Ophthalmology (Eye & Ear Hospital) - Research Publications
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ItemUse of antihypertensive medications and the risk of glaucoma onset: Findings from the 45 and Up Study(WILEY, 2022-08)BACKGROUND: Abnormal blood pressure is a potential risk factor for glaucoma. However, the role of antihypertensive medications on glaucoma pathogenesis is controversial. This study aims to investigate the association between the use of antihypertensive medications and glaucoma onset. METHODS: This nested case-control study, based on a large-scale longitudinal cohort in Australia, retrieved participants' claims records on drugs and Medicare services from national health databases. Participants with three or more claim records of anti-glaucoma medications from 2009 to 2016 were classified as glaucoma patients; those with none were classified as controls. Claim records of antihypertensive medications were identified within the 5 years before glaucoma onset and contemporary periods in matched controls without glaucoma. The association between the use of antihypertensive medications and glaucoma onset was assessed by multivariable logistic regression models. RESULTS: A total of 6748 cases and 13 496 controls were analysed. Compared with controls, the proportion of users of antihypertensive medications was slightly higher in glaucoma patients (46.9% vs. 46.0%, p > 0.05). After adjustments for demographics, health-related factors and medical history, the association between the use of antihypertensive medications and glaucoma onset was nonsignificant (OR 0.95, 95% CI = 0.89-1.02). As for specific subtypes, only beta-blocking agents (BBA) (OR 0.82, 95% CI = 0.75-0.90) and diuretics (OR 0.85, 95% CI = 0.77-0.95) were significantly associated with reduced risks of glaucoma onset. CONCLUSIONS: This study indicated that the use of antihypertensive medications was not associated with glaucoma onset. Decreased risks of glaucoma onset in users of BBA and diuretics require further validation.
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ItemLongitudinal Changes in Lens Thickness and Lens Power Among Persistent Non-Myopic and Myopic Children.(The Association for Research in Vision and Ophthalmology, 2022-09-15)PURPOSE: To assess the longitudinal changes in crystalline lens in persistent non-myopic and myopic children. METHODS: Four cohorts of children were recruited from Guangzhou, China, from first year of kindergarten (G0, n = 1129), first year of primary school (G1, n = 1324), fourth year of primary school (G4, n = 1854), and first year of junior high school (G7, n = 867) in 2018 and followed up annually for 2 years. All children received cycloplegic autorefraction and ocular biometry measurement. Children were classified into categories of persistent non-myopia (PNM; spherical equivalent refraction [SER] ≥-0.5 diopter [D] at baseline and during follow-up), persistent myopia (PM; SER <-0.5 D at baseline and during follow-up), or newly developed myopia (NDM: SER ≥-0.5 D at baseline and <-0.5 D during follow-up). RESULTS: The mean (SD) age was 3.69 (0.34) years for children in G0, 6.79 (0.35) years in G1, 9.52 (0.42) years in G4, and 12.56 (0.38) years in G7. A LOWESS plot showed a three-stage pattern of change in lens thickness (LT) in PNM children including a rapid decrease from 3 to 7 years of age and a slower decrease from 7 to 11 years, followed by an increase thereafter. Similar trends were observed in the PM and NDM groups, although there was less change in LT. In contrast, lens power (LP) decreased consistently in all cohorts during the follow-up. No significant changes in LT or LP were observed around myopia onset. CONCLUSIONS: The lens showed a three-stage pattern of change in LT, whereas there was continuous loss of LP in children ages 3 to 15 years.
