Deep Learning Models for the Screening of Cognitive Impairment Using Multimodal Fundus Images.

OBJECTIVE: We aimed to develop a deep learning system capable of identifying subjects with cognitive impairment quickly and easily based on multimodal ocular images. DESIGN: Cross sectional study. SUBJECTS: Participants of Beijing Eye Study 2011 and patients attending Beijing Tongren Eye Center and Beijing Tongren Hospital Physical Examination Center. METHODS: We trained and validated a deep learning algorithm to assess cognitive impairment using retrospectively collected data from the Beijing Eye Study 2011. Cognitive impairment was defined as a Mini-Mental State Examination score < 24. Based on fundus photographs and OCT images, we developed 5 models based on the following sets of images: macula-centered fundus photographs, optic disc-centered fundus photographs, fundus photographs of both fields, OCT images, and fundus photographs of both fields with OCT (multimodal). The performance of the models was evaluated and compared in an external validation data set, which was collected from patients attending Beijing Tongren Eye Center and Beijing Tongren Hospital Physical Examination Center. MAIN OUTCOME MEASURES: Area under the curve (AUC). RESULTS: A total of 9424 retinal photographs and 4712 OCT images were used to develop the model. The external validation sets from each center included 1180 fundus photographs and 590 OCT images. Model comparison revealed that the multimodal performed best, achieving an AUC of 0.820 in the internal validation set, 0.786 in external validation set 1, and 0.784 in external validation set 2. We evaluated the performance of the multi-model in different sexes and different age groups; there were no significant differences. The heatmap analysis showed that signals around the optic disc in fundus photographs and the retina and choroid around the macular and optic disc regions in OCT images were used by the multimodal to identify participants with cognitive impairment. CONCLUSIONS: Fundus photographs and OCT can provide valuable information on cognitive function. Multimodal models provide richer information compared with single-mode models. Deep learning algorithms based on multimodal retinal images may be capable of screening cognitive impairment. This technique has potential value for broader implementation in community-based screening or clinic settings. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Lens-induced myopization and body weight in young guinea pigs.

BACKGROUND: To investigate the relationship between body weight and Axial length in guinea pigs. METHODS: Forty pigmented guinea pigs were randomly divided into two groups, namely control group and negative lens-induced myopization (LIM) group. After measuring the baseline axial length and body weight (BW), guinea pigs of LIM group received bilateral negative lens-induced myopization using - 10.0 diopters lenses. One week later, the lenses were removed and biometric and ophthalmoscopic examinations were repeated. RESULTS: Two groups of guinea pigs showed no statistical difference in initial body weight and eye axis length. Compared to the control group, the lens-induced group had a lower weight (P = 0.02) and a longer axial length (P < 0.01) at the end of study Neither at baseline nor at week 1 did AL correlate with BW in both groups (Control Baseline: r = 0.306, P = 0.19; Control Week1: r = 0.333, P = 0.15; LIM Baseline: r=-0.142, P = 0.55; LIM Week 1: r = 0.189, P = 0.42). Lens-induction had a significant effect on axial elongation (P < 0.01) while body weight had no impact on such aspect (P > 0.05). CONCLUSION: In guinea pigs of the same age, axial length was not correlated with body weight. Also, baseline body weight had no impact on natural axial length growth or lens-induced myopia. Lens-induction caused a significant reduction in body weight gain.

Association between weight-adjusted waist index and myopia in adolescents and young adults: results from NHANES 1999-2008.

BACKGROUND: Previous studies have indicated a possible link between obesity and myopia, although the results have varied. The objective of this study was to investigate the correlation between a new measure of obesity, the weight-adjusted waist index (WWI), and myopia. METHOD: This cross-sectional study included individuals between the ages of 12 and 25 who participated in a noncycloplegic vision examination as part of the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2008. WWI was calculated as waist circumference divided by the square root of body weight. Myopia was characterized by a spherical equivalent (SE) of ≤ - 0.5 diopters (D) and further categorized into mild (-3.00D < SE≤-0.50 D), moderate (-6.00D < SE ≤-3.00 D), or high (SE≤-6.00 D). We utilized a weighted multivariable logistic regression and a generalized additive model to evaluate the correlation between WWI and myopia. Threshold effects were analyzed, and we performed subgroup analysis and interaction tests. RESULTS: A grand total of 11,180 individuals were registered for the study. Decreased myopia severity was observed with higher WWI, as evidenced by elevated SE (ß = 0.098, 95% CI: 0.028-0.167). Individuals in the top tertile of WWI experienced a 19.8% decrease in risk compared to those in the lowest group (OR = 0.802, 95% CI: 0.800-0.804; P for trend < 0.001). Similar associations were observed for high myopia. Gender-specific nonlinear associations were found, with different breakpoints for males (10.774) and females (10.025). In males, a significant positive association was found on the right side of the breakpoint (OR = 1.398, 95% CI: 1.038-1.884), while no significant association was found on the left side. Conversely, among females, a negative association was observed on the left side of the breakpoint (OR = 0.679, 95% CI: 0.512-0.899), whereas no notable correlation was detected on the right side. CONCLUSION: Increased WWI level was linked to a lower risk of myopia and high myopia in the overall sample, with gender-specific variations.

