Prevalence of Myopic Maculopathy Among the Very Old: The Ural Very Old Study.

Purpose: To assess the prevalence of myopic macular degeneration (MMD) in very old individuals. Methods: The population-based Ural Very Old Study (UVOS) included 1526 (81.1%) of 1882 eligible inhabitants aged ≥85 years. Assessable fundus images were available for 930 (60.9%) individuals (mean age, 88.6 ± 2.7 years). MMD was defined by macular patchy atrophies (i.e., MMD stage 3 and 4 as defined by the Pathologic Myopia Study Group). Results: MMD prevalence was 21 of 930 (2.3%; 95% CI, 1.3-3.3), with 10 individuals (1.1%; 95% CI, 0.4-1.7) having MMD stage 3 and 11 participants (1.2%; 95% CI, 0.5-1.9) MMD stage 4 disease. Within MMD stage 3 and 4, prevalence of binocular moderate to severe vision impairment was 4 of 10 (40%; 95% CI, 31-77) and 7 of 11 (64%; 95% CI, 30-98), respectively, and the prevalence of binocular blindness was 2 of 10 (20%; 95% CI, 0-50) and 3 of 11 (27%; 95% CI, 0-59), respectively. In minor myopia (axial length, 24.0 to <24.5 mm), moderate myopia (axial length, 24.5 to <26.5 mm), and high myopia (axial length, ≥26.5 mm), MMD prevalence in the right eyes was 0 of 46 eyes (0%), 3 of 40 eyes (8%; 95% CI, 0-16), and 7 of 9 (78%; 95% CI, 44-100), respectively; MMD prevalence in the left eyes was 1 in 48 eyes (2%; 95% CI, 0-6), 4 of 36 eyes (11%; 95% CI, 0-22), and 3 of 4 eyes (75%; 95% CI, 0-100), respectively. In multivariable analysis, a higher MMD prevalence (odds ratio, 8.89; 95% CI, 3.43-23.0; P < 0.001) and higher MMD stage (beta, 0.45; B, 19; 95% CI, 0.16-0.22; P < 0.001) were correlated with longer axial length but not with any other ocular or systemic parameter. Conclusions: MMD prevalence (stages 3 and 4) in very old individuals increased 8.89-fold for each mm axial length increase, with a prevalence of ≥75% in highly myopic eyes. In old age, highly myopic individuals have a high risk of eventually developing MMD with marked vision impairment.

Intraocular pressure and its determinants in a very old population. The ural very old study.

Purpose: To explore intraocular pressure (IOP) and its associated parameters in an aged population. Methods: The epidemiologic Ural Very Old Study (UVOS) conducted in Bashkortostan/Russia included 1526 participants with an age of ≥85 years. Besides a whole series of ocular and systemic examinations, IOP was determined applying non-contact tonometry. Body mass index, diastolic blood pressure and age were the factors used to estimate the cerebrospinal fluid pressure (CSFP). Results: The study consisted of 904 participants (age: 88.6 ± 2.7 years) with available IOP readings and without anti-glaucomatous therapy. Mean IOP was 14.5 ± 5.1 mmHg (median: 14 mm Hg; Q1:11; Q3:16; 95%CI:8,25) and 14.8 ± 4.6 mmHg (median: 14 mm Hg; Q1:12; Q3:17; 95%CI:8,28) in the right and left eyes, respectively. Higher IOP correlated (multivariable analysis; correlation coefficient r2:0.32) with female sex (P < 0.001), more sedentary lifestyle (P = 0.006), higher estimated CSFP (P < 0.001), higher total protein serum concentration (P < 0.001), stronger hand grip force (P = 0.01), thicker central cornea (P < 0.001), longer axial length (P = 0.01), absence of previous cataract surgery (P = 0.001), higher degree of pseudoexfoliation (P = 0.02, and thinner peripapillary retinal nerve fiber layer thickness (P = 0.004). Using this that model, IOP reading enlarged by 0.22 mmHg (95% CI: 0.09, 0.35) for each increase in estimated CSFP by 1 mm Hg, by 0.03 mm Hg (95% CI: 0.02,0.05) for each thickening in central corneal thickness by 1 µm, by 0.56 mm Hg (95%CI: 0.13,1.00) for each axial elongation by 1 mm, and by 0.40 mmHg (95% CI: 0.06,0.74) for each increase in the degree of pseudoexfoliation, and it decreased by 0.40 mmHg (95% CI: 0.06,0.74) by cataract surgery. Conclusions: In this study population aged 85+years, IOP readings showed similar relationships as in younger study populations, including positive associations with higher estimated CSFP and longer axial length and a negative association with cataract surgery.

Prevalence and associated factors of myopia in children and adolescents in Russia: the Ural Children Eye Study.

