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.

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.

Large language models and their impact in ophthalmology.

The advent of generative artificial intelligence and large language models has ushered in transformative applications within medicine. Specifically in ophthalmology, large language models offer unique opportunities to revolutionise digital eye care, address clinical workflow inefficiencies, and enhance patient experiences across diverse global eye care landscapes. Yet alongside these prospects lie tangible and ethical challenges, encompassing data privacy, security, and the intricacies of embedding large language models into clinical routines. This Viewpoint highlights the promising applications of large language models in ophthalmology, while weighing up the practical and ethical barriers towards their real-world implementation. This Viewpoint seeks to stimulate broader discourse on the potential of large language models in ophthalmology and to galvanise both clinicians and researchers into tackling the prevailing challenges and optimising the benefits of large language models while curtailing the associated risks.

Combined transcriptomic and metabolomic analysis of alginate oligosaccharides alleviating salt stress in rice seedlings.

BACKGROUND: Salt stress is one of the key factors limiting rice production. Alginate oligosaccharides (AOS) enhance plant stress resistance. However, the molecular mechanism underlying salt tolerance in rice induced by AOS remains unclear. FL478, which is a salt-tolerant indica recombinant inbred line and IR29, a salt-sensitive rice cultivar, were used to comprehensively analyze the effects of AOS sprayed on leaves in terms of transcriptomic and metabolite profiles of rice seedlings under salt stress. RESULTS: In this experiment, exogenous application of AOS increased SOD, CAT and APX activities, as well as GSH and ASA levels to reduce the damage to leaf membrane, increased rice stem diameter, the number of root tips, aboveground and subterranean biomass, and improved rice salt tolerance. Comparative transcriptomic analyses showed that the regulation of AOS combined with salt treatment induced the differential expression of 305 and 1030 genes in FL478 and IR29. The expressed genes enriched in KEGG pathway analysis were associated with antioxidant levels, photosynthesis, cell wall synthesis, and signal transduction. The genes associated with light-trapping proteins and RLCK receptor cytoplasmic kinases, including CBA, LHCB, and Lhcp genes, were fregulated in response to salt stress. Treatment with AOS combined with salt induced the differential expression of 22 and 50 metabolites in FL478 and IR29. These metabolites were mainly related to the metabolism of amino and nucleotide sugars, tryptophan, histidine, and ß -alanine. The abundance of metabolites associated with antioxidant activity, such as 6-hydroxymelatonin, wedelolactone and L-histidine increased significantly. Combined transcriptomic and metabolomic analyses revealed that dehydroascorbic acid in the glutathione and ascorbic acid cycles plays a vital role in salt tolerance mediated by AOS. CONCLUSION: AOS activate signal transduction, regulate photosynthesis, cell wall formation, and multiple antioxidant pathways in response to salt stress. This study provides a molecular basis for the alleviation of salt stress-induced damage by AOS in rice.

OCT Optic Nerve Head Morphology in Myopia II: Peri-Neural Canal Scleral Bowing and Choroidal Thickness in High Myopia-An American Ophthalmological Society Thesis.

