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.

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.

Retinal Nerve Fiber Layer Thickness and Rim Area Profiles in Asians: Pooled Analysis from the Asian Eye Epidemiology Consortium.

PURPOSE: To evaluate ethnic variations, ocular and systemic determinants of retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim area among Asians using a large consortium of population-based eye studies. DESIGN: Cross-sectional pooled analysis. PARTICIPANTS: Twenty-two thousand four hundred thirty-six participants (22 436 eyes) from 10 population-based studies (in China, Hong Kong, India, Japan, Russia, and Singapore) of the Asian Eye Epidemiology Consortium. METHODS: Participants 40 years of age or older without glaucoma were included. All participants underwent spectral-domain OCT imaging and systemic and ocular examinations. Data were pooled from each study. Multivariable regression was performed to evaluate interethnic differences, intermachine variations, and ocular and systemic factors associated with RNFL thickness and rim area, adjusting for age, gender, diabetes, intraocular pressure (IOP), spherical equivalent (SE), ethnicity, OCT model, and study group. When evaluating body mass index, smoking, and hypertension as exposures, these factors were additionally adjusted for in the model. MAIN OUTCOME MEASURES: Average RNFL thickness (in micrometers) and rim area (in square millimeters). RESULTS: Indian and Japanese eyes have thinner RNFLs than those of other Asian ethnicities (ß values range, 7.31-12.76 µm; P < 0.001 for all pairwise comparisons). Compared with measurements by Cirrus HD-OCT (Carl Zeiss Meditec, Inc), RNFL on average was 7.29 µm thicker when measured by Spectralis (Heidelberg Engineering), 12.85 µm thicker when measured by RS-3000 (NIDEK Co, Ltd), and 17.48 µm thicker when measured by iVue/RTVue (Optovue, Inc) devices (all P < 0.001). Additionally, older age (per decade, ß = -2.70), diabetes (ß = -0.72), higher IOP (per 1 mmHg, ß = -0.07), more myopic SE (per diopter, ß = -1.13), cardiovascular disease (ß = -0.94), and hypertension (ß = -0.68) were associated with thinner RNFL (all P ≤ 0.003). Similarly, older age (ß = -0.019), higher IOP (ß = -0.010), and more myopic SE (ß = -0.025) were associated with smaller rim area (all P < 0.001). CONCLUSIONS: In this large pooled analysis of Asian population studies, Indian and Japanese eyes were observed to have thinner RNFL profiles. These findings suggest the need for an ethnic-specific normative database to improve glaucoma detection.

DeepLensNet: Deep Learning Automated Diagnosis and Quantitative Classification of Cataract Type and Severity.

PURPOSE: To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs. DESIGN: DeepLensNet was trained by applying deep learning models to the Age-Related Eye Disease Study (AREDS) dataset. PARTICIPANTS: A total of 18 999 photographs (6333 triplets) from longitudinal follow-up of 1137 eyes (576 AREDS participants). METHODS: Deep learning models were trained to detect and quantify nuclear sclerosis (NS; scale 0.9-7.1) from 45-degree slit-lamp photographs and cortical lens opacity (CLO; scale 0%-100%) and posterior subcapsular cataract (PSC; scale 0%-100%) from retroillumination photographs. DeepLensNet performance was compared with that of 14 ophthalmologists and 24 medical students. MAIN OUTCOME MEASURES: Mean squared error (MSE). RESULTS: On the full test set, mean MSE for DeepLensNet was 0.23 (standard deviation [SD], 0.01) for NS, 13.1 (SD, 1.6) for CLO, and 16.6 (SD, 2.4) for PSC. On a subset of the test set (substantially enriched for positive cases of CLO and PSC), for NS, mean MSE for DeepLensNet was 0.23 (SD, 0.02), compared with 0.98 (SD, 0.24; P = 0.000001) for the ophthalmologists and 1.24 (SD, 0.34; P = 0.000005) for the medical students. For CLO, mean MSE was 53.5 (SD, 14.8), compared with 134.9 (SD, 89.9; P = 0.003) for the ophthalmologists and 433.6 (SD, 962.1; P = 0.0007) for the medical students. For PSC, mean MSE was 171.9 (SD, 38.9), compared with 176.8 (SD, 98.0; P = 0.67) for the ophthalmologists and 398.2 (SD, 645.4; P = 0.18) for the medical students. In external validation on the Singapore Malay Eye Study (sampled to reflect the cataract severity distribution in AREDS), the MSE for DeepSeeNet was 1.27 for NS and 25.5 for PSC. CONCLUSIONS: DeepLensNet performed automated and quantitative classification of cataract severity for all 3 types of age-related cataract. For the 2 most common types (NS and CLO), the accuracy was significantly superior to that of ophthalmologists; for the least common type (PSC), it was similar. DeepLensNet may have wide potential applications in both clinical and research domains. In the future, such approaches may increase the accessibility of cataract assessment globally. The code and models are available at https://github.com/ncbi/deeplensnet.

Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis.

TOPIC: To provide updated estimates on the global prevalence and number of people with diabetic retinopathy (DR) through 2045. CLINICAL RELEVANCE: The International Diabetes Federation (IDF) estimated the global population with diabetes mellitus (DM) to be 463 million in 2019 and 700 million in 2045. Diabetic retinopathy remains a common complication of DM and a leading cause of preventable blindness in the adult working population. METHODS: We conducted a systematic review using PubMed, Medline, Web of Science, and Scopus for population-based studies published up to March 2020. Random effect meta-analysis with logit transformation was performed to estimate global and regional prevalence of DR, vision-threatening DR (VTDR), and clinically significant macular edema (CSME). Projections of DR, VTDR, and CSME burden were based on population data from the IDF Atlas 2019. RESULTS: We included 59 population-based studies. Among individuals with diabetes, global prevalence was 22.27% (95% confidence interval [CI], 19.73%-25.03%) for DR, 6.17% (95% CI, 5.43%-6.98%) for VTDR, and 4.07% (95% CI, 3.42%-4.82%) for CSME. In 2020, the number of adults worldwide with DR, VTDR, and CSME was estimated to be 103.12 million, 28.54 million, and 18.83 million, respectively; by 2045, the numbers are projected to increase to 160.50 million, 44.82 million, and 28.61 million, respectively. Diabetic retinopathy prevalence was highest in Africa (35.90%) and North American and the Caribbean (33.30%) and was lowest in South and Central America (13.37%). In meta-regression models adjusting for habitation type, response rate, study year, and DR diagnostic method, Hispanics (odds ratio [OR], 2.92; 95% CI, 1.22-6.98) and Middle Easterners (OR, 2.44; 95% CI, 1.51-3.94) with diabetes were more likely to have DR compared with Asians. DISCUSSION: The global DR burden is expected to remain high through 2045, disproportionately affecting countries in the Middle East and North Africa and the Western Pacific. These updated estimates may guide DR screening, treatment, and public health care strategies.

Rare single nucleotide variants in COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.

BACKGROUND: Keratoconus is a chronic degenerative disorder of the cornea characterized by thinning and cone-shaped protrusions. Although genetic factors play a key role in keratoconus development, the etiology is still under investigation. The occurrence of single-nucleotide polymorphisms (SNPs) associated with keratoconus in Russian patients is poorly studied. The purpose of this study was to validate whether three reported keratoconus-associated SNPs (rs1536482 near the COL5A1 gene, rs2721051 near the FOXO1 gene, rs1324183 near the MPDZ gene) are also actual for a Russian cohort of patients. Additionally, we investigated the COL5A1 promoter sequence for single-nucleotide variants (SNVs) in a subgroup of keratoconus patients with at least one rs1536482 minor allele (rs1536482+) to assess the role of these SNVs in keratoconus susceptibility associated with rs1536482. METHODS: This case-control study included 150 keratoconus patients and two control groups (main and additional, 205 and 474 participants, respectively). We performed PCR targeting regions flanking SNVs and the COL5A1 promoter, followed by Sanger sequencing of amplicons. The additional control group was genotyped using an SNP array. RESULTS: The minor allele frequency was significantly different between the keratoconus and control cohorts (main and combined) for rs1536482, rs2721051, and rs1324183 (p-value < 0.05). The rare variants rs1043208782 and rs569248712 were found in the COL5A1 promoter in two out of 94 rs1536482+ keratoconus patients. CONCLUSION: rs1536482, rs2721051, and rs1324183 were associated with keratoconus in a Russian cohort. SNVs in the COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.

Compatibility of intravitreally applied epidermal growth factor and amphiregulin.