BACKGROUND: To assess the prevalence of myopia and the distribution of ocular axial length as surrogate for myopic refractive error in school children in a population in Russia. METHODS: The Ural Children Eye Study, a school-based case-control study, was conducted in Ufa/Bashkortostan/Russia from 2019 to 2022 and included 4933 children (age: 9.7±2.6 years; range: 6.2-18.8 years). The parents underwent a detailed interview and the children an ophthalmological and general examination. RESULTS: Prevalence of any myopia (≤-0.50 dioptres (D)), minor myopia (-0.50 D to -1.0 D), moderate myopia (-1.01 D to -5.99 D) and high myopia (≤-6.0D) was 2187/3737 (46.2%; 95% CI 44.8% to 48.6%), 693/4737 (14.6%; 95% CI 13.6% to 15.6%), 1430/4737 (30.2%; 95% CI 28.9% to 31.5%) and 64/4737 (1.4%; 95% CI 1.0% to 1.7%), respectively. In the children aged 17+ years, prevalence of any, minor, moderate and high myopia was 170/259 (65.6%; 95% CI 59.8% to 71.5%), 130/259 (50.2%; 95% CI 44.1% to 56.3%), 28/259 (10.8%; 95% CI 7.0% to 14.6%) and 12/259 (4.6%; 95% CI 2.1% to 7.2%), respectively. After adjusting for corneal refractive power (beta: 0.09) and lens thickness (beta: -0.08), larger myopic refractive error was associated (r2=0.19) with older age (beta: 0.33), female sex (beta: 0.04), higher prevalence of maternal (beta: 0.15) and paternal (beta: 0.12) myopia, more time spent in school, with reading books or playing with the cell phone (beta: 0.05) and less total time spent outdoors (beta: 0.05). Axial length and myopic refractive error increased by 0.12 mm (95% CI 0.11 to 0.13) and -0.18 D (95% CI 0.17 to 0.20), respectively, per year of age. CONCLUSIONS: In this ethnically mixed urban school children population from Russia, prevalence of any myopia (65.6%) and high myopia (4.6%) in children aged 17+ years was higher than in adult populations in the same region and it was lower than in East Asian school children, with similar associated factors.

Associations between axial length, corneal refractive power and lens thickness in children and adolescents: The Ural Children Eye Study.

PURPOSE: To assess relationships between ocular biometric parameters in dependence of age and sex in children and adolescents. METHODS: In the Ural Children Eye Study, a school-based cohort study, 4933 children underwent an ophthalmological and general examination. RESULTS: Complete biometric measurements were available for 4406 (89.3%) children. Cycloplegic refractive error (mean: -0.87 ± 1.73 diopters (D); median: -0.38 D; range: -19.75 D to +11.25 D) increased (multivariable analysis; r2 = 0.73) with shorter axial length (ß: -0.99; non-standardized regression coefficient B: -1.64; 95% CI: -1.68, -1.59) and lower corneal refractive power (ß: -0.55; B: -0.67; 95% CI: -0.70, -0.64), in addition to higher cylindrical refractive error (ß: 0.10; B: 0.34; 95% CI: 0.27, 0.41), thinner lens (ß: -0.11; -0.85; 95% CI: -1.02, -0.69) and male sex (ß: 0.15; B: 0.50; 95% CI: 0.42, 0.57). In univariate analysis, decrease in refractive error with older age was more significant (ß: -0.38 vs. ß: -0.25) and steeper (B: -0.22 (95% CI: -0.24, -0.20) vs. B: -0.13 (95% CI: -0.15, -0.11)) in girls than boys, particularly for an age of 11+ years. Axial length increased with older age (steeper for age <11 years) (B: 0.22 (95% CI: 0.18, 0.25) vs. 0.07 (95% CI: 0.05, 0.09)). In multivariable analysis, axial length increased with lower refractive error (ß: -0.77; B: -0.42; 95% CI: -0.43, -0.40) and lower corneal refractive power (ß: -0.54; B: -0.39; 95% CI: -0.41, -0.38), in addition to older age (ß: 0.04; B: 0.02; 95% CI: 0.01, 0.03), male sex (ß: 0.13; B: 0.23; 95% CI: 0.21, 0.32), higher cylindrical refractive error (ß: 0.05; B: 0.09; 95% CI: 0.05, 0.14) and thinner lens (ß: -0.14; B: -0.62; 95% CI: -0.72, -0.51). The axial length/corneal curvature (AL/CR) ratio increased until the age of 14 years (ß: 0.34; B: 0.017; 95% CI: 0.016, 0.019; p < 0001), and then became independent of age. The AL/CR ratio increased (r2 = 0.78) mostly with higher corneal refractive power (ß: 0.25; B: 0.02; 95% CI: 0.02, 0.02; p < 0.001), lower refractive error (ß: -0.75; B: -0.05; 95% CI: -0.05, -0.05; p < 0.001), thinner lens thickness (ß: -01.6; B: -0.09; 95% CI: -0.10, -0.08; p < 0.001) and older age (ß: 0.16; B: 0.006; 95% CI: 0.005, 0.007; p < 0.001). CONCLUSIONS: In this multiethnic group of school children in Russia, the age-related increase in myopic refractive error was more significant and steeper in girls, particularly for the age group of 11+ years. Determinants of higher myopic refractive error were longer axial length, higher corneal refractive power, lower cylindrical refractive error, thicker lens and female sex.

Is Kidney Function Associated with Age-Related Macular Degeneration?: Findings from the Asian Eye Epidemiology Consortium.

