Publications by authors named "Jost B Jonas"

890 Publications

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 Jun 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Intraocular epidermal growth factor concentration, axial length, and high axial myopia.

Graefes Arch Clin Exp Ophthalmol 2021 May 29. Epub 2021 May 29.

Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Purpose: Various molecules such as dopamine have been found to be associated with axial elongation in experimental studies. Here, we examined whether intraocular EGF is associated with axial length in myopic patients.

Methods: The hospital-based investigation included patients of European descent without optic nerve, retinal, or macular diseases except for myopic maculopathy. Using aqueous humor samples collected during surgery, the EGF concentration was examined applying a cytometric bead array. High myopia was defined by an axial length of ≥ 27.0 mm.

Results: The study included a non-highly myopic group of 11 patients (mean age, 72.9 ± 10.8 years; mean axial length, 24.3 ± 1.1 mm) and a highly myopic group of three patients (age, 81.11 ± 12.3 years; axial length, 29.5 ± 1.3 mm), with one of them having pathologic myopic maculopathy. In multivariable linear regression analysis, higher EGF concentration was correlated with the highly myopic versus non-highly myopic group (beta, 1.24; non-standardized correlation coefficient B, 6.24; 95% confidence interval (CI), 0.10,12.4;P = 0.047) after adjusting for axial length. The amount of intraocular EGF was significantly higher in the highly myopic group than in the non-highly myopic group (89.1 ± 40.8 pg versus 34.1 ± 13.2 pg; P = 0.005), and it was highest in the eye with myopic maculopathy (135 pg).

Conclusions: The intraocular amount of EGF is higher in highly myopic versus non-highly myopic eyes.
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http://dx.doi.org/10.1007/s00417-021-05200-5DOI Listing
May 2021

Prevalence of Retinal Vein Occlusions and Estimated Cerebrospinal Fluid Pressure: The Kailuan Eye Study.

Eye Brain 2021 21;13:147-156. Epub 2021 May 21.

Beijing Institute of Ophthalmology and Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China.

Purpose: To investigate the prevalence of retinal vein occlusions (RVOs) and associated factors in a Chinese population.

Patients And Methods: The cross-sectional community-based Kailuan Eye Study included individuals who participated in the Kailuan Study. RVOs were diagnosed on the fundus photographs. Estimated cerebrospinal fluid pressure (eCSFP) was calculated as "eCSFP=0.44*Body Mass Index+0.16*Diastolic Blood Pressure-0.18*Age".

Results: The study included 12,499 participants with a mean age of 52.9±13.1 years. The overall prevalence of RVO was 120/12,499 or 0.96%, with branch RVOs observed in 116/12,499 individuals and central RVOs in 4/12,499 individuals. RVOs started at the optic disc in 19 participants (15.8% of all RVOs), and in 101 (84.2%) individuals arterio-venous crossings outside the optic disc. In multivariable analysis, a higher RVO prevalence was associated with older age (<0.001), higher eCSFP (<0.001), and higher fasting serum glucose concentration (<0.001). Differentiating between RVOs at arterio-venous crossings and RVOs at the optic disc revealed that the prevalence of both RVO types was associated with higher eCSFP (<0.001 and =0.004, respectively) after adjusting for age and fasting serum glucose concentration.

Conclusion: In this adult Chinese population recruited on a community basis, the prevalence of any RVO (mean: 0.96) was associated with older age, higher eCSFP and higher fasting serum glucose concentration. Higher eCSFP may play an etiologic role in RVOs.
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http://dx.doi.org/10.2147/EB.S290107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149277PMC
May 2021

Neural Network-Based Retinal Nerve Fiber Layer Profile Compensation for Glaucoma Diagnosis in Myopia: Model Development and Validation.

JMIR Med Inform 2021 May 18;9(5):e22664. Epub 2021 May 18.

Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.

Background: Due to the axial elongation-associated changes in the optic nerve and retina in high myopia, traditional methods like optic disc evaluation and visual field are not able to correctly differentiate glaucomatous lesions. It has been clinically challenging to detect glaucoma in highly myopic eyes.

Objective: This study aimed to develop a neural network to adjust for the dependence of the peripapillary retinal nerve fiber layer (RNFL) thickness (RNFLT) profile on age, gender, and ocular biometric parameters and to evaluate the network's performance for glaucoma diagnosis, especially in high myopia.

Methods: RNFLT with 768 points on the circumferential 3.4-mm scan was measured using spectral-domain optical coherence tomography. A fully connected network and a radial basis function network were trained for vertical (scaling) and horizontal (shift) transformation of the RNFLT profile with adjustment for age, axial length (AL), disc-fovea angle, and distance in a test group of 2223 nonglaucomatous eyes. The performance of RNFLT compensation was evaluated in an independent group of 254 glaucoma patients and 254 nonglaucomatous participants.

Results: By applying the RNFL compensation algorithm, the area under the receiver operating characteristic curve for detecting glaucoma increased from 0.70 to 0.84, from 0.75 to 0.89, from 0.77 to 0.89, and from 0.78 to 0.87 for eyes in the highest 10% percentile subgroup of the AL distribution (mean 26.0, SD 0.9 mm), highest 20% percentile subgroup of the AL distribution (mean 25.3, SD 1.0 mm), highest 30% percentile subgroup of the AL distribution (mean 24.9, SD 1.0 mm), and any AL (mean 23.5, SD 1.2 mm), respectively, in comparison with unadjusted RNFLT. The difference between uncompensated and compensated RNFLT values increased with longer axial length, with enlargement of 19.8%, 18.9%, 16.2%, and 11.3% in the highest 10% percentile subgroup, highest 20% percentile subgroup, highest 30% percentile subgroup, and all eyes, respectively.

Conclusions: In a population-based study sample, an algorithm-based adjustment for age, gender, and ocular biometric parameters improved the diagnostic precision of the RNFLT profile for glaucoma detection particularly in myopic and highly myopic eyes.
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http://dx.doi.org/10.2196/22664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170554PMC
May 2021

Obesity and risk of age-related eye diseases: a systematic review of prospective population-based studies.

Int J Obes (Lond) 2021 May 7. Epub 2021 May 7.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.

Background: Obesity is a public health challenge worldwide. The relationship between obesity and age-related eye diseases including cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR) have remained elusive.

Design And Methods: We conducted a systematic review of three electronic databases for longitudinal population-based studies that described associations between measures of obesity including body mass index (BMI), waist-circumference (WC), and waist-to-hip ratio (WHR), and age-related eye diseases.