Intraocular schwannoma: case series of 28 patients and literature review.

PURPOSE: Intraocular schwannoma is a rare tumour, which is often misdiagnosed. We presented the demographics and clinical characteristics of patients with intraocular schwannoma. METHODS: Retrospective case series were collected between May 2005 and July 2021 in Beijing Tongren Hospital. RESULTS: A total of 28 patients were diagnosed with intraocular schwannoma on histopathological examination of surgical specimen. The median age was 39 years (range: 12-64). Fourteen patients were female and 14 were male. Among the all subjects, 21/28 patients (75.0%) presented as visual loss, and 3/28 patients (10.7%) had visual field loss. Intraocular schwannoma presented as nonpigmented mass in the ciliary body in 12/28 cases (42.9%), in the choroid in 9/28 cases (32.1%), and in ciliochoroid in 7/28 cases (25.0%). Intraocular schwannoma was often clinically misdiagnosed as uveal melanoma, which occurred in 16/28 patients (57.1%). Tumour excision with pars plana vitrectomy was performed for all included patients. Endoresection with lens removal was performed for tumours in the choroid, while transscleral resection was performed for tumours located in ciliary body or ciliochoroid. Increased light transmission was detected in 12/28 cases (42.9%). In the consecutive follow-up (median: 73 months, range: 7-193 months), no cases of recurrence or metastatic disease were detected. CONCLUSIONS: Intraocular schwannoma is a rare benign tumour. It usually presents as nonpigmented mass, which can easily be misdiagnosed as nonpigmented uveal melanoma.

Intraocular cetuximab: Safety and effect on axial elongation in young Guinea pigs with lens-induced myopization.

This study aimed to examine the intraocular tolerability of the epidermal growth factor receptor antibody cetuximab, when applied intravitreally, and its effect on axial elongation. Guinea pigs aged 2-3 weeks were subjected to bilateral plano glasses and bilateral lens-induced myopization (LIM) as a single procedure for group I (n = 8) and group II (n = 8), respectively. In the animals of group III (n = 8), group IV (n = 8), and group V (n = 8), the right eyes of the animals, in addition to LIM, received four weekly intravitreal injections of cetuximab (Erbitux®) in doses of 6.25 µg, 12.5 µg, and 25 µg, respectively. As controls, the left eyes, in addition to LIM, received corresponding intraocular injections of phosphate-buffered saline. The animals underwent regular ophthalmoscopic examinations and biometry for axial length measurements. With increasing doses of cetuximab, the inter-eye difference in axial elongation (at study end, left eyes minus right eyes) were significantly the smallest in group I (0.00 ± 0.02 mm) and group II (-0.01 ± 0.02 mm), they were larger in group III (0.04 ± 0.04 mm) and group IV (0.10 ± 0.03 mm), and they were the largest in group V (0.11 ± 0.01 mm). The inter-eye difference in axial elongation enlarged (P < 0.001) with the number of injections applied. Retinal thickness at the posterior pole (right eyes) was significantly thicker in group V than in group II (P < 0.01). The density of apoptotic cells (visualized by TUNEL-staining) did not vary significantly between any of the groups (all P > 0.05). The results suggest that intravitreal injections of cetuximab in young guinea pigs with LIM resulted in a reduction in axial elongation in a dose-dependent and number of treatment-dependent manner. Intraocular toxic effects, such as intraocular inflammation, retinal thinning, or an increased density of apoptotic cells in the retina, were not observed in association with the intravitreally applied cetuximab.

Reduction of experimental ocular axial elongation by neuregulin-1 antibody.