PURPOSE: To use optical coherence tomography (OCT) to characterize optic nerve head (ONH) peri-neural canal (pNC) scleral bowing (pNC-SB) and pNC choroidal thickness (pNC-CT) in 69 highly myopic and 138 healthy, age-matched, control eyes. DESIGN: Cross-sectional, case control study. METHODS: Within ONH radial B-scans, Bruch membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and pNC scleral surface were segmented. BMO and ASCO planes and centroids were determined. pNC-SB was characterized within 30° foveal-BMO (FoBMO) sectors by 2 parameters: pNC-SB-scleral slope (pNC-SB-SS), measured within 3 pNC segments (0-300, 300-700, and 700-1000 µm from the ASCO centroid); and pNC-SB-ASCO depth relative to a pNC scleral reference plane (pNC-SB-ASCOD). pNC-CT was calculated as the minimum distance between the scleral surface and BM at 3 pNC locations (300, 700, and 1100 µm from the ASCO). RESULTS: pNC-SB increased and pNC-CT decreased with axial length (P < .0133; P < .0001) and age (P < .0211; P < .0004) among all study eyes. pNC-SB was increased (P < .001) and pNC-CT was decreased (P < .0279) in the highly myopic compared to control eyes, and these differences were greatest in the inferior quadrant sectors (P < .0002). Sectoral pNC-SB was not related to sectoral pNC-CT in control eyes, but was inversely related to sectoral pNC-CT (P < .0001) in the highly myopic eyes. CONCLUSIONS: Our data suggest that pNC-SB is increased and pNC-CT is decreased in highly myopic eyes and that these phenomena are greatest in the inferior sectors. They support the hypothesis that sectors of maximum pNC-SB may predict sectors of greatest susceptibility to aging and glaucoma in future longitudinal studies of highly myopic eyes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Impact of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) GFR Estimating Equations on CKD Prevalence and Classification Among Asians.

Background: In 2021, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) validated a new equation for estimated glomerular filtration rate (eGFR). However, this new equation is not ethnic-specific, and prevalence of CKD in Asians is known to differ from other ethnicities. This study evaluates the impact of the 2009 and 2021 creatinine-based eGFR equations on the prevalence of CKD in multiple Asian cohorts. Methods: Eight population-based studies from China, India, Russia (Asian), Singapore and South Korea provided individual-level data (n = 67,233). GFR was estimated using both the 2009 CKD-EPI equation developed using creatinine, age, sex, and race (eGFRcr [2009, ASR]) and the 2021 CKD-EPI equation developed without race (eGFRcr [2021, AS]). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 (G3-G5). Prevalence of eGFR categories was compared within each study and within subgroups of age, sex, body mass index (BMI), diabetes, and hypertension status. The extent of reclassification was examined using net reclassification improvement (NRI). Findings: Of 67,233 adults, CKD prevalence was 8.6% (n = 5800/67,233) using eGFRcr (2009, ASR) and 6.4% (n = 4307/67,233) using eGFRcr (2021, AS). With the latter, CKD prevalence was reduced across all eight studies, ranging from -7.0% (95% CI -8.5% to -5.4%) to -0.4% (-1.3% to 0.5%), and across all subgroups except those in the BMI < 18.5% subgroup. Net reclassification index (NRI) was significant at -2.33% (p < 0.001). No individuals were reclassified as a higher (more severe) eGFR category, while 1.7%-4.2% of individuals with CKD were reclassified as one eGFR category lower when eGFRcr (2021, AS) rather than eGFRcr (2009, ASR) was used. Interpretation: eGFRcr (2021, AS) consistently provided reduced CKD prevalence and higher estimation of GFR among Asian cohorts than eGFRcr (2009, ASR). Based on current risk-stratified approaches to CKD management, more patients reclassified to lower-risk GFR categories could help reduce inappropriate care and its associated adverse effects among Asian renal patients. Comparison of both equations to predict progression to renal failure or adverse outcomes using prospective studies are warranted. Funding: National Medical Research Council, Singapore.

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.

Association between Body Mass Index and Chronic Kidney Disease in Asian Populations: A Participant-level Meta-Analysis.

