UNASSIGNED: To assess and compare choroidal morphometric vascular parameters, using optical coherence tomographic angiography (OCTA), in highly myopic adults with and without myopic macular degeneration (MMD).
UNASSIGNED: This is a clinic-based observational study of 148 eyes with axial length (AL) ≥25mm, enrolled from the high myopia clinic of the Singapore National Eye Centre. MMD was graded from fundus photographs. Swept source OCT (SS-OCT) and OCTA were performed and assessed for choroidal layer thickness (CT) and choroidal vasculature (choroidal vessel density (CVD), choroidal branch area (CBA) and mean choroidal vessel width (MCVW)) in the different choroidal layers (overall choroidal layer (CL), medium-vessel choroidal layer (MVCL), large-vessel choroidal layer (LVCL)).
UNASSIGNED: CTCL (r=-0.58, p<0.001), CTMVCL (r=-0.22, p=0.04), MCVWCL (r=-0.58, p<0.001), and CVDCL (r=-0.19, p=0.02) were negatively correlated with AL, while CBACL (r=0.61, p<0.001) was positively correlated. Compared to eyes with no MMD, eyes with MMD2 had lower CTCL (120.37±47.18µm vs 218.33±92.70µm, p<0.001), CTMVCL (70.57±15.28µm vs 85.32±23.71µm, p=0.04), CTLVCL (101.65±25.36µm vs 154.55±68.41µm, p=0.001) and greater CVDCL (71.10±3.97% vs 66.97±3.63%, p<0.001), CVDMVCL (66.96±2.35% vs 65.06±2.69%, p=0.002), CVDLVCL (68.36±2.56% vs 66.58±2.88%, p=0.012), MCVWMVCL (6.14±0.34µm vs 5.90±0.35µm, p=0.007), and CBACL (12.69±1.38% vs 11.34±1.18%, p<0.001). After adjusting for age, thicker CTCL (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.97-0.99, p<0.001), CTMVCL (OR 0.97 (0.94-0.99), p=0.002) and CTLVCL (OR 0.97 (0.96-0.98, p<0.001) were significantly associated with lower odds of MMD2, while increased CVDCL (OR 1.37 (1.20-1.55), p<0.001), CVDMVCL (OR 1.39 (1.12-1.73), p=0.003), CVDLVCL (OR 1.31 (1.07-1.60), p=0.009), CBACL (OR 2.19 (1.55-3.08), p<0.001) and MCVWMVCL (OR 6.97 (1.59-30.51), p=0.01) was significantly associated with higher odds of MMD2.
UNASSIGNED: Decrease in choroidal vessel width, density and thickness, and an increase in vascular branching were observed in eyes with long AL. A thinner and denser choroid with greater branching area and vessel width, which may all be signs of hypoxia, were associated with greater odds of MMD2.

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.

OBJECTIVE: To explore the usage of choroidal thickness measured by swept-source optical coherence tomography (SS-OCT) to detect myopic macular degeneration (MMD) in high myopic participants.
METHODS: Participants with bilateral high myopia (≤-6 diopters) were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study. SS-OCT was performed to determine the choroidal thickness, and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia (META-PM) Classification. Presence of MMD was defined as META-PM category 2 or above.
RESULTS: A total of 568 right eyes were included for analysis. Eyes with MMD (n=106, 18.7%) were found to have older age, longer axial lengths (AL), higher myopic spherical equivalents (SE), and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector (P<0.001). The area under the receiver operating characteristic (ROC) curves (AUC) for subfoveal choroidal thickness (0.907) was greater than that of the model, including age, AL, and SE at 0.6249, 0.8208, and 0.8205, respectively. The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD (AUC of 0.928 and 0.923, respectively). An outer nasal sector choroidal thickness of less than 74 µm demonstrated the highest odds of predicting MMD (OR=33.8).
CONCLUSIONS: Choroidal thickness detects the presence of MMD with high agreement, particularly of the inner and outer nasal sectors of the posterior pole, which appears to be a biometric parameter more precise than age, AL, or SE.