INTRODUCTION: To examine the compatibility of intravitreally injected epidermal growth factor (EGF) and amphiregulin as EGF family member. METHODS: Four rabbits (age: 4 months; body weight: 2.5 kg) received three intravitreal injections of EGF (100 ng) uniocularly in monthly intervals and underwent ocular photography, tonometry, biometry, and optical coherence tomography. After sacrificing the rabbits, the globes were histomorphometrically examined. In a second study part, eyes of 22 guinea pigs (age: 2-3 weeks) received two intravitreal administrations of amphiregulin (10 ng) or phosphate buffered solution (PBS) in 10-day interval, or were left untouched. Ten days after the second injection, the guinea pigs were sacrificed, the enucleated eyes underwent histological and immune-histological examinations. RESULTS: The rabbit eyes with EGF injections versus the contralateral untouched eyes did not show significant differences in intraocular pressure (7.5 ± 2.4 mmHg vs. 6.8 ± 2.2 mmHg; P = 0.66), retinal thickness (158 ± 5 µm vs. 158 ± 3 µm; P = 1.0), cell counts in the retinal ganglion cell layer (3.3 ± 1.7 cells/150 µm vs. 3.0 ± 1.4 cells/150 µm; P = 0.83), inner nuclear layer (46.4 ± 23.2 cells/150 µm vs. 39.6 ± 6.4 cells/150 µm; P = 0.61), and outer nuclear layer (215 ± 108 cells/150 µm vs. 202 ± 47 cells/150 µm; P = 0.83), or any apoptotic retinal cells. The guinea pig eyes injected with amphiregulin versus eyes with PBS injections did not differ (P = 0.72) in the degree of microglial activation, and both groups did not differ from untouched eyes in number of apoptotic retinal cells and retinal gliosis. CONCLUSIONS: Intravitreal applications of EGF (100 ng) in rabbits nor intravitreal applications of amphiregulin (10 ng) in guinea pigs led to intraocular specific inflammation or any observed intraocular destructive effect. The findings support the notion of a compatibility of intraocular applied EGF and amphiregulin.

Prevalence and Pattern of Geographic Atrophy in Asia: The Asian Eye Epidemiology Consortium.

PURPOSE: Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC). DESIGN: Cross-sectional meta-analyses. PARTICIPANTS: A total of 97 213 individuals aged 40 years and older. METHODS: Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA. MAIN OUTCOME MEASURES: Prevalence of GA per 1000 persons. RESULTS: The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04-2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97-6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07-0.62) to 2.90 per 1000 persons (95% CI, 1.55-4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22-3.23) and rural residents (1.33; 95% CI, 0.70-1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72-5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31-1.22, P = 0.005). CONCLUSIONS: Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention.

Chronic kidney disease in Russia: the Ural eye and medical study.

BACKGROUND: To examine the prevalence of chronic kidney disease (CKD) and its associations in a Russian population. METHODS: Out of 7328 eligible individuals, the population-based cross-sectional Ural Eye and Medical Study included 5899 (80.5%) individuals aged 40+ years and undergoing a detailed medical examination. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic-Kidney-Disease-Epidemiology-Collaboration (CKD-EPI) equation. RESULTS: The mean eGFR was 72.3 ± 19.1 mL/min/1.73m2 (median:70.3 mL/min/1.73m2). Prevalence of CKD stage 3a (eGFR< 60 mL/min/1.73m2 and > 45 mL/min/1.73m2), CKD stage 3b (eGFR< 45 mL/min/1.73m2 and > 30 mL/min/1.73m2) and CKD stage 4+ (eGFR< 30 mL/min/1.73m2) were 1351/5841 (23.1%;95% confidence interval (CI):22.1,24.2), 294/5841 (5.0%;95%CI:4.5,5.6), and 29/5841 (0.5%;95%CI:0.3,0.7), respectively. The CKD stage 3+ prevalence increased (P < 0.001) from 11.1% (95%CI:8.4,13.9) in 40-44-year-olds to 56.8% (95%CI:52.8,60.8) in 75 + year-olds. In univariate analysis, CKD stage 3a + prevalence increased with higher systolic blood pressure (P < 0.001). In multivariable analysis, higher prevalence of CKD stage 3a + was associated with older age (P < 0.001;odds ratio (OR):1.06;95%CI:1.05,1.07), female sex (P < 0.001;OR:2.29;95%CI:1.94,2.69), rural region of habitation (P = 0.001;OR:1.29;95%CI:1.11,1.50), higher body mass index (P = 0.03;OR:1.02;95%CI:1.002,1.03), lower prevalence of house ownership (P = 0.02;OR:0.57;95%CI:0.35,0.92), higher prevalence of mostly sitting or standing during work (P < 0.001;OR:1.40;95%CI:1.20,1.64), higher serum concentration of triglycerides (P < 0.001;OR:1.23;95%CI:1.12,1.35) and blood urea nitrogen (P < 0.001;OR:1.33;95%CI:1.27,1.40), lower serum concentration of hemoglobin (P = 0.03;OR:0.99;95%CI:0.99,0.999), and lower prevalence of chronic obstructive pulmonary disease (P < 0.001;OR:0.57;95%CI:0.42,0.78). CONCLUSIONS: In this population from Russia aged 40+ years, prevalence of CKD stage 3+ (28.7%;95%CI:27.5,29.8) was relatively high as compared to populations from other countries. Associated factors were older age, female sex, rural region, higher body mass index, a sedentary lifestyle, and lower socioeconomic background.

