Inverted Internal Limiting Membrane Flap Coverage With Autologous Blood Technique After Air-Fluid Exchange and Silicone Oil Tamponade for Extensive Macular Hole Retinal Detachment in Highly Myopic Eyes.

PURPOSE: To report a technique consisting of inverted internal limiting membrane (ILM) flap coverage with autologous blood after air-fluid exchange and silicone oil tamponade in treating extensive retinal detachment secondary to a myopic macular hole (MH). METHODS: This was a retrospective case series. 18 eyes with MHRD extending beyond the equator were included in this study with a minimum follow-up of 6 months. The procedures for pars plan vitrectomy (PPV) included the following: 1) The ILM was peeled to the superior and inferior arcade margins and, except for the ILM in the temporal region, was hinged toward the edge of the MH. 2) Air-fluid exchange was then performed to drain the subretinal fluid through the MH with a flute needle, ensuring that a small amount of subretinal fluid remained to facilitate ILM flap inversion. 3) The ILM flap was used to cover the MH with the assistance of autologous blood. RESULTS: Six months after surgery, the MH was successfully anatomically closed, and retinal reattachment was observed in all 18 eyes of 18 patients. The mean best-corrected visual acuity logarithm of the minimum angle of resolution (logMAR) improved from 2.03 ± 0.61 (ranging from hand motion [2.6] to finger counting [2.3]) to 1.23 ± 0.63 (ranging from hand motion [2.6] to 20/28 [0.15]) ( P < 0.01) at 6 months. CONCLUSION: This surgical technique using an inverted ILM flap combined with autologous blood provides an option for the treatment of extensive MHRD.

Secondary choroidal neovascularization due to choroidal osteoma after 9 years follow-up.

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.

Choroidal remodeling distribution pattern in the macular region in Chinese young patients with myopia.

BACKGROUND: The pathogenesis of myopia has been found to be associated with the blood supply of the choroid. This study aimed to determine the relationship between the distribution pattern of choroidal remodeling and the degree of myopia in young patients. METHODS: Young patients (age < 18 years) with the spherical equivalent of less than - 12 diopters (D) were included. Spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) modality was used to measure the choroidal thickness (CT) and choroidal vascularity index (CVI) in the macular regions. CVI was calculated as the proportion of luminal area to choroidal area and was measured within 1 mm and 3 mm nasal (N1 and N3), temporal (T1 and T3), superior (S1 and S3), and inferior (I1 and I3) to the foveal center. CVI was compared across different ages (i.e., 5 ~ 9 years, 10 ~ 13 years, and 14 ~ 18 years), axial lengths (ALs) (i.e., 21.00 ~ 25.00 mm and 25.01 ~ 29.00 mm), and spherical equivalents (SEs) (i.e., SE > -0.5D, - 0.5 ~ - 3.0D, - 3.01 ~ - 6.0D, and < - 6.0D). Linear regression analysis was applied to assess the association between independent (i.e., age, AL, SE, and intraocular pressure) and dependent variables (i.e., CVI of different regions). RESULTS: One hundred sixty-four eyes from 85 volunteers were included. The mean CT in the central foveal was 269.87 ± 63.32 µm (93.00 µm to 443.00 µm). The mean subfoveal-CVI was 67.66 ± 2.40% (57.84 to 79.60%). Multiple linear regression results revealed significant correlations between SE and T1-CVI (p < 0.05, r2 = 0.082, ß = 0.194), N1-CVI (p < 0.05, r2 = 0.039, ß = 0.212). Simple linear regression results revealed that T1-CVI (p < 0.05, r2 = 0.09) and T3-CVI (p < 0.05, r2 = 0.05) were negatively correlated with SE; N1-CVI (p < 0.05, r2 = 0.05) and N3-CVI (p < 0.05, r2 = 0.04) were negatively correlated with SE. CONCLUSIONS: CVI in the horizontal meridian underwent the largest change as myopia worsened. Temporal and nasal CVIs within the r = 1 mm, and r = 3 mm subfoveal range were positively associated with the degree of myopia in young patients. The CVI value may be used to assess the vascular status of the choroid and be a potential marker of myopic progression.

Inhibition of Mitochondrial Fission Preserves Photoreceptors after Retinal Detachment.