Obesity and chronic kidney disease (CKD) are major public health problems worldwide. However, the association between body mass index (BMI) and CKD is inconclusive in Asians. In this meta-analysis, eight population-based studies, from China, India, Russia (Asian), Singapore and South Korea, provided individual-level data (n=50037). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. BMI was analyzed both as a continuous variable and in three categories: <25kg/m2, normal; 25-29.9kg/m2, overweight; and ≥30kg/m2, obese. The association between BMI and CKD was evaluated in each study using multivariable logistic regression models and individual estimates were pooled using random-effect meta-analysis to obtain the pooled odds ratio (OR) and 95% confidence interval (CI). Associations were also evaluated in subgroups of age, gender, smoking, diabetes, and hypertension status. Of 50037 adults, 4258 (8.5%) had CKD. 13328 (26.6%) individuals were overweight while 4440 (8.9%) were obese. The prevalence of any CKD ranged from 3.5% to 29.1% across studies. In pooled analysis, both overweight and obesity were associated with increased odds of CKD, with pooled OR (95% CI) of 1.15 (1.03-1.29) and 1.23 (1.06-1.42), respectively. In subgroup analyses, significant associations between BMI and CKD were observed in adult males, non-smokers, and those with diabetes and arterial hypertension (all p<0.05). When evaluated as a continuous variable, BMI was not significantly associated with CKD. If confirmed in longitudinal studies, these results may have clinical implications in risk stratification and preventive measures, given that obesity and CKD are two major chronic diseases with substantial public health burden worldwide.

Influencing factors for peripheral and posterior lesions in mild non-proliferative diabetic retinopathy-the Kailuan Eye Study.

AIM: To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy (NPDR) in the Kailuan area of Tangshan, Hebei Province, China. METHODS: In this non-interventional, retrospective study, 683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study. Based on the undilated ultra-wide field (200°; UWF) images and partial dilated digital fundus images, the diabetic retinopathy (DR) of the surveyed population was graded. Interobserver agreement was estimated by using Cohen's Kappa statistics. The main outcome indicators included gender, age, weight, height, body mass index, blood pressure, circumferences of neck, waist and hip, current smoking, levels of fasting plasma glucose (FPG), hypersensitive C-reactive protein, creatinine, and cholesterol, etc. According to different lesions' locations of patients with mild NPDR, logistic regression models were used to estimate the odds ratios (ORs) and their 95%CIs of each risk factor. RESULTS: The study group of 683 patients included 570 males and 113 females. The mean age of the patients was 62.18±9.41y. Compared with dilated fundus examinations, there was fair agreement with the level of DR identified on UWF images in 63.91% of eyes (k=0.369, 95%CI, 0.00-0.00). Detected by UWF images, there were 98 patients with mild NPDR having peripheral retinal lesions, 35 patients with mild NPDR having posterior lesions, 44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area, and 336 patients with non obvious DR. Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance (OR, 1.124; 95%CI, 1.044-1.211), and with posterior lesions were FPG (OR, 1.052; 95%CI, 1.007-1.099). CONCLUSION: UWF is an effectiveness means of DR screening. Moreover, it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR. The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found. And the influencing factors in mild NPDR are differing by different lesions' locations.

Prevalence and Risk Factors of Epiretinal Membranes in a Chinese Population: The Kailuan Eye Study.

Purpose: To investigate the prevalence of epiretinal membranes (ERMs) and their risk factors in a Chinese population. Methods: The community-based Kailuan Eye Study included 14,440 participants (9835 male, 4605 female) with a mean age of 54.0 ± 13.3 years (range, 20-110 years). They underwent a systemic and ophthalmologic examination. ERMs were diagnosed on fundus photographs. Results: Retinal photographs assessable for the presence of ERMs were available for 13,295 (92.0%) individuals (9094 male) with a mean age of 53.6 ± 13.3 years (range, 20-110 years). ERMs were found in 1013 participants (1489 eyes) with a prevalence of 7.6% (95% confidence interval [CI], 7.1%-8.1%). Secondary ERMs caused by intraocular reasons were found 46 (4.5%) individuals (69 [4.6%] eyes). A higher prevalence of any ERMs (and of primary ERMs) was associated with older age (odds ratio [OR]: 1.08; 95% CI:1.07-1.10), higher body mass index (OR: 1.05; 95% CI: 1.00-1.11), higher prevalence of smoking (OR:1.43; 95% CI: 1.01-2.03), higher serum concentration of glucose (OR: 1.08; 95% CI: 1.04-1.13), and lower serum concentration of uric acid (OR: 0.99; 95% CI: 0.99-1.00). Visual acuity was significantly (P = 0.002) lower in eyes with premacular fibroses than in eyes with cellophane macular reflexes. Conclusions: In our cross-sectional community-based study, the prevalence of all ERMs was 7.6%. Among the group of participants with ERMs, secondary ERMs caused by intraocular reasons were detected in 46 (4.5%) individuals (69 [4.6%] eyes). A higher prevalence of any ERM and of primary ERMs was associated with older age, higher body mass index, higher prevalence of smoking, a higher serum concentration of glucose, and a lower serum concentration of uric acid.