Results: Our search yielded 1731 articles, of which 14, 10, 16 and 8 articles met our eligibility criteria for cataract, glaucoma, AMD and DR, respectively. BMI-defined obesity was positively associated with incident cataract, incident AMD and incident DR in Western populations, but in Asian populations associations for incident AMD were not significant and associations for incident DR were inverse. WC-defined obesity was associated with incident glaucoma in non-Western populations. WHR-defined obesity but not BMI-defined obesity was associated with the incidence or progression of AMD in two Western studies.

Conclusions: Overall, we found strong evidence supporting associations between obesity and age-related eye diseases. Further research on the association of abdominal obesity and effect of weight loss and physical activity on age-related eye diseases is warranted to support clinical and public health recommendations.
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http://dx.doi.org/10.1038/s41366-021-00829-yDOI Listing
May 2021

Histopathology of myopic cobblestones.

Acta Ophthalmol 2021 May 6. Epub 2021 May 6.

Department of Ophthalmology, Medical Faculty Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.

Purpose: To search for the histological correlate of peripheral 'cobblestones' in highly myopic eyes.

Methods: The histomorphometric investigation included histologic sections of enucleated eyes of Caucasian patients. Using light microscopy, we measured the thickness of the retina, Bruch's membrane (BM) and choriocapillaris.

Results: The study included 50 eyes (mean age:60.6 ± 18.7 years;axial length:26.5 ± 3.8 mm), with cobblestone regions detected in 7 eyes. BM thickness and choriocapillaris thickness in the cobblestone region were thinner (1.1 ± 0.2 µm versus 2.4 ± 0.8 µm; p < 0.001 and 1.6 ± 0.5 µm versus 2.6 ± 1.9 µm; p = 0.02, respectively), and just outside of the cobblestone region they were thicker (3.3 ± 0.6 µm versus 2.4 ± 0.8 µm; p = 0.005 and 5.7 ± 1.6 µm versus 2.6 ± 1.9 µm; p = 0.002, respectively) than in corresponding regions of eyes without cobblestones. Within the group of eyes with cobblestones, BM thickness (1.1 ± 0.2 mm versus 3.3 ± 0.6 mm; p < 0.001), choriocapillaris thickness (1.6 ± 0.5 mm versus 5.7 ± 1.6 mm; p < 0.001) and choriocapillaris density (48±15 µm/300 µm versus 159 ± 66 µm/300 µm;PP=0.002) were significantly lower in the cobblestone region than just outside of the cobblestone region. The cobblestone regions were characterized by firm adhesion of disorganized retina with thinned BM, few retinal pigment epithelium (RPE) islands within cobblestone regions, and absence of regional scleral or overall choroidal thinning. BM was mono-layered within, and double-layered outside of cobblestone regions, with the inner layer missing within the cobblestone region (except for the RPE islands).

Conclusions: Peripheral cobblestone regions in highly myopic eyes are characterized by marked BM thinning with absence of an inner BM layer, almost complete RPE absence, choriocapillaris thinning and firm connection of a disorganized retina to BM. These findings may help elucidating the process of axial elongation in myopic eyes.
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http://dx.doi.org/10.1111/aos.14894DOI Listing
May 2021

Myelinated Retinal Nerve Fiber Progression in a 10-Year Follow-Up. The Beijing Eye Study 2001/2011.

Am J Ophthalmol 2021 May 2. Epub 2021 May 2.

Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China; Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Mannheim, Germany; Institute of Clinical and Scientific Ophthalmology and Acupuncture Jonas & Panda, Heidelberg, Germany; Institute of Molecular and Clinical Ophthalmology Basel, Switzerland.

Purpose: To assess the prevalence of myelinated retinal nerve fibers (MRNFs), the rate of their change in a 10-year follow-up, and associations with ocular and systematic parameters in a population-based cohort.

Design: Longitudinal population-based cohort study.

Methods: The Beijing Eye study including 4439 participants aged 40+ years in 2001 and was repeated in 2011, with 2695 individuals (66.4% of the surviving) being re-examined in 2011. All participants underwent detailed physical and ocular examinations. MRNFs were diagnosed on fundus photographs and their change was assessed using a flicker method of fundus photographs.

Results: Out of 35 eyes (29 participants) with detected MRNFs at baseline (mean prevalence:0.4±0.26% per eye or 0.7%±0.41% per individual), 23 eyes from 20 individuals (17 (85%) participants with unilateral MRNFs) were re-examined in 2011. MRNF enlargement was detected in all 19 eyes (100%) with clear fundus photographs. The mean MRNF area increased from 4233±3670 µm (range:178-11643 µm) at baseline to 5243±4092 µm (range:196-13297µm) at follow-up (P<0.001), by 1010±1026 µm (18-3967 µm) or by 47%±74% (9-315%). A larger MRNF increase was associated with an MRNF location distant from the optic disc as compared to a juxtapapillary location (P=0.001, standardized regression coefficient beta:-0.53), smaller MRNF area at baseline (P=0.006, beta:-0.34), and higher serum concentration of low-density lipoproteins (LDL) (P<0.001, beta:0.57).

Conclusions: MRNFs (mean prevalence per eye:0.4%) showed, in association with higher LDL serum concentration and peripheral located MRNF, an enlargement during a 10-year follow-up, while in the same period no new MRNFs were detected in the total study cohort.
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http://dx.doi.org/10.1016/j.ajo.2021.04.018DOI Listing
May 2021

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

Ophthalmology 2021 May 1. Epub 2021 May 1.

Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Republic of Singapore; Duke-NUS Medical School, Singapore, Republic of Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore. Electronic address:

Topic: To provide updated estimates on the global prevalence and number of people with diabetic retinopathy (DR) through 2045.

Clinical Relevance: The International Diabetes Federation (IDF) estimated the global population with diabetes mellitus (DM) to be 463 million in 2019 and 700 million in 2045. Diabetic retinopathy remains a common complication of DM and a leading cause of preventable blindness in the adult working population.

Methods: We conducted a systematic review using PubMed, Medline, Web of Science, and Scopus for population-based studies published up to March 2020. Random effect meta-analysis with logit transformation was performed to estimate global and regional prevalence of DR, vision-threatening DR (VTDR), and clinically significant macular edema (CSME). Projections of DR, VTDR, and CSME burden were based on population data from the IDF Atlas 2019.