Previous studies have reported that inflammatory cytokine levels increase in the intraocular fluids (aqueous humor and vitreous) of highly myopic eyes, However, there has been currently no study revealing the levels of inflammatory cytokines in tear. Therefore, this study aimed to determine tear cytokine levels of highly myopic eyes, and their relationships with myopic macular degeneration (MMD). This case-control study screened inflammatory cytokines of tear samples from 132 highly myopic and 105 emmetropic eyes using a multiplex cytokine antibody array, and cytokines showing significant intergroup differences were further validated using ProQuantum immunoassays in tear samples from another 60 highly myopic and 60 emmetropic eyes. Ultra-widefield fundus photographs of eyes were classified according to the meta-analyses of the Pathologic Myopia Classification. Associations between tear cytokine levels and MMD category were investigated. As a result, tear levels of interleukin (IL)-6, IL-13 and monocyte chemoattractant protein (MCP)-1 were screened significantly higher in highly myopic eyes than in emmetropic controls (IL-6: 11.70 ± 16.81 versus 8.22 ± 10.76 pg/mL; MCP-1: 63.60 ± 54.40 versus 33.87 ± 43.82 pg/mL; both P < 0.05). Validation assays further demonstrated the elevated concentrations of IL-6 and MCP-1 (IL-6: 13.97 ± 8.41 versus 8.06 ± 7.94 pg/mL, P < 0.001; MCP-1: 32.69 ± 8.41 versus 18.07 ± 8.41 pg/mL, P = 0.003). Tear levels of IL-6 and MCP-1 differed significantly among MMD categories (both P < 0.05). The area under receiver operating characteristic curve were 0.783 and 0.682 respectively (both P < 0.05), when using tear IL-6 and MCP-1 levels to predict the presence of MMD (category ≥2). The ordered logistic regression model also indicated that longer axial length, and higher IL-6 and MCP-1 tear levels were independent predictors of higher MMD category. In our study, highly myopic eyes presented significantly higher levels of tear IL-6 and MCP-1, which may also serve as potential biomarkers for MMD.

OBJECTIVE: To explore the prevalence and causes of loss of visual acuity and visual field in highly myopic eyes.
METHODS: Population-based study.
METHODS: 4439 subjects of the Beijing Eye Study underwent ophthalmological and systemic examinations including frequency doubling technology perimetry.
METHODS: High myopia was defined by a refractive error of ≤-6 diopters (D) or axial length >26.0 mm.
METHODS: Prevalence of vision impairment causes.
RESULTS: 212 highly myopic eyes from 154 participants were included with a mean age of 56.2 ± 9.6 years, a mean refractive error of -9.87 ± 3.70 D and a mean axial length of 27.2 ± 1.3 mm. We observed moderate/severe vision impairment (MSVI) in 40 eyes (18.9%; 95% confidence interval [CI], 13.6-24.2) and blindness in 10 eyes (4.7%; 95% CI, 1.8-7.6). Primary causes for MSVI and blindness were myopic macular degeneration (MMD) (29/50; 58%), age-related macular degeneration (1/50; 2%), and branch macular retinal vein occlusion (1/50; 2%). Secondary causes were MMD (4/50; 8%) and optic nerve atrophy (14/50, 28%), further differentiated into non-glaucomatous optic atrophy (NGOA) (9/50; 18%) and glaucomatous optic atrophy (GOA) (5/50; 10%). Prevalence of MMD as vision impairment cause increased significantly from 1/61 (1.6%) in the refractive error group of -6.00 to ≥-7.00 D, to 16/25 (64%) in the group of <-15.0 D. Higher MMD prevalence correlated with higher myopic refractive error (P < 0.001) and increased likelihood of concomitant optic neuropathy (P < 0.001). Similarly, prevalence of optic neuropathy as vision impairment cause increased from 0/61 (0%) in the refractive error group of -6.00 D to ≥-7.00 D, to 9/25 (36%) in the group of <-15.0 D. Higher optic neuropathy prevalence correlated with more myopic refraction (P < 0.001) and older age (P = 0.02).
CONCLUSIONS: In this population-based recruited cohort of highly myopic patients, optic neuropathy accounted for vision impairment in 9.0% eyes, which was lower than the prevalence of MMD as vision impairment cause (18.9%). Notably, optic neuropathy became a significant contributor to vision impairment in more advanced high myopia, reaching 36% in the group with refractive error of <-15.0 D.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The prevalence of myopic macular degeneration (MMD) in the general population and patients with high myopia worldwide has not been fully investigated. Therefore, we screened all population-based studies that reported the prevalence of MMD, and pooled prevalence of MMD using a random-effect model. Subgroup analyses were performed to explore the differences in MMD prevalence in the general population and patients with high myopia according to ethnicity, region of residence (urban/rural), and grading system. Finally, 16 studies were included in this meta-analysis. Results obtained from 2,963 patients from seven countries on four continents indicated that the pooled prevalence of MMD in patients with high myopia was 49.0% (95% CI: 31.5%-66.7%). Results obtained from 71,052 participants from 10 countries on four continents suggested that the pooled prevalence of MMD in the general population was 1.7% (95% CI: 1.1%-2.6%). In the general population, living in urban areas and East Asians were associated with a high prevalence of MMD. Among patients with high myopia, only East Asians were at a higher risk of developing MMD. In conclusion, MMD was particularly prevalent in patients with high myopia. Compared with Europeans, East Asians (Chinese and Japanese) have a higher propensity of developing MMD, both in the general population and in patients with high myopia. It remains unclear whether the higher prevalence of MMD in patients with high myopia in East Asia is caused by differences in given age or given degree of myopia.Systematic review registration number: 202270014 (INPLASY.COM).