PURPOSE: Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-one thousand two hundred fifty-three participants from 10 distinct population-based Asian studies. METHODS: Age-related macular degeneration was defined using the Wisconsin Age-Related Maculopathy Grading System, the International Age-Related Maculopathy Epidemiological Study Group Classification, or the Beckman Clinical Classification. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m2. A pooled analysis using individual-level participant data was performed to examine the associations between CKD and eGFR with AMD (early and late), adjusting for age, sex, hypertension, diabetes, body mass index, smoking status, total cholesterol, and study groups. MAIN OUTCOME MEASURES: Odds ratio (OR) of early and late AMD. RESULTS: Among 51 253 participants (mean age, 54.1 ± 14.5 years), 5079 had CKD (9.9%). The prevalence of early AMD was 9.0%, and that of late AMD was 0.71%. After adjusting for confounders, individuals with CKD were associated with higher odds of late AMD (OR, 1.46; 95% confidence interval [CI], 1.11-1.93; P = 0.008). Similarly, poorer kidney function (per 10-unit eGFR decrease) was associated with late AMD (OR, 1.12; 95% CI, 1.05-1.19; P = 0.001). Nevertheless, CKD and eGFR were not associated significantly with early AMD (all P ≥ 0.149). CONCLUSIONS: Pooled analysis from 10 distinct Asian population-based studies revealed that CKD and compromised kidney function are associated significantly with late AMD. This finding further underscores the importance of ocular examinations in patients with CKD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Anterior chamber depth and angle and associations in a pediatric and adult population in Russia.

Purpose: To investigate the normative data of anterior chamber depth (ACD) and angle (ACA) and their associations in multiethnic cohorts spanning three generations in Russia. Methods: The study cohort included the participants of three population-based studies performed in urban and rural Bashkortostan/Russia: The Ural Eye and Medical Study (UEMS; age:40+ years), Ural Children Eye Study (UCES; age:6-18 years), and Ural Very Old Study (UVOS; age:85+ years). Using Scheimflug camera-based anterior chamber imaging, we measured ACD and ACA as part of a comprehensive ophthalmological and systemic examination. Exclusion criterion was previous cataract surgery. Results: The study included 4869 (98.7 %) children out of 4933 children of the UCES, 5426 (92.0 %) out of 5899 UEMS participants, and 268 (16.3 %) out of 1526 UVOS participants. In the UEMS, shallower ACD (mean:3.14 ± 0.37 mm) correlated (multivariable analysis; r[2] = 0.57) with older age (beta: 0.08;P < 0.001), shorter body height (beta:0.03;P = 0.003), shorter axial length (beta:0.34;P < 0.001), lower corneal volume (beta:0.06;P < 0.001) and corneal refractive power (beta:0.12;P < 0.001), thicker lens (beta: 0.09;P < 0.001), higher IOP (beta: 0.03;P = 0.02), higher prevalence of angle-closure glaucoma (beta: 0.03;P = 0.003) and lower prevalence of open-angle glaucoma (beta:0.03;P = 0.007). Similar associations were found in the UCES (ACD mean:3.70 ± 0.27 mm) and UVOS (ACD mean:2.96 ± 0.56 mm). Conclusions: In this population-based cohort of three generations from rural and urban Bashkortostan, ACD decreased from the children cohort (mean:3.70 ± 0.27 mm) to the adult cohort (mean:3.14 ± 0.37 mm) and to the very old cohort (2.96 ± 0.56 mm). Determinants of shallow ACD were older age and lower body height, in addition to the ocular biometric parameters of shorter axial length, lower corneal volume, corneal refractive power, and thinner lens thickness.

Prevalence and Associations of Keratoconus Among Children, Adults, and Elderly in the Population-Based Ural Eye Studies.

PURPOSE: To estimate prevalence and associations of keratoconus in populations in Russia with an age from childhood to seniority. METHODS: The study population consisted of the cohorts of 3 population-based studies performed in urban and rural areas within the same geographical region in Bashkortostan/Russia: the Ural Children Eye Study (UCES; age = 6-18 y; n = 4890), the Ural Eye and Medical Study (UEMS; age = >40 y; n = 5314), and the Ural Very Old Study (UVOS; age = >85 y; n = 651). Based on Scheimflug imaging, keratoconus was defined by a keratometric reading of ≥48 diopters (D) in any eye. RESULTS: The mean maximal and minimal corneal refractive power increased from the UCES (43.58 ± 1.50 D and 42.70 ± 1.42 D, respectively) to the UEMS (44.26 ± 1.70 D and 43.61 ± 1.76 D, respectively) and to the UVOS (45.1 ± 1.72 D and 43.98 ± 1.68 D, respectively). Correspondingly, keratoconus prevalence increased from the UCES (42/4890; 0.086%; 95% CI = 0.060, 0.112) to the UEMS (112/5314; 2.11%; 95% CI = 1.72, 2.49) and to the UVOS (42/651; 6.45%; 95% CI = 4.56, 8.34). In the UCES, higher keratoconus prevalence was associated (multivariable analysis) with higher birth order [odds ratio (OR) = 2.34; 95% CI = 1.32, 4.15; P = 0.004], lower birth weight (OR = 0.99; 95% CI = 0.99, 0.99; P < 0.001), and shorter axial length (OR = 0.15; 95% CI = 0.08, 0.30; P < 0.001). In the UEMS, keratoconus prevalence correlated with shorter axial length (OR = 0.15; 95% CI = 0.10, 0.23; P < 0.001), larger corneal volume (OR = 1.17; 95% CI = 1.09, 1.25; P = 0.001), thicker lens (OR = 2.27; 95% CI = 1.06, 5.28; P = 0.04), cortical cataract degree (OR = 1.02; 95% CI = 1.01, 1.04; P = 0.01), and higher stage of age-related macular degeneration (OR = 1.65; 95% CI = 1.09, 2.51; P = 0.02). In the UVOS, keratoconus prevalence correlated with lower educational level (OR = 0.84; 95% CI = 0.71, 0.99; P = 0.04) and lower dynamometric handgrip force (OR = 0.92; 95% CI = 0.88, 0.97; P = 0.003). CONCLUSIONS: In this study on multiethnic groups from Russia, keratoconus prevalence increased from the pediatric group (0.09%) to the adult group (2.11%) and seniority group (6.45%), correlated mostly with biometric ocular parameters and was in all age groups statistically independent of most systemic parameters.