Evaluation of Chemical Bonding in Actinyl(VI/V) Oxo-Crown-Ether Complexes for Actinide Series from Uranium to Curium.

The separation and management of nuclear waste is one of the problems that needs to be solved urgently, so finding a new radiation-proof and durable extractant to deal with nuclear waste is a difficult but desirable task. Since the successful isolation of the first pentavalent plutonium crown ether complex recently (Wang et al. CCS Chem. 2020, 2, 425-431), complexes with actinyl(V/VI) inserted into the cavity of 18-crown-6 ether (oxo-18C6), as well as their bonding character, need to be explored. Here we present a series of novel crown ether complexes containing actinyl(V/VI) and oxo-18C6 via computational prediction and analysis. On the basis of the calculations, actinyl(V/VI) are thermodynamically feasible and can be stabilized by oxo-18C6 ligand via six dative bonds between An ions and the oxo-18C6 O atoms in the "insertion" structure of [AnO2(18C6)]2+/+ complexes. The stability of actinyl(VI) species generally falls at minor actinides, ascribed to the reduced highest possible oxidation states of curium, which is mainly attributed to the mixing of bonding orbitals and non-bonding orbitals as well as the increase of occupation on partially 5f antibonding orbitals. It is found that the interactions between the actinyl(V/VI) and oxo-18C6 are mainly electronic interactions, with the well-known covalency contributions generally decreasing from uranium to curium due to energy degeneracy and spatial orbital contraction. This work would give a basic understanding of the coordination chemistry of actinyl(V/VI), which also provides inspirations on the design of new extractants for actinide separations.

Blockade of epidermal growth factor and its receptor and axial elongation in experimental myopia.

To examine the influence of epidermal growth factor (EGF) and its receptor (EGFR) on axial ocular elongation, we intraocularly injected an EGF antibody and an EGFR antibody into young guinea pigs with lens-induced axial elongation (myopization). Mean axial elongation was reduced in the eyes injected with the EGF/EGFR-antibody compared with the contralateral control eyes injected with PBS (phosphate-buffered solution) (0.43 ± 0.13 mm vs 0.53 ± 0.13 mm; P < .001). The intereye difference in axial length increased (P = .005) as the doses of the EGF antibody and EGFR antibody increased. As a corollary, the thickness of the retina at the posterior pole was dose-dependently increased in the injected eyes compared to the contralateral control eyes. Immunohistochemical staining for EGF and the relative mRNA expression of EGF and EGFR were the highest in eyes not injected with the EGF antibody or EGFR antibody and decreased (P < .05) as the dose of EGF antibody or EGFR antibody increased. In an in vitro study, EGF had a stimulating effect and the EGF antibody had an inhibitory effect on the proliferation and migration of RPE cells. The findings showed that the intravitreal application of an EGF antibody and EGFR antibody is associated with a dose-dependent reduction in lens-induced axial elongation in young guinea pigs. The EGFR family may play a role in axial elongation of the eye and in the development of myopia.

Optical Coherence Tomography Optic Nerve Head Morphology in Myopia I: Implications of Anterior Scleral Canal Opening Versus Bruch Membrane Opening Offset.