UNASSIGNED: To examine histologic characteristics of macular Bruchś membrane defects (BMD) in axially elongated eyes.
UNASSIGNED: Histomorphometric study.
UNASSIGNED: Using light microscopy, we examined enucleated human globes for BMDs.
UNASSIGNED: In 247 eyes, BMDs were detected in 15 (6.1%) eyes (axial length:27.0-36.0 mm), in 10 of them in the macular region. Prevalence and size of BMDs (mean:1.93 ± 1.62 mm; range:0.22mm-6.24 mm) correlated with longer axial length (OR:1.52; 95%CI:1.19,1.94; P = 0.001) and higher prevalence of scleral staphylomas (OR:16.3; 95%CI:2.67,99.3; P < 0.001). The BMDs were smaller than corresponding gaps in the retinal pigment epithelium (RPE) (1.93 ± 1.62 mm versus 2.61 mm ± 1.73 mm; P = 0.003), and larger than corresponding gaps in the inner nuclear layer (0.43 ± 0.76 mm; P = 0.008) and inner limiting membrane bridges (0.13 ± 0.33 mm; P = 0.001). Choriocapillaris thickness, BM thickness and RPE cell density did not vary (all P > 0.05) between the BDM border and adjacent areas. In the BMD, choriocapillaris and RPE were absent. The sclera was thinner in the BDM area than in adjacent areas (0.28 ± 0.19 mm versus 0.36 ± 0.13 mm; P = 0.006).
UNASSIGNED: BMDs as hallmarks of myopic macular degeneration are characterized by longer gaps in the RPE and smaller gaps in the outer nuclear layer and inner nuclear layer, by localized scleral thinning, and by a spatial association with scleral staphylomas. Thickness of the choriocapillaris and density of the RPE cell layer, both absent within the BDMs, do not vary between the BMD border and adjacent regions. The results suggest an association between BDMs and absolute scotomas, stretching of the adjacent retinal nerve fiver layer, and an axial elongation-associated stretching effect on BM as etiology of the BDMs.

