± 159.4 µm (range, 34-573 µm). Sixteen of 34 ILM peels (47%) resulted in MTMH closure. At postoperative month 6, VA was stable at 0.602 ± 0.516 logMAR (P = 0.65). VA improved by at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was 0.878 ± 0.552 logMAR. MHD was 440.8 ± 175.5 µm (range, 97-697 µm), which was significantly larger than for ILM peels (P < 0.01). Twenty of 22 ILM flaps (90%) resulted in MTMH closure, which was significantly higher than for ILM peels (P < 0.01). At postoperative month 6, VA improved to 0.555 ± 0.405 logMAR (P < 0.05). VA improved by at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was 1.460 ± 0.391 logMAR. MHD was 390.2 ± 203.7 µm (range, 132-687 µm). All 5 ARTs (100%) resulted in MTMH closure. At postoperative month 6, VA was stable at 1.000 ± 0.246 logMAR (P = 0.08). Visual acuity improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. Internal limiting membrane flaps achieved better anatomic and functional outcomes than ILM peeling alone. Autologous retinal transplantation may be an option for refractory MTMHs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association of sodium-glucose cotransporter-2 inhibitors and the risk of retinal vascular occlusion: A real-world retrospective cohort study in Taiwan.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. MATERIALS AND METHODS: This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). RESULTS: In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). CONCLUSIONS: In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.

A comparative study of stereopsis in term and preterm children with and without retinopathy of prematurity.

PURPOSE: To evaluate stereopsis in term-born, preterm, and preterm children with and without retinopathy of prematurity (ROP) and its treatment. METHODS: The cross-sectional study included 322 children between 3 and 11 years of age born term or preterm, with or without ROP, and with or without treatment for ROP. The ROP treatments were laser therapy, intravitreal injection (IVI) of anti-vascular endothelial growth factor, or their combination. Stereoacuity was measured using the Titmus Stereo Test, and the results among various age groups were analyzed. RESULTS: Stereopsis was found to improve with increasing age at testing (P < 0.001) across the entire study population. The term group exhibited significantly better stereoacuity than the preterm group (P < 0.001). At 3-5 years and 6-8 years, the preterm children without ROP exhibited significantly better stereoacuity than did those with ROP (P < 0.001 and P = 0.02, respectively); however, at 9-11 years, both groups exhibited similar stereoacuity (P = 0.34). The stereoacuity in the children with untreated ROP was similar to that of the children with treated ROP in all age groups (P > 0.05). No significant differences in stereopsis were identified between children with ROP treated with laser versus with IVI (P > 0.05). From multivariate analysis, younger age at testing (P = 0.001) and younger gestational age (P < 0.001) were associated with poorer stereopsis. CONCLUSIONS: Stereopsis development gradually improved with age in all groups. The children born preterm exhibited poorer stereoacuity than those born term. Children with ROP treated with laser photocoagulation versus IVI may exhibit similar levels of stereoacuity. Younger age at testing and gestational age were independent risk factors for poorer stereoacuity.

LONGITUDINAL CHANGES IN CHOROIDAL THICKNESS IN CHILDREN WITH A HISTORY OF PREMATURITY: An 18-Month Prospective Cohort Study.

PURPOSE: To evaluate choroidal changes over time in school-age children with a history of prematurity. METHODS: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.

PRESENTATIONS AND FACTORS AFFECTING OUTCOME OF RHEGMATOGENOUS RETINAL DETACHMENT WITH CHOROIDAL DETACHMENT: An Indo-Taiwanese Study.

PURPOSE: To report the clinical settings, management, and factors associated with outcomes of rhegmatogenous retinal detachment with concurrent choroidal detachment. METHODS: Retrospective, consecutive, multicenter case series from January 2014 to January 2021 were included. Cases were from a tertiary eye care center in India and Taiwan. RESULTS: Overall 303 eyes were included. Mean age was 43.72 ± 20.64 years (median 46). Best-corrected presenting visual acuity was 1.79 ± 0.92 logMAR (median 2.10) (Snellen 20/1,233). Forty-four patients (17.91%) received preoperative steroids. Final visual acuity was 1.33 ± 0.94 logMAR (median 1.10) (Snellen 20/427). Favorable anatomic outcome was seen in 200/303 (66%), whereas favorable functional outcome was seen in 128/303 (42.20%). Factors predicting favorable anatomic outcome were absence of phakic lens status (odds ratio [OR] 2.76), absence of proliferative vitreoretinopathy worse than Grade A (OR 7.69), use of preoperative steroids (OR 4.50), and use of an encircling band (3.85). Factors predicting favorable functional outcome were better presenting visual acuity (OR 3.03), absence of phakic lens status (OR 4.93), absence of proliferative vitreoretinopathy worse than Grade A (OR 10.41), and use of preoperative steroids (OR 7.24). CONCLUSION: Administration of preoperative steroids, use of an encircling band during surgery, and pseudophakic status of the eye were found to have better outcomes in rhegmatogenous retinal detachment with concurrent choroidal detachment.

Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.

PEELING AND INTERNAL LIMITING MEMBRANE REPOSITION (PAIR) FOR MYOPIC FOVEOSCHISIS.

PURPOSE: To report the outcomes of the Peeling and Internal Limiting Membrane Reposition (PAIR) technique in myopic foveoschisis. METHODS: A retrospective case series of eyes with myopic foveoschisis that underwent vitrectomy and PAIR. Visual acuity, fundus photographs, and optical coherence tomography measurements were obtained and analyzed. Data are presented as medians (ranges). RESULTS: A total of seven eyes underwent PAIR and were followed up for 339 days (188-436 days). No intraoperative complications were noted. One eye exhibited postoperative macular hole formation, but the hole was healed through fluid-gas exchange. At the last follow-up, the visual acuity had improved from 20/66 (20/332-20/40) to 20/40 (20/100-20/25), and the central foveal thickness had decreased from 576 µ m to 269 µ m. A repositioned internal limiting membrane (ILM) was observed in six of the eyes, and inner retinal dimples were noted in only two eyes. However, retinal wrinkles under the repositioned or perifoveal ILM were noted in five eyes. CONCLUSION: The PAIR technique relieved traction, restored the ILM, and achieved functional and morphological improvement in eyes with myopic foveoschisis. Limited occurrence of inner retinal dimples and retinal thinning was noted, but retinal wrinkles occurred, likely due to ILM contracture.

Retrospective Analysis of Surgical Outcomes on Axial Length Elongation in Eyes with Posterior and Combined Persistent Fetal Vasculature.

This study aims to investigate the outcomes and risk factors associated with poor vision (vision less than counting fingers, 2.0 logMAR, Snellen vision 20/2000) in patients with posterior or combined persistent fetal vasculature (PFV), with or without surgery. We retrospectively reviewed the medical records of patients who were diagnosed with PFV from January 2008 to April 2021. We included 51 eyes of 44 patients who presented with PFV, of which 38 eyes underwent surgical correction (pars plicata/plana vitrectomy, with or without lensectomy, and intraocular lens implantation) at the median age of 6.0 months (range: 0.7 to 82.0). The mean follow-up was 68.8 months ± 38.0 months. The axial length change in the eyes undergoing surgery was significantly higher than the eyes without surgery (p = 0.025). Initial anterior chamber collapse and retinal detachment were associated with poor vision (p = 0.006 and p = 0.002, respectively). In addition, 37% of eyes with posterior or combined PFV had vision better than counting fingers. Surgery for eyes with PFV could result in better eye growth. Visual outcomes remained poor and were associated with the level of macular abnormality. Initial anterior chamber collapse and retinal detachment at presentation were the risk factors for poor visual outcomes. Vitrectomy for selected PFV eyes is valuable and associated with a better cosmetic outcome (better eye growth).

MicroRNA-152-3p and MicroRNA-196a-5p Are Downregulated When Müller Cells Are Promoted by Components of the Internal Limiting Membrane: Implications for Macular Hole Healing.