PURPOSE: To measure the magnitude and direction of anterior scleral canal opening (ASCO) offset relative to the Bruch membrane opening (BMO) (ASCO/BMO offset) to characterize neural canal obliqueness and minimum cross-sectional area (NCMCA) in 69 highly myopic and 138 healthy, age-matched, control eyes. DESIGN: Cross-sectional study. METHODS: Using optical coherence tomography (OCT) scans of the optic nerve head (ONH), BMO and ASCO were manually segmented and their centroids and size and shape were calculated. ASCO/BMO offset magnitude and direction were measured after projecting the ASCO/BMO centroid vector onto the BMO plane. Neural canal axis obliqueness was defined as the angle between the ASCO/BMO centroid vector and the vector perpendicular to the BMO plane. NCMCA was defined by projecting BMO and ASCO points onto a plane perpendicular to the neural canal axis and measuring their overlapping area. RESULTS: ASCO/BMO offset magnitude was greater (highly myopic eyes 264.3 ± 131.1 µm; healthy control subjects 89.0 ± 55.8 µm, P < .001, t test) and ASCO centroid was most frequently nasal relative to BMO centroid (94.2% of eyes) in the highly myopic eyes. BMO and ASCO areas were significantly larger (P < .001, t test), NCMCA was significantly smaller (P < .001), and all 3 were significantly more elliptical (P ≤ .001) in myopic eyes. Neural canal obliqueness was greater in myopic (65.17° ± 14.03°) compared with control eyes (40.91° ± 16.22°; P < .001, t test). CONCLUSIONS: Our data suggest that increased temporal displacement of BMO relative to the ASCO, increased BMO and ASCO area, decreased NCMCA, and increased neural canal obliqueness are characteristic components of ONH morphology in highly myopic eyes.

Peripapillary Scleral Bowing Increases with Age and Is Inversely Associated with Peripapillary Choroidal Thickness in Healthy Eyes.

PURPOSE: To use optical coherence tomography (OCT) to 3-dimensionally characterize the optic nerve head (ONH) in peripapillary scleral bowing in non-highly myopic healthy eyes. DESIGN: Cross-sectional, multicenter study. METHODS: A total of 362 non-highly myopic (+6 diopters [D] > spherical equivalent > -6D) eyes of 362 healthy subjects from 20-90 years old underwent OCT ONH radial B-scan imaging. Bruch's membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and the peripapillary scleral surface were segmented. BMO and ASCO planes were fit, and their centroids, major axes, ovality, areas and offsets were determined. Peripapillary scleral bowing was characterized by 2 parameters: peripapillary scleral slope (ppSS) of 3 anterior peripapillary scleral segments (0-300, 300-700, and 700-1,000 µm from the ASCO centroid); and ASCO depth relative to a peripapillary scleral reference plane (ASCOD-ppScleral). Peripapillary choroidal thickness (ppCT) was calculated relative to the ASCO as the minimum distance between the anterior scleral surface and BM. RESULTS: Both ppSS and ASCOD-ppScleral ranged from slightly inward through profoundly outward in direction. Both parameters increased with age and were independently associated with decreased ppCT. CONCLUSIONS: In non-highly myopic healthy eyes, outward peripapillary scleral bowing achieved substantial levels, was markedly increased with age, and was independently associated with decreased peripapillary choroidal thickness. These findings provide a normative foundation for characterizing this anatomy in cases of high myopia and glaucoma and in eyes with optic disc tilt, torsion, and peripapillary atrophy.

Is kidney function associated with primary open-angle glaucoma? Findings from the Asian Eye Epidemiology Consortium.

