Drusen in the macula and parapapillary region.

PURPOSE: To examine histological characteristics and differences between drusen beneath the retinal pigment epithelium (small hard drusen) located in the macula and located in the parapapillary region. METHODS: We histomorphometrically examined human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma. RESULTS: The study included 106 eyes (age, 62.6 ± 15.2 years) with macular drusen (n = 7 globes) or parapapillary drusen (n = 29 eyes) and 70 eyes without drusen. In all drusen, periodic-acid-Schiff-positive material was located between the RPE basal membrane and the inner collagenous layer of Bruch's membrane (BM). Macular drusen as compared with parapapillary drusen had lower height (15.2 ± 10.1 µm versus 34.3 ± 19.8 µm; P = 0.003), while both groups did not differ significantly in basal drusen width (74.0 ± 36.3 µm versus 108.7 ± 101.0 µm; P = 0.95). Eyes with macular drusen and eyes without drusen did not differ significantly in BM thickness (2.74 ± 0.44 µm versus 2.55 ± 0.88 µm; P = 0.57) or in RPE cell density (35.4 ± 10.4 cells/480 µm versus 32.8 ± 7.5 cells/480 µm; P = 0.53), neither in the drusen region nor in the drusen vicinity, while BM thickness (4.60 ± 1.490 µm; P < 0.001) and RPE cell density (56.9 ± 26.8 cells/480 µm; P = 0.005) were higher at the parapapillary drusen. Eyes with macular drusen, eyes with parapapillary drusen, and eyes without drusen did not differ significantly in choriocapillaris density (all P > 0.10) and thickness (all P > 0.35). Limitations of the study, among others, were a small number and size of drusen examined, diseases leading to enucleation, lack of serial sections, limited resolution of light microscopy, and enucleation-related and histological preparation-associated artefacts. CONCLUSIONS: The findings of this study, also taking into account its methodological limitations, suggest that macular drusen and parapapillary drusen shared the morphological feature of periodic-acid-Schiff-positive material between the RPE basal membrane and BM and that they did not vary significantly in choriocapillaris thickness and density. RPE cell density and BM thickness were higher in parapapillary drusen than in macular drusen.

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.

Bruch's membrane and Brücke's muscle in the pars plana region.

PURPOSE: To examine Bruch's membrane (BM) in association with the longitudinal part of the ciliary muscle (LPCM) in the pars plana region. METHODS: Using light microscopy, we histomorphometrically assessed BM and the LPCM in the pars plana region. RESULTS: The histomorphometric study included 51 eyes (51 patients; mean age: 60.8 ± 15.0 years; axial length: 26.0 ± 3.3 mm; range: 21.0-36.0 mm). The LPCM (total length: 4.60 ± 1.10 mm) ended 1.15 ± 0.56 mm anterior to the ora serrata. Within the pars plana region, the LPCM (length: 2.58 ± 0.98 mm) had direct contact with BM for 1.95 ± 0.99 mm (71.1 ± 18.4% of the BM undersurface), while a capillary layer was interposed between the BM and the LPCM for 0.70 ± 0.40 mm (29.0 ± 18.4%). In the pars plana region free of LPCM close to the ora serrata, the percentage of BM covered by the capillary layer was higher than in the pars plana region containing the LPCM (63.0 ± 42.1% vs. 29.0 ± 18.4%; p < 0.001). At the LPCM end, BM was in direct contact with a collagenous tissue from the LPCM and was focally thickened as compared to BM with an underlying capillary layer (9.5 ± 5.3 µm vs. 4.3 ± 1.2 µm; p < 0.001). CONCLUSIONS: The direct contact of BM with the LPCM in the pars plana in association with focal BM thickening at the LPCM end suggests an insertion of LPCM on the BM. Taking into account the biomechanical strength of BM, it may imply a functional unit of the LPCM with BM in the process of accommodation with a secondary movement of the posterior BM and tertiary thickening of the subfoveal choroidal space.

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.

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.

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.

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.

Ciliary body size in chronic angle-closure glaucoma.

To examine the size of the ciliary body stroma (CBS) in dependence of the morphology of the anterior chamber angle in enucleated human eyes, we histomorphometrically examined human enucleated eyes. The study included 107 eyes (with a mean axial length of 25.1 ± 2.8 mm (range 21.0-36.0 mm). The anterior chamber angle was open in 68 eyes and it was closed and endothelialized in 39 eyes. The maximal CBS width (541 ± 210 µm versus 59 ± 179 µm; P < 0.001) and the minimal CBS width (214 ± 107 µm versus 17 ± 55 µm; P < 0.001) and maximal ciliary muscle height (593 ± 557 µm versus 293 ± 111 µm; P = 0.001) were significantly smaller in the angle-closure group than in the open-angle group. Maximal CBS width increased with presence of an open anterior chamber angle (beta: 0.82; B: 517; 95% CI 435, 599; P < 0.001) and longer axial length (beta: 0.17; B: 18.2; 95% CI 4.2, 32.2; P = 0.01). Minimal CBS width increased with the presence of an open anterior chamber angle (beta: 0.48; B: 131; 95% CI 80.4, 181; P < 0.001) and a larger maximal ciliary muscle height (beta: 0.33; B: 0.28; 95% CI 0.12, 0.44; P = 0.001). Maximal ciliary muscle height correlated with the maximal CBS height (beta: 0.35; B: 0.53; 95% CI 0.25, 0.81; P < 0.001). The findings suggest that the CBS size is markedly smaller in eyes with a chronically closed endothelialized anterior chamber angle than in eyes with open angles. The tightening of the angle in eyes with angle-closure may prevent the access of aqueous humor not only to the trabecular meshwork but also to the ciliary body and may reduce the uveoscleral or uveovortex outflow pathway.