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.

Identification of novel PROM1 mutations responsible for autosomal recessive maculopathy with rod-cone dystrophy.

PURPOSE: To characterize two patients with macular and rod-cone dystrophy and identify the genetic basis for disease. METHOD: 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. RESULT: 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. CONCLUSION: Our findings have identified two novel deleterious mutations in PROM1 gene that are associated with hereditary macular and rod-cone dystrophy in human.

Autophagy activated by SIRT6 regulates Aß induced inflammatory response in RPEs.

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-ß is accumulated and in amyloid-ß 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-ß stimulated inflammatory response in RPEs. Collectively, our findings uncover the autophagy modulated by SIRT6 may be a proinflammatory mechanism for amyloid-ß induced RPE dysfunction.

Reliability of Vessel Density Measurements in the Peripapillary Retina and Correlation with Retinal Nerve Fiber Layer Thickness in Healthy Subjects Using Optical Coherence Tomography Angiography.

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.

Repeatability and Reproducibility of Foveal Avascular Zone Area Measurements Using AngioPlex Spectral Domain Optical Coherence Tomography Angiography in Healthy Subjects.

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.

Clinical evaluation of rigid gas permeable contact lenses and visual outcome after repaired corneal laceration.

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 (<10 years) developed amblyopia. In both zones, the difference in RGPCLVA outcome between zone I and zone II was not statistically significant (F=0.060, P=0.809). The difference between SVA in zones I and II was found to be statistically significant (F=6.131, P=0.026), as were the differences between SVA and RGPCLVA (F=8.598, P=0.010). The scar size had no significant influence on RGPCLVA, SVA, or UCVA. Four participants (22.2%) were successfully fit. Dropout characteristics included ocular discomfort, inconvenience, parental apprehension, and low motivation. CONCLUSIONS: Rigid gas permeable contact lens is an ideal method for evaluating visual potential in patients with traumatic corneal astigmatism. Pentacam examinations of those patients with poor RGPCLVA can help an ophthalmologist find and understand existing problems in suture techniques.

Myopic choroidal neovascularization with neovascular signal around perforating scleral vessel prone to recur after anti-VEGF therapy.

BACKGROUND: To compare the recurrence of myopic choroidal neovascularization (mCNV) based on the neovascular signal of mCNV around the perforating scleral vessel (PSV). METHODS: A consecutive series of naïve patients with mCNV accepted anti-VEGF therapy with a minimum 12-month follow-up period. The neovascular signal relationship between PSV and mCNV were classified into the presence of neovascular signal of CNV around PSV or not. The recurrence of mCNV, best-corrected visual acuity (BCVA), hyperreflective foci height, CNV area and CNV flow area were analyzed between two groups. RESULTS: Neovascular signal of CNV around PSV was detected in 20 eyes (39.2%). The one-year recurrence rate in the group with neovascular signal of CNV around PSV was significantly higher than that in the group without neovascular signal of CNV around PSV (P = 0.045). The recurrence time in the group with neovascular signal around PSV was shorter than that in the group without neovascular signal around PSV (P = 0.030). Cox proportional hazard model showed that the presence of neovascular signal of CNV around PSV [hazard ratio (HR): 2.904] and subfoveal choroidal thickness ≤ 50 µm (HR: 0.368) were risk factors for recurrence of mCNV. In the group with neovascular signal around PSV, the BCVA was worse (P = 0.024) and the CNV flow area was more unstable (P = 0.027) after therapy. CONCLUSIONS: PSV was commonly detected in patients with mCNV. The presence of neovascular signal of CNV around PSV was prone to recur with a shorter time in mCNV patients.

Retained Intraocular Iron Foreign Body Leading to Late-Onset Siderotic Glaucoma: A Challenging Case Report.