Prevalence of depression, anxiety and suicidal ideas and associated factors, in particular sensory impairments, in a population of Bashkortostan in Russia.

To assess prevalence and associated factors of depression, anxiety and suicidal ideas in populations from Russia, we conducted in rural and urban regions in Bashkortostan/Russia two population-based studies (Ural Eye and Medical Study (UEMS), performed from 2015 to 2017; Ural Very Old Study (UVOS), performed from 2017 to 2020) which included participants aged 40 + years and 85 + years, respectively. Depression was assessed using the questionnaire of the Center for Epidemiologic Studies Depression Scale Scoresheet, and anxiety was examined applying the State Trait Inventory Anxiety Test. Suicidal ideas were explored by the question whether suicide had previously been thought of or attempted (and if yes, for what reasons). In the statistical analysis we assessed the mean of the main outcome parameter (depression score and anxiety score) and searched for associations between these parameters and other parameters in univariable and multivariable regression analyses. In the UEMS with 5893 individuals (age: 59.0 ± 10.7 years; range 40-94 years), higher depression score and anxiety score were associated (multivariable analysis) with more marked hearing loss (beta: 0.07; P < 0.001, and beta: 0.07; P < 0.0012, respectively) and worse visual acuity (beta: 0.04; P = 0.02; and beta: 0.03; P = 0.03, resp.), in addition to female sex, Russian ethnicity, lower educational level, less alcohol consumption, weaker hand grip strength, less physical activity, and higher prevalence of dry eye disease. Attempted suicide was reported by 88 (1.5%; 95% CI 1.2, 1.8) participants. Having thought of suicide within the last 6 months was reported by 63 (1.1%) individuals. Out of 1491 UVOS participants (age: 88.2 ± 2.8 years; range 85-100 years) with a mean depression score of 20.0 ± 10.3 (median 18; range 0-58), 916 (61.4%; 95% CI 59.0, 63.9) fulfilled the definition of depression (depressions core ≥ 16). Higher depression score and higher anxiety score correlated (multivariable analysis) with higher hearing loss score (beta: 0.07; P = 0.02, and beta: 0.08; P = 0.009, resp.) and worse visual acuity (beta: 0.13; P < 0.001, and beta: 0.09; P = 0.007, resp.), in addition to female sex, urban region, less physical activity, less fruit intake, and lower cognitive function. Overall, 15 (1.0%; 95% CI 0.50, 1.50) individuals had attempted or thought of suicide. In conclusion, the findings suggest that besides female sex, lower level of education and lower cognitive function, it was sensory impairment, namely vision and hearing impairment, which belonged to the determinants of depression and anxiety in these populations from Russia.

Intravitreal panitumumab and myopic macular degeneration.

BACKGROUND: In experimental studies, intravitreally applied antibodies against epidermal growth factor (EGF), EGF family members (amphiregulin, neuregulin-1, betacellulin, epigen, epiregulin) and against the EGF receptor (EGFR) were associated with a reduction in lens-induced axial elongation and decrease in physiological eye elongation in guinea pigs and in non-human primates. Here, we investigated the intraocular tolerability and safety of a fully human monoclonal IgG2-antibody against EGFR, already in clinical use in oncology, as a potential future therapeutic approach for axial elongation in adult eyes with pathological myopia. METHODS: The clinical, monocentre, open-label, multiple-dose, phase-1 study included patients with myopic macular degeneration of stage 4, who received intravitreal injections of panitumumab in various doses and in intervals ranging between 2.1 months and 6.3 months. RESULTS: The study included 11 patients (age:66.8±6.3 years), receiving panitumumab injections in doses of 0.6 mg (4 eyes; 1×1 injection, 3×2 injections), 1.2 mg (4 eyes; 1×1 injection, 2×2 injections, 1×3 injections) and 1.8 mg (3 eyes; 1×1 injection, 2×2 injections), respectively. None of the participants showed treatment-emergent systemic adverse events or intraocular inflammatory reactions. Best-corrected visual acuity (1.62±0.47 logarithm of the minimal angle of resolution (logMAR) vs 1.28±0.59 logMAR; p=0.08) and intraocular pressure (13.8±2.4 mm Hg vs 14.3±2.6 mm Hg; p=0.20) remained unchanged. In nine patients with a follow-up of >3 months (mean:6.7±2.7 months), axial length did not change significantly (30.73±1.03 mm vs 30.77±1.19 mm; p=0.56). CONCLUSIONS: In this open-labelled, phase-1 study with a mean follow-up of 6.7 months, panitumumab repeatedly administered intravitreally up to a dose of 1.8 mg was not associated with intraocular or systemic adverse effects. During the study period, axial length remained unchanged. TRIAL REGISTRATION NUMBER: DRKS00027302.