Results: We included 59 population-based studies. Among individuals with diabetes, global prevalence was 22.27% (95% confidence interval [CI], 19.73%-25.03%) for DR, 6.17% (95% CI, 5.43%-6.98%) for VTDR, and 4.07% (95% CI, 3.42%-4.82%) for CSME. In 2020, the number of adults worldwide with DR, VTDR, and CSME was estimated to be 103.12 million, 28.54 million, and 18.83 million, respectively; by 2045, the numbers are projected to increase to 160.50 million, 44.82 million, and 28.61 million, respectively. Diabetic retinopathy prevalence was highest in Africa (35.90%) and North American and the Caribbean (33.30%) and was lowest in South and Central America (13.37%). In meta-regression models adjusting for habitation type, response rate, study year, and DR diagnostic method, Hispanics (odds ratio [OR], 2.92; 95% CI, 1.22-6.98) and Middle Easterners (OR, 2.44; 95% CI, 1.51-3.94) with diabetes were more likely to have DR compared with Asians.

Discussion: The global DR burden is expected to remain high through 2045, disproportionately affecting countries in the Middle East and North Africa and the Western Pacific. These updated estimates may guide DR screening, treatment, and public health care strategies.
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http://dx.doi.org/10.1016/j.ophtha.2021.04.027DOI Listing
May 2021

IMI 2021 Reports and Digest - Reflections on the Implications for Clinical Practice.

Invest Ophthalmol Vis Sci 2021 Apr;62(5)

Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan.

The International Myopia Institute's (IMI) mission is to advance research, education, and management of myopia to decrease future vision impairment and blindness associated with increasing myopia. Its approach is to bring together scientists, clinicians, policymakers, government members, and educators into the field of myopia to stimulate collaboration and sharing of knowledge. The latest reports are on pathologic myopia, the impact of myopia, risk factors for myopia, accommodation and binocular vision in myopia development and progression, and the prevention of myopia and its progression. Together with the digest updating the 2019 International Myopia Institute white papers using the research published in the last 18 months, these evidence-based consensus white papers help to clarify the imperative for myopia control and the role of environmental modification initiatives, informing an evidence-based clinical approach. This guidance includes who to treat and when to start or stop treatment, and the advantages and limitations of different management approaches.
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http://dx.doi.org/10.1167/iovs.62.5.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083124PMC
April 2021

IMI Pathologic Myopia.

Invest Ophthalmol Vis Sci 2021 Apr;62(5)

Department of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Pathologic myopia is a major cause of visual impairment worldwide. Pathologic myopia is distinctly different from high myopia. High myopia is a high degree of myopic refractive error, whereas pathologic myopia is defined by a presence of typical complications in the fundus (posterior staphyloma or myopic maculopathy equal to or more serious than diffuse choroidal atrophy). Pathologic myopia often occurs in eyes with high myopia, however its complications especially posterior staphyloma can also occur in eyes without high myopia. Owing to a recent advance in ocular imaging, an objective and accurate diagnosis of pathologic myopia has become possible. Especially, optical coherence tomography has revealed novel lesions like dome-shaped macula and myopic traction maculopathy. Wide-field optical coherence tomography has succeeded in visualizing the entire extent of large staphylomas. The effectiveness of new therapies for complications have been shown, such as anti-VEGF therapies for myopic macular neovascularization and vitreoretinal surgery for myopic traction maculopathy. Myopia, especially childhood myopia, has been increasing rapidly in the world. In parallel with an increase in myopia, the prevalence of high myopia has also been increasing. However, it remains unclear whether or not pathologic myopia will increase in parallel with an increase of myopia itself. In addition, it has remained unclear whether genes responsible for pathologic myopia are the same as those for myopia in general, or whether pathologic myopia is genetically different from other myopia.
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http://dx.doi.org/10.1167/iovs.62.5.5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083114PMC
April 2021

IMI Prevention of Myopia and Its Progression.

Invest Ophthalmol Vis Sci 2021 Apr;62(5)

School of Optometry, Aston University, Birmingham, United Kingdom.

The prevalence of myopia has markedly increased in East and Southeast Asia, and pathologic consequences of myopia, including myopic maculopathy and high myopia-associated optic neuropathy, are now some of the most common causes of irreversible blindness. Hence, strategies are warranted to reduce the prevalence of myopia and the progression to high myopia because this is the main modifiable risk factor for pathologic myopia. On the basis of published population-based and interventional studies, an important strategy to reduce the development of myopia is encouraging schoolchildren to spend more time outdoors. As compared with other measures, spending more time outdoors is the safest strategy and aligns with other existing health initiatives, such as obesity prevention, by promoting a healthier lifestyle for children and adolescents. Useful clinical measures to reduce or slow the progression of myopia include the daily application of low-dose atropine eye drops, in concentrations ranging between 0.01% and 0.05%, despite the side effects of a slightly reduced amplitude of accommodation, slight mydriasis, and risk of an allergic reaction; multifocal spectacle design; contact lenses that have power profiles that produce peripheral myopic defocus; and orthokeratology using corneal gas-permeable contact lenses that are designed to flatten the central cornea, leading to midperipheral steeping and peripheral myopic defocus, during overnight wear to eliminate daytime myopia. The risk-to-benefit ratio needs to be weighed up for the individual on the basis of their age, health, and lifestyle. The measures listed above are not mutually exclusive and are beginning to be examined in combination.
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http://dx.doi.org/10.1167/iovs.62.5.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083117PMC
April 2021

IMI 2021 Yearly Digest.

Invest Ophthalmol Vis Sci 2021 Apr;62(5)

College of Optometry, University of Houston, Houston, Texas, United States.

Purpose: The International Myopia Institute (IMI) Yearly Digest highlights new research considered to be of importance since the publication of the first series of IMI white papers.

Methods: A literature search was conducted for articles on myopia between 2019 and mid-2020 to inform definitions and classifications, experimental models, genetics, interventions, clinical trials, and clinical management. Conference abstracts from key meetings in the same period were also considered.

Results: One thousand articles on myopia have been published between 2019 and mid-2020. Key advances include the use of the definition of premyopia in studies currently under way to test interventions in myopia, new definitions in the field of pathologic myopia, the role of new pharmacologic treatments in experimental models such as intraocular pressure-lowering latanoprost, a large meta-analysis of refractive error identifying 336 new genetic loci, new clinical interventions such as the defocus incorporated multisegment spectacles and combination therapy with low-dose atropine and orthokeratology (OK), normative standards in refractive error, the ethical dilemma of a placebo control group when myopia control treatments are established, reporting the physical metric of myopia reduction versus a percentage reduction, comparison of the risk of pediatric OK wear with risk of vision impairment in myopia, the justification of preventing myopic and axial length increase versus quality of life, and future vision loss.