Müller cells play a critical role in the closure of macular holes, and their proliferation and migration are facilitated by the internal limiting membrane (ILM). Despite the importance of this process, the underlying molecular mechanism remains underexplored. This study investigated the effects of ILM components on the microRNA (miRNA) profile of Müller cells. Rat Müller cells (rMC-1) were cultured with a culture insert and varying concentrations of ILM component coatings, namely, collagen IV, laminin, and fibronectin, and cell migration was assessed by measuring cell-free areas in successive photographs following insert removal. MiRNAs were then extracted from these cells and analyzed. Mimics and inhibitors of miRNA candidates were transfected into Müller cells, and a cell migration assay and additional cell viability assays were performed. The results revealed that the ILM components promoted Müller cell migration (p < 0.01). Among the miRNA candidates, miR-194-3p was upregulated, whereas miR-125b-1-3p, miR-132-3p, miR-146b-5p, miR-152-3p, miR-196a-5p, miR-542-5p, miR-871-3p, miR-1839-5p, and miR-3573-3p were significantly downregulated (p < 0.05; fold change > 1.5). Moreover, miR-152-3p and miR-196a-5p reduced cell migration (p < 0.05) and proliferation (p < 0.001), and their suppressive effects were reversed by their respective inhibitors. In conclusion, miRNAs were regulated in ILM component-activated Müller cells, with miR-152-3p and miR-196a-5p regulating Müller cell migration and proliferation. These results serve as a basis for understanding the molecular healing process of macular holes and identifying potential new target genes in future research.

Experiences of oncology healthcare personnel in international medical service quality: a phenomenological study.

BACKGROUND: With the globalization of medical services on the rise, Asia has ascended to a destination of choice for its high-quality medical services at very reasonable rates. Monitoring the quality of the international medical industry is vital to maintain service demand. The experiences of healthcare personnel (HCP) involved in international medical services (IMS) regarding the provision of services to international cancer patients have not yet been discussed. This study aimed to explore oncology HCP experiences of IMS quality in caring for international cancer patients in Taiwan. METHODS: Descriptive phenomenological method and were analyzed through Colaizzi's seven-step approach. In this study, 19 respondents were collected data by using in-depth semi-structured interviews. An average interview lasted approximately 45 min. RESULTS: Four major themes were identified from the interviews: patient selection, psycho-oncology care, predicaments, and promoting suggestions. Additionally, thirteen subthemes emerged, including necessary selection of patients, reasons for unwillingness to enroll international patients, helpless patients, emotional distress, care with warmth, insufficient manpower, an unfair reward mechanism, poor hardware equipment, the predicaments of oncology care, various publicity strategies, one-on-one service model, design of a designated area, and reasonable benefit distribution. CONCLUSIONS: This study explored oncology HCP experiences of IMS quality in caring for international cancer patients, with implications for hospitals in developing high-quality IMS. Due to the fact that IMS is a global trend, HCPs, administrators, and policy-makers are advised to improve the quality of IMS in the oncology department, which has been the least studied field in IMS quality.

COMPARISON BETWEEN ORAL AND INTRAVENOUS ULTRAWIDE-FIELD FLUORESCEIN ANGIOGRAPHY IN THE CLINICAL FOLLOW-UP OF CHILDREN WITH A HISTORY OF RETINOPATHY OF PREMATURITY OR PREMATURITY.

PURPOSE: To compare between oral and intravenous (IV) ultrawide-field fluorescein angiography in pediatric patients with a history of prematurity of retinopathy or prematurity. METHODS: Pediatric patients (<18 year old; n = 107 patients) who underwent ultrawide-field fluorescein angiography for retinopathy of prematurity were categorized into oral and IV fluorescein angiography (FA) groups. Quality of FA images was graded on the order of retinal vessels visible. Reported outcomes were proportions of graded FA images, peak fluorescein intensity, and the time to first dye appearance and to reach peak fluorescence. RESULTS: Image quality analysis revealed that 91.5% of IV FA images had excellent image quality compared with only 55.6% of oral FA images (P < 0.01). There were still 83.3% of oral-contrast images with good or excellent image quality. The average time required for first dye appearance and peak fluorescence were significantly shorter in the IV FA group than in the oral FA group (P < 0.01). Peak intensity was greater in the IV group (141.41 ± 29.09) than in the oral group (111.25 ± 45.68; P < 0.01). Adverse reaction rates were similar between the two groups (P = 0.22). CONCLUSION: Ultrawide-field fluorescein angiography provides excellent-quality imaging of the retina in the pediatric population. Overall, oral FA is still an effective and useful alternative to IV FA in children with prematurity history.

SURGICAL OUTCOME AND PROGNOSTIC FACTORS AFTER OPHTHALMIC SURGERY IN ABUSIVE HEAD TRAUMA.