Prevalence and Associations of Nonglaucomatous Optic Nerve Atrophy in High Myopia: The Ural Eye and Medical Study.

PURPOSE: To assess the prevalence of nonglaucomatous optic nerve atrophy (NGOA) in highly myopic individuals. DESIGN: Population-based study. PARTICIPANTS: The Ural Eye and Medical Study included 5899 (80.5%) of 7328 eligible individuals (80.5%). METHODS: Nonglaucomatous optic nerve atrophy, graded into 5 arbitrary stages, was characterized by decreased visibility of the retinal nerve fiber layer (RNFL) on photographs, neuroretinal rim pallor, abnormally thin retinal arteriole diameter, and abnormally thin peripapillary RNFL as measured by OCT. MAIN OUTCOME MEASURES: Nonglaucomatous optic nerve atrophy prevalence and degree. RESULTS: Of 5709 participants (96.9%) with axial length measurements, 130 individuals (2.3%) were highly myopic, of whom 116 individuals (89.2%; age, 57.8 ± 11.1 years; axial length, 27.0 ± 1.2 mm) had available fundus photographs and OCT images and were included into the study. Nonglaucomatous optic nerve atrophy prevalence was 34/116 individuals (29.3%; 95% confidence interval [CI], 21.0-38.0), and mean NGOA degree in eyes with NGOA was 1.7 ± 1.0 arbitrary units. Higher NGOA degree correlated (multivariable analysis; regression coefficient, r2 = 0.59) with longer axial length (ß, 0.22; P = 0.007), wider temporal parapapillary γ zone width (ß, 0.50; P < 0.001), higher prevalence of diabetes (ß, 0.20; P = 0.005), and higher systolic blood pressure (ß, 0.15; P = 0.03). Higher NGOA prevalence was associated with longer axial length (odds ratio [OR], 7.45; 95% CI, 2.15-25.7), wider temporal parapapillary γ zone (OR, 6.98; 95% CI, 2.61-18.7), and higher systolic blood pressure (OR, 1.05; 95% CI, 1.01-1.10). CONCLUSIONS: In this ethnically mixed population from Russia with an age of 40 years or more, high axial myopia showed a relatively high prevalence of NGOA, increasing with longer axial length and wider temporal parapapillary γ zone. For each 1 mm of axial elongation and γ zone widening, the odds for NGOA increased 7.45-fold and 6.98-fold, respectively. The axial elongation-associated and γ zone-related increase in the distance between the retinal ganglion cells and the optic disc may lead to a lengthening and stretching of the retinal ganglion cell axons and may be of importance pathogenetically. In highly myopic eyes, NGOA may be a reason for visual field and central visual acuity loss, unexplainable by myopic macular pathologic features. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Diabetic Neuropathy of the Retina and Inflammation: Perspectives.

A clear connection exists between diabetes and atherosclerotic cardiovascular disease. Consequently, therapeutic approaches that target both diseases are needed. Clinical trials are currently underway to explore the roles of obesity, adipose tissue, gut microbiota, and pancreatic beta cell function in diabetes. Inflammation plays a key role in diabetes pathophysiology and associated metabolic disorders; thus, interest has increased in targeting inflammation to prevent and control diabetes. Diabetic retinopathy is known as a neurodegenerative and vascular disease that occurs after some years of poorly controlled diabetes. However, increasing evidence points to inflammation as a key figure in diabetes-associated retinal complications. Interconnected molecular pathways, such as oxidative stress, and the formation of advanced glycation end-products, are known to contribute to the inflammatory response. This review describes the possible mechanisms of the metabolic changes in diabetes that involve inflammatory pathways.

Association of Systemic Medication Use with Glaucoma and Intraocular Pressure: The European Eye Epidemiology Consortium.

PURPOSE: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. DESIGN: Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium. PARTICIPANTS: The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants. METHODS: We examined associations of 4 categories of systemic medications-antihypertensive medications (ß-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications-with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only. MAIN OUTCOME MEASURES: Glaucoma prevalence and IOP. RESULTS: In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic ß-blockers was associated with a lower IOP (ß coefficient, -0.33 mmHg; 95% CI, -0.57 to -0.08 mmHg). Monotherapy of both selective systemic ß-blockers (ß coefficient, -0.45 mmHg; 95% CI -0.74 to -0.16 mmHg) and nonselective systemic ß-blockers (ß coefficient, -0.54 mmHg; 95% CI, -0.94 to -0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (ß coefficient, -0.30 mmHg; 95% CI, -0.47 to -0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP. CONCLUSIONS: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic ß-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Anatomic Peculiarities Associated with Axial Elongation of the Myopic Eye.

