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Objectives: To present the characteristics of paravascular vitreous adhesions in patients with myopia under 30 years by SS-OCT. Methods: This was a cross-sectional study. One eye of each subject was enrolled in the study, and the paravascular, macular and optic disc regions were scanned by SS-OCT.The PVA was classified to 4 degrees, Grade 1: No visible separation. Grade2: A slit structure visible, Grade 3: Distinguished separation, but remains to the retina. Grade 4: Complete separation. The degree of macular posterior vitreous detachment (PVD), location of vitreoschisis and presence of granular hyper reflection structure were evaluated and compared within high myopic groups using SPSS. Results: A total of 31 highly myopic eyes and 78 non-highly myopic eyes were enrolled from 5 to 29 years. The varying degrees of PVA in the superior and inferior vascular arch was 29.9% (32), 19.6% (21), 27.1%(29) and 23.4%(25) and 28.6%(30), 17.1%(18), 23.8%(25) and 30.5%(32) separately for 1 to 4 degree of PVA. The degrees of PVA were higher in patients with high myopia than in normal people (P< 0.01). A higher degree of PVA was related to macular PVD and the presence of vitreoschisis (P< 0.05). The granular hyper-reflection structure was mainly in patients without high myopia and was positively related to vitreoschisis (P=0.006, r=0.265). Conclusions: Highly myopic subjects had a higher grade of paravascular vitreous adhesion and the presence of vitreoschisis. The degree of PVA was associated with the macular vitreous adhesion. The granular hyper-reflection structure may play a role in vitreous adhesion.

Objectives: To analyzed the recurrence of myopic choroidal neovascularization (mCNV) based on the neovascular signal from perforating scleral vessel (PSV) by optical coherence tomography angiography (OCTA) after anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods:A consecutive series of naïve patients with mCNV accepted anti-VEGF therapy with a minimum 12-month follow-up period. The location of PSV with CNV were classified into PSV adjacent to CNV or not by B scan and the flow signal of CNV was classified into the neovascular signal of CNV from PSV or not by OCTA. The recurrence of mCNV in various PSV with CNV types were compared. K-M survival and Cox proportional hazard model analysis were used to identify risk factors associated with recurrence of mCNV. Results: PSVs were found in 59 of 63 eyes (93.7%) with mCNV in the macular region. The eyes with presence of neovascular signal of CNV from PSV were detected 25 eyes (39.7%). The overall mCNV recurrence rate was 46.0% (29/63) during the follow-up period. According to K-M analysis, the presence of neovascularization with mCNV from PSV predicted a higher recurrence of 60% and a shorter recurrent duration (χ2 =4.486, P=0.034). The Cox proportional hazard model demonstrated that the presence of neovascularization with mCNV from PSV was an independent risk factor for recurrence (HR: 2.19, 95%Cl 1.04-4.62). Conclusions:PSV was mainly detected with mCNV. When the neovascularization of the mCNV comes from PSV, it has a greater recurrence rate with a shorter recurrence duration.

The aim of this study was to compare intraocular cytokines among different types of pigment epithelial detachments (PEDs) in patients with chronic central serous chorioretinopathy (CSC) and to investigate the association of cytokine levels and PED types with response to anti-vascular endothelial growth factor (VEGF) therapy.We included 88 patients with chronic CSC and 30 controls. The anti-VEGF agent conbercept was given intravitreally to chronic CSC patients. Cytokines VEGF, interleukin-6 (IL-6), IL-8, IL-10, interferon-inducible protein-10 and monocyte chemoattractant protein-1 in aqueous humour were measured. Treatment efficacy, cytokine levels, changes in best-corrected visual acuity (BCVA) and optical coherence tomography parameters were assessed at baseline and 1 month after treatment.Patients were divided into three groups: flat irregular PED (FIPED) with choroidal neovascularization (CNV), FIPED without CNV and focal PED. Vascular endothelial growth factor (VEGF) was the only cytokine significantly higher in chronic CSC FIPED patients. There were no significant differences in VEGF between FIPED patients with or without CNV (p = 0.234). At 1 month after conbercept injection, treatment effective rates in FIPED patients with or without CNV were significantly higher than in patients with focal PED (p 0.05). Best-corrected visual acuity (BCVA) was improved in both FIPED groups (p 0.05), but not in the focal PED group (p = 0.180). All three groups had significant decreases in central macular thickness (p 0.05), and PED heights in FIPED patients were reduced (p 0.05).Patients with FIPED in chronic CSC had elevated intraocular VEGF levels and responded favourably to conbercept. Anti-VEGF treatment may be an option for FIPED CSC patients with or without secondary CNV.