Background: Since the mechanisms underlying myopic axial elongation have remained unclear, we examined the effect of neuregulin-1 (NRG-1), an epidermal growth factor family member, on myopic axial elongation. Methods: The guinea pigs aged two to three weeks were subjected to bilateral negative lens-induced axial elongation and received weekly intravitreal injections into their right eyes of NRG-1 antibody (doses: 5 µg, n = 8; 10 µg, n = 8, 20 µg, n = 9) or of NRG-1 (doses: 0.05 µg, n = 8; 0.01 µg, n = 9; 0.2 µg, n = 8), underwent only bilateral negative lens-induced axial elongation (myopia control group, n = 10), or underwent no intervention (control group, n = 10). The contralateral eyes received corresponding intravitreal phosphate-buffered solution injections. One week after the last injection, the guinea pigs were sacrificed, the eyeballs were removed, the thicknesses of the retina and sclera were histologically examined, the expression of NRG-1 and downstream signal transduction pathway members (ERK1/2 and PI3K/AKT) and the mRNA expression of NRG-1 in the retina was assessed. Results: The inter-eye difference in axial length at study end increased (p < 0.001) from the normal control group (-0.02 ± 0.09 mm) and the myopia control group (-0.01 ± 0.09 mm) to the low-dose NRG-1 antibody group (-0.11 ± 0.05 mm), medium-dose NRG-1 antibody group (-0.17 ± 0.07 mm), and high-dose NRG-1 antibody group (-0.28 ± 0.06 mm). The relative expression of NRG-1, ERK1/2, and PI3K/AKT in the retina decreased in a dose-dependent manner from the myopia control group to the NRG-1 antibody groups and the normal control group. The relative NRG-1 mRNA expression in the retina was higher (p < 0.01) in the myopic control group than in the NRG-1 antibody groups and normal control group. Scleral and retinal thickness decreased from the normal control group to the NRG-1 antibody groups to the myopic control group. After intraocular injection of NRG-1 protein, there was a slight dose-dependent increase in the difference in axial length between the right and left eye, however not statistically significantly, from the normal control group (-0.02 ± 0.09 mm) to the high-dose NRG-1 protein group (0.03 ± 0.03 mm; p = 0.12). Conclusion: Intravitreal NRG-1 antibody application was dose-dependently and time-dependently associated with a reduction in negative lens-induced axial elongation in young guinea pigs.

Relationships between quantitative retinal microvascular characteristics and cognitive function based on automated artificial intelligence measurements.

Introduction: The purpose of this study is to assess the relationship between retinal vascular characteristics and cognitive function using artificial intelligence techniques to obtain fully automated quantitative measurements of retinal vascular morphological parameters. Methods: A deep learning-based semantic segmentation network ResNet101-UNet was used to construct a vascular segmentation model for fully automated quantitative measurement of retinal vascular parameters on fundus photographs. Retinal photographs centered on the optic disc of 3107 participants (aged 50-93 years) from the Beijing Eye Study 2011, a population-based cross-sectional study, were analyzed. The main parameters included the retinal vascular branching angle, vascular fractal dimension, vascular diameter, vascular tortuosity, and vascular density. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Results: The results showed that the mean MMSE score was 26.34 ± 3.64 (median: 27; range: 2-30). Among the participants, 414 (13.3%) were classified as having cognitive impairment (MMSE score < 24), 296 (9.5%) were classified as mild cognitive impairment (MMSE: 19-23), 98 (3.2%) were classified as moderate cognitive impairment (MMSE: 10-18), and 20 (0.6%) were classified as severe cognitive impairment (MMSE < 10). Compared with the normal cognitive function group, the retinal venular average diameter was significantly larger (p = 0.013), and the retinal vascular fractal dimension and vascular density were significantly smaller (both p < 0.001) in the mild cognitive impairment group. The retinal arteriole-to-venular ratio (p = 0.003) and vascular fractal dimension (p = 0.033) were significantly decreased in the severe cognitive impairment group compared to the mild cognitive impairment group. In the multivariate analysis, better cognition (i.e., higher MMSE score) was significantly associated with higher retinal vascular fractal dimension (b = 0.134, p = 0.043) and higher retinal vascular density (b = 0.152, p = 0.023) after adjustment for age, best corrected visual acuity (BCVA) (logMAR) and education level. Discussion: In conclusion, our findings derived from an artificial intelligence-based fully automated retinal vascular parameter measurement method showed that several retinal vascular morphological parameters were correlated with cognitive impairment. The decrease in retinal vascular fractal dimension and decreased vascular density may serve as candidate biomarkers for early identification of cognitive impairment. The observed reduction in the retinal arteriole-to-venular ratio occurs in the late stages of cognitive impairment.

Intravitreal Short-Hairpin RNA Attenuated Adeno-Associated Virus-Induced Knockdown of Amphiregulin and Axial Elongation in Experimental Myopia.