BACKGROUND A retained ferrous intraocular foreign body (IOFB), introduced via penetrating ocular trauma, may result in ocular siderosis and visual loss that may occur after days or years. If diagnosis is delayed, therapy may also be delayed, resulting in a poor outcome. The present report presents the case of a 58-year-old man with a retained iron IOFB and late-onset siderotic glaucoma 1 month after the initial trauma. CASE REPORT A 58-year-old man presented with redness and eye pain in the right eye for 1 month after ocular trauma. His visual acuity was very good, with no sign of eye strain. High intraocular pressure had been detected for several weeks, but the B-scan ultrasound and fundus examination were normal and the reason for the high intraocular pressure was unknown. He was later transferred to our senior hospital. The diagnosis of IOFB was confirmed by computed tomography (CT) scan and ultrasound biomicroscopy (UBM). The patient was successfully managed by vitrectomy. CONCLUSIONS This report highlights that a retained IOFB can be challenging to diagnose and that cases associated with siderotic glaucoma require multiple investigations. Early detection of the IOFB using the right tools is vital to reduce the risk of siderotic glaucoma. Although the fundus examination was normal after ocular trauma, the use of CT scan and UBM assisted in finding the IFOB and the patient was successfully treated by vitrectomy.

Metabolomic Study of a Rat Model of Retinal Detachment.

Retinal detachment is a serious ocular disease leading to photoreceptor degeneration and vision loss. However, the mechanism of photoreceptor degeneration remains unclear. The aim of this study was to investigate the altered metabolism pathway and physiological changes after retinal detachment. Eight-week-old male SD rats were fed, and the model of retinal detachment was established by injecting hyaluronic acid into the retinal space. The rats were euthanized 3 days after RD, and the retinal tissues were sectioned for analysis. Untargeted lipid chromatography-mass spectrometry lipidomic was performed to analyze the metabolite changes. A total of 90 significant metabolites (34 in anionic and 56 in cationic models) were detected after retinal detachment. The main pathways were (1) histidine metabolism; (2) phenylalanine, tyrosine, and tryptophan biosynthesis; and (3) glycine, serine, and threonine metabolism. The key genes corresponding to each metabolic pathway were verified from the Gene Expression Omnibus (GEO) database of human retinal samples. The results indicated that the production of histamine by histidine decarboxylase from histidine reduced after RD (p < 0.05). Xanthine, hypoxanthine, guanine, and guanosine decreased after RD (p < 0.05). Decreased xanthine and hypoxanthine may reduce the antioxidant ability. The decreased guanosine could not provide enough sources for inosine monophosphate production. Tyrosine is an important neurotransmitter and was significantly reduced after RD (p < 0.05). Citrate was significantly reduced with the increase of ATP-citrate lyase enzyme (ACLY) (p < 0.05). We inferred that lipid oxidation might increase rather than lipid biogenesis. Thus, this study highlighted the main changes of metabolite and physiological process after RD. The results may provide important information for photoreceptor degeneration.

Predictors of anti-VEGF efficacy in chronic central serous chorioretinopathy based on intraocular cytokine levels and pigment epithelium detachment subtypes.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Hypodense regions in the peripapillary region increased the risk of macular retinoschisis detected by optical coherence tomography.

Purpose: The purpose of the present study was to investigate the clinical features of peripapillary regions in patients with myopic macular retinoschisis (MRS) and its association with the development of retinoschisis (RS). Methods: In this cross-sectional study, high-myopic patients with or without MRS were recruited, and the hypodense regions were analyzed in the peripapillary regions. The vitreoretinal adhesions around both macular and paravascular arcades were compared between groups. The risk factors for the development of MRS were analyzed by logistic regression. Results: Of 88 myopic eyes, MRS was detected in 45 eyes (51%). The eyes with MRS showed a higher rate of peripapillary and paravascular retinoschisis (P < 0.001 and P = 0.006). Hypodense regions were detected in 25 eyes (20.35%). Higher rates of horizontal and vertical macular MRS were detected in the hypodense group (P = 0.012 and P = 0.002). Lower refractive error, longer axial length, and higher rates of outer retinoschisis both in horizontal and vertical macular regions were observed in the hypodense group (P = 0.012, P = 0.006, P = 0.038, and P = 0.034). Higher rates of inner and outer retinoschisis, vitreoschisis, and microfolds along superior vascular arcade were detected in the hypodense group (P = 0.005, P = 0.001, P = 0.014, and P = 0.014). Higher rates of internal limiting membrane (ILM) detachment, inner and outer RS were detected along the inferior vascular arcade in the hypodense group (P = 0.008, P = 0.001, and P = 0.028). Hypodense regions, the axial length and PICC (peripapillary intrachoroidal cavitation) were significantly correlated with the severity of MRS (Odds ratio = 0.207, P = 0.010; Odds ratio = 1.399, P = 0.016; Odds ratio = 0.142, P = 0.010). Conclusions: The hypodense regions were likely to affect outer retinoschisis both in macular and paravascular regions. It was a risk factor for the development of MRS.

