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.

Traumatic terson syndrome with a peculiar mass lesion and tractional retinal detachment: a case report.

BACKGROUND: To report a case with bilateral Terson syndrome presented with a unique mushroom-like mass lesion on the optic disc along with proliferative vitreoretinopathy and tractional retinal detachment. CASE PRESENTATION: A 33-year-old man was injured during a traffic accident and had diffuse brain swelling and intraocular hemorrhage. Poor vision in both eyes was noted after the patient regained consciousness. B-scan ultrasonography showed extensive vitreous opacity with a posterior vitreous detachment and without obvious retinal detachment. Vitrectomy was performed in both eyes five months after the accident. After clearing up the vitreous opacity, a peculiar pigmented mushroom-like mass lesion was noted in the posterior pole and had severe adhesion to the underneath optic disc. Extensive multilayered peripapillary epiretinal membrane was found covering the posterior pole and led to tractional retinal detachment around the macula. The mass was presumed to be an organized vitreous hemorrhage originated from the optic disc. The extensive and adherent epiretinal membrane together with the mass lesion were removed as much as possible and silicon oil was injected for tamponade. However, in the right eye, the retina redetached under silicon oil, whereas in the left eye, his vision improved to 20/100. CONCLUSIONS: Terson syndrome usually has a favorable prognosis but may be complicated by proliferative vitreoretinopathy and tractional retinal detachment. Careful monitoring is warranted and early vitrectomy should be considered in cases suspecting additional pathologies.

Enhancement of bicycle exercise capacity in patients with chronotropic incompetence through closed-loop stimulation: a randomized crossover trial.

AIMS: This study aimed to investigate the effectiveness of closed-loop stimulation (CLS) pacing compared with the traditional DDD mode in patients with chronotropic incompetence (CI) using bicycle-based cardiopulmonary exercise testing (CPET). METHODS AND RESULTS: This single-centre, randomized crossover trial involved 40 patients with CI. Patients were randomized to receive either DDD-CLS or DDD mode pacing for 2 months, followed by a crossover to the alternative mode for an additional 2 months. Bicycling-based CPET was conducted at the 3- and 5-month follow-up visits to assess exercise capacity. Other cardiopulmonary exercise outcome measures and health-related quality of life (QoL) were also assessed. DDD-CLS mode pacing significantly improved exercise capacity, resulting in a peak oxygen uptake (14.8 ± 4.0 vs. 12.0 ± 3.6 mL/kg/min, P < 0.001) and oxygen uptake at the ventilatory threshold (10.0 ± 2.2 vs. 8.7 ± 1.8 mL/kg/min, P < 0.001) higher than those of the DDD mode. However, there were no significant differences in other cardiopulmonary exercise outcome measures such as ventilatory efficiency of carbon dioxide production slope, oxygen uptake efficiency slope, and end-tidal carbon dioxide between the two modes. Patients in the DDD-CLS group reported a better QoL, and 97.5% expressed a preference for the DDD-CLS mode. CONCLUSION: DDD-CLS mode pacing demonstrated improved exercise capacity and QoL in patients with CI, highlighting its potential as an effective pacing strategy for this patient population.

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.

Postvitrectomy endophthalmitis caused by Morganella morganii: a case report and literature review.

BACKGROUND: Postvitrectomy endophthalmitis is a rare and serious complication following vitreoretinal surgeries. Morganella morganii, an emerging gram-negative, facultative anaerobic rod, is related to severe nosocomial infections in various organs and thus has gained importance in recent decades. Morganella morganii infection following intraocular surgery is rarely reported. CASE PRESENTATION: We report an immunocompetent patient with Morganella morganii-related endophthalmitis after vitrectomy for retinal detachment who presented with hand motion visual acuity, hypopyon and a unique retrolental exudative membrane. Initially, the patient was unresponsive to empirical intravitreal ceftazidime and vancomycin but recovered with vision preservation (20/63) after surgical removal of the membrane and silicone oil tamponade. CONCLUSIONS: Morganella morganii intraocular infection is often devastating, likely due to its high multidrug-resistance rate via intrinsic ß-lactamase production, multiple acquired traits related to additional genetic mechanisms, and fimbrial adhesion, urease production, and type III secretion system-associated biofilm formation. The above characteristics of M. morganii may lead to an inadequate response to empirical intravitreal antibiotics, and early surgical intervention should be considered.

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.

Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder primarily responsible for deaf-blindness. Patients with subtype Usher syndrome type 1 (USH1) typically experience congenital sensorineural hearing loss, abnormal vestibular function, and retinitis pigmentosa (RP). Here we present a case of Usher syndrome type 1F (USH1F) with a novel homozygous variant in the calcium-dependent cell-cell adhesion protocadherin-15 (PCDH15) gene. CASE PRESENTATION: Ophthalmic examinations were evaluated over a course of 10 years and the disease-causing variant was identified by whole exome sequencing (WES). Initial and follow-up examination of color fundus photos after 10 years revealed an increase in bone spicule pigment deposits in both eyes. A parafoveal hyper-AF ring in both eyes was shown in fundus autofluorescence (FAF) with a progressive diameter-wise constriction observed over 8 years. Outer nuclear layer (ONL) loss was observed in parafoveal and perifoveal regions of both eyes on spectral domain-optical coherence tomography (SD-OCT). Full-field electroretinography (ffERG) showed extinguished global retinal function. WES identified a novel two-base-pair deletion, c.60_61del (p.Phe21Ter), in the PCDH15 gene, confirming the diagnosis of USH1F. CONCLUSIONS: We report a novel homozygous PCDH15 pathogenic variant expected to lead to nonsense-mediated decay (NMD) of PCDH15 mRNA. The patient exhibits a loss of function with USH1F, experiencing congenital hearing loss and syndromic RP.

