Purpose. To evaluate the refractive status and optical components in school age children born prematurely and to examine the risk factors associated with refractive errors. Methods. The participants were a cohort of children aged 7 to 9 years with gestational age less than 35 weeks or birth weight less than 1500 g. The participants' neonatal histories were reviewed; their refractive status and optical components were measured. The study results were compared with the results of age-matched children from a national survey. Results. Of the 108 children studied, 48 (44%) had retinopathy of prematurity (ROP); 29 (27%) had ROP ≥ stage 3. Compared with the control subjects, the study cases showed higher prevalence of myopia (48% vs. 29%), hyperopia (23% vs. 15%), and astigmatism (73% vs. 41%). Common ocular features included shallow anterior chamber depth (ACD), thick lenses, and steep corneal curvature. The hyperopic cases had the shortest axial length (AL), whereas the myopia cases had significantly shallower ACD and greater LT. Those with a history of ROP had more prominent changes in the anterior segment. Generalized estimating equations showed that refractive errors could be predicted by a combination of optical components. Conclusions. In children born prematurely, the development of myopia is mainly influenced by anterior segment components, whereas hyperopia is mainly attributable to short AL. Astigmatism is primarily cornea-related. A combination of various optical components results in complicated refractive outcomes. The presence of ROP may be associated with significantly shorter ACD, thicker lens, and higher myopia and astigmatism. (ClinicalTrials.gov number, NCT01045616.)

Leber’s congenital amaurosis (LCA), one of the most severe inherited retinal dystrophies, is typically associated with extremely early onset of visual loss, nystagmus, and amaurotic pupils, and is responsible for 20% of childhood blindness. With advances in molecular diagnostic technology, the knowledge about the genetic background of LCA has expanded widely, while disease-causing variants have been identified in 38 genes. Different pathogenetic mechanisms have been found among these varieties of genetic mutations, all of which result in the dysfunction or absence of their encoded proteins participating in the visual cycle. Hence, the clinical phenotypes also exhibit extensive heterogenicity, including the course of visual impairment, involvement of the macular area, alteration in retinal structure, and residual function of the diseased photoreceptor. By reviewing the clinical course, fundoscopic images, optical coherent tomography examination, and electroretinogram, genotype-phenotype correlations could be established for common genetic mutations in LCA, which would benefit the timing of the diagnosis and thus promote early intervention. Gene therapy is promising in the management of LCA, while several clinical trials are ongoing and preliminary success has been announced, focusing on RPE65 and other common disease-causing genes. This review provides an update on the genetics, clinical examination findings, and genotype-phenotype correlations in the most well-established causative genetic mutations of LCA.

Inherited retinal degenerations (IRDs) are a group of phenotypically and genotypically heterogeneous disorders with substantial socioeconomic impact. In this cohort study, we tried to address the genetic characteristics and epidemiology of IRDs in Taiwan. Totally, 312 families with IRDs were identified and recruited and genetic testing was performed via probe capture-based NGS targeting 212 IRD-related genes. Statistical analysis was based on the proband of each affected family. Disease-causing genotypes were identified in 178 families (57.1%). ABCA4 variants were the most common cause of disease in this cohort (27 families, 15.2%), whereas CYP4V2 variants were the most common cause for the single phenotype—Bietti’s crystalline dystrophy (12 families, 3.8%). Some variants such as ABCA4:c.1804C>T, CYP4V2:c.802-8_810delinsGC, and EYS:c6416G>A were population-specific disease-causing hotspots. Probands affected by ABCA4, RPGR, RP1L1, and CEP290 sought medical help earlier while patients affected by EYS and CYP4V2 visited our clinic at an older age. To evaluate the representativeness of our cohort in the genetic epidemiology of IRDs in Taiwan, our demographic data were compared with that of the total IRD population in Taiwan, obtained from the National Health Insurance Research Database. This is currently the largest-scale, comprehensive study investigating the genetic characteristics and epidemiology of IRD in Taiwan. These data could help patients and caregivers to adopt precision genomic medicine and novel gene therapies in near future.