Conclusions: Large amounts of research in myopia have been published since the IMI 2019 white papers were released. The yearly digest serves to highlight the latest research and advances in myopia.
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http://dx.doi.org/10.1167/iovs.62.5.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088231PMC
April 2021

Elongation of the disc-fovea distance and retinal vessel straightening in high myopia in a 10-year follow-up of the Beijing eye study.

Sci Rep 2021 Apr 26;11(1):9006. Epub 2021 Apr 26.

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China.

To assess changes in the disc-fovea distance (DFD) in highly myopic eyes in a 10-year population-based follow-up study. The case control study included all highly myopic eyes (myopic refractive error ≥ - 6.0 diopters or axial length ≥ 26.0 mm) and a randomized group of non-highly myopic eyes examined in the population-based Beijing Eye Study 2001 and 2011. Using fundus photographs and optical coherence tomographic images, we assessed changes in DFD, parapapillary gamma zone, angle kappa (angle between the temporal arterial arcades), and course of papillo-macular retinal vessels. The study included 89 highly myopic eyes and 86 non-highly myopic eyes. DFD elongation, gamma zone widening, angle kappa decrease and straightening of papillo-macular retinal vessels were detected more often (all P < 0.001) in the highly myopic group than in the non-highly myopic group (63/89 versus 9/86;75/89 versus 18/86;61/89 versus 9/86; and 58/89 versus 7/86,respectively). Gamma zone enlargement, angle kappa reduction and papillo-macular retinal vessel straightening were significantly (all P < 0.001) associated with DFD elongation. The length of macular Bruch's membrane on the disc-fovea line and the vertical distance between the temporal arterial arcade did not change during follow-up. DFD elongation (10-year incidence 70.8% in highly myopic eyes) was associated with gamma zone enlargement, while macular Bruch's membrane length remained unchanged. It supports the notion of a temporal shift of an otherwise stable posterior Bruch's membrane in axially elongated eyes. Straightening of the papillo-macular vessels with increasing gamma zone width suggests a coincident stretching of the papillo-macular retinal nerve fibers and inner limiting membrane.
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http://dx.doi.org/10.1038/s41598-021-88579-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076186PMC
April 2021

Deep Learning-Based Estimation of Axial Length and Subfoveal Choroidal Thickness From Color Fundus Photographs.

Front Cell Dev Biol 2021 9;9:653692. Epub 2021 Apr 9.

Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology and Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

This study aimed to develop an automated computer-based algorithm to estimate axial length and subfoveal choroidal thickness (SFCT) based on color fundus photographs. In the population-based Beijing Eye Study 2011, we took fundus photographs and measured SFCT by optical coherence tomography (OCT) and axial length by optical low-coherence reflectometry. Using 6394 color fundus images taken from 3468 participants, we trained and evaluated a deep-learning-based algorithm for estimation of axial length and SFCT. The algorithm had a mean absolute error (MAE) for estimating axial length and SFCT of 0.56 mm [95% confidence interval (CI): 0.53,0.61] and 49.20 μm (95% CI: 45.83,52.54), respectively. Estimated values and measured data showed coefficients of determination of = 0.59 (95% CI: 0.50,0.65) for axial length and = 0.62 (95% CI: 0.57,0.67) for SFCT. Bland-Altman plots revealed a mean difference in axial length and SFCT of -0.16 mm (95% CI: -1.60,1.27 mm) and of -4.40 μm (95% CI, -131.8,122.9 μm), respectively. For the estimation of axial length, heat map analysis showed that signals predominantly from overall of the macular region, the foveal region, and the extrafoveal region were used in the eyes with an axial length of < 22 mm, 22-26 mm, and > 26 mm, respectively. For the estimation of SFCT, the convolutional neural network (CNN) used mostly the central part of the macular region, the fovea or perifovea, independently of the SFCT. Our study shows that deep-learning-based algorithms may be helpful in estimating axial length and SFCT based on conventional color fundus images. They may be a further step in the semiautomatic assessment of the eye.
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http://dx.doi.org/10.3389/fcell.2021.653692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063031PMC
April 2021

The influence of axial myopia on optic disc characteristics of glaucoma eyes.

Sci Rep 2021 Apr 23;11(1):8854. Epub 2021 Apr 23.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0946, USA.

This study characterizes differences in glaucomatous eyes with and without high axial myopia using custom automated analysis of OCT images. 452 eyes of 277 glaucoma patients were stratified into non (n = 145 eyes), mild (n = 214 eyes), and high axial myopia (axial length (AL) > 26 mm, n = 93 eyes). Optic disc ovality index, tilt and rotation angle of Bruch´s membrane opening (BMO) and peripapillary choroidal thickness (PCT) were calculated using automated and deep learning strategies. High myopic optic discs were more oval and had larger BMO tilt than mild and non-myopic discs (both p < 0.001). Mean PCT was thinnest in high myopic eyes followed by mild and non-myopic eyes (p < 0.001). BMO rotation angle, global retinal nerve fiber layer (RNFL) thickness and BMO-minimum rim width (MRW) were similar among groups. Temporal RNFL was thicker and supranasal BMO-MRW was thinner in high myopic eyes. BMO tilt and PCT showed moderate and temporal RNFL and nasal BMO-MRW showed weak but significant associations with AL in multivariable analyses (all p < 0.05). Large BMO tilt angle and thin PCT are characteristics of highly myopic discs and were not associated with severity of glaucoma. Caution should be exercised when using sectoral BMO-MRW and RNFL thickness for glaucoma management decisions in myopic eyes.
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http://dx.doi.org/10.1038/s41598-021-88406-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065167PMC
April 2021

Retinal photograph-based deep learning algorithms for myopia and a blockchain platform to facilitate artificial intelligence medical research: a retrospective multicohort study.

Lancet Digit Health 2021 05;3(5):e317-e329

Peking Union Medical College Hospital, Beijing, China.

Background: By 2050, almost 5 billion people globally are projected to have myopia, of whom 20% are likely to have high myopia with clinically significant risk of sight-threatening complications such as myopic macular degeneration. These are diagnoses that typically require specialist assessment or measurement with multiple unconnected pieces of equipment. Artificial intelligence (AI) approaches might be effective for risk stratification and to identify individuals at highest risk of visual loss. However, unresolved challenges for AI medical studies remain, including paucity of transparency, auditability, and traceability.

Methods: In this retrospective multicohort study, we developed and tested retinal photograph-based deep learning algorithms for detection of myopic macular degeneration and high myopia, using a total of 226 686 retinal images. First we trained and internally validated the algorithms on datasets from Singapore, and then externally tested them on datasets from China, Taiwan, India, Russia, and the UK. We also compared the performance of the deep learning algorithms against six human experts in the grading of a randomly selected dataset of 400 images from the external datasets. As proof of concept, we used a blockchain-based AI platform to demonstrate the real-world application of secure data transfer, model transfer, and model testing across three sites in Singapore and China.