Background: Epidermal growth factor (EGF) and its family members have been reported to be involved in myopic axial elongation. We examined whether short hairpin RNA attenuated adeno-associated virus (shRNA-AAV)-induced knockdown of amphiregulin, an EGF family member, has an influence on axial elongation. Methods: Three-week-old pigmented guinea pigs underwent lens-induced myopization (LIM) without additional intervention (LIM group; n = 10 animals) or additionally received into their right eyes at baseline an intravitreal injection of scramble shRNA-AAV (5 × 1010 vector genome [vg]) (LIM + Scr-shRNA group; n = 10) or of amphiregulin (AR)-shRNA-AAV (5 × 1010 vg/5 µL) (LIM + AR-shRNA-AAV group; n = 10), or they received an injection of AR-shRNA-AAV at baseline and three weekly amphiregulin injections (20 ng/5 µL) (LIM + AR-shRNA-AAV + AR group; n = 10). The left eyes received equivalent intravitreal injections of phosphate-buffered saline. Four weeks after baseline, the animals were sacrificed. Results: At study end, interocular axial length difference was higher (P < 0.001), choroid and retina were thicker (P < 0.05), and relative expression of amphiregulin and p-PI3K, p-p70S6K, and p-ERK1/2 was lower (P < 0.05) in the LIM + AR-shRNA-AAV group than in any other group. The other groups did not differ significantly when compared with each other. In the LIM + AR-shRNA-AAV group, the interocular axial length difference increased with longer study duration. TUNEL assay did not reveal significant differences among all groups in retinal apoptotic cell density. In vitro retinal pigment epithelium cell proliferation and migration were the lowest (P < 0.05) in the LIM + AR-shRNA-AAV group, followed by the LIM + AR-shRNA-AAV + AR group. Conclusions: shRNA-AAV-induced knockdown of amphiregulin expression, in association with suppression of epidermal growth factor receptor signaling, attenuated axial elongation in guinea pigs with LIM. The finding supports the notion of EGF playing a role in axial elongation.

Association between vitamin D and myopia in adolescents and young adults: Evidence of national cross-sectional study.

PURPOSE: Studies have indicated that the observed association between vitamin D and myopia was confounded by time spent outdoors. This study aimed to elucidate this association using a national cross-sectional dataset. METHODS: Participants with 12 to 25 years who participated in non-cycloplegic vision exam from National Health and Nutrition Examination Survey (NHANES) 2001 to 2008 were included in the present study. Myopia was defined as spherical equivalent of any eyes ≤ -0.5 diopters (D). RESULTS: 7,657 participants were included. The weighted proportion of emmetropes, mild myopia, moderate myopia, and high myopia were 45.5%, 39.1%, 11.6%, and 3.8%, respectively. After adjusting for age, gender, ethnicity, TV/computer usage, and stratified by education attainment, every 10 nmol/L increment of serum 25(OH)D concentration was associated with a reduced risk of myopia (odds ratio [OR] = 0.96, 95% confidence interval [95%CI] 0.93-0.99 for any myopia; OR = 0.96, 95%CI 0.93-1.00 for mild myopia; OR = 0.99, 95%CI 0.97-1.01 for moderate myopia; OR = 0.89, 95%CI 0.84-0.95 for high myopia). Serum 25(OH)D level was closely correlated with time spent outdoors. After categorizing time spent outdoors into quarters (low, low-medium, medium-high, and high), every 1 quarter increment of time spent outdoors was associated with 2.49 nmol/L higher serum 25(OH)D concentration. After adjusting for time spent outdoors, serum 25(OH)D level did not show significant association with myopia (OR = 1.01, 95%CI 0.94-1.06 for 10 nmol/L increment). CONCLUSIONS: The association between high serum vitamin D and reduced risk of myopia is confounded by longer time spent outdoors. Evidence from the present study does not support that there is a direct association between serum vitamin D level with myopia.

Development and validation of medical record-based logistic regression and machine learning models to diagnose diabetic retinopathy.

PURPOSES: Many factors were reported to be associated with diabetic retinopathy (DR); however, their contributions remained unclear. We aimed to evaluate the prognostic and diagnostic accuracy of logistic regression and three machine learning models based on various medical records. METHODS: This was a cross-sectional study. We investigated the prevalence and associations of DR among 757 participants aged 40 years or older in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). We trained the models to predict if the participants had DR with 15 predictor variables. Area under the receiver operating characteristic (AUROC) and mean squared error (MSE) of each algorithm were compared in the external validation dataset using a replicate cohort from NHANES 2007-2008. RESULTS: Among the 757 participants, 53 (7.00%) subjects had DR, the mean (standard deviation, SD) age was 57.7 (13.04), and 78.0% were male (n = 42). Logistic regression revealed that female gender (OR = 4.130, 95% CI: 1.820-9.380; P < 0.05), HbA1c (OR = 1.665, 95% CI: 1.197-2.317; P < 0.05), serum creatine level (OR = 2.952, 95% CI: 1.274-6.851; P < 0.05), and eGFR level (OR = 1.009, 95% CI: 1.000-1.014, P < 0.05) increased the risk of DR. The average performance obtained from internal validation was similar in all models (AUROC ≥ 0.945), and k-nearest neighbors (KNN) had the highest value with an AUROC of 0.984. In external validation, they remained robust or with modest reductions in discrimination with AUROC still ≥ 0.902, and KNN also performed the best with an AUROC of 0.982. Both logistic regression and machine learning models had good performance in the clinical diagnosis of DR. CONCLUSIONS: This study highlights the utility of comparing traditional logistic regression to machine learning models. We found that logistic regression performed as well as optimized machine learning methods when classifying DR patients.