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ItemSustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study(WILEY, 2022-12)BACKGROUND: To evaluate the long-term efficacy and safety of continued repeated low-level red-light (RLRL) therapy on myopia control over 2 years, and the potential rebound effect after treatment cessation. METHODS: The Chinese myopic children who originally completed the one-year randomised controlled trial were enrolled. Children continued RLRL-therapy were defined as RLRL-RLRL group, while those who stopped and switched to single-vision spectacle (SVS) in the second year were RLRL-SVS group. Likewise, those who continued to merely wear SVS or received additional RLRL-therapy were SVS-SVS and SVS-RLRL groups, respectively. RLRL-therapy was provided by an at-home desktop light device emitting red-light of 650 nm and was administered for 3 min at a time, twice a day and 5 days per week. Changes in axial length (AL) and cycloplegic spherical equivalence refraction (SER) were measured. RESULTS: Among the 199 children who were eligible, 138 (69.3%) children attended the examination and 114 (57.3%) were analysed (SVS-SVS: n = 41; SVS-RLRL: n = 10; RLRL-SVS: n = 52; RLRL-RLRL: n = 11). The baseline characteristics were balanced among four groups. In the second year, the mean changes in AL were 0.28 ± 0.14 mm, 0.05 ± 0.24 mm, 0.42 ± 0.20 mm and 0.12 ± 0.16 mm in SVS-SVS, SVS-RLRL, RLRL-SVS and RLRL-RLRL group, respectively (p < 0.001). The respective mean SER changes were -0.54 ± 0.39D, -0.09 ± 0.55D, -0.91 ± 0.48D, and -0.20 ± 0.56D (p < 0.001). Over the 2-year period, axial elongation and SER progression were smallest in RLRL-RLRL group (AL: 0.16 ± 0.37 mm; SER: -0.31 ± 0.79D), followed by SVS-RLRL (AL: 0.44 ± 0.37 mm; SER: -0.96 ± 0.70D), RLRL-SVS (AL: 0.50 ± 0.28 mm; SER: -1.07 ± 0.69D) and SVS-SVS group (AL: 0.64 ± 0.29 mm; SER: -1.24 ± 0.63D). No self-reported adverse events, functional or structural damages were noted. CONCLUSIONS: Continued RLRL therapy sustained promising efficacy and safety in slowing myopia progression over 2 years. A modest rebound effect was noted after treatment cessation.
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ItemRetinopathy of prematurity screening: A narrative review of current programs, teleophthalmology, and diagnostic support systems(WOLTERS KLUWER MEDKNOW PUBLICATIONS, 2022)PURPOSE: Neonatal care in middle-income countries has improved over the last decade, leading to a "third epidemic" of retinopathy of prematurity (ROP). Without concomitant improvements in ROP screening infrastructure, reduction of ROP-associated visual loss remains a challenge worldwide. The emergence of teleophthalmology screening programs and artificial intelligence (AI) technologies represents promising methods to address this growing unmet demand in ROP screening. An improved understanding of current ROP screening programs may inform the adoption of these novel technologies in ROP care. METHODS: A critical narrative review of the literature was carried out. Publications that were representative of established or emerging ROP screening programs in high-, middle-, and low-income countries were selected for review. Screening programs were reviewed for inclusion criteria, screening frequency and duration, modality, and published sensitivity and specificity. RESULTS: Screening inclusion criteria, including age and birth weight cutoffs, showed significant heterogeneity globally. Countries of similar income tend to have similar criteria. Three primary screening modalities including binocular indirect ophthalmoscopy (BIO), wide-field digital retinal imaging (WFDRI), and teleophthalmology were identified and reviewed. BIO has documented limitations in reduced interoperator agreement, scalability, and geographical access barriers, which are mitigated in part by WFDRI. Teleophthalmology screening may address limitations in ROP screening workforce distribution and training. Opportunities for AI technologies were identified in the context of these limitations, including interoperator reliability and possibilities for point-of-care diagnosis. CONCLUSION: Limitations in the current ROP screening include scalability, geographical access, and high screening burden with low treatment yield. These may be addressable through increased adoption of teleophthalmology and AI technologies. As the global incidence of ROP continues to increase, implementation of these novel modalities requires greater consideration.