Protective Effect of Pioglitazone on Retinal Ganglion Cells in an Experimental Mouse Model of Ischemic Optic Neuropathy.

The aim was to assess the protective effect of pioglitazone (PGZ) on retinal ganglion cells (RGCs) after anterior ischemic optic neuropathy (AION) in diabetic and non-diabetic mice. Adult C57BL/6 mice with induced diabetes were divided into three groups: group 1: oral PGZ (20 mg/kg) in 0.1% dimethyl sulfoxide (DMSO) for 4 weeks; group 2: oral PGZ (10 mg/kg) in 0.1% DMSO for 4 weeks; and group 3: oral DMSO only for 4 weeks (control group). Two weeks after treatment, AION was induced through photochemical thrombosis. For non-diabetic mice, adult C57BL/6 mice were divided into four groups after AION was induced: group 1: oral DMSO for 4 weeks; group 2: oral PGZ (20 mg/kg) in 0.1% DMSO for 4 weeks; group 3: oral PGZ (20 mg/kg) in 0.1% DMSO + peritoneal injection of GW9662 (one kind of PPAR-γ inhibitor) (1 mg/kg) for 4 weeks; group 4: peritoneal injection of GW9662 (1 mg/kg) for 4 weeks; One week after the induction of AION in diabetic mice, apoptosis in RGCs was much lower in group 1 (8.0 ± 4.9 cells/field) than in group 2 (24.0 ± 11.5 cells/field) and 3 (25.0 ± 7.7 cells/field). Furthermore, microglial cell infiltration in the retina (group 1: 2.0 ± 2.6 cells/field; group 2: 15.6 ± 3.5 cells/field; and group 3: 14.8 ± 7.5 cells/field) and retinal thinning (group 1: 6.7 ± 5.7 µm; group 2: 12.8 ± 6.1 µm; and group 3: 15.8 ± 5.8 µm) were also lower in group 1 than in the other two groups. In non-diabetic mice, preserved Brn3A+ cells were significantly greater in group 2 (2382 ± 140 Brn3A+ cells/mm2, n = 7) than in group 1 (1920 ± 228 Brn3A+ cells/mm2; p = 0.03, n = 4), group 3 (1938 ± 213 Brn3A+ cells/mm2; p = 0.002, n = 4), and group 4 (2138 ± 126 Brn3A+ cells/mm2; p = 0.03, n = 4), respectively; PGZ confers protection to RGCs from damage caused by ischemic optic neuropathy in diabetic and non-diabetic mice.

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.

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.

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.

Predicting visual acuity in Bietti crystalline dystrophy: evaluation of image parameters.

BACKGROUND: To analyze multiple imaging modalities in patients with Bietti crystalline dystrophy (BCD) and to investigate which factors from these modalities are associated with best corrected visual acuity (BCVA). METHODS: In this retrospective study, 40 eyes from 22 patients with BCD were included and were separated into group 1 (BCVA ≤20/200) and group 2 (BCVA > 20/200). Data including BCVA and characteristic findings from near-infrared reflectance (NIR) imaging, fundus autofluorescence (FAF), and spectral domain-optic coherence tomography (SD-OCT) were analyzed and compared. The outcome measures of multimodal imaging were evaluated for correlation with BCVA. RESULTS: NIR is a good diagnostic tool for detecting either crystalline or sclerotic vessels in BCD. Patients in group 1 tended to have a thinner choroid (P = 0.047) with ellipsoid zone (EZ) disruption (P = 0.011). Calculation of the area under the curve indicated that EZ disruption detected on SD-OCT could be a good predictor of legal blindness in BCD. CONCLUSION: For the diagnosis of BCD, NIR could be a good diagnostic tool. Of the studied imaging modalities, we found that EZ disruption at the fovea were strongly associated with legal blindness, which could be easily assessed by SD-OCT.

Baseline clinical features predict visual outcome in young patients with central retinal vein occlusion.

PURPOSE: To evaluate prognostic factors in young patients with central retinal vein occlusion (CRVO). METHODS: Retrospective case series. CRVO patients aged ≤ 50 and follow-up ≥ 6 months were enrolled. The best corrected visual acuity (BCVA) and central retinal thickness (CRT) at baseline, 3 months, 6 months, and last visit were documented. Severity of retinopathy was graded by comparing to standard photos. Prognostic factors associated with visual outcome at 6 months were evaluated by multiple linear regression models. RESULTS: A total of 73 eyes from 69 patients with mean age 37.6 ± 8.5 were enrolled. Forty-seven (68%) patients were male. The mean follow-up duration was 25.9 ± 23.0 months. LogMAR BCVA improved from 0.979 ± 0.785 at baseline to 0.594 ± 0.748 at the 6 months (p < 0.001) and CRT improved from 475 ± 222 µm to 299 ± 104 µm (p < 0.001). Forty-eight (66%) eyes required anti-vascular endothelial growth factor (anti-VEGF) treatment. The mean number of injections was 2.25 ± 1.41 in the first 6 months and 75% of eyes received ≦ 3 injections during the clinical course. The baseline BCVA (coefficient 0.518, p < 0.001), grade of retinal hemorrhage (coefficient 0.230, p = 0.006), grade of retinal venous engorgement (coefficient 0.238, p = 0.011), grade of optic disc edema (coefficient - 0.226, p = 0.005), and diabetes mellitus (coefficient 0.264, p = 0.047) were the independent factors associated with visual outcome at 6 months. CONCLUSIONS: Baseline clinical features are useful for the prediction of visual outcome at 6 months in young CRVO patients.