Thickness of retinal pigment epithelium-Bruch's membrane complex in adult Chinese using optical coherence tomography.

PURPOSE: To study thickness of RPE-BM complex in adult Chinese subjects and its correlation with systemic and ocular biometric parameters. DESIGN: Population-based longitudinal study. Cross-sectional study. PARTICIPANTS: The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6 ± 9.8 years (range: 50-93 years). METHODS: A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD OCT) for measurement of the thickness of RPE-BM complex. Use Heidelberg software "Heidelberg Eye Explorer" for segmentation and measurements. MAIN OUTCOME MEASURE: Thickness of RPE-BM complex. RESULTS: In total, 3276 people (6530 eyes) were included in the study. In total, 1844 (56.3%) subjects were female. The mean age was 64.3 ± 9.6 years (range: 50-93 years). The mean refractive error (spherical equivalent) was -0.18 ± 2.04 diopters (range: -22.0 to +7.50 diopters). Mean thickness of the RPE-BM complex at the foveal center was 25.09 ± 3.98 µm (range: 17-37 µm). In multiple regression analysis, subfoveal thickness of the RPE-BM complex was associated with age (p = 0.039; beta: 0.22; B: 0.10 (95% CI: 0.01, 0.20)) and hypertension history (p = 0.038; beta: 0.23; B: 1.96 (95% CI: 0.12, 3.81)). CONCLUSION: Mean subfoveal thickness of the RPE-BM complex was 25.09 ± 3.98 µm in elderly subjects with a mean age of 64.3 years increased with age and hypertension history. The increase in the thickness of RPE-BM complex may play a role in the pathophysiologic features of various age-related ocular conditions.

Visual impairment and major eye diseases in stroke: a national cross-sectional study.

OBJECTIVES: Major ocular diseases share common risk factors and pathogeneses with stroke. This study aimed to evaluate the relation between stroke and ocular diseases including visual impairment (VI). METHODS: The cross-sectional study investigated the prevalence and associations of VI and major eye diseases with stroke among 4570 participants in the 2005-2008 National Health and Nutrition Examination Survey (NHANES). The association of VI and major ocular diseases with stroke were estimated using univariate and multivariate logistic regression crude models and models adjusted for demographics and clinical factors. We also conducted stratified analyses by diabetes and hypertension status. RESULTS: VI was associated with stroke, and the odds ratios (ORs) for mild and moderate and severe visual impairment (MSVI) were 6.79 (95% confidence interval (CI): 2.44-18.88) and 9.46 (95% CI: 2.19-40.94) after adjusting for age and gender (all P < 0.05). Ocular disease was associated with stroke with OR reaching 5.54 (95% CI: 1.83-16.74), and the OR was 9.61 (95% CI: 3.05-30.23) for stroke patients suffering DR after adjusting for age and gender (all P < 0.05). After multivariable adjustment, the associations were limited to mild VI (OR = 10.00, 95% CI: 3.16-30.58), MSVI (OR = 8.57, 95% CI: 1.58-43.36), and any ocular disease (OR = 5.18, 95% CI: 1.46-18.42) (all P < 0.05). Significant associations between stroke and any ocular disease and DR were observed among diabetic participants, and significant relation between stroke and MSVI was found among hypertension patients. CONCLUSIONS: The sample of the US population demonstrates significant associations between VI and major ocular disease with stroke.

Prevalence and associations of asteroid hyalosis: the Beijing Eye Study.