AIM: To comprehensively examine the association between kidney function and primary open angle glaucoma (POAG) in a large consortium of multiple Asian population-based studies. METHODS: 28 925 participants (57 340 eyes) from 9 population-based studies (from China, Hong Kong, India, Korea, Russia, Singapore) of the Asian Eye Epidemiology Consortium were included. Across all studies, POAG was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Chronic kidney disease (CKD) was defined as eGFR<60 mL/min/1.73 m2. Eye-specific data were pooled from each study. Multivariable regression analysis with generalised estimating equation models was performed to evaluate the associations between kidney function with POAG and intraocular pressure (IOP). RESULTS: After adjusting for age, gender, study group, hypertension, diabetes, hyperlipidaemia, body mass index, smoking status and IOP, lower eGFR (per 10 mL/min/1.73 m2 decrease) was not significantly associated with POAG (OR=1.01; p=0.77). Presence of CKD was also not significantly associated with POAG (OR=1.01; p=0.739). Furthermore, lower eGFR and presence of CKD were not associated with IOP (all p≥0.12), However, in the subgroup of combined Korean and Chinese individuals, significant associations between lower eGFR (OR=1.09; 95% CI 1.00 to 1.18; p=0.048) and severe kidney function decline (<45 mL/min/1.73 m2; OR=2.57; 95% CI 1.34 to 4.93; p=0.004) with POAG, were observed. CONCLUSION: In this large pooled-analysis of multiple Asian population-based studies, our findings suggest that the association between CKD and POAG may only be present in East Asians specifically but not in the overall Asian population. Further evaluation in Japanese population is warranted to confirm this observation.

Amphiregulin and ocular axial length.

PURPOSE: To assess the potential role of amphiregulin as messenger molecule in ocular axial elongation. METHODS: The experimental study included guinea pigs (total n = 78) (age: 3-4 weeks) which underwent bilateral lens-induced myopization and received 15 days later three intraocular injections in weekly intervals of amphiregulin antibody (doses:5 µg, 10 µg, 20 µg) into their right eyes, and three phosphate-buffered saline injections into their left eyes; and guinea pigs without lens-induced myopization and which received three unilateral intraocular injections of amphiregulin antibody (dose: 20 µg) or amphiregulin (doses: 1 ng; 10 ng; 20 ng) into their right eyes, and three phosphate-buffered saline injections into their left eyes. Seven days later, the animals were sacrificed. Intravitally, we performed biometry, and histology and immunohistochemistry post-mortem. RESULTS: In animals with bilateral lens-induced myopization, the right eyes receiving amphiregulin antibody showed reduced axial elongation in a dose-dependent manner (dose: 5 µg: side difference: 0.14 ± 0.05 mm;10 µg: 0.22 ± 0.06 mm; 20 µg: 0.32 ± 0.06 mm; p < 0.001), thicker sclera (all p < 0.05) and higher cell density in the retinal nuclear layers and retinal pigment epithelium (RPE) (all p < 0.05). In animals without lens-induced myopia, the right eyes with amphiregulin antibody application (20 µg) showed reduced axial elongation (p = 0.04), and the right eyes with amphiregulin injections experienced increased (p = 0.02) axial elongation in a dose-dependent manner (1 ng: 0.04 ± 0.06 mm; 10 ng: 0.10 ± 0.05 mm; 20 ng: 0.11 ± 0.06 mm). Eyes with lens-induced axial elongation as compared to eyes without lens-induced axial elongation revealed an increased visualization of amphiregulin upon immunohistochemistry and higher expression of mRNA of endogenous amphiregulin and epidermal growth factor receptor, in particular in the outer part of the retinal inner nuclear layer and in the RPE. CONCLUSION: Amphiregulin may be associated with axial elongation in young guinea pigs.

Systemic inflammation and eye diseases. The Beijing Eye Study.