PURPOSE: To describe anatomical peculiarities associated with axial elongation in the human myopic eye. METHODS: Reviewing the results of previous histomorphometrical investigations of enucleated human globes, as well as reviewing findings obtained in population-based studies and hospital-based clinical investigations of myopic patients and non-myopic individuals. RESULTS: Myopic axial elongation is associated with a change from a mostly spherical eye shape to a prolate ellipsoid form. It is combined with choroidal and scleral thinning, most pronounced at the posterior pole and less pronounced in the fundus midperiphery. In the fundus midperiphery, the retina and density of the retinal pigment epithelium (RPE) and photoreceptors decrease with a longer axial length, while in the macular region, retinal thickness, RPE cell density, and choriocapillaris thickness are not related to axial length. With axial elongation, a parapapillary gamma zone develops, leading to an enlargement of the optic disc-fovea distance and a decrease in angle kappa. Axial elongation is also correlated with an increase in the surface and volume of Bruch's membrane (BM), while BM thickness remains unchanged. Axial elongation causes moderately myopic eyes to show a shift of BM opening to the foveal direction so that the horizontal disc diameter becomes shorter (with a consequent vertical ovalization of the optic disc shape), a temporal gamma zone develops, and the optic nerve exit takes an oblique course. Features of high myopia are an enlargement of the RPE opening (myopic parapapillary beta zone) and BM opening (secondary macrodisc), elongation and thinning of the lamina cribrosa, peripapillary scleral flange (parapapillary delta zone) and peripapillary choroidal border tissue, secondary BM defects in the macular region, myopic maculoschisis, macular neovascularization, and cobblestones in the fundus periphery. CONCLUSIONS: These features combined may be explained by a growth in BM in the fundus midperiphery leading to axial elongation.

Myopic axial elongation in school children and the COVID-19 lockdown in Russia: The Ural Children Myopia Study.

BACKGROUND: To explore an influence of the COVID-19-related lockdown on ocular axial elongation in school children in Russia. METHODS: The participants of the school-based Ufa Children Myopia Study in Ufa/Russia underwent, at baseline in 2019/2020 before the COVID-19 outbreak and after a COVID-19-related lockdown, a detailed interview and ophthalmological examination including laser interferometric biometry for axial length measurement. RESULTS: The study included 461 children (age:10.7±2.1 years;range:6.8-16.9 years). The mean follow-up was 1.41±0.33 years. Mean axial length at baseline was 23.96±0.95mm and 23.94±0.95mm in the right and left eyes, respectively. During the study period, annual axial elongation (right/left eyes) was 0.19±0.17mm/0.19±0.22mm. Before the COVID-19 lockdown, the age-dependent coefficient for axial length (ADCAL) for the right/left eyes was 0.21mm (95%CI:0.17,0.25)/0.20mm (95%CI:0.16,0.24). In children younger than 9.6 years (n = 157), annual axial elongation (right eyes) during the study period was larger than the ADCAL before the COVID-19 outbreak (0.29 mm (95%:0.00,0.66) versus 0.21 mm (95%CI:0.02,0.41)). In the groups aged 9.6 to 11.4 years (n = 148) and aged >11.4 years (n = 156), annual axial elongation during the study period was comparable to the ADCAL before the COVID-19 outbreak (0.18mm (95%CI:-0.07,0.46) versus 0.22mm (95%CI:-0.05,0.48), and (0.09mm (95%CI:-0.15,0.34) versus 0.14mm (95%CI:0.00,0.28), respectively). In children aged ≤9 years at study end, axial length at study end was 0.20 mm larger than axial length at baseline in the participants aged ≤9 years at baseline. Larger axial elongation during the study period was associated (multivariable analysis) with younger age (beta:-0.62;P<0.001), female sex (beta:0.21;P<0.001), longer study period (beta:0.22;P<0.001), and longer axial length at baseline (beta:0.28;P<0.001), and marginally, with less time spent outdoors (beta:-0.07;P = 0.06). CONCLUSIONS: The COVID-19-related lockdown in the Russian city of Ufa was associated with a relatively minor increase in axial elongation, detected only in children aged <9.6 years.

Myopia: Histology, clinical features, and potential implications for the etiology of axial elongation.

Myopic axial elongation is associated with various non-pathological changes. These include a decrease in photoreceptor cell and retinal pigment epithelium (RPE) cell density and retinal layer thickness, mainly in the retro-equatorial to equatorial regions; choroidal and scleral thinning pronounced at the posterior pole and least marked at the ora serrata; and a shift in Bruch's membrane opening (BMO) occurring in moderately myopic eyes and typically in the temporal/inferior direction. The BMO shift leads to an overhang of Bruch's membrane (BM) into the nasal intrapapillary compartment and BM absence in the temporal region (i.e., parapapillary gamma zone), optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter, fovea-optic disc distance elongation, reduction in angle kappa, and straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibers. Highly myopic eyes additionally show an enlargement of all layers of the optic nerve canal, elongation and thinning of the lamina cribrosa, peripapillary scleral flange (i.e., parapapillary delta zone) and peripapillary choroidal border tissue, and development of circular parapapillary beta, gamma, and delta zone. Pathological features of high myopia include development of macular linear RPE defects (lacquer cracks), which widen to round RPE defects (patchy atrophies) with central BM defects, macular neovascularization, myopic macular retinoschisis, and glaucomatous/glaucoma-like and non-glaucomatous optic neuropathy. BM thickness is unrelated to axial length. Including the change in eye shape from a sphere in emmetropia to a prolate (rotational) ellipsoid in myopia, the features may be explained by a primary BM enlargement in the retro-equatorial/equatorial region leading to axial elongation.