BACKGROUND: To determine the prevalence and associations of asteroid hyalosis (AH) in a Chinese population-based cohort. METHODS: The retrospective, cross-sectional, population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6 ± 9.8 years (range: 50-93 years). Participants underwent detailed ophthalmic examinations including fundus photographs for diagnosis of AH. Data on systemic and ocular factors were collected for all participants according to the standardized protocol. Multiple linear regression and multivariate Logistic regression analysis were performed. RESULTS: Fundus photographs were gradable in 3419 subjects. AH was detected in 63 (0.9%, 95% CI: 0.7%, 1.1%) eyes of 53 (1.6%, 95% CI: 1.1%, 2.0%) subjects. AH was bilateral in 18.9%. Mean age of all subjects with AH was 69.2 ± 9.5 years (median, 71.0 years; range, 51-91 years), mean spherical equivalent was 0.63 ± 1.53D (median, 0.75 D; range, -4.12 to 4.00D). In multivariate analysis, prevalence of AH was associated with elder age (P = 0.014, OR 1.057), thicker lens (P = 0.032, OR 3.887), higher spherical equivalent (P = 0.017, OR 1.396). CONCLUSIONS: In adult Chinese in Beijing, the prevalence of AH was 0.9% for eyes or 1.6% for subjects. AH was associated with elder age, thicker lens, and higher spherical equivalent. It was not associated with diabetes or other systemic indicators.

Circulating MicroRNAs as Quantitative Biomarkers for Diagnosis and Prognosis of Uveal Melanoma.

For uveal melanoma (UM) patients, it is significant to establish diagnosis and prognosis evaluation systems through imaging techniques. However, imaging examinations are short of quantitative biomarkers and it is difficult to finish early diagnosis of UM. In order to discover new molecular biomarkers for the diagnosis and prognostic evaluation of UM, six circulating miRNAs (mir-132-3p, mir-21-5p, mir-34a-5p, mir-126-3p, mir-199a-3p, mir-214-3p) were chosen as candidates for independent validation. Validation of these miRNAs was performed in a cohort of 20 patients, including 10 spindle-shaped melanoma and 10 epithelioid cell melanoma, and 10 healthy donors. Then 5 patients with metastatic UM were included to validate the performance of miRNAs in advanced UM. Serum levels of miRNAs were determined using quantitative real-time PCR. We confirmed significantly higher levels of three miRNAs in serum of UM patients in comparison to healthy controls, and miR-199a-3p had the best performance (p < 0.0001; AUC = 0.985). MiR-214-3p and miR-21-5p were significantly upregulated in serum of epithelioid cell melanoma patients compared to spindle-shaped melanoma patients and miR-132-3p and, conversely, were significantly downregulated in serum of epithelioid cell melanoma patients. MiR-21-5p shows their best performance (p < 0.0001; AUC = 0.980). Both miR-199a-3p and miR-21-5p showed great performance in advanced UM. Significantly higher levels of miR-21-5p (p < 0.001) were found in serum of metastatic UM patients compared to patients with localized spindle-shaped melanoma, and significantly higher levels of miR-199a-3p (p < 0.001) were detected in serum of metastatic UM patients compared to healthy controls. Our preliminary data indicate promising diagnostic utility of circulating miR-199a-3p and promising prognostic utility of circulating miR-21-5p in both early and advanced UM patients.

Prevalence, Years Lived With Disability, and Time Trends for 16 Causes of Blindness and Vision Impairment: Findings Highlight Retinopathy of Prematurity.

Background: Cause-specific prevalence data of vision loss and blindness is fundamental for making public health policies and is essential for prioritizing scientific advances and industry research. Methods: Cause-specific vision loss data from the Global Health Data Exchange was used. The burden of vision loss was measured by prevalence and years lived with disability (YLDs). Findings: In 2019, uncorrected refractory error and cataract were the most common causes for vision loss and blindness globally. Women have higher rates of cataract, age-related macular degeneration (AMD), and diabetic retinopathy (DR) than men. In the past 30 years, the prevalence of moderate/severe vision loss and blindness due to neonatal disorders has increased by 13.73 and 33.53%, respectively. Retinopathy of prematurity (ROP) is the major cause of neonatal disorders related vision loss. In 2019, ROP caused 101.6 thousand [95% uncertainty intervals (UI) 77.5-128.2] cases of vision impairment, including 49.1 thousand (95% UI 28.1-75.1) moderate vision loss, 27.5 thousand (95% UI 19.3-36.60) severe vision loss and, 25.0 thousand (95% UI 14.6-35.8) blindness. The prevalence of new-onset ROP in Africa and East Asia was significantly higher than other regions. Variation of preterm birth prevalence can explain 49.8% geometry variation of ROP-related vision loss burden among 204 countries and territories. After adjusting for preterm prevalence, government health spending per total health spending (%), rather than total health spending per person, was associated with a reduced burden of ROP-related vision loss in 2019 (-0.19 YLDs for 10% increment). By 2050, prevalence of moderate, severe vision loss and blindness due to ROP is expected to reach 43.6 (95% UI 35.1-52.0), 23.2 (95% UI 19.4-27.1), 31.9 (95% UI 29.7-34.1) per 100,000 population. Conclusion: The global burden of vision loss and blindness highlights the prevalent of ROP, a major and avoidable cause for childhood vision loss. Advanced screening techniques and treatments have shown to be effective in preventing ROP-related vision loss and are urgently needed in regions with high ROP-related blindness rates, including Africa and East Asia.