PURPOSE: Systemic inflammation is potentially associated with ocular diseases such as late age-related macular degeneration (AMD). Using the serum concentration of high-sensitive C-reactive protein (hs-CRP) as surrogate of systemic inflammation, we examined potential associations between the serum hs-CRP concentration and the presence and degree of eye diseases. METHODS: The population-based Beijing Eye Study included 3468 Chinese individuals. The study participants underwent a standardized interview and a detailed ophthalmic examination. The serum concentration of hs-CRP was determined. RESULTS: Out of 3468 participants, 2452 (70.7%) individuals (mean age:63.4±9.4 year; range:50-91 years) had hs-CRP measurements (mean:1.96±4.07mg/L). In multivariate analysis, higher serum concentration of hs-CRP was significantly (regression coefficient r: 0.21) associated with a higher level of diabetic retinopathy (P = 0.007; standardized regression coefficient beta:0.06; non-standardized regression coefficient B:1.35; 95% confidence interval (CI):0.37,2.22) and polypoidal choroidal vasculopathy (P = 0.002;beta:0.06;B:6.22;95%CI:2.24,10.2) after adjusting for higher serum concentration of high-density lipoproteins (P<0.001;beta:-0.12;B:-1.31;95%CI:-1.77,-0.85), higher body mass index (P = 0.01;beta:0.06;B:0.06;95%CI:0.01, 0.11), lower level of education (P = 0.04;beta:-0.06;B:-0.22;95%CI:-0.42,-0.02), lower cognitive function score (P = 0.01;beta:-0.07;B:-0.08;95%CI:-0.13,-0.02). If the presences of other ocular diseases were added to the model, the presence of glaucoma (P = 0.99), open-angle glaucoma (P = 0.80), angle-closure glaucoma (P = 0.67), pseudoexfoliation (P = 0.18), nuclear cataract (P = 0.30), cortical cataract (P = 0.15), subcapsular cataract (P = 0.59), retinal vein occlusions (P = 0.33), central serous choroidopathy (P = 0.44), early stage of age-related macular degeneration (AMD) (P = 0.46), intermediate stage of AMD (P = 0.20) and late stage of AMD (P = 0.91) including geographic atrophy (P = 0.60) or neovascular AMD (P = 0.68) were not significantly associated with the serum concentration of hs-CRP. CONCLUSIONS: In Chinese aged 50+ years, higher serum concentration of hs-CRP was significantly associated with a higher level of diabetic retinopathy and higher frequency of polypoidal choroidal vasculopathy. Other major ocular disorders, namely glaucoma including open-angle glaucoma and angle-closure glaucoma, pseudoexfoliation, nuclear, cortical or subcapsular cataract, retinal vein occlusions, central serous choroidopathy, early, intermediate or late stage of AMD including geographic atrophy, were not significantly associated with hs-CRP serum concentrations. It suggests that these diseases, in contrast to diabetic retinopathy and polypoidal choroidal vasculopathy, were not associated with a major systemic inflammatory component.

10-year fundus tessellation progression and retinal vein occlusion.

AIM: To access the 10-year fundus tessellation progression in patients with retinal vein occlusion. METHODS: The Beijing Eye Study 2001/2011 is a population-based longitudinal study. The study participants underwent a detailed physical and ophthalmic examination. Degree of fundus tessellation was graded by using fundus photographs of the macula and optic disc. Progression of fundus tessellation was calculated by fundus tessellation degree of 2011 minus degree of 2001. Fundus photographs were used for assessment of retinal vein occlusion. RESULTS: The Beijing Eye Study included 4403 subjects in 2001, 3468 subjects was repeated in 2011. Assessment of retinal vein obstruction and fundus tessellation progression were available for 2462 subjects (71.0%), with 66 subjects fulfilled the diagnosis of retinal vein occlusion. Of the 66 participants, 59 participants with unilateral branch retinal vein occlusion, 5 participants with unilateral central retinal vein occlusion, 1 participant with bilateral branch retinal vein occlusion, and 1 participant with branch retinal vein occlusion in one eye and central retinal vein occlusion in the other eye. Mean degree of peripapillary fundus tessellation progression were significantly higher in the whole retinal vein occlusion group (0.33±0.39, P<0.001), central retinal vein occlusion group (0.71±0.8, P=0.025) and branch retinal vein occlusion group (0.29±0.34, P=0.006) than the control group (0.20±0.26). After adjustment for age, prevalence of tilted disc, change of best corrected visual acuity, axial length, progression of peripapillary fundus tessellation was associated with the presence of retinal vein occlusion (P=0.004; regression coefficient B, 0.094; 95%CI, 0.029, 0.158; standardized coefficient B, 0.056). As a corollary, after adjusting for smoking duration, systolic blood pressure, anterior corneal curvature, prevalence of RVO was associated with more peripapillary fundus tessellation progression (P<0.001; regression coefficient B: 1.257; OR: 3.517; 95%CI: 1.777, 6.958). CONCLUSION: Peripapillary fundus tessellation progresses faster in individuals with retinal vein occlusion. This may reflect the thinning and hypoperfusion of choroid in patients with retinal vein occlusion.