Findings: The deep learning algorithms showed robust diagnostic performance with areas under the receiver operating characteristic curves [AUC] of 0·969 (95% CI 0·959-0·977) or higher for myopic macular degeneration and 0·913 (0·906-0·920) or higher for high myopia across the external testing datasets with available data. In the randomly selected dataset, the deep learning algorithms outperformed all six expert graders in detection of each condition (AUC of 0·978 [0·957-0·994] for myopic macular degeneration and 0·973 [0·941-0·995] for high myopia). We also successfully used blockchain technology for data transfer, model transfer, and model testing between sites and across two countries.

Interpretation: Deep learning algorithms can be effective tools for risk stratification and screening of myopic macular degeneration and high myopia among the large global population with myopia. The blockchain platform developed here could potentially serve as a trusted platform for performance testing of future AI models in medicine.

Funding: None.
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http://dx.doi.org/10.1016/S2589-7500(21)00055-8DOI Listing
May 2021

Peaks of circumpapillary retinal nerve fibre layer and associations in healthy eyes: the Beijing Eye Study 2011.

Br J Ophthalmol 2021 Apr 15. Epub 2021 Apr 15.

Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.

Aims: To investigate the distribution and associations of the circumpapillary retinal nerve fibre layer thickness (RNFLT) profile, characterised as peak height and peak position, in healthy eyes.

Methods: 667 healthy participants (294 male) were randomly selected from the Beijing Eye Study 2011. RNFLT was measured at 768 points at 3.4 mm circumpapillary position using spectral-domain optical coherence tomography (OCT). The location and height of the superior temporally peak (Peak), superior nasal peak (Peak) and inferior temporal peak (Peak) were assessed.

Results: The RNFLT was thickest at Peak (194±25 µm; location: 288±12°), followed by Peak (182±25 µm; 73±10°) and Peak (125±23 µm; 135°±13°). In multivariable analysis, peak RNFLT decreased with longer axial length (p<0.001; correlation coefficient beta: -0.18 to -0.15; all peaks), older age (all p<0.01, beta: -0.10; Peak and Peak), female gender (p=0.026, beta: -0.09; Peak), and larger parapapillary gamma zone and beta zone width (p≤0.004, beta: -0.16 to-0.11; Peak). The temporal peaks were located more closely to the horizontal line in women (p≤0.020, beta: 0.09-0.11) and with longer axial length (p<0.001, beta: 0.27-0.31), while they were located more inferiorly in eyes with larger Bruch's membrane openings (BMOs) (p≤0.01, beta:0.10~0.11).

Conclusions: Peak RNFLT decreased by 0.34 µm for each increase of year in age (Peak and Peak), by 3.2-3.5 µm for each 1 mm increase in axial length (all three peaks), and was 4.5 µm thinner in women than in men. The position of temporal peaks depended on gender, axial length and BMO diameter. These associations should be taken into count in OCT-based RNFLT assessment for disease finding, especially in glaucoma evaluation.
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http://dx.doi.org/10.1136/bjophthalmol-2021-318869DOI Listing
April 2021

Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia.

JAMA Ophthalmol 2021 Apr 8. Epub 2021 Apr 8.

Cardiff University School of Optometry and Vision Sciences, Cardiff, United Kingdom.

Importance: Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets.

Objective: To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia.

Design, Setting, And Participants: This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020.

Exposures: Four refractive error groups were defined: HM, -6.00 diopters (D) or less; LM, -3.00 to -1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry.

Main Outcomes And Measures: Odds ratios (ORs) of polygenic risk scores in replication samples.

Results: A total of 51 841 unrelated individuals of European ancestry and 2165 unrelated individuals of Asian ancestry were assigned to a specific refractive error group and included in our analyses. Polygenic risk scores derived from all 4 GWAS analyses were predictive of all categories of refractive error in both European and Asian replication samples. For example, the polygenic risk score derived from the HM vs emmetropia GWAS was predictive in the European sample of HM vs emmetropia (OR, 1.58; 95% CI, 1.41-1.77; P = 1.54 × 10-15) as well as LM vs emmetropia (OR, 1.15; 95% CI, 1.07-1.23; P = 8.14 × 10-5), hyperopia vs emmetropia (OR, 0.83; 95% CI, 0.77-0.89; P = 4.18 × 10-7), and LM vs hyperopia (OR, 1.45; 95% CI, 1.33-1.59; P = 1.43 × 10-16).

Conclusions And Relevance: Genetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033508PMC
April 2021

Making the Impossible Possible - Insights From the Eye Hospital of the Wenzhou Medical University.

Asia Pac J Ophthalmol (Phila) 2021 Mar 23;10(2):133-134. Epub 2021 Mar 23.

C-MER (Shenzhen) Dennis Lam Eye Hospital, Shenzhen, Guangdong, China.

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http://dx.doi.org/10.1097/APO.0000000000000387DOI Listing
March 2021

Peripheral Monocyte Count and Age-Related Macular Degeneration. The Tongren Health Care Study.

Am J Ophthalmol 2021 Jul 15;227:143-153. Epub 2021 Mar 15.

From the Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China (C.C.X., Y.X.W., J.B.J.); Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Mannheim, Germany (J.B.J.); Institute of Clinical and Scientific Ophthalmology and Acupuncture Jonas & Panda, Heidelberg, Germany; Institute of Molecular and Clinical Ophthalmology, Basel, Switzerland (J.B.J.).

Purpose: To assess potential associations between the prevalence of age-related macular degeneration (AMD) and systemic parameters in a Chinese population.

Design: Cross-sectional study.

Methods: The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital from 2017 to 2019. Detailed medical examinations and ophthalmic examinations were applied, including fundus photography. AMD was evaluated according to the Beckman Initiative guidelines.