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Item25-Gauge pars plana vitrectomy combined with air tamponade for primary rhegmatogenous retinal detachment.(SAGE Publishing, 2022-12)OBJECTIVE: This study was performed to evaluate the outcomes of 25-gauge (25-G) pars plana vitrectomy (PPV) with air tamponade for primary rhegmatogenous retinal detachment (RRD). METHODS: This retrospective consecutive case series included 126 eyes of 125 patients with primary RRD who underwent 25-G PPV with air tamponade. The patients were followed up for at least 6 months following surgery. The main outcome measures were the primary and final anatomical success rates and postoperative complications. RESULTS: The mean age of the 125 patients (80 men and 45 women) was 53.7 ± 10.0 years. The mean follow-up period was 8.3 ± 2.2 months (range, 6-18 months). Twenty-four eyes (19.0%) presented with high myopia, and 13 eyes (10.3%) were pseudophakic. Of the 126 eyes, 37 (29.4%) had inferior breaks, 2 (1.6%) had choroidal detachment, and 86 (68.3%) had macular detachment. The single- and final-operation success rates were 96.0% and 100%, respectively. Postoperative complications included macular hole formation in two eyes. During follow-up, secondary cataract surgery was performed in 27 (23.9%) of the 113 phakic eyes. CONCLUSION: 25-G PPV with air tamponade is effective and safe in treating selected patients with primary RRD with a high anatomical success rate.
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ItemRetinal age gap as a predictive biomarker of stroke risk(BMC, 2022-11-30)BACKGROUND: The aim of this study is to investigate the association of retinal age gap with the risk of incident stroke and its predictive value for incident stroke. METHODS: A total of 80,169 fundus images from 46,969 participants in the UK Biobank cohort met the image quality standard. A deep learning model was constructed based on 19,200 fundus images of 11,052 disease-free participants at baseline for age prediction. Retinal age gap (retinal age predicted based on the fundus image minus chronological age) was generated for the remaining 35,917 participants. Stroke events were determined by data linkage to hospital records on admissions and diagnoses, and national death registers, whichever occurred earliest. Cox proportional hazards regression models were used to estimate the effect of retinal age gap on risk of stroke. Logistic regression models were used to estimate the predictive value of retinal age and well-established risk factors in 10-year stroke risk. RESULTS: A total of 35,304 participants without history of stroke at baseline were included. During a median follow-up of 5.83 years, 282 (0.80%) participants had stroke events. In the fully adjusted model, each one-year increase in the retinal age gap was associated with a 4% increase in the risk of stroke (hazard ratio [HR] = 1.04, 95% confidence interval [CI]: 1.00-1.08, P = 0.029). Compared to participants with retinal age gap in the first quintile, participants with retinal age gap in the fifth quintile had significantly higher risks of stroke events (HR = 2.37, 95% CI: 1.37-4.10, P = 0.002). The predictive capability of retinal age alone was comparable to the well-established risk factor-based model (AUC=0.676 vs AUC=0.661, p=0.511). CONCLUSIONS: We found that retinal age gap was significantly associated with incident stroke, implying the potential of retinal age gap as a predictive biomarker of stroke risk.
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ItemShared genetic architecture between the two neurodegenerative diseases: Alzheimer's disease and glaucoma(FRONTIERS MEDIA SA, 2022-09-01)BACKGROUND: Considered as the representatives of neurodegenerative diseases, Alzheimer's disease (AD) and glaucoma are complex progressive neuropathies affected by both genetic and environmental risk factors and cause irreversible damages. Current research indicates that there are common features between AD and glaucoma in terms of epidemiology and pathophysiology. However, the understandings and explanations of their comorbidity and potential genetic overlaps are still limited and insufficient. METHOD: Genetic pleiotropy analysis was performed using large genome-wide association studies summary statistics of AD and glaucoma, with an independent cohort of glaucoma for replication. Conditional and conjunctional false discovery rate methods were applied to identify the shared loci. Biological function and network analysis, as well as the expression level analysis were performed to investigate the significance of the shared genes. RESULTS: A significant positive genetic correlation between AD and glaucoma was identified, indicating that there were significant polygenetic overlaps. Forty-nine shared loci were identified and mapped to 11 shared protein-coding genes. Functional