Long-term Progression and Risk Factors of Fundus Tessellation in the Beijing Eye Study.

To assess the progression of fundus tessellation, color fundus photographs of the participants of the longitudinal population-based Beijing Eye Study were examined. The study included 4439 subjects in 2001 and 2695 (66.4% of the surviving) individuals in 2011. Larger progression in macular fundus tessellation (mean: 0.24 ± 0.48 grades) was associated (multivariate analysis; correlation coefficient r: 0.53) with thinner subfoveal choroidal thickness in 2011 (P < 0.001; standardized regression coefficient beta: -0.37), older age (P < 0.001; beta: 0.22), higher level of education (P < 0.001; beta: 0.09), more myopic change in refractive error (P < 0.001; beta: -0.09) and lower cognitive function score (P = 0.02; beta: -0.05). Larger increase in peripapillary fundus tessellation (mean: 0.19 ± 0.26 grades) correlated with thinner peripapillary choroidal thickness in 2011 (P < 0.001; beta: -0.35), older age (P < 0.001; beta: 0.20), worse best corrected visual acuity (P = 0.001; beta: 0.07), more myopic change in refractive error (P < 0.001; beta: -0.07) and higher prevalence of ever smoking (P = 0.004; beta: 0.05). The increase in macular fundus tessellation, as a surrogate for thinning of the posterior choroid, was associated with lower cognitive function, after adjusting for choroidal thickness, age, educational level and change in refractive error. The findings point to the clinical value of the assessment of fundus tessellation and suggest potential associations between cognitive function and fundus tessellation/choroidal thickness.

Ten-year cumulative incidence of epiretinal membranes assessed on fundus photographs. The Beijing Eye Study 2001/2011.

PURPOSE: To assess the 10-year incidence and progression of epiretinal membranes (ERMs). METHODS: The population-based longitudinal Beijing Eye Study, which included 4439 subjects (age:40+years) in 2001, was repeated in 2011 with 2695 subjects participating (66.4% of the survivors). The study participants underwent a detailed ophthalmic examination, including retinal photography. Assessing fundus photograohs, ERMs were classified as cellophane macular reflex (CMR) without retinal folds, or as preretinal macular fibrosis (PMF) without or with retinal folds. RESULTS: Fundus photographs were available for 2476 subjects with a mean age of 69.0±7.8 years (range:51-93 years) and mean axial length of 23.3±0.9 mm (range:19.92-26.33mm). The 10-year incidence of ERMs was 8.4% (208/2476 participants; 95% confidence interval (CI):7.4,9.5). ERMs developed bilaterally in 50 (24%) individuals and unilaterally in 158 (76%) persons. The incidence of PMFs with 2.5% (95% CI: 1.9, 3.1) was lower than the incidence of CMRs with 5.9% (95% CI: 5.0, 6.9). Higher 10-year incidence of ERMs was associated with older age (P<0.001; odds ratio (OR): 1.06; 95%CI:1.04,1.09), previous cataract surgery (P = 0.003;OR:3.32;95%CI:1.51,7.29) and presence of a complete posterior vitreous detachment (P = 0.02;OR:1.84;95%CI:1.12,3.02). In the age groups of <60 years, 60-69 years, 70-79 years and 80+years, incidence of ERMs was 3.1%, 10.0%, 14.4% and 10.9%, respectively, with no significant gender difference. CONCLUSIONS: In Chinese aged 40+ years, the 10-year incidence of ERMs (8.4%) increased with older age, previous cataract surgery and complete posterior vitreous detachment. The ten-year incidence was lower for PMFs (2.5%) than for CMRs (5.9%).