Perforating scleral vessels adjacent to myopic choroidal neovascularization achieved a poor outcome after intravitreal anti-VEGF therapy.

Background: This study aimed to summarize the features of perforating scleral vessels (PSVs) in patients with myopic choroidal neovascularization (CNV) (mCNV) using optical coherence tomography angiography (OCTA) and to identify the associations with the response after intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: A consecutive series of naïve patients who had mCNV and received intravitreal anti-VEGF therapy with a follow-up duration of 12 months or more were enrolled. The prevalence, location, and branches of PSVs were analyzed. Projection-resolved OCTA (PR-OCTA) was used to analyze the neovascular signals between CNV and PSVs. Best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured. The proportion of CMT change relative to baseline was used to assess therapeutic response. Results: A total of 44 eyes from 42 patients with mCNV were enrolled. PSVs were identified in 41 out of 44 eyes. Branches were identified in the PSVs of 24 eyes (57.14%), and 20 eyes did not have PSV branches (47.62%). In eight eyes (18.18%), PSVs were adjacent to mCNV, and in 36 eyes (81.82%), PSVs were not adjacent to mCNV. After anti-VEGF therapy for mCNV, BCVA increased (F = 6.119, p < 0.001) and CMT decreased (F = 7.664, p < 0.001). In the eyes where PSVs were adjacent to mCNV, BCVA improvements (F = 7.649, p = 0.009) were poor, and changes in CMT were small. Conclusion: The eyes with PSVs adjacent to mCNV showed poor therapeutic responses after intravitreal anti-VEGF therapy.

Association of sex with the global burden of glaucoma: an analysis from the global burden of disease study 2017.

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 < .01) in 2017. Men had higher rates than women of the same age, and sexual differences increased with age. t-Test revealed that age-standardized DALY rates among men were higher than those among women for low-HDI countries (t = 3.102; p < .01) and high-HDI countries (t = 2.110; p < .05). The difference (male minus female) in age-standardized DALY rates (standardized ß = -0.434, p < .001) and the female-to-male age-standardized DALY rate ratios (standardized ß = -0.315, p < .001) were inversely correlated with HDI. CONCLUSION: Although global glaucoma health care is progressing, sexual differences in glaucoma burden showed little improvement in the past few decades. Worldwide, men have higher glaucoma burden than women. Older age and lower socio-economic status are associated with greater sex differences in glaucoma burden. Our findings may enhance public awareness of sexual differences in global glaucoma burden and emphasize the importance of making sex-sensitive health policy to manage global vision loss caused by glaucoma.

Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment.

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-1ß, 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.

Characteristics of Posterior Precortical Vitreous Pockets and Cloquet's Canal in Patients with Myopia by Optical Coherence Tomography.

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.

Modulation of α-adrenoceptor signalling protects photoreceptors after retinal detachment by inhibiting oxidative stress and inflammation.

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 α1 -adrenoceptor antagonist doxazosin and the α2 -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-1ß 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.

Cooperation of Rel family members in regulating Aß1-40-mediated pro-inflammatory cytokine secretion by retinal pigment epithelial cells.

Amyloid-beta (Aß) 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 Aß1-40 stimulation, but few focused on the other two Rel transcription factor members - RelB and c-Rel - and their role in Aß1-40-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 Aß1-40-mediated inflammation targets not only the classical inflammation regulator, RelA, but also RelB and c-Rel. In this study, we demonstrate that intravitreally injected Aß1-40 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 Aß1-40-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 Aß1-40, all of which mediate pro-inflammatory cytokine transcription and RPE damage. Our findings imply that RPE-mediated inflammation under the stimulation of Aß1-40 is multi-targeted and RelA, RelB and c-Rel proteins may be the new targets of anti-inflammatory agents.