Background Choroidal osteoma is a benign intraocular tumor that can increase risk of developing choroidal neovascularization. The visual prognosis is influenced by the tumor location, decalcification status, overlying RPE atrophy, presence of choroidal neovascularization, persistence of subretinal fluid and occurrence of subretinal hemorrhages. Case presentation The authors present a 40-year-old woman diagnosed with choroidal osteoma of the right eye. Her best corrected visual acuity was 12/20 but decreased to 5/20 due to secondary choroidal neovascularization after 8 years follow up. Fundus examination revealed an enlarged choroidal osteoma in most margins at posterior pole with schistose hemorrhage beside macula. Optical coherence tomography angiography revealed unique features in the vascular changes of choroidal neovascularization in choroidal osteoma in the outer retinal layer and choroid capillary layers, and subretinal neovascularization. Indocyanine green fluorescence angiography showed there was hypo-fluorescence at the peripapillary with faint hyper-fluorescence at the macular, corresponding to the location on the fundus photograph. The patient received 3 injections of intravitreal ranibizumab. After 1 year follow up, her visual acuity of the right eye was 18/20 and the CNV had regressed. Conclusions We present the findings and treatment of a case of choroidal osteoma with secondary choroidal neovascularization. Optical coherence tomography angiography combined with FFA and ICGA is used to analysis the characteristics of secondary choroidal neovascularization. Optical coherence tomography angiography can reveal some unique characteristics in the vascular changes compared to fundus fluorescein angiography.

PURPOSE To investigate the association of sex with the global burden of glaucoma by year, age and socio-economic status using disability-adjusted life years (DALYs). METHOD The global, regional and national sex-specific DALY numbers, crude DALY rates and age-standardized DALY rates caused by glaucoma, by year and age, were obtained from the Global Burden of Disease Study 2017. Human development index (HDI) in 2017 as a national socio-economic indicator was obtained from the Human Development Report. t-Test and linear regression were performed to explore the association between sex difference in age-standardized DALY rates and HDI. RESULTS Globally, changes in glaucoma DALY number and crude rates were similar of both sexes between 1990 and 2017. After controlling for population size and age structure, age-standardized DALY rates decreased consistently from 10.7 in 1990 to 9.4 in 2017 among men and from 8.8 in 1990 to 8.0 in 2017 among women. In 2017, the global average age-standardized DALY rates were 11.6 ± 8.6 (mean ± standard deviation) in women and 14.9 ± 12.1 in men. The sex difference in age-standardized DALY of 195 countries was significant (t = 3.109; p

Purpose: To evaluate the reliability of vessel density measurements in the peripapillary retina using optical coherence tomography angiography (OCT-A) and to analyze the correlation with retinal nerve fiber layer (RNFL) thickness in healthy subjects. Method: Thirty-five healthy volunteers were recruited in the study. The optic disc region was scanned three times with spectral-domain OCT (SD-OCT) and split-spectrum amplitude decorrelation angiography by two skilled examiners. Vessel density of the peripapillary retina was automatically calculated by the software RTVue-XR (version 2015.1.1.98). The RNFL thickness on the optic nerve head was measured by SD-OCT. The coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficients (ICC) were calculated for intraobserver repeatability. The Bland-Altman analysis was used to determine interobserver reproducibility. Correlations between peripapillary retinal vessel density and RNFL thickness were analyzed using a multivariable linear regression. Results: The mean age of the volunteers was 47.0 ± 29.7 years. The intraobserver repeatability in different sectors of the peripapillary retina was good with a high coefficient of repeatability, low CV (< 0.2%), and high ICC (0.847–0.952). The interobserver reproducibility was also good in different sectors, but should be interpreted with caution due to the difference bias caused by different observers in some quadrants. There was a significant positive correlation between vessel density and RNFL thickness; optic disc rim area and disc area were negatively related to vessel density (p = 0.008 and p = 0.001, respectively). Conclusion: Vessel density measurements showed good repeatability and reproducibility by OCT-A in the peripapillary retina, the vessel density was positively related to RNFL thickness and negatively related to optic disc area and rim area.