Choriocapillaris, Photoreceptors, and Inner Retinal Layer in Spatial Relationship to Parapapillary Alpha, Beta, Gamma, and Delta Zones.

Purpose: To examine the spatial relationships between the retinal inner nuclear layer (INL), outer nuclear layer (ONL), retinal pigment epithelium (RPE) layer, Bruch's membrane (BM), and choriocapillaris in the parapapillary region. Methods: Human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma were histomorphometrically examined. We compared the tissue dimensions between four groups of eyes categorized based on the presence/absence of high myopia and glaucoma. Results: The investigation consisted of 100 globes (axial length: 25.6 ± 3.1 mm; range: 20.0-35.0 mm). In non-highly myopic nonglaucomatous eyes, the INL, ONL, RPE, BM, and choriocapillaris ended approximately at the end of the RPE layer, with no significant (all P ≥ 0.10) difference between the layers in their distance to the RPE-layer end. From non-highly myopic nonglaucomatous eyes to non-highly myopic glaucomatous eyes, highly myopic nonglaucomatous eyes, and eventually highly myopic glaucomatous eyes, the choriocapillaris, INL, and ONL increasingly extended into the beta zone, most marked for the choriocapillaris and least marked for the ONL. A larger extension of the choriocapillaris into the parapapillary beta zone correlated with longer axial length (standardized regression coefficient ß, 0.24; B, 23.0; 95% confidence interval [CI], 1.6-44.5; P = 0.04) and wider parapapillary beta zone (ß, 0.59; B, 0.32; 95% CI, 0.22-0.41; P < 0.001); a larger extension of the INL correlated with longer axial length (ß, 0.34; B, 43.7; 95% CI, 11.6-75.7; P = 0.009), longer gamma zone (ß, 0.52; B, 0.28; 95% CI, 0.15-0.41; P < 0.001), and diagnosis of non-highly myopic glaucoma (ß, 0.28; B, 267; 95% CI, 80.8-454; P = 0.006); and a larger extension of the ONL into parapapillary beta zone correlated with longer axial length (ß, 0.50; B, 32.2; 95% CI, 21.6-42.8; P < 0.001) and wider parapapillary beta zone (ß, 0.28; B, 0.10; 95% CI, 0.04-0.16; P < 0.001). Conclusions: Nonglaucomatous non-highly myopic eyes differ from highly myopic eyes and glaucomatous eyes in the spatial relationship of the parapapillary tissue layers.

Parapapillary drusen of the retinal pigment epithelium.

PURPOSE: To describe the occurrence, morphology and associations of parapapillary drusen of the retinal pigment epithelium (RPE-drusen). METHODS: Using light microscopy, we histomorphometrically examined enucleated human eyes. RESULTS: The study included 83 eyes (axial length: 25.9 ± 3.2 mm; range: 20.0-35.0 mm). Eyes with parapapillary RPE-drusen (n = 29 (35%) eyes) as compared to those without drusen had a significantly shorter axial length (24.0 ± 1.8 mm vs 27.0 ± 3.3 mm; p < 0.001), higher prevalence (27/29 vs 12/54; p < 0.001) and longer width (213 ± 125 µm vs 96 ± 282 µm; p < 0.0001) of parapapillary alpha zone, and thicker BM in parapapillary beta zone (8.4 ± 2.7 µm vs 3.9 ± 2.0 µm; p < 0.001) and alpha zone (6.6 ± 3.9 µm vs 4.4 ± 1.5 µm; p = 0.02). Prevalence of parapapillary RPE-drusen was 27 (69%) out of 39 eyes with alpha zone. Beneath the RPE-drusen and in total alpha zone, choriocapillaris was open, while it was closed in the central part of parapapillary beta zone. BM thickness was thicker (p = 0.001) in alpha zone than beta zone, where it was thicker (p < 0.001) than in the region outside of alpha/beta zone. BM thickness outside of alpha/beta zone was not correlated with prevalence of parapapillary RPE-drusen (p = 0.47) or axial length (p = 0.31). RPE cell density was higher in alpha zone than in the region adjacent to alpha zone (22.7 ± 7.3 cells/240 µm vs 18.3 ± 4.1 cells/240 µm; p < 0.001). In the parapapillary RPE-drusen, RPE cells were connected with a PAS-positive basal membrane. CONCLUSIONS: Parapapillary RPE-drusen as fibrous pseudo-metaplasia of the RPE were associated with shorter axial length, higher prevalence and larger size of alpha zone, and thicker BM in alpha zone and beta zone. The RPE-drusen may be helpful to differentiate glaucomatous parapapillary beta zone from myopic beta zone.