Prediction of the Fundus Tessellation Severity With Machine Learning Methods.

Purpose: To predict the fundus tessellation (FT) severity with machine learning methods. Methods: A population-based cross-sectional study with 3,468 individuals (mean age of 64.6 ± 9.8 years) based on Beijing Eye Study 2011. Participants underwent detailed ophthalmic examinations including fundus images. Five machine learning methods including ordinal logistic regression, ordinal probit regression, ordinal log-gamma regression, ordinal forest and neural network were used. Main Outcome Measure: FT precision, recall, F1-score, weighted-average F1-score and AUC value. Results: Observed from the in-sample fitting performance, the optimal model was ordinal forest, which had correct classification rate (precision) of 81.28%, while 34.75, 93.73, 70.03, and 24.82% in each classified group by FT severity. The AUC value was 0.7249. And the F1-score was 65.05%, weighted-average F1-score was 79.64% on the whole dataset. For out-of-sample prediction performance, the optimal model was ordinal logistic regression, which had precision of 77.12% on the validation dataset, while 19.57, 92.68, 64.74, and 6.76% in each classified group by FT severity. The AUC value was 0.7187. The classification accuracy of light FT group was the highest, while that of severe FT group was the lowest. And the F1-score was 54.46%, weighted-average F1-score was 74.19% on the whole dataset. Conclusions: The ordinal forest and ordinal logistic regression model had the strong prediction in-sample and out-sample performance, respectively. The threshold ranges of the ordinal forest model for no FT and light, moderate, severe FT were [0, 0.3078], [0.3078, 0.3347], [0.3347, 0.4048], [0.4048, 1], respectively. Likewise, the threshold ranges of ordinal logistic regression model were ≤ 3.7389, [3.7389, 10.5053], [10.5053, 13.9323], > 13.9323. These results can be applied to guide clinical fundus disease screening and FT severity assessment.

Epiregulin, epigen and betacellulin antibodies and axial elongation in young guinea pigs with lens-induced myopization.

BACKGROUND: To examine an effect of intravitreally applied antibodies against epidermal growth factor family members, namely epiregulin, epigen and betacellulin, on ocular axial elongation. METHODS: The experimental study included 30 guinea pigs (age:3-4 weeks) which underwent bilateral lens-induced myopization and received three intraocular injections of 20 µg of epiregulin antibody, epigen antibody and betacellulin antibody in weekly intervals into their right eyes, and of phosphate-buffered saline into their left eyes. Seven days after the last injection, the animals were sacrificed. Axial length was measured by sonographic biometry. RESULTS: At baseline, right eyes and left eyes did not differ (all P > 0.10) in axial length in neither group, nor did the interocular difference in axial length vary between the groups (P = 0.19). During the study period, right and left eyes elongated (P < 0.001) from 8.08 ± 0.07 mm to 8.59 ± 0.06 mm and from 8.08 ± 0.07 mm to 8.66 ± 0.07 mm, respectively. The interocular difference (left eye minus right eye) in axial elongation increased significantly in all three groups (epiregulin-antibody:from 0.03 ± 0.06 mm at one week after baseline to 0.16 ± 0.08 mm at three weeks after baseline;P = 0.001); epigen-antibody group:from -0.01 ± 0.06 mm to 0.06 ± 0.08 mm;P = 0.02; betacellulin antibody group:from -0.05 ± 0.05 mm to 0.02 ± 0.04 mm;P = 0.004). Correspondingly, interocular difference in axial length increased from -0.02 ± 0.04 mm to 0.13 ± 0.06 mm in the epiregulin-antibody group (P < 0.001), and from 0.01 ± 0.05 mm to 0.07 ± 0.05 mm in the epigen-antibody group (P = 0.045). In the betacellulin-antibody group the increase (0.01 ± 0.04 mm to 0.03 ± 0.03 mm) was not significant (P = 0.24). CONCLUSIONS: The EGF family members epiregulin, epigen and betacellulin may be associated with axial elongation in young guinea pigs, with the effect decreasing from epiregulin to epigen and to betacellulin.

Prevalence and Associations of Vitreomacular Traction: The Beijing Eye Study.