Results: The study included 7,719 participants (mean age: 60.5 ± 8.1 years; range: 50-97 years). The prevalence of any, early, intermediate, and late AMD was 1,607 of 7,719 (20.8%; 95% confidence interval [CI]: 20.1%, 21.9%), 832 of 7,719 (10.8%; 95% CI: 10.1%, 11.5%), 733 of 7,719 (9.5%; 95% CI: 8.9%, 10.2%), and 42 of 7,719 (0.50%; 95% CI: 0.40%, 0.70%), respectively. In multivariate analysis, the prevalence of any AMD increased with higher blood monocyte count (odds ratio [OR]:3.49; 95% CI: 2.26, 5.38; P < .001), after adjusting for older age (OR: 1.06; 95% CI: 1.05, 1.07; P < .001), higher serum concentration of calcium (OR: 2.52; 95% CI: 1.32, 4.84; P = .005), high-density lipoproteins (OR: 1.39; 95% CI: 1.19, 1.61; P < .001), and lower lipoprotein a (OR: 0.99; 95% CI: 0.98, 0.99; P = .02). Similar findings were obtained for the prevalence of intermediate and late AMD combined. The association between higher monocyte count and higher AMD prevalence showed the highest odds ratio for the age group of 50-59 years (any AMD: OR: 4.35, P < .001; intermediate and late AMD: OR: 6.14, P < .001). Individuals with a monocyte count of ≥0.5 × 10/L as compared to participants with a monocyte of 0.1-0.4 × 10/L had a 1.45-fold increased risk for any AMD (OR: 1.45; 95% CI: 1.27, 1.64; P < .001) and 1.58 fold increase risk for intermediate/late AMD (OR: 1.58; 95% CI: 1.33, 1.87; P < .001).

Conclusion: A higher prevalence of early AMD, intermediate AMD, late AMD, and any AMD was associated with a higher peripheral monocyte count. In agreement with previous studies, the observation suggests monocytes playing a role in the pathogenesis of AMD.
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http://dx.doi.org/10.1016/j.ajo.2021.03.010DOI Listing
July 2021

Referral for disease-related visual impairment using retinal photograph-based deep learning: a proof-of-concept, model development study.

Lancet Digit Health 2021 01;3(1):e29-e40

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Duke-NUS Medical School, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background: In current approaches to vision screening in the community, a simple and efficient process is needed to identify individuals who should be referred to tertiary eye care centres for vision loss related to eye diseases. The emergence of deep learning technology offers new opportunities to revolutionise this clinical referral pathway. We aimed to assess the performance of a newly developed deep learning algorithm for detection of disease-related visual impairment.

Methods: In this proof-of-concept study, using retinal fundus images from 15 175 eyes with complete data related to best-corrected visual acuity or pinhole visual acuity from the Singapore Epidemiology of Eye Diseases Study, we first developed a single-modality deep learning algorithm based on retinal photographs alone for detection of any disease-related visual impairment (defined as eyes from patients with major eye diseases and best-corrected visual acuity of <20/40), and moderate or worse disease-related visual impairment (eyes with disease and best-corrected visual acuity of <20/60). After development of the algorithm, we tested it internally, using a new set of 3803 eyes from the Singapore Epidemiology of Eye Diseases Study. We then tested it externally using three population-based studies (the Beijing Eye study [6239 eyes], Central India Eye and Medical study [6526 eyes], and Blue Mountains Eye Study [2002 eyes]), and two clinical studies (the Chinese University of Hong Kong's Sight Threatening Diabetic Retinopathy study [971 eyes] and the Outram Polyclinic Study [1225 eyes]). The algorithm's performance in each dataset was assessed on the basis of the area under the receiver operating characteristic curve (AUC).

Findings: In the internal test dataset, the AUC for detection of any disease-related visual impairment was 94·2% (95% CI 93·0-95·3; sensitivity 90·7% [87·0-93·6]; specificity 86·8% [85·6-87·9]). The AUC for moderate or worse disease-related visual impairment was 93·9% (95% CI 92·2-95·6; sensitivity 94·6% [89·6-97·6]; specificity 81·3% [80·0-82·5]). Across the five external test datasets (16 993 eyes), the algorithm achieved AUCs ranging between 86·6% (83·4-89·7; sensitivity 87·5% [80·7-92·5]; specificity 70·0% [66·7-73·1]) and 93·6% (92·4-94·8; sensitivity 87·8% [84·1-90·9]; specificity 87·1% [86·2-88·0]) for any disease-related visual impairment, and the AUCs for moderate or worse disease-related visual impairment ranged between 85·9% (81·8-90·1; sensitivity 84·7% [73·0-92·8]; specificity 74·4% [71·4-77·2]) and 93·5% (91·7-95·3; sensitivity 90·3% [84·2-94·6]; specificity 84·2% [83·2-85·1]).

Interpretation: This proof-of-concept study shows the potential of a single-modality, function-focused tool in identifying visual impairment related to major eye diseases, providing more timely and pinpointed referral of patients with disease-related visual impairment from the community to tertiary eye hospitals.

Funding: National Medical Research Council, Singapore.
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http://dx.doi.org/10.1016/S2589-7500(20)30271-5DOI Listing
January 2021

Compatibility of intravitreally applied epidermal growth factor and amphiregulin.

Int Ophthalmol 2021 Jun 13;41(6):2053-2063. Epub 2021 Mar 13.

Department of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Universitäts-Augenklinik, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Introduction: To examine the compatibility of intravitreally injected epidermal growth factor (EGF) and amphiregulin as EGF family member.

Methods: Four rabbits (age: 4 months; body weight: 2.5 kg) received three intravitreal injections of EGF (100 ng) uniocularly in monthly intervals and underwent ocular photography, tonometry, biometry, and optical coherence tomography. After sacrificing the rabbits, the globes were histomorphometrically examined. In a second study part, eyes of 22 guinea pigs (age: 2-3 weeks) received two intravitreal administrations of amphiregulin (10 ng) or phosphate buffered solution (PBS) in 10-day interval, or were left untouched. Ten days after the second injection, the guinea pigs were sacrificed, the enucleated eyes underwent histological and immune-histological examinations.

Results: The rabbit eyes with EGF injections versus the contralateral untouched eyes did not show significant differences in intraocular pressure (7.5 ± 2.4 mmHg vs. 6.8 ± 2.2 mmHg; P = 0.66), retinal thickness (158 ± 5 µm vs. 158 ± 3 µm; P = 1.0), cell counts in the retinal ganglion cell layer (3.3 ± 1.7 cells/150 µm vs. 3.0 ± 1.4 cells/150 µm; P = 0.83), inner nuclear layer (46.4 ± 23.2 cells/150 µm vs. 39.6 ± 6.4 cells/150 µm; P = 0.61), and outer nuclear layer (215 ± 108 cells/150 µm vs. 202 ± 47 cells/150 µm; P = 0.83), or any apoptotic retinal cells. The guinea pig eyes injected with amphiregulin versus eyes with PBS injections did not differ (P = 0.72) in the degree of microglial activation, and both groups did not differ from untouched eyes in number of apoptotic retinal cells and retinal gliosis.