Purpose: To investigate the long-term results of a novel technique to preserve the foveolar cone without peeling off the foveolar internal limiting membrane (ILM) during myopic traction maculopathy surgery. Methods: Nineteen patients (19 eyes) were retrospectively studied and divided into 2 groups by the extent of ILM peeled and followed for more than 3 years. Group 1: foveolar ILM nonpeeling group (FN) (12 eyes) and Group 2: total peeling of foveal ILM group (TP) (7 eyes). A donut-shaped ILM was peeled off, leaving a 400-μm diameter ILM over foveola with a sharp margin in FN group. Results: Macular hole was developed in 2 of the 7 eyes (28.6%) in the TP group and none in the FN group. Long-term central fovea thickness thinning and decrease of vision were found in the TP group, but not in the FN group (P < 0.05). Inner segment/outer segment line recovered in 75% of the 12 eyes in the FN group, but in only 14.3% of the 7 eyes in the TP group. Conclusion: Preservation of the foveolar cone by foveola nonpeeling surgery correlates with better anatomical and visual results than total peel, prevents long-term foveolar retinal thinning, and successfully saves the fovea from macular hole formation.

Moxifloxacin (MOX), a fourth generation fluoroquinolone (FQ), has a wide antibacterial spectrum, but may show cytotoxicity characterized by high productions of reactive oxygen species (ROS). This study investigated the protective role of a common antioxidant agent, resveratrol (trans-3,5,4'-trihydroxystilbene), against the cytotoxicity caused by MOX. Experiments were performed with a human corneal epithelial cell line (HCECs; ATCC-CRL-11515). Another commonly used FQ, levofloxacin (LEV), and the most commonly used preservatives, benzalkonium chloride (BAC), were also used for comparison with MOX. Cell viability and morphologic changes after treatment were evaluated with trypan blue exclusion assay, propidium iodine/annexin V-FITC staining, and flow cytometry. Chemiluminescence immunoassay was used for ROS quantification. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, wound healing assay, and intracellular detections of oxidative stress were performed to evaluate the effects of resveratrol. The MOX group, similar to the BAC group, showed significant cell shrinkage and death compared with the LEV group. High ROS production in HCECs of MOX group was observed both by chemiluminescence immunoassay and intracellular images. Within the observations of MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, live cell images, and wound healing process in vitro, the cytotoxic effects of the MOX and BAC groups were opposed by resveratrol. Human corneal epithelial cells pretreated with resveratrol demonstrated better cell viability and healing rate in the early stage. The protective effects of antioxidant agents indicate that MOX, similar to BAC, causes oxidative stress-related cell damage. The results also inspired us to think about a "supplementary regimen" to increase safety and decrease the adverse effect in the treatment of corneal infections.

Optic neuropathy is one of the leading causes of irreversible blindness caused by retinal ganglion cell (RGC) degeneration. The development of induced pluripotent stem cell (iPSC)-based therapy opens a therapeutic window for RGC degeneration, and tissue engineering may further promote the efficiency of differentiation process of iPSCs. The present study was designed to evaluate the effects of a novel biomimetic polybenzyl glutamate (PBG) scaffold on culturing iPSC-derived RGC progenitors. The iPSC-derived neural spheres cultured on PBG scaffold increased the differentiated retinal neurons and promoted the neurite outgrowth in the RGC progenitor layer. Additionally, iPSCs cultured on PBG scaffold formed the organoid-like structures compared to that of iPSCs cultured on cover glass within the same culture period. With RNA-seq, we found that cells of the PBG group were differentiated toward retinal lineage and may be related to the glutamate signaling pathway. Further ontological analysis and the gene network analysis showed that the differentially expressed genes between cells of the PBG group and the control group were mainly associated with neuronal differentiation, neuronal maturation, and more specifically, retinal differentiation and maturation. The novel electrospinning PBG scaffold is beneficial for culturing iPSC-derived RGC progenitors as well as retinal organoids. Cells cultured on PBG scaffold differentiate effectively and shorten the process of RGC differentiation compared to that of cells cultured on coverslip. The new culture system may be helpful in future disease modeling, pharmacological screening, autologous transplantation, as well as narrowing the gap to clinical application.