Purpose: The aim of this study was to evaluate the repeatability and reproducibility of foveal avascular zone (FAZ) area measurements using AngioPlex spectral domain optical coherence tomography (OCT) angiography in normal subjects. Methods: Twenty-two healthy subjects (25 eyes) underwent FAZ area measurements with AngioPlex OCT. Each volunteer was separately examined 3 consecutive times by the 2 experienced observers. The FAZ area was measured using ImageJ software. Intraobserver repeatability was evaluated by calculating the coefficient of variation (CoV) and intraclass correlation coefficient (ICC). Interobserver reproducibility was also assessed using the Bland-Altman test and concordance correlation coefficient (CCC). Results: The FAZ areas were measured as 0.373 ± 0.109 and 0.377 ± 0.112 mm2 by observers 1 and 2, respectively. The repeatability assessment of the FAZ area measurements yielded CoV values of 0.029 and 0.034 and ICC values of 0.997 and 0.996 by observers 1 and 2, respectively. The mean difference between the 2 observers was 0.004. CCC values ranged from 0.9705 to 0.9844. Conclusions: The FAZ area measurements obtained using AngioPlex OCT showed a good repeatability and reproducibility in healthy subjects. Excellent reliability makes AngioPlex OCT a valid device for measuring the FAZ area.

Purpose Gasdermin D (GSDMD) is crucial in neuronal pyroptosis. GSDMD-N and GSDMD-C are two subdomains of the protein GSDMD. GSDMD-N is an executor of pyroptosis, and GSDMD-C has an inhibitory effect on pyroptotic cell death. This study evaluated the role of GSDMD in photoreceptor cell pyroptosis caused by retinal detachment (RD). Methods RD models were established in rats, and GSDMD cleavage was detected by western blotting. The morphology of photoreceptors was assessed by transmission electron microscopy. Some rats were given subretinal injections of recombinant adeno-associated virus 2/8 (rAAV2/8)-GSDMD-C before RD surgery. We documented the expression of caspase-1 and GSDMD-N in retinas by western blot. Levels of IL-1β, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) were detected by quantitative RT-PCR. The membrane integrity of photoreceptors was evaluated by TOTO-3 iodide staining. Retinal function was measured by electroretinography, and the thickness of the outer nuclear layer was also recorded. We measured the activation of glial fibrillary acidic protein (GFAP), F4/80, and ionized calcium binding adaptor molecule 1 (Iba-1) by immunofluorescence. Results The cleavage of GSDMD peaked at 1 day after RD. The administration of rAAV2/8-GSDMD-C reduced the pyroptosis and subsequent apoptosis of photoreceptors and preserved the retinal function after RD. Expression of IL-1, TNF-α, and MCP-1 was decreased in the rAAV2/8-GSDMD-C group. In addition, the activation of GFAP, Iba-1, and F4/80 in retinas was alleviated by administering rAAV2/8-GSDMD-C after RD. Conclusions GSDMD participates in the pyroptosis of photoreceptor after RD. Overexpression of GSDMD-C may block GSDMD cleavage and attenuate photoreceptor degeneration.

To characterize two patients with macular and rod-cone dystrophy and identify the genetic basis for disease. Ophthalmic examinations were performed for the family and the peripheral blood samples were collected for whole exome sequencing. The mutated sequences of PROM1 gene were cloned and expressed in cultured cell lines after transient transfection followed by analysis with confocal microscopy and bridge-PCR. We reported that two patients, brothers in a family, were diagnosed with macular and rod-cone dystrophy. Phenotypically, both patients experience progressive visual impairment and nyctalopia. The fundus examination showed macular and choroid dystrophy with pigment deposits in the macular region. Functionally, photoreceptor response to electrophysiological stimulation was significantly compromised with more severe decline in rods. Genetic analysis by whole exome sequencing revealed two novel compound heterogeneous point mutations in PROM1 gene that co-segregate with patients in an autosomal recessive manner. Specifically, the c.C1902G(p.Y634X) nonsense mutation results in a truncated, labile, and mislocalized protein, while the c.C1682+3A>G intronic mutation disrupts messenger RNA splicing. Our findings have identified two novel deleterious mutations in PROM1 gene that are associated with hereditary macular and rod-cone dystrophy in human.