Conclusions: Intravitreal applications of EGF (100 ng) in rabbits nor intravitreal applications of amphiregulin (10 ng) in guinea pigs led to intraocular specific inflammation or any observed intraocular destructive effect. The findings support the notion of a compatibility of intraocular applied EGF and amphiregulin.
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http://dx.doi.org/10.1007/s10792-021-01761-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172503PMC
June 2021

Update and guidance on management of myopia. European Society of Ophthalmology in cooperation with International Myopia Institute.

Eur J Ophthalmol 2021 Mar 5:1120672121998960. Epub 2021 Mar 5.

School of Optometry and Vision Science, University of New South Wales, Sydney, Australia.

The prevalence of myopia is increasing extensively worldwide. The number of people with myopia in 2020 is predicted to be 2.6 billion globally, which is expected to rise up to 4.9 billion by 2050, unless preventive actions and interventions are taken. The number of individuals with high myopia is also increasing substantially and pathological myopia is predicted to become the most common cause of irreversible vision impairment and blindness worldwide and also in Europe. These prevalence estimates indicate the importance of reducing the burden of myopia by means of myopia control interventions to prevent myopia onset and to slow down myopia progression. Due to the urgency of the situation, the European Society of Ophthalmology decided to publish this update of the current information and guidance on management of myopia. The pathogenesis and genetics of myopia are also summarized and epidemiology, risk factors, preventive and treatment options are discussed in details.
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http://dx.doi.org/10.1177/1120672121998960DOI Listing
March 2021

Association between body mass index and diabetic retinopathy in Asians: the Asian Eye Epidemiology Consortium (AEEC) study.

Br J Ophthalmol 2021 Feb 23. Epub 2021 Feb 23.

Beijing Institute of Ophthalmology, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Background/aims: Obesity is a well-known risk factor for diabetes, but its association with diabetic retinopathy (DR) is inconclusive, in particular in Asians. We aimed to assess whether body mass index (BMI) is associated with the presence and severity of DR in Asian populations with diabetes.

Methods: Pooled analysis of individual-level cross-sectional data from 10 010 adults with diabetes who participated in 12 population-based studies conducted in China, India, Japan, Russia (Asian), Singapore and South Korea that were part of the Asian Eye Epidemiology Consortium (AEEC). BMI was calculated as weight in kilograms divided by height in square metres and categorised into normal (<25 kg/m, reference), overweight (25-29.9 kg/m) and obese (≥30 kg/m). Any-DR (n=1669) and vision-threatening DR (VTDR, n=489) were assessed from digital retinal photographs and graded according to standard protocols. Each study was analysed separately using multivariable logistic regression models adjusted for age, sex, haemoglobin A1c%, systolic blood pressure and diabetes duration, and the estimated odds ratios (ORs) and 95% confidence interval (CIs) from all studies were then combined using random-effects models.

Results: In multivariable models, obesity showed a significant inverse association with any-DR (pooled OR (95% CI) =0.74 (0.59 to 0.91)) and VTDR (0.75 (0.60 to 0.93)). Similarly, in continuous analysis, BMI showed a significant inverse association with both any-DR (0.93 (0.87 to 0.99)) and VTDR (0.79 (0.68 to 0.92) per SD increase). Overweight did not show a significant association with any-DR.

Conclusions: Among Asian adults with diabetes, both BMI and obesity showed an inverse association with DR. These findings warrant confirmation in further longitudinal studies.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318208DOI Listing
February 2021

Blood pressure control and progression of arteriosclerosis in hypertension.

J Hypertens 2021 Jun;39(6):1221-1229

Department of Cardiology, Kailuan General Hospital, North China University of Science and Technology.

Objective: Using the brachial--ankle pulse wave velocity (baPWV) as a biomarker for arteriosclerosis, we studied the effect of blood pressure (BP) and BP control on arteriosclerosis progression.

Methods And Results: The community-based longitudinal Kailuan study included 6552 participants [4938 (75.37%) men] with a mean follow-up of 4.62 ± 2.21 years. Hypertension was defined based on the Joint National Committee (JNC7) criteria and the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines. All study participants had hypertension and were stratified as follows according to BP at baseline and follow-up: the normal--normal [normal BP (under therapy) at baseline and final follow-up], normal--hypertensive, hypertensive--normal, and hypertensive--hypertensive groups. Using the JNC7-based hypertension definition, the annual baPWV increase was the highest (P < 0.001) in the hypertensive--hypertensive group [17.32 cm/s; 95% confidence interval [CI]:9.7--24.9], followed by the normal--hypertensive group (14.44 cm/s; 95% CI:5.5--23.4), and the hypertensive--normal group (0.88 cm/s; 95% CI: -7.84 to 9.60), with the normal--normal group as the reference group in a multivariable model. The model additionally included parameters, such as age, baseline baPWV, heart rate, BMI, serum glucose concentration, prevalence of antihypertensive treatment and alcohol consumption, heart rate, and estimated glomerular filtration rate. Applying the ACC/AHA guidelines and the same multivariable model, the annual baPWV increase was the highest (P < 0.001) in the hypertensive--hypertensive group (43.54 cm/s; 95% CI: 22.54--64.55), followed by the normal--hypertensive group (34.01 cm/s; 95% CI: 10.39--57.62) and the hypertensive--normal group (24.12 cm/s; 95% CI: 1.24--47.00).

Conclusion: Lower BP and medical reduction in increased BP were associated with a reduction in the baPWV increase and may delay the progression of arteriosclerosis in hypertensive patients.
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http://dx.doi.org/10.1097/HJH.0000000000002758DOI Listing
June 2021

Location of Parapapillary Gamma Zone and Vertical Fovea Location. The Beijing Eye Study 2011.

Invest Ophthalmol Vis Sci 2021 01;62(1):18

Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Purpose: To assess the spatial relationship between the locations of the parapapillary gamma zone and the fovea.

Methods: In a non-glaucomatous subgroup of the population-based Beijing Eye Study population, we measured the mean angle between the optic disc-fovea line and the horizontal (disc-fovea angle), the vertical distance of the fovea from the horizontal through the optic disc center (fovea vertical distance), and the location and width of the widest part of parapapillary gamma zone.