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.

IMI-Nonpathological Human Ocular Tissue Changes With Axial Myopia.

Purpose: To describe nonpathological myopia-related characteristics of the human eye. Methods: Based on histomorphometric and clinical studies, qualitative and quantitative findings associated with myopic axial elongation are presented. Results: In axial myopia, the eye changes from a spherical shape to a prolate ellipsoid, photoreceptor, and retinal pigment epithelium cell density and total retinal thickness decrease, most marked in the retroequatorial region, followed by the equator. The choroid and sclera are thin, most markedly at the posterior pole and least markedly at the ora serrata. The sclera undergoes alterations in fibroblast activity, changes in extracellular matrix content, and remodeling. Bruch's membrane (BM) thickness is unrelated to axial length, although the BM volume increases. In moderate myopia, the BM opening shifts, usually toward the fovea, leading to the BM overhanging into the nasal intrapapillary compartment. Subsequently, the BM is absent in the temporal region (such as parapapillary gamma zone), the optic disc takes on a vertically oval shape, the fovea-optic disc distance elongates without macular BM elongation, the angle kappa reduces, and the papillomacular retinal vessels and nerve fibers straighten and stretch. In high myopia, the BM opening and the optic disc enlarge, the lamina cribrosa, the peripapillary scleral flange (such as parapapillary delta zone) and the peripapillary choroidal border tissue lengthen and thin, and a circular gamma and delta zone develop. Conclusions: A thorough characterization of ocular changes in nonpathological myopia are of importance to better understand the mechanisms of myopic axial elongation, pathological structural changes, and psychophysical sequelae of myopia on visual function.

Myopic Versus Glaucomatous Parapapillary Beta Zone in Myopic Eyes Versus Eyes With Secondary Angle-Closure Glaucoma.

Purpose: To search for histologic differences in the beta zone between myopic eyes versus eyes with secondary angle-closure glaucoma. Methods: The histomorphometric study consisted of human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma. Results: The study included 100 eyes (age: 62.1 ± 15.1 years; axial length: 25.6 ± 3.1 mm; range: 20.0-35.0 mm). In non-highly myopic glaucomatous eyes compared with non-highly myopic nonglaucomatous eyes, the parapapillary alpha zone was longer (223 ± 168 µm vs. 125 ± 128 µm; P = 0.03), beta zone prevalence (15/20 vs. 6/41; P < 0.001) and length (277 ± 245 µm vs. 44 ± 150 µm; P = 0.001) were higher, and RPE cell density in the alpha zone and alpha zone border was lower (all P < 0.05). In highly myopic nonglaucomatous eyes compared with non-highly myopic glaucomatous eyes, parapapillary RPE drusen prevalence (2/19 vs. 10/10; P = 0.01) and alpha zone prevalence (2/19 vs. 16/20; P < 0.001) and length (23 ± 68 µm vs. 223 ± 168 µm; P < 0.001) were lower. In non-highly myopic glaucomatous eyes, Bruch's membrane (BM) thickness decreased (P < 0.001) from the beta zone (6.0 ± 3.1 µm) to the alpha zone (5.1 ± 4.3 µm) and peripheral to it (3.0 ± 0.9 µm). In highly myopic nonglaucomatous eyes, BM thickness did not differ (P > 0.10) between all three regions. In the total study population, RPE cell density in the alpha zone (24.5 ± 9.3 cells/240 µm) was higher than at the alpha zone border (19.2 ± 4.8 cells/240 µm; P < 0.001) or peripheral to it (19.0 ± 3.6 cells/240 µm; P < 0.001). Conclusions: The glaucomatous beta zone in eyes with chronic angle-closure glaucoma (with the alpha zone, parapapillary RPE drusen, thickened BM, and higher RPE cell count in the adjacent alpha zone) differs histologically from the myopic beta zone (characterized by the absence of the alpha zone and parapapillary RPE drusen, unremarkable BM thickness, and unremarkable parapapillary RPE). The differences suggest different etiologies of the glaucomatous versus myopic beta zone.

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.

Myopic macular Bruch's membrane defects.

Purpose: To examine histologic characteristics of macular Bruchs membrane defects (BMD) in axially elongated eyes. Design: Histomorphometric study. Methods: Using light microscopy, we examined enucleated human globes for BMDs. Results: 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). Conclusions: 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.

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.