A potential role for inflammatory cytokines in a rare late-onset capsular block syndrome: a case report.

BACKGROUND: Late-onset capsule block syndrome (CBS) is a rare complication of cataract phacoemulsification and the implantation of a posterior chamber intraocular lens (PCIOL), which manifests six months to years after surgery. The hallmark of CBS is the formation of an opaque liquid substance between the implanted intraocular lens (IOL) and the posterior capsule. However, its pathogenesis remains unclear. CASE PRESENTATION: A 64-year-old female patient with chronic angle-closure glaucoma (axis length < 21 mm) underwent trabeculectomy surgery combined with phacoemulsification and PCIOL. After a 4-year follow-up, a decline in visual acuity occurred in her right eye due to the location of opaque fluid in the visual axis and distension of the capsular bag. The initial course of action was to release the trapped fluid. Neodymium: yttrium-aluminum-garnet (Nd: YAG) laser capsulotomy could not be employed due to her non-dilating pupil and high extension of the posterior capsule. Subsequently, anterior capsule peeling and anterior segment vitrectomy surgery were performed. The depth of the anterior chamber (ACD), the distance between the face of the retro-IOL and the posterior capsule, the best-corrected visual acuity (BCVA), and the visual quality (VQ) were measured both before and after surgery. Inflammatory cytokine levels in the opaque substances (OS) trapped between the PCIOL and the posterior capsule were assessed using a flow cytometer and compared to normal statistical data in aqueous humor. After surgery, the patient experienced a significant improvement in BCVA and VQ. The distance between the face of the retro-IOL and the posterior capsule was on the verge of disappearing. However, ACD did not differ between pre- and post-operatively. Interleukin-8 (IL-8) and basic fibroblast growth factor (BFGF) concentrations were higher in the OS than in aqueous humor, especially in the former. However, the concentration of vascular cell adhesion molecule (VCAM) in the OS was lower than in aqueous humor. CONCLUSIONS: Anterior segment vitrectomy surgery proved to be a successful treatment for late-onset CBS, presenting a challenging case. In the human lens, inflammatory cytokines originating from the opaque substances may contribute to abnormal metabolism in the sealed area, a consequence of late-onset CBS.

New treatment for amblyopia based on rules of synaptic plasticity: a randomized clinical trial.

Amblyopia resulting from early deprivation of vision or defocus in one eye reflects an imbalance of input from the eyes to the visual cortex. We tested the hypothesis that asynchronous stimulation of the two eyes might induce synaptic plasticity and rebalance input. Experiments on normal adults showed that repetitive brief exposure of grating stimuli, with the onset of each stimulus delayed by 8.3 ms in one eye, results in a shift in perceptual eye dominance. Clinical studies (Clinical trial registration number: ChiCTR2100049130), using popular 3D movies with similar asynchrony between the two eyes (amblyopic eye stimulated first) to treat anisometropic amblyopia, established that just 10.5 h of conditioning over <3 weeks produced improvement that met criteria for successful treatment. The benefits of asynchronous conditioning accumulate over 20-30 45 min sessions, and are maintained for at least 2 years. Finally, we demonstrate that asynchronous binocular treatment alone is more effective than patching only. This novel treatment is popular with children and is some 50 times more efficient than patching alone.

Triamcinolone as an adjunct to the combination of anti-VEGF for the management of diabetic macular edema.

AIM: To assess the efficacy of intravitreal triamcinolone (IVTA) as an adjunct to the combination of anti-vascular endothelial growth factor (VEGF) for the management of diabetic macular edema (DME). METHODS: A total of 51 patients with visual disabilities causing by DME from two sites were retrospectively collected and assigned to two groups according to the therapeutic method: intravitreal conbercept (IVC) combined with focal laser (24 eyes) and IVC combined with focal laser and IVTA (27 eyes). Best-corrected visual acuity (BCVA), the required number of IVCs, central retinal thickness (CRT), the mean costs of treatment burden and safety were compared over 12mo. RESULTS: From baseline to month 1 through month 12, IVC combined with focal laser and IVTA improved the mean average change in BCVA superior to IVC combined with focal laser (+5.20 vs +2.71 letters). At month 12, 20.83% of the IVC combined with focal laser and 37.04% of IVC combined with focal laser and IVTA arms gained more than 10 BCVA letters. During the period, the mean CRT decreased significantly in the IVC combined with focal laser and IVTA arm (-245.9 µm) compared to the IVC combined with focal laser arm (-98.45 µm). The average of 6.45 and 1.25 conbercept injections performed in the IVC combined with focal laser and IVC combined with focal laser and IVTA arms, respectively. The mean cost of treatment burden for 12mo was $6247.44±4069.18 in the IVC combined with focal laser arm and $1679.19±542.73 in the IVC combined with focal laser and IVTA arm, with a statistically significant difference. Apart from occasional minor subconjunctival hemorrhage, no other significant ocular adverse events (AEs) were observed in either group during the12-month period. CONCLUSION: It is effective and cost-effective to treat DME by utilizing triamcinolone as an adjunct to the combination of anti-VEGF.