Results: The study included 203 individuals (203 eyes; mean axial length, 24.4 ± 1.5 mm; range, 22.03-28.87 mm). The widest gamma zone part was located most often temporal horizontally (51.7%), then inferiorly (43.8%), superiorly (2.5%), and nasally (2.0%). The disc-fovea angle (mean, 7.50° ± 4.00°; range, -6.30° to -23.25°) was significantly higher (P = 0.003; i.e., fovea located more inferiorly) in eyes with the widest gamma zone inferiorly (8.46° ± 4.37°) than in eyes with the widest gamma zone temporally (6.71° ± 3.46°) and in eyes with the widest gamma zone temporally, superiorly, or nasally combined (6.75° ± 3.53°; P = 0.003). The fovea vertical distance (mean, 0.65 ± 0.33 mm; range, -0.20 to 1.67 mm) was longer (P = 0.001; i.e., fovea located more inferiorly) in eyes with the widest gamma zone inferiorly (0.73 ± 0.33 mm) than in eyes with the widest gamma zone temporally (0.58 ± 0.30 mm) and in eyes with a temporal, superior, or nasal gamma zone combined (0.58 ± 0.31 mm; P = 0.001). The fovea vertical distance increased (multivariate analysis) with the widest gamma zone location inferiorly (β = 0.25; P = 0.001) and wider width of the gamma zone (β = 0.19; P = 0.01).

Conclusions: An inferior fovea location is associated with a wider inferior gamma zone and vice versa, supporting the notion of an inferior shifting of Bruch's membrane as the cause for an inferior gamma zone.
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http://dx.doi.org/10.1167/iovs.62.1.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817880PMC
January 2021

Estimated pulse wave velocity and cardiovascular events in Chinese.

Int J Cardiol Hypertens 2020 Dec 11;7:100063. Epub 2020 Nov 11.

Institute of Clinical and Scientific Ophthalmology and Acupuncture Jonas & Panda, Heidelberg, Germany.

The estimated pulse-wave velocity (ePWV) as measure for arterial wall stiffness is associated with an increased risk of cardiovascular disease (CVDs) and all-cause death in Western populations. We investigated the association between ePWV and the incidence of CVDs (myocardial infarction, cerebral infarction, cerebral hemorrhage) and all-cause death in Chinese. The community-based longitudinal Kailuan Study included 98,348 participants undergoing biennial clinical examinations. During a mean follow-up of 10.32 ± 2.14 years, 6967 CVD events (myocardial infarction, n = 1610; cerebral infarction, n = 4634; cerebral hemorrhage, n = 1071) and 9780 all-cause deaths occurred. Stratified by age, sex and presence of cardiovascular risk factors, the incidence of CVDs and all-cause death were higher ( < 0.01) in individuals with ePWV values ≥ 10 m/s than in those with ePWV values < 10 m/s. After adjusting for age, age squared and other conventional cardiovascular risk factors, an ePWV value of ≥10 m/s or each ePWV increase by 1 m/s increased ( < 0.01) the risk for CVDs by 32% (Hazard ratio (HR):1.32; 95% confidence interval (CI):1.23-1.42) and 22% (HR:1.22; 95%CI:1.18-1.27), respectively, and increased the risk for all-cause death significantly ( < 0.01) by 28% (HR:1.28; 95%CI:1.20-1.37) and 10% (HR:1.10; 95%CI:1.07-1.13), respectively. The mean brachial-ankle PWV, measured in 43,208 individuals, was 15.30 ± 3.51 cm/s, with a mean difference of 6.45 m/s (95% limits of agreement:1.24-11.7) to the ePWV. Independently of cardiovascular risk factors, ePWV was associated with CVDs and all-cause mortality in Chinese.
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http://dx.doi.org/10.1016/j.ijchy.2020.100063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803041PMC
December 2020

MicroRNA-93/STAT3 signalling pathway mediates retinal microglial activation and protects retinal ganglion cells in an acute ocular hypertension model.

Cell Death Dis 2021 01 4;12(1):41. Epub 2021 Jan 4.

Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, 510060, China.

Glaucoma is a common neurodegenerative disease and a leading cause of irreversible blindness worldwide. Retinal microglia-mediated neuroinflammation is involved in the process of optic nerve damage, but the mechanisms driving this microglial activation remain mostly elusive. Previous investigations reported that microRNAs are associated with the retinal microglial reaction and neural apoptosis. In the present study, we found that microRNA-93-5p (miR-93) played a key role in the reaction of retinal microglial cells in vivo and in vitro. The miR-93 level was significantly reduced in the retinae of rat acute ocular hypertension (AOH) models, which were accompanied by retinal microglial activation, overproduction of inflammatory cytokines, and subsequent retinal ganglion cells (RGCs) death, versus the retinae of controls. The induction of miR-93 overexpression significantly reduced microglial proliferation, migration and cytokine release, inhibited the expression of the target gene signal transducer and activator of transcription 3 (STAT3) and p-STAT3, and was associated with a reduced loss of RGCs. Treatment with a STAT3 inhibitor also decreased retinal microglial activation after AOH injury. Taken together, these results suggest that the miR-93/STAT3 pathway is directly related to the downregulation of retinal microglia-mediated neuro-inflammation and showed a neuroprotective effect. Regulating microglial activation through miR-93 may serve as a target for neuroprotective therapy in pathological ocular hypertension.
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http://dx.doi.org/10.1038/s41419-020-03337-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791106PMC
January 2021

Natural history of glaucomatous optic neuropathy in highly myopic Chinese: study protocol for a registry cohort study.

BMJ Open 2020 12 30;10(12):e039183. Epub 2020 Dec 30.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

Introduction: Myopic maculopathy and glaucoma belong to the most common causes of irreversible blindness worldwide and, having an ocular axial elongation as one of their main risk factors, can occur together. The detection of glaucomatous optic neuropathy (GON) in highly myopic eyes is clinically and technically difficult, and there is no information available, neither about the natural course of GON or about the course of GON under intraocular pressure-lowering therapy. We therefore designed this study to explore the natural course of GON in highly myopic eyes.

Methods And Analysis: In this single-centred longitudinal registry cohort study, 813 highly myopic individuals will be recruited and undergo detailed ophthalmic examinations. High myopia is defined by a myopic refractive error of ≥-6 D or an axial length of ≥26.5 mm. GON is defined by a glaucomatous appearance of the optic nerve head or glaucomatous visual field (VF) defects. GON progression is defined by either change of the optic disc or VF.

Ethics And Dissemination: Ethical approval has been obtained from the ethical committee of the Zhongshan Ophthalmic Center (ZOC), Sun Yat-sen University, China (ID: 2019KYPJ079). All the participants are required to provide informed consents. Results will be disseminated through scientific meetings and published in peer-reviewed journals. The data will be deposited at the clinical research centre in ZOC using electronic data capture system, and a copy of paper files will also be kept. Only members of the project team will have access to these data.

Trial Registration Number: NCT04302220.
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http://dx.doi.org/10.1136/bmjopen-2020-039183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780524PMC
December 2020