PURPOSE: To explore the prevalence and associations of vitreous macular traction (VMT) in Chinese population. METHODS: A population-based cross-sectional study with 3468 individuals (mean age of 64.6 ± 9.8 years) based on Beijing Eye Study 2011. Participants underwent detailed ophthalmic examinations, including spectral domain optical coherence tomography (SD-OCT). VMT was defined as abnormal posterior vitreous detachment with anatomical deformation of the fovea, which may include pseudocyst, macular schisis, cystoid macular edema, and subretinal fluid. MAIN OUTCOME MEASURE: Prevalence of VMT. RESULTS: A VMT was detected in 151 (2.3%) eyes (prevalence rate (mean ± SE): 2.3± 0.2%; 95% CI: 1.9%, 2.7%) of 80 (2.4%) subjects (prevalence rate: 2.4± 0.3%; 95% CI: 1.9%, 2.9%). Mean age of all subjects with VMT was 70.1± 8.7 years (median, 70.0 years; range, 50-90 years), mean refractive error was -0.22 ± 2.38D (median, 0.25 D; range, -15.00 to 5.25D). In multivariate analysis, prevalence of VMT was associated with elder age (P=0.001, OR 1.06), female gender (P = 0.036, OR 1.77), subfoveal retinal thickness (P = 0.005, OR 1.01), and subfoveal choroidal thickness (P = 0.026, OR 0.10). CONCLUSION: In adult Chinese in Greater Beijing, the prevalence of VMT was 2.3% for eyes or 2.4% for subjects. While it was associated with elder age, female gender, thicker subfoveal retinal thickness and thinner subfoveal choroidal thickness.

Global, regional, and national prevalence, disability adjusted life years, and time trends for refraction disorders, 1990-2019: findings from the global burden of disease study 2019.

BACKGROUND: To evaluate global burden of refraction disorders by year, age, region, gender, socioeconomic status and other national characteristics in terms of disability adjusted life years (DALYs) and prevalence from Global Burden of Disease (GBD) study 2019 and World Bank Open Data 2019. METHODS: Global, regional, and national DALY numbers, crude DALY rates, age-standardized DALY and prevalence rates of refraction disorders were acquired from the GBD study 2019. Mobile cellular subscriptions, urban population, GDP per capita, access to electricity and total fertility rate were obtained from the World Bank to explore the factors that influenced the health burden of refraction disorders. Kruskal-Wallis test, linear regression and multiple linear regression were performed to evaluate the associations between the health burden with socioeconomic levels and other national characteristics. Wilcoxon Signed-Rank Test was used to investigate the gender disparity. RESULTS: Globally, age-standardized DALY rates of refraction disorders decreased from 88.9 (95% UI: 60.5-120.3) in 1990 to 81.5 (95% UI: 55.0-114.8) in 2019, and might fall to 73.16 (95% UI: 67.81-78.51) by 2050. Age-standardized prevalence rates would also reduce to 1830 (95% UI: 1700-1960) by 2050, from 2080 (95% UI: 1870-2310) in 1990 to 1960 (95% UI: 1750-2180) in 2019. In low SDI region, age-standardized DALY rates (equation: Y = 114.05*X + 27.88) and prevalence rates (equation: Y = 3171.1*X + 403.2) were positively correlated with SDI in linear regression respectively. East Asia had the highest blindness rate caused by refraction disorders in terms of age-standardized DALY rates (11.20, 95% UI: 7.38-16.36). Gender inequality was found among different age groups and SDI regions. CONCLUSION: Health burden of refraction disorders decreased in recent years, and may continue to alleviate in the next three decades. Older ages, females and lower socioeconomic status were associated with higher refraction disorders health burden.

Non-linear association of anthropometric measurements and pulmonary function.

This study examined the association of anthropometric measurements [body mass index (BMI), waist circumference (WC), percentage body fat (PBF), body roundness index (BRI) and A Body Shape Index (ABSI)] with pulmonary function using a United States national cohort. This cross-sectional study included 7346 participants. The association between anthropometric measurements and pulmonary function was assessed by multivariable linear regression. Where there was evidence of non-linearity, we applied a restricted cubic spline to explore the non-linear association. All analyses were weighted to represent the U.S. population and to account for the intricate survey design. After adjusting for age, race, education, smoking, and physical activity, both underweight and obesity were associated with reduced forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Furthermore, the associations between BMI and FEV1, as well as FVC, were reversed U-shape in both males and females. Similar non-linear association shape occurred in WC, PBF, BRI and ABSI. Conclusion: BMI, WC, PBF, BRI, ABSI are non-linearly associated with pulmonary function. Reduced pulmonary function is a risk factor for future all-cause mortality and cardiovascular events; thus, this nonlinearity may explain the U-shape or J-shape association of BMI with overall mortality and cardiovascular events.