ube3d, a New Gene Associated with Age-Related Macular Degeneration, Induces Functional Changes in Both In Vivo and In Vitro Studies.

Neovascular age-related macular degeneration (AMD) is characterized by the formation of choroidal neovascularization, which is responsible for more than 80% of cases of severe vision loss. Ubiquitin protein ligase E3D (UBE3D) gene missense has been proven to be associated with neovascular AMD in the East Asian population based on our previous study. In vivo, we explored the role of ube3d in eye development and the mechanisms underlying the development of neovascular AMD in a zebrafish model. In vitro, we investigated the function and mechanism of ube3d in oxidative damage in human retinal pigment epithelium (hRPE) cells. The ube3d gene was knocked down in zebrafish in our experiments, and rescue of ube3d morphants was also performed. We observed the zebrafish model at the molecular level and functional and morphological changes in vivo. Lentivirus-based gene transfer technology was used to overexpress/knockdown ube3d expression in hRPE cells in vitro. hRPE oxidative damage was induced by tert-butyl hydroperoxide (t-TBH). Cell proliferation and migration were assessed. Quantitative real-time PCR and western blot were used to measure the expression levels of UBE3D and CyclinB1. Abnormal eye development was found in zebrafish in this study, including small eyes, delayed retinal development, delayed retrograde melanosome transport, and reduced dark-induced hyper-locomotor activity under light-off conditions. In addition, increased angiogenesis was observed in ube3d morphants. A negative correlation between UBE3D and CyclinB1 was observed. Low UBE3D expression can promote oxidative damage and inflammatory reactions. UBE3D and autophagy have a synergetic effect on anti-oxidative damage. These findings indicate that ube3d may play an important role in the pathogenesis of AMD by affecting retinal development, oxidative damage, and autophagy.

Protective effects of autophagy against blue light-induced retinal degeneration in aged mice.

The aim of this study was to explore the role of autophagy in response to blue light damage in aged mice and in human retinal pigmented epithelium (hRPE) cells. Blue light damage to the retina was induced in 10-month-old (10 mo) C57 mice and hRPE cells. Flash electroretinography was used to assess retinal function. Retinal structure changes were observed by electron microscopy. Western blot was conducted to determine the expression levels of the following proteins: cleaved caspase-3, p38 mitogen-activated protein kinases, protein kinase R-like endoplasmic reticulum kinase (PERK), autophagy marker light chain 3 (LC3), P62, and Beclin-1. On day 1 after light damage to the 10 mo mice, retinal function was changed. The latent periods of a-wave and b-wave were delayed, and amplitude was reduced. The electron microscopy results revealed mitochondria damage in the retinal pigmented epithelium and a disorganized photoreceptor outer segment (OS). PERK, LC3, and Beclin-1 were upregulated, whereas P62 was not. On day 5 after the blue light damage, restoration of electroretinography and OS was observed. PERK, LC3, and Beclin-1 were downregulated, whereas P62 was not. Protein changes in vitro were consistent with in vivo. The present study provided structural and functional evidence that autophagy plays an important role in the response to blue lightinduced retinal damage.

Genetic analysis and clinical features of X-linked retinoschisis in Chinese patients.

Many mutations in the retinoschisis (RS1) gene have been identified, but there are limited clinical data relating to the different genotypes. This study investigated the genotype, clinical phenotype and therapies for X-linked juvenile retinoschisis (XLRS) patients in China to evaluate the effects of gene mutations and therapies on the prognosis of the disease. Thirty patients were recruited in the study. Genetic examination identified 8 novel RS1 gene mutations. Twenty-four patients were identified as missense mutation, which was the most common gene mutation in XLRS patients. Amino acids 102 and 209 were the most common mutation areas, accounting for a total 35.7% of all patients. Mutations affecting amino acid 102 were associated with poor results on the flash electroretinogram (ERG). Sixteen patients had various complications. Anti-vascular endothelial growth factor (VEGF) drugs were given to four patients with hemorrhage or other complications, and serious adverse events did not occur. Our outcome demonstrates that missense mutation was the leading cause of XLRS and more than half of the patients with this missense had various complications. Anti-VEGF drugs may be an effective and safe way to prevent deterioration of XLRS with certain complications. There is wide genotypic and phenotypic variability in Chinese patients with XLRS.