Prevalence of and factors associated with low Back pain, thoracic spine pain and neck pain in Bashkortostan, Russia: the Ural Eye and Medical Study.

BACKGROUND: Back pain and neck pain are leading causes of the burden of disease worldwide, while information about their prevalence in Russia is missing. METHODS: The population-based Ural Eye and Medical Study was conducted in a rural and urban region in Bashkortostan/Russia. As part of a detailed systematic examination, we assessed the prevalence of low back pain, thoracic spine pain and neck pain in an interview with standardized questions in 5397 study participants (mean age:58.6 ± 10.6 years;range:40-94 years). RESULTS: The mean prevalence of low back pain, thoracic spine pain and neck pain was 2912/5397 (54.0%;95% confidence interval (CI):52.6,55.3), 1271/5397 (23.6%;95%CI:22.4,24.7), and 1570/5397 (29.1%;95%CI:27.9,30.3), respectively. A higher prevalence of low back pain was associated with females (P = 0.04;odds ratio (OR):1.14;95%CI:1.004,1.30), younger age (P < 0.001;OR:0.99;95%CI:0.98,0.99), higher body mass index (P = 0.002;OR:1.02;95%CI:1.01,1.03), lower frequency of vigorous activities during leisure time (P = 0.001;OR:0.79;95%CI:0.69,0.90), more time spent sitting and reclining (P = 0.03;OR:1.00;95%CI:1.00,1.00), higher serum concentration of high-density lipoproteins (P = 0.004;OR:1.10;95%CI:1.03,1.18), higher prothrombin index (P = 0.003;OR:1.01;95%CI:1.003,1.01), higher prevalence of a history of cardiovascular disease (P = 0.004;OR:1.23;95%CI:1.07,1.42), falls (P < 0.004;OR:1.71;95%CI:1.45,2.00), bone fractures (P = 0.01;OR:1.18;95% CI:1.03,1.34), unconsciousness (P < 0.001;OR:1.78;95%CI:1.40,2.25), osteoarthritis (P < 0.001;OR:2.76;95%CI:2.34,3.26), iron-deficiency anemia (P < 0.001;OR:1.87;95%CI:1.41,2.50), and thyroid disorder (P = 0.004;OR:1.37;95%CI:1.10,1.70), fewer days of vegetable intake (P < 0.001;OR:0.89;95%CI:0.85,0.93), smaller amounts of salt intake (P = 0.008;OR:0.97;95%CI:0.94,0.99), higher anxiety score (P < 0.001;OR:1.05;95%CI:1.03,1.06), and in women, history of menopause (P = 0.02;OR:1.36;95%CI:1.05,1.75). The prevalence of thoracic spine pain and neck pain showed similar associations. CONCLUSIONS: In a Russian population, the prevalence of low back pain, thoracic spine pain and neck pain (54.0, 23.6 and 29.1%, respectively) were correlated with parameters such as the female sex, younger age, higher body mass index, higher anxiety score, higher prevalence of a history of cardiovascular disease, lower frequency of vigorous activities and more time spent sitting or reclining. These data may be of interest for assessing the burden of back and neck pain in Russia as part of the global burden of disease.

Prevalence and associated factors of anemia in a Russian population: the Ural eye and medical study.