PURPOSE: To analyze the clinical characteristics, surgical outcomes, and risk factors associated with visual outcomes in patients with abusive head trauma (AHT). METHODS: We retrospectively reviewed surgical outcomes of patients with AHT who underwent vitrectomy from 2001 to 2019. The patients' demographics, comprehensive preoperative and postoperative ocular findings, surgical treatments, visual outcomes, and postoperative complications in the medical records were reviewed. Univariable and multivariable analyses were performed to identify the prognostic factors associated with visual outcomes. RESULTS: Fourteen children (18 eyes) diagnosed with AHT who underwent vitrectomy were evaluated. The most common surgical indication was vitreous hemorrhage (n = 6, 33%). Retinal attachment at the final visit was noted in 17 eyes (94%). Thirteen eyes (72%) had a best-corrected visual acuity less than 20/200 after vitrectomy. In the multivariable analysis, optic nerve atrophy (n = 9, 50%) was significantly associated with a poor visual prognosis (final best-corrected visual acuity worse than 20/200) after vitrectomy in children with AHT (95% confidence interval, 1.041-517.963, P = 0.0471). CONCLUSION: The general visual prognosis was poor for patients with AHT needing vitrectomy, although a high rate of retinal attachment was observed. Optic nerve atrophy is a prognostic factor for poor visual outcomes in patients with AHT who received ophthalmic surgery.

Treatment responses for branch retinal vein occlusion predicted by semi-automated fluorescein angiography quantification.

BACKGROUNDS: Branch retinal vein occlusion (BRVO) is one of the most important causes of visual loss in retinal vascular diseases. The aim of this study is to predict the treatment response of anti-vascular endothelial growth factor (anti-VEGF) therapy in BRVO using semi-automated quantified fluorescein angiography (FA) features. METHODS: This retrospective case-control study enrolled patients with BRVO who are receiving anti-VEGF therapy and have been followed up for > 1 year. Those receiving < 5 anti-VEGF injections in the first year were classified as the responsive group, while those receiving ≥5 injections were the refractory group. The FA images were subjected to semi-automated pre-processing. Fluorescein leakages at the 5-min image were represented by mean gray value over parafoveal and perifoveal regions. FA leakages and central retinal thickness (CRT) on optical coherence tomography (OCT) were used for predicting the treatment response and compared using area under receiver operating characteristic curve (AUC). RESULTS: Eighty-nine patients (56 males, 33 females, mean age 62.5 ± 10.9 years) with BRVO were enrolled. Of the 89 eyes, 47 (53%) were in the responsive group and 42 (47%) were in the refractory group. The refractory group had a significantly higher number of anti-VEGF injections in the first year (5.9 ± 1.6 versus 2.4 ± 1.2, p < 0.001) when compared with that of the responsive group. It had thicker pre-treatment CRT (p = 0.011), post-treatment best CRT (p < 0.001) and CRT at 1-year (p < 0.001). It also had a higher mean gray value over the parafoveal (p < 0.001) and the perifoveal (p < 0.001) regions. The mean gray value over perifoveal (AUC 0.846) and parafovel (AUC 0.818) had significantly larger AUC than that of the pre-treatment OCT (AUC 0.653; p = 0.005 and p = 0.016, respectively) when predicting treatment response. CONCLUSION: The refractory group had a more severe fluorescein leakage over the parafoveal and the perifoveal regions than the responsive group had. Semi-automated quantified FA leakage can be used as a biomarker for the prediction of anti-VEGF treatment response in macular edema due to BRVO.

Elevated Risk of Mood Disorders after the Occurrence of Recurrent Retinal Detachment: A Population-Based Cohort Study.

INTRODUCTION: The aim of this study was to investigate the risk of mood disorders in patients who experienced retinal detachment (RD) by using the National Health Insurance Research Database in Taiwan. METHODS: Participants with a diagnosis of RD were regarded as the study group, and an age- and sex-matched group without a diagnosis of RD served as the control group. The outcomes related to mood disorders after RD included: (1) psychiatric outpatient department visits; (2) behavioural therapy; (3) sleep or anxiety-related disorders; and (4) major depressive disorder (MDD). RESULTS: A total of 4,129 participants diagnosed with RD and 16,516 non-RD individuals were enrolled in the study. There were no significant differences in the four mood disorder-related outcomes between the study and control groups. However, the patients with recurrent RD who received more than two treatments and female patients with RD who needed surgical treatment showed a higher probability of developing MDD than did the non-RD subjects (incidence rate: 0.96 vs. 0.36; adjusted hazard ratio [aHR]: 2.382, 95% confidence interval [CI]: 1.032-5.496, log-rank p = 0.0325; and aHR: 6.895, 95% CI: 1.659-28.656, log-rank p = 0.0060, respectively). CONCLUSION: Patients with recurrent RD and multiple surgeries and females with RD who needed surgical treatment were at greater risk for developing MDD.