Purpose To describe the morphological features of posterior precortical vitreous pockets (PPVP) and Cloquet's Canal in patients with myopia using swept-source optical coherence tomography (SS OCT). Methods A total of 96 eyes of 51 volunteers (range, 5-18 years) were enrolled in this study, and all individuals underwent OCT (Optovue Inc., Fremont, CA, USA) examinations. From the collected PPVPs images, the widths and heights of the PPVPs were measured, and connections between PPVPs and Cloquet's Canal were identified. The PPVPs widths and heights, width:height ratios and proportions of connections were compared among different age (5-8, 9-14, 15-18 years), axial length (AL; 21-23, 23-25, 25-29 mm) and myopia groups (hyperopia, low to moderate myopia, high myopia); the group data were analyzed to determine their relationship with myopia. Results PPVPs were identified in 89 of 96 eyes; 6 eyes were excluded for poor image quality. The PPVPs width was positively correlated with age, especially in the low to moderate myopia group (F = 7.715, P = 0.001). There was a significant difference in the PPVPs height between the refractive error groups in the 9 to 14 years group (F = 4.905, P = 0.005). The PPVPs width:height ratio was different among the refractive error groups in the 9 to 14 years group (F = 3.335, P = 0.041) and among the different age groups in the low to moderate myopia group (F = 6.077, P = 0.004). A total of 22 eyes (22.4%) were identified as having a connection between the PPVP and Cloquet's Canal. The connections began to increase with AL at 5 to 8 years (χ2 = 7.363, P = 0.025). Conclusions PPVPs existed in most myopia patients from 5 to 18 years old. PPVPs width was positively correlated with age, especially in the low to moderate myopia group. PPVPs height decreased in the 9 to 14 years group with myopia. An imbalance in the horizontal and vertical enlargement of PPVP was the main feature in the 9- to 14-year-old group with myopia. The connections between the PPVP and Cloquet's Canal were associated with AL extension in the 5- to 8-year-old group.

Age-associated dysfunction of retinal pigment epithelial cells (RPEs) is considered to be the initial trigger of retinal diseases such as age-related macular degeneration. Although autophagy is upregulated in RPEs during the course of aging, little is known about how autophagy is regulated and its functional role in RPEs. In this study, we found that expression of Sirtuin 6 (SIRT6) and autophagic markers are upregulated in RPEs of aged mice where subretinal deposition of amyloid-β is accumulated and in amyloid-β stimulated RPEs. In addition, gain and loss-of-function studies confirmed the positive role of SIRT6 in regulating autophagy. Interesting, inhibition of autophagy attenuates amyloid-β stimulated inflammatory response in RPEs. Collectively, our findings uncover the autophagy modulated by SIRT6 may be a proinflammatory mechanism for amyloid-β induced RPE dysfunction.

BACKGROUND AND PURPOSE: Currently available treatments do not halt progression of photoreceptor death and subsequent visual impairment related to retinal detachment (RD) which is observed in various retinal disorders. This study investigated the neuroprotective effects of two adrenoceptor ligands, the α(1)‐adrenoceptor antagonist doxazosin and the α(2)‐adrenoceptor agonist guanabenz, against photoreceptor cell death in RD. EXPERIMENTAL APPROACH: We used a model of experimental RD in Brown‐Norway rats induced by subretinal injection of sodium hyaluronate. Oxidative stress biomarkers and cytokine production were quantified with elisa. Protein expression levels and immunofluorescent labelling were determined in rats with RD and controls for mechanistic elucidation. The effects of systemic (i.p.) administration of doxazosin or guanabenz on photoreceptor apoptosis, retinal histology and electroretinography were evaluated in rats with RD and compared to the effects in vehicle controls. KEY RESULTS: Photoreceptors were the major source of RD‐induced ROS overproduction in the rat retina through the regulation of NADPH oxidase. Systemic administration of doxazosin or guanabenz decreased the RD‐induced production of ROS and proinflammatory cytokines, including IL‐1β and the chemokine CCL2, and suppressed retinal gliosis, resulting in attenuation of photoreceptor death and preservation of retinal structures and functions in RD. CONCLUSIONS AND IMPLICATIONS: Our findings point to α‐adrenoceptors as novel therapeutic targets to provide photoreceptor protection and suggest that both doxazosin and guanabenz, two FDA‐approved drugs, could be further explored to treat retinal diseases.