BACKGROUND: Although anemia is one of the leading causes of the global burden of disease, information about its prevalence in Russia is mostly missing. We therefore assessed its prevalence and associated factors in a Russian population. METHODS: The population-based Ural Eye and Medical Study included 5899 (80.5%) out of 7328 eligible individuals (mean age:59.0 ± 10.7 years;range:40-94 years) who underwent a standardized interview and detailed general examination. The definition of anemia was based on the hemoglobin concentration (definition #1:hemoglobin concentration < 140 g/L in men,< 130 g/L in women; definition #2:hemoglobin concentration < 130 g/L in men,< 120 g/L in women [World Health Organization definition]). RESULTS: Higher hemoglobin concentration (mean:142.6 ± 14.8 g/L; range:80-171 g/L) was associated (multivariable analysis) with male gender (P < 0.001; standardized regression coefficient beta:-0.20), higher waist-hip circumference ratio (P < 0.001;beta:0.05), higher prevalence of car ownership (P < 0.001;beta:0.05), higher blood concentrations of bilirubin (P < 0.001;beta:0.05) and triglycerides (P < 0.001;beta:0.06), lower erythrocyte sedimentation rate (P < 0.001;beta:-0.32), and shorter blood clotting time (P < 0.001;beta:-0.39). Using definition #1 and #2, anemia was detected in 1385 individuals (23.6%;95% confidence interval CI)CI:22.5,24.7) and in 453 individuals (7.7%;95%CI:7.0,8.4), respectively. Prevalence of moderate anemia (hemoglobin concenttration:110 g/L-80 g/L), detected in 165 individuals (2.8%;95%CI:2.4,3.2), increased with younger age (P = 0.008;odds ratio (OR):0.98;95%CI:0.96,0.99), female gender (P < 0.001;OR:2.52;95%CI:1.47,4.33), higher erythrocyte sedimentation rate (P < 0.001;OR:1.08;95%CI:1.06,1.09), longer blood clotting time (P < 0.001;OR:8.56;95%CI:5.68,12.9), and marginally significantly, with a lower waist-hip circumference ratio (P = 0.058;OR:0.13;95%CI:0.02,1.07). In women, it was significantly (P < 0.001) higher before menopause (8.8%;95%CI:6.4,11.1) than after menopause (3.5%;95%CI:2.8,4.3). CONCLUSIONS: In this Russian population as compared to populations from countries with a similar socio-demographic index, anemia prevalence was relatively low. As in other populations, higher anemia prevalence was strongly and inversely associated with menopause, and to a minor degree, with lower waist-hip circumference ratio and lower socio-economic background.

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.

Atrial fibrillation and flutter and ocular diseases. The Ural eye and medical study and the Ural very old study.

PURPOSE: To assess associations between atrial fibrillation/atrial flutter (AF) and ocular parameters and diseases. METHODS: The population-based Ural Eye and Medical Study (UEMS) and the Ural Very Old Study (UVOS) included 4894 individuals (age: 40+ years) and 835 individuals (age: 85+ years), respectively. RESULTS: In the UEMS, AF prevalence (80/4894; 1.6%; 95% CI: 1.3, 2.0) increased from 1/1029 (0.1%) in the age group of 40 to <50 years to 29/619 (4.7%) and 12/159 (7.5%) in the age groups of 70 to <80 years and 80+ years, respectively. Higher AF prevalence correlated with older age (OR: 1.08; 95% CI: 1.04, 1.12; p < 0.001), urban region of habitation (OR: 1.08; 95% CI: 1.04, 1.12; p < 0.001), higher prevalence of cardiovascular disease/stroke (OR: 2.50; 95% CI: 1.32, 4.72; p < 0.001) and lower prevalence of neck pain (OR: 0.35; 95% CI: 0.14, 0.85; p = 0.02), higher serum concentration of bilirubin (OR: 1.03; 95% CI: 1.02, 1.05; p < 0.001) and lower prothrombin index (OR: 0.96; 95% CI: 0.93, 0.99; p = 0.003), higher stage of arterial hypertension (OR: 1.52; 95% CI: 1.01, 2.28; p = 0.04) and higher ankle-brachial index (OR: 22.1; 95% CI: 4.45, 1.10; p < 0.001). In that model, AF prevalence was not associated with ocular parameters such as intraocular pressure (p = 0.52), retinal nerve fibre layer thickness (p = 0.70), refractive error (p = 0.13), axial length (p = 0.14), nuclear cataract degree (p = 0.50) and prevalence (p = 0.40), cortical cataract degree (p = 0.43) and presence (p = 0.17), lens pseudoexfoliation (p = 0.58), status after cataract surgery (p = 0.38), age-related macular degeneration prevalence (p = 0.63), open-angle glaucoma presence (p = 0.90) and stage (p = 0.55), angle-closure glaucoma prevalence (p = 0.99) and stage (p = 0.99), diabetic retinopathy prevalence presence (p = 0.37) and stage (p = 0.32), and myopic macular degeneration (p = 0.98). In the UVOS, similar results were obtained. CONCLUSIONS: In these multi-ethnic populations from Russia, AF prevalence was not associated with any major ocular disease and may not play a major role in the pathogenesis of these disorders.