Association of lipid-lowering drugs and antidiabetic drugs with age-related macular degeneration: a meta-analysis in Europeans.

BACKGROUND/AIMS: To investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population. METHODS: We included 38 694 adults from 14 population-based and hospital-based studies from the European Eye Epidemiology consortium. We examined associations between the use of systemic medications and any prevalent AMD as well as any late AMD using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis. RESULTS: Between studies, mean age ranged from 61.5±7.1 to 82.6±3.8 years and prevalence ranged from 12.1% to 64.5% and from 0.5% to 35.5% for any and late AMD, respectively. In the meta-analysis of fully adjusted multivariable models, lipid-lowering drugs (LLD) and antidiabetic drugs were associated with lower prevalent any AMD (OR 0.85, 95% CI=0.79 to 0.91 and OR 0.78, 95% CI=0.66 to 0.91). We found no association with late AMD or with any other medication. CONCLUSION: Our study indicates a potential beneficial effect of LLD and antidiabetic drug use on prevalence of AMD across multiple European cohorts. Our findings support the importance of metabolic processes in the multifactorial aetiology of AMD.

Hand grip strength and ocular associations: the Ural Eye and Medical Study.

PURPOSE: To explore the associations between hand grip strength (HGS) and ocular parameters and diseases. DESIGN: Population-based cohort study. METHODS: Participants of the Ural Eye and Medical Study, including 5899 (80.5%) out of 7328 eligible individuals aged 40+ years, underwent systemic and ophthalmological examinations including dynamometric HGS measurement. RESULTS: The study included 5381 (90.4%) individuals (age: 58.6±10.6 years; range: 40-94 years) with HGS measurements. Higher HGS (mean: 30.6±11.7 dekaNewton) correlated (multivariable analysis) with better visual acuity (beta: 0.02, p=0.02), longer ocular axial length (beta: 0.03, p=0.003), higher intraocular pressure (beta: 0.03, p=0.001), thicker peripapillary retinal nerve fibre layer (beta: 0.03, p=0.001) and lower prevalence of diabetic retinopathy (beta: -0.03, p=0.007), after adjusting for younger age, male sex, Russian ethnicity, higher body height and waist to hip ratio, higher educational level, higher physical total score, lower smoking package years, higher serum concentration of haemoglobin, higher prothrombin index, lower leucocyte cell count, lower prevalence of non-alcoholic fatty liver disease, lower depression score and lower prevalence of arthritis. In the model, HGS was not correlated with prevalence of nuclear cataract (p=0.38), cortical cataract (p=0.67), subcapsular posterior cataract (p=0.50), open-angle glaucoma (p=0.22) or angle-closure glaucoma (p=0.27). CONCLUSIONS AND RELEVANCE: In addition to parameters such as lower physical activity, higher depression score and worse general health status, a reduced HGS is associated with visual impairment, shorter axial length, lower intraocular pressure, thinner peripapillary retinal nerve fibre layer and higher prevalence of diabetic retinopathy. HGS dynamometry or a handshake may provide the ophthalmologist additional clinical information about the general health and ocular parameters of the patient.

Central corneal thickness and its associations in a Russian population. The Ural eye and Medical Study.

BACKGROUND: To assess central corneal thickness (CCT) and its associations in a Russian population. METHODS: The population-based Ural Eye and Medical Study included 5899 (80.5%) out of 7328 eligible individuals. As part of an ophthalmological and general examination, CCT was measured by Scheimflug imaging. RESULTS: The study included 5792 (98.2%) participants (age:58.8 ± 10.6 years;range: 40-94 years) with available bilateral CCT measurements. Mean CCT was larger in Russians than non-Russians (549.5 ± 32.8 µm versus 539.2 ± 33.9 µm; P < 0.001). In multivariable analysis, thicker CCT was associated (regression coefficient r:0.43) with younger age (standardized regression coefficient beta:-0.09; non-standardized regression coefficient B:-0.29;95% confidence interval (CI):-0.39,-0.20; P < 0.001), male sex (beta:0.05; B:3.10; 95%CI:1.18,5.03; P = 0.002), urban region of habitation (beta:0.10; B:6.83; 95%CI:4.61, 9.05; P < 0.001), Russian ethnicity (beta:0.04; B:3.48; 95%CI:1.04, 5.91; P = 0.005), higher level of education (beta:0.04; B:0.97;95%CI:0.29,1.66; P = 0.006), higher serum bilirubin concentration (beta:0.05;B:0.15; 95%CI:0.07,0.23;P < 0.001), lower corneal refractive power (beta:-0.09;B:11.92; 95%CI:-2.50,-1.35; P < 0.001), smaller anterior chamber angle (beta:-0.07;B:-0.38;95%CI:-0.52,-0.24;P < 0.001), higher IOP readings (beta:0.38; B:3.47; 95%CI:3.21,3.73; P < 0.001), and higher rise in IOP readings by medical mydriasis (beta:0.07; B:0.88;95%CI:0.54,1.22;P < 0.001). In that model, CCT was not associated with body height (P = 0.14), previous cataract surgery (P = 0.10), axial length (P = 0.18) or prevalence of glaucoma (P = 0.11). The mean inter-eye difference in CCT was 8.52 ± 13.9 µm (median:6.0;95CI:8.16,8.88). A higher inter-eye CCT difference was associated with older age (beta:0.08; B:0.11;95%CI:0.07,0.15; P = 0.01), lower level of education (beta:-0.04;B:-0.34; 95%CI:-0.60,-0.08; P < 0.001) and status after cataract surgery (beta:0.04; B:2.92;95%CI:1.02,4.83; P = 0.003). INTRODUCTION CONCLUSIONS: In this ethnically mixed population from Russia with an age of 40+ years, mean CCT (541.7 ± 33.7 µm) was associated with parameters such as younger age, male sex, Russian ethnicity, and higher educational level. These associations may be taken into account when the dependence of IOP readings on CCT are considered. Glaucoma prevalence was unrelated to CCT.