Ranibizumab reimbursement and treatment patterns for neovascular age-related macular degeneration in Taiwan - Results from the 12-month, observational RENOWNED study.

BACKGROUND: The RENOWNED study investigated the treatment patterns, real-world effectiveness and safety of ranibizumab in Taiwanese patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg in accordance with the first reimbursement scheme effective from 2012 to 2014. METHODS: This study was a Phase IV, 12-month, open-label, prospective, observational study conducted in Taiwan. Patients with visual impairment due to nAMD initiating treatment with ranibizumab 0.5 mg were included. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from Baseline at Month 3. RESULTS: Overall, 202 patients with nAMD were included. Mean (standard deviation [SD]) BCVA Early Treatment Diabetic Retinopathy Study letters improved from Baseline (49.6 [21.5] letters) at Month 3 (+4.9 [11.8], P < 0.0001), and at Month 12 (+3.5 [14.1], P = 0.0043). The proportion of patients with nAMD who lost ≥5 letters at Months 3 and 12 was 13.6% (n = 27) and 26.6% (n = 37), respectively. Mean (SD) central retinal thickness decreased from Baseline (320.1 [127.2] µm) with a mean reduction of 49.1 (107.3) µm at Month 3 (P < 0.0001), but was not significant at Month 12 with a mean reduction of 11.6 (115.6) µm (P = 0.2861). Mean (SD) number of ranibizumab injections over 12 months was 3.1 (1.0). A mean treatment interval of 109.5 days was observed between the third and fourth injections. After limited reimbursed ranibizumab injections, 43.8% patients received other treatments. The safety findings are consistent with previous studies. CONCLUSION: Ranibizumab 0.5 mg treatment for 12 months under real-world settings improved visual outcomes in Taiwanese patients with nAMD.

Effects of TIMP-2 Polymorphisms on Retinopathy of Prematurity Risk, Severity, Recurrence, and Treatment Response.

Tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in endogenous angiogenesis besides the regulation of matrix metalloproteinase (MMP) activity. Associations between TIMP-2 gene polymorphisms and the risk of retinopathy of prematurity (ROP) were examined. Premature infants born between 2009 and 2018 were included. Five single-nucleotide polymorphisms (SNPs) of TIMP-2 were analyzed with real-time polymerase chain reaction (PCR). Multivariate logistic regression was applied to model associations between TIMP-2 polymorphisms and ROP susceptibility and severity. The GA+AA genotype in individuals with the TIMP-2 polymorphism of rs12600817 was associated with a higher risk of ROP (odds ratio [OR]: 1.518, 95% confidence interval [CI]: 1.028-2.242) compared with their wild-type genotypes. The AA genotype (OR: 1.962, 95% CI: 1.023-3.762) and the AA+GA genotype (OR: 1.686, 95% CI: 1.030-2.762) in individuals with the rs12600817 polymorphism had higher risks of severe, treatment-requiring ROP relative to their wild-type counterparts. In patients with treatment-requiring ROP, the AG+GG genotypes in the TIMP-2 polymorphism of rs2889529 were correlated with the treatment response (p = 0.035). The TIMP-2 polymorphism of rs12600817 help in predicting ROP risks in preterm infants, while the polymorphism of rs2889529 can serve as a genetic marker in evaluating the ROP treatment response.

The Mutation Hotspots at UGT1A Locus May Be Associated with Gilbert's Syndrome Affecting the Taiwanese Population.

Gilbert's syndrome is mainly diagnosed through genetic analysis and is primarily detected through a mutation in the promoter region of the UGT1A1 gene. However, most of the research has been conducted on Caucasian populations. In this study, we studied the Han population in Taiwan to investigate the possibility of other mutations that could cause Gilbert's syndrome. This study comprised a test group of 45 Taiwanese individuals with Gilbert's syndrome and 180 healthy Taiwanese individuals as a control group. We extracted DNA from the blood samples and then used Axiom Genome-Wide TWB 2.0 array plates for genotyping. Out of 302,771 single nucleotide polymorphisms (SNPs) from 225 subjects, we detected 57 SNPs with the most significant shift in allele frequency; 27 SNPs among them were located in the UGT1A region. Most of the detected SNPs highly correlated with each other and are located near the first exon of UGT1A1, UGT1A3, UGT1A6, and UGT1A7. We used these SNPs as an input for the machine learning algorithms and developed prediction models. Our study reveals a good association between the 27 SNPs detected and Gilbert's syndrome. Hence, this study provides a reference for diagnosing Gilbert's syndrome in the Taiwanese population in the future.