X-Linked Retinoschisis in Juveniles: Follow-Up by Optical Coherence Tomography.

Purpose. To explore the structural progression of X-linked retinoschisis (XLRS) in patients by using spectral-domain optical coherence tomography (SD-OCT). Design. Retrospective, observational study. Methods. Patients who were diagnosed with XLRS by genetic testing underwent comprehensive ophthalmological examinations from December 2014 to October 2016. Each eye was measured by SD-OCT using the same clinical protocol. A correlation between best-corrected visual acuity (VA) and SD-OCT measurements was observed. Results. Six patients demonstrated retinoschisis (12 eyes) and typical foveal cyst-like cavities (10 eyes) on SD-OCT images with a mean logMAR VA of 0.48. The median age was 7.5 years at the initial visit. Their foveal retinal thickness (516.9 µm) and choroid thickness (351.4 µm) decreased at a rate of 38.1 and 7.5 µm, respectively, at the 10.5-month follow-up visit; however, there were no significant differences (P = 0.622 and P = 0.406, resp.). There was no significant correlation between VA, the foveal retinal thickness, and subfoveal choroid thickness. Conclusions. SD-OCT images for XLRS patients during the juvenile period revealed no significant changes in the fundus structure, including the foveal retinal thickness and choroid thickness within one-year follow-up. There was a lack of correlation between VA, foveal retinal thickness, and subfoveal choroid thickness.

Protective Effect of ALA in Crushed Optic Nerve Cat Retinal Ganglion Cells Using a New Marker RBPMS.

In this study we first sought to determine whether RNA-binding protein with multiple splicing (RBPMS) can serve as a specific marker for cat retina ganglion cells (RGCs) using retrograde labeling and immunohistochemistry staining. RBPM was then used as an RGC marker to study RGC survival after optic nerve crush (ONC) and alpha-lipoic acid (ALA) treatment in cats. ALA treatment yielded a peak density of RBPMS-alpha cells within the peak isodensity zone (>60/mm2) which did not differ from ONC retinas. The area within the zone was significantly enlarged (control: 2.3%, ONC: 0.06%, ONC+ALA: 0.1%). As for the 10-21/mm2 zone, ALA treatment resulted in a significant increase in area (control: 34.5%, ONC: 12.1%, ONC+ALA: 35.9%). ALA can alleviate crush-induced RGC injury.

Effects of Tauroursodeoxycholic Acid and Alpha-Lipoic-Acid on the Visual Response Properties of Cat Retinal Ganglion Cells: An In Vitro Study.

PURPOSE: To investigate the effects of tauroursodeoxycholic acid (TUDCA) and alpha-lipoic-acid (ALA) on the visual response properties of cat retinal ganglion cells (RGCs) in wholemount retinas. METHODS: Young adult cats were divided into three groups: control, ALA, and TUDCA. In vitro single-unit extracellular recordings were performed on wholemount retinas to objectively evaluate the visual response properties of RGCs prior and post to antioxidant treatment. The visual responses properties of RGCs, including receptive field size, luminance threshold, and contrast sensitivity, were collected online and analyzed off-line with Axon Pclamp9. RESULTS: Most of the RF sizes were larger than those plotted prior to the 60 minutes dark adaptation. The luminance threshold was elevated in the control group (no treatment) but reduced post ALA treatment and significantly reduced post TUDCA treatment. The contrast threshold was significantly elevated in the control group (no treatment) and clearly elevated post ALA treatment but effectively sustained post TUCDA treatment. CONCLUSIONS: Retinal neurocircuitry deteriorates in wholemount retinas, resulting in abnormal visual response properties in RGCs. Alpha-lipoic-acid and TUDCA exerted beneficial neuroprotective effects by activating the antioxidant pathway, partially restoring the functionality of retinal neurocircuitry and significantly improving the visual response properties of RGCs. However, TUDCA appears to be more effective than ALA in reducing irradiance thresholds and improving contrast sensitivity.