Prevalence and associations of dry eye disease and meibomian gland dysfunction in the ural eye and medical study.

To assess the prevalence of dry eye disease (DED) and Meibomian gland dysfunction (MGD) in a population in Russia. The population-based Ural Eye and Medical Study was conducted in an urban and rural region in Bashkortostan/Russia and included 5899 (80.5%) out of 7328 eligible persons, aged 40 + years. DED and MGD were assessed by Schirmer´s test, slit-lamp based examination of the Meibomian glands, and an interview with DED-related questions. The study included 5153 (87.4%) individuals with DED and MGD assessments (mean age: 58.5 ± 10.5 years). The mean Schirmer´s test result was 11.8 ± 6.8 mm and 12.5 ± 7.1 mm for the right/left eye, with a result of ≤ 5 mm measured in 1098 (21.3%; 95% confidence intervals (CI) 20.2, 22.4) of the worse eyes. The mean subjective dry eye symptoms score was 1.37 ± 1.82. MGD grade 1 (telangiectasia at the lid margin), 2, 3, 4 or any grade in the worse eye was diagnosed in 901 (21.1%), 1161 (27.1%), 158 (3.7%), 32 (0.7%), and 2252 (52.6%; 95% CI 51.1, 54.1) eyes respectively. The prevalence of DED diagnosis #1, #2 and #3 (Schirmer´s test ≤ 5 mm, and dry eye score ≥ 1, ≥ 2, and ≥ 3, respectively), #4 (dry eye score ≥ 1, Schirmer test ≤ 5 mm, MGD grade 1 +), and #5 (dry eye score ≥ 1, Schirmer test ≤ 5 mm, MGD grade 2 +) were 598/5142 (11.6%), 426/5153 (8.3%), 273/5142 (5.3%), 335/5142 (6.5%), and 186/5142 (3.6%), respectively. Mean depression score as applied was 5.1 ± 3.8. Higher DED prevalence (definition #4) was associated (multivariable analysis) with female sex (odds ratio (OR) 1.71; 95% CI 1.31, 2.22; P < 0.001), higher depression score (OR 1.04; 95% CI 101, 1.07; P = 0.009), and higher prevalence of thyroid disease history (OR 1.63; 95% CI 1.19, 2.24; P = 0.006). DED and MGD were common in this rural and urban population, and their prevalence was associated with female sex, thyroid disease, and depression.

Effective refractive error coverage in adults aged 50 years and older: estimates from population-based surveys in 61 countries.

BACKGROUND: In 2021, WHO Member States endorsed a global target of a 40-percentage-point increase in effective refractive error coverage (eREC; with a 6/12 visual acuity threshold) by 2030. This study models global and regional estimates of eREC as a baseline for the WHO initiative. METHODS: The Vision Loss Expert Group analysed data from 565 448 participants of 169 population-based eye surveys conducted since 2000 to calculate eREC (met need/[met need + undermet need + unmet need]). A binary logistic regression model was used to estimate eREC by Global Burden of Disease (GBD) Study super region among adults aged 50 years and older. FINDINGS: In 2021, distance eREC was 79·1% (95% CI 72·4-85·0) in the high-income super region; 62·1% (54·7-68·8) in north Africa and Middle East; 49·5% (45·0-54·0) in central Europe, eastern Europe, and central Asia; 40·0% (31·7-48·2) in southeast Asia, east Asia, and Oceania; 34·5% (29·4-40·0) in Latin America and the Caribbean; 9·0% (6·5-12·0) in south Asia; and 5·7% (3·1-9·0) in sub-Saharan Africa. eREC was higher in men and reduced with increasing age. Global distance eREC increased from 2000 to 2021 by 19·0%. Global near vision eREC for 2021 was 20·5% (95% CI 17·8-24·4). INTERPRETATION: Over the past 20 years, distance eREC has increased in each super region yet the WHO target will require substantial improvements in quantity and quality of refractive services in particular for near vision impairment. FUNDING: WHO, Sightsavers, The Fred Hollows Foundation, Fondation Thea, Brien Holden Vision Institute, Lions Clubs International Foundation.