To identify the risk factors associated with myopic macular neovascularization (mMNV)-related complications in patients treated with intravitreal anti-VEGF agents.
Longitudinal cohort study.
Myopic eyes (n = 313) with active mMNV and median (interquartile range) follow-up of 42 months (interquartile range, 18-68 months) after initiation of anti-VEGF treatment.
Data regarding patients\' clinical and mMNV-related characteristics were collected at baseline. Subsequent OCT scans were inspected for mMNV-related complications. Best-measured visual acuity (BMVA) values were retrieved from each visit.
Incidence rate and hazard ratio (HR, with 95% confidence interval [CI]) of risk factors for fibrosis and macular atrophy calculated with Kaplan-Meier curves and Cox regression models. Crude incidence of macular hole (MH). Longitudinal BMVA changes.
Five-year incidence of fibrosis, atrophy, and MH were 34%, 26%, and 8%, respectively. The rate of fibrosis was 10.3 (95% CI, 8.25-12.6) per 100 person-years. Risk factors were subfoveal mMNV location (HR [95% CI] = 12.7 [2.70-56.7] vs. extrafoveal, P = 0.001) and intraretinal fluid at baseline (HR [95% CI] = 1.75 [1.05-2.98], P = 0.03). The rate of macular atrophy was 6.5 (95% CI, 5-8.3) per 100 person-years. Risk factors were diffuse (HR, 2.20 vs. tessellated fundus; 95% CI, 1.13-5.45; P = 0.02) or patchy chorioretinal atrophy (HR, 3.17 vs. tessellated fundus; 95% CI, 1.32-7.64; P = 0.01) at baseline and more numerous anti-VEGF injections before baseline (HR, 1.21; 95% CI, 1.06-1.38 for each treatment; P = 0.005). Eyes with fibrosis and macular atrophy had faster BMVA decay over follow-up. Twenty eyes (6%) developed MH. Two subtypes of MH were identified: \"atrophic\" and \"tractional.\"
Myopic MNV-related complications are common in the long term despite initially successful treatment and have detrimental effects on visual acuity. Insights into their incidence and risk factors may help for future treatments to mitigate sight-threatening outcomes.

暂无摘要。

To evaluate the transancestry portability of current myopia polygenic risk scores (PRSs) to predict high myopia (HM) and myopic macular degeneration (MMD) in an Asian population.
Population-based study.
A total of 5894 adults (2141 Chinese, 1913 Indian, and 1840 Malay) from the Singapore Epidemiology of Eye Diseases study were included in the analysis. The mean ± standard deviation age was 57.05 ± 9.31 years. A total of 361 adults had a diagnosis of HM (spherical equivalent [SE] < -5.00 diopters [D]) from refraction measurements, 240 individuals had a diagnosis of MMD graded by the International Photographic Classification and Grading System for Myopic Maculopathy criteria from fundus photographs, and 3774 individuals were control participants without myopia (SE > -0.5 D).
The PRS, derived from 687 289 HapMap3 single nucleotide polymorphisms (SNPs) from the largest genome-wide association study of myopia in Europeans to date (n = 260 974), was assessed on its ability to predict patients with HM and MMD versus control participants.
The primary outcomes were the area under the receiver operating characteristic curve (AUC) to predict HM and MMD.
The PRS had an AUC of 0.73 (95% confidence interval [CI], 0.70-0.75) for HM and 0.66 (95% CI, 0.63-0.70) for MMD versus no myopia. The inclusion of the PRS with other predictors (age, sex, educational attainment [EA], and ancestry; age-by-ancestry, sex-by-ancestry, and EA-by-ancestry interactions; and 20 genotypic principal components) increased the AUC to 0.84 (95% CI, 0.82-0.86) for HM and 0.79 (95% CI, 0.76-0.82) for MMD. Individuals with a PRS in the top 5% showed up to a 4.66 (95% CI, 3.34-6.42) times higher risk of HM developing and up to a 3.43 (95% CI, 2.27-5.05) times higher risk of MMD developing compared with the remaining 95% of individuals.
The PRS is a good predictor for HM and facilitates the identification of high-risk children to prevent myopia progression to HM. In addition, the PRS also predicts MMD and helps to identify high-risk adults with myopia who require closer monitoring for myopia-related complications.