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.

Unintentional injuries and falls in populations in Russia. The Ural eye and medical study and the Ural very old study.

Background: To explore the prevalence of self-reported unintentional injuries and falls (UIFs) in medium-aged and old populations in Russia and factors associated with them. Methods: Two population-based studies (Ural Eye and Medical Study (UEMS), Ural Very Old Study (UVOS)) were carried out urban and rural areas in Bashkortostan/Russia. They consisted of 5899 individuals (age: 40+ years) and 1526 participants (age: 85+ years), respectively. We assessed previous falls as part of an interview with standardized questions, conducted in the framework of a series medical and ophthalmological assessments. Results: In the UEMS with 5894 individuals (age:59.0 ± 10.7 years), UIF prevalence was 1101/5894 (18.7 %; 95 % confidence interval (CI)CI:17.7,19.7), with 1,2,3,4,5,6,7,8,9, or 10+ UIFs reported by 766 (69.6 %),146 (13.3 %),56 (1.4 %),15 (1.4 %),19 (1.7 %),3 (0.3 %),2 (0.2 %),1 (0.01 %), and 10 (0.9 %) participants, respectively. The UIFs had occurred as outdoor incidents (n = 594; 53.8 %), at home (n = 162; 14.7 %), on the road or traffic accidents (n = 109; 9.9 %), at work (n = 77; 7.0 %), during garden work (n = 24; 2.2 %) or as falls from a higher level (n = 17; 1.5 %) or from house roofs (n = 16; 1.4 %). In 100 (1.7 % of the total study population; 9.1 % of the group with UIFs) participants, low vision was reported as a major cause for the UIF. Higher UIF prevalence was associated (multivariable analysis) with older age (odds ratio (OR):1.01; 95%CI:1.005,1.02;P < 0.001), urban region of habitation (OR:1.59; 95%CI:1.37,1.85;P = 0.001), higher smoking package number (OR:1.01; 95%CI:1.004,1.01;P = 0.001), longer waist circumference (OR:1.01; 95%CI:1.002,1.01;P = 0.008), higher prevalence of a history of arthritis (OR:1.38; 95%CI:1.18,1.62;P < 0.001) and backache (OR:1.73; 95%CI:1.49,2.02;P < 0.001), and higher depression score (OR:1.05; 95%CI:1.03,1.07;P < 0.001). Out of 1525 UVOS participants (age:88.8 ± 2.9 years; range:85-103.1 years), the UIF prevalence was 780/1525 (51.1 %; 95%CI: 48.6, 53.6), with 390 (50.0 %), 116 (14.8 %), 49 (6.3 %), 12 (1.5 %), 8 (1.0 %), 2 (0.3 %), 4 (0.5 %), 1 (0.1 %), and 15 (1.9 %) participants reported about 1,2,3,4,5,6,7,8,9,or 10+ UIFs, respectively. The UIFs had occurred as outdoor incidents (n = 386; 25.3 %), at home (n = 214; 14.0 %), on the road or traffic accidents (n = 22; 1.4 %), at work (n = 21; 1.4 %), during garden work (n = 10; 0.7 %) or as falls from a higher level (n = 11; 0.7 %) or from house roofs (n = 1; 0.1 %). A higher UIC prevalence correlated with female sex (OR:1.65; 95%CI:1.30,2.09;P < 0.001) and Russian ethnicity (OR:1.26; 95%CI:1.02,1.56;P = 0.03). Conclusions: UIFs have occurred to a substantial part of the adult and very old population in Russia.

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.

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.

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.