Congenital Stationary Night Blindness: Clinical and Genetic Features.

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert-Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype-phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype-phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed.

Autologous Retinal Transplantation for Primary and Refractory Macular Holes and Macular Hole Retinal Detachments: The Global Consortium.

PURPOSE: To report the anatomic and functional outcomes of autologous retinal transplantation (ART). DESIGN: Multicenter, retrospective, interventional, consecutive case series. PARTICIPANTS: One hundred thirty eyes of 130 patients undergoing ART for the repair of primary and refractory macular holes (MHs), as well as combined MH-rhegmatogenous retinal detachment (MH-RRD), between January 2017 and December 2019. METHODS: All patients underwent pars plana vitrectomy and ART, with surgeon modification of intraoperative variables. A large array of preoperative, intraoperative, and postoperative data was collected. Two masked reviewers graded OCT images. Multivariate statistical analysis and subgroup analysis were performed. MAIN OUTCOME MEASURES: Macular hole closure rate, visual acuity (VA), external limiting membrane and ellipsoid zone (EZ) band integrity, and alignment of neurosensory layers (ANL) on OCT. RESULTS: One hundred thirty ART surgeries were performed by 33 vitreoretinal surgeons worldwide. Patient demographics were: mean age of 63 ± 6.3 years, 58% female, 41% White, 23% Black, 19% Asian, and 17% Latino. Preoperative VA was 1.37 ± 0.12 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/500), which improved significantly to 1.05 ± 0.09 logMAR (Snellen equivalent, approximately 20/225; P < 0.001) after surgery (mean follow-up, 8.6 ± 0.8 months). Autologous retinal transplantation was performed for primary MH repair in 27% of patients (n = 35), for refractory MH in 58% of patients (n = 76; mean number of previous surgeries, 1.6 ± 0.2), and for MH-RRD in 15% of patients (n = 19). Mean maximum MH diameter was 1470 ± 160 µm, mean minimum diameter was 840 ± 94 µm, and mean axial length was 24.6 ± 3.2 mm. Overall, 89% of MHs closed (78.5% complete; 10% small eccentric defect), with a 95% closure rate in MH-RRD (68.4% complete; 26.3% small eccentric defect). Visual acuity improved by at least 3 lines in 43% of eyes and by at least 5 lines in 29% of eyes. Reconstitution of the EZ (P = 0.02) and ANL (P = 0.01) on OCT were associated with better final VA. Five cases of ART graft dislocation (3.8%), 5 cases of postoperative retinal detachment (3.8%), and 1 case of endophthalmitis (0.77%) occurred. CONCLUSIONS: In this global experience, patients undergoing ART for large primary and refractory MHs and MH-RRDs achieved good anatomic and functional outcomes, with low complication rates despite complex surgical pathologic features.

Role of growth factors and internal limiting membrane constituents in müller cell migration.

This study investigated the effects of growth factors and internal limiting membrane components on Müller cell migration. We studied the effects of epidermal growth factor (EGF), fibroblast growth factor (FGF), somatomedin (IGF-1), platelet derived growth factor (PDGF), and stromal cell-derived factor-1 alpha (SDF-1α) as well as collagen IV, laminin, and fibronectin on the proliferative and migratory activities of rat Müller cells in vitro. A water soluble tetrazolium-1 assay was used to quantify the viability of Müller cells in respective cultures, and analysis was performed using an enzyme-linked immunosorbent assay reader. All the factors examined had significant proliferative effects on cultured Müller cells (p < .05). A two-well Ibidi silicone culture insert was used to assess Müller cell migration. Müller cells cultured in EGF, FGF, IGF-1, collagen IV, and laminin but not in SDF, PDGF, or fibronectin effectively increased the cell migratory activity (p < .001). In addition, combined EGF and collagen IV, combined FGF and collagen IV, and combined IGF-1 and laminin exhibited more significant (p < .001) effects on Müller cell migration compared with culture a single factor. In summary, this study revealed the combinatorial effects of various growth factors and individual internal limiting membrane constituents. This may assist Müller cell migration together with the macular hole healing process.