OBJECTIVE To evaluate the clinical value of rigid gas permeable contact lenses (RGPCLs) in patients with traumatic corneal scarring and address implications of primary corneal repair. METHODS Eighteen subjects with a history of corneal laceration were fit with RGPCLs. Scar locations were divided into two zones; each patient was examined using Pentacam. Entering data included uncorrected visual acuity (UCVA), spectacle-corrected visual acuity (SVA), time between injury and RGPCL fitting, location and size of scar, and amount of corneal astigmatism. Follow-up data included RGPCL visual acuity (RGPCLVA), RGPCL-related complications, and dropout characteristics. Visual acuity values were converted to logMAR for analysis. RESULTS No serious complications occurred. The average time between suture removal and RGPCL fitting was 5.7±5.5 months. Average corneal astigmatism was -3.44±2.09 diopters. One subject had developed corneal ectasia. RGPCLVA was more than 0.1 in three subjects: one experienced primary corneal repair complications, and two subjects (

Photoreceptor degeneration is a leading cause of visual impairment worldwide. Separation of neurosensory retina from the underlying retinal pigment epithelium is a prominent feature preceding photoreceptor degeneration in a variety of retinal diseases. Although ophthalmic surgical procedures have been well developed to restore retinal structures, postoperative patients usually experience progressive photoreceptor degeneration and irreversible vision loss that is incurable at present. Previous studies point to a critical role of mitochondria-mediated apoptotic pathway in photoreceptor degeneration, but the upstream triggers remain largely unexplored. In this study, we show that after experimental retinal detachment induction, photoreceptors activate dynamin-related protein 1 (Drp1)–dependent mitochondrial fission pathway and subsequent apoptotic cascades. Mechanistically, endogenous reactive oxygen species (ROS) are necessary for Drp1 activation in vivo , and exogenous ROS insult is sufficient to activate Drp1-dependent mitochondrial fission in cultured photoreceptors. Accordingly, inhibition of Drp1 activity effectively preserves mitochondrial integrity and rescues photoreceptors. Collectively, our data delineate an ROS-Drp1-mitochondria axis that promotes photoreceptor degeneration in retinal diseased models.

Amyloid-beta (Aβ) is a hallmark component of age-related macular degeneration (AMD), which induces secretion of pro-inflammatory cytokines from retinal pigment epithelium (RPE). Previous studies have shown that p50/RelA (p65), a member of NF-κB family, is an essential pro-inflammatory transcription factor responding to Aβ1-40 stimulation, but few focused on the other two Rel transcription factor members – RelB and c-Rel – and their role in Aβ1-40-mediated inflammation. It was reported that RelA, RelB and c-Rel are also implicated in various NF-κB-mediated inflammatory diseases. Therefore, we infer that Aβ1-40-mediated inflammation targets not only the classical inflammation regulator, RelA, but also RelB and c-Rel. In this study, we demonstrate that intravitreally injected Aβ1-40 mice develop AMD-like pathologic changes, coupled with Rel protein (RelA, RelB and c-Rel) synthesis and nuclear translocation. To focus on the interaction mechanism of Rel proteins, we found that RelB and c-Rel formed a heterodimer with RelA in mice model. We also found that c-Rel silencing decreased the levels of Aβ1-40-dependent RelA expression, indicating that RelB and c-Rel may interact with RelA as coactivator and c-Rel is required to activate the expression of RelA. Moreover, Rel protein silencing decreased the expression of distinct pro-inflammatory cytokines. Together, we demonstrate that besides RelA, RelB and c-Rel can also be activated by Aβ1-40, all of which mediate pro-inflammatory cytokine transcription and RPE damage. Our findings imply that RPE-mediated inflammation under the stimulation of Aβ1-40 is multi-targeted and RelA, RelB and c-Rel proteins may be the new targets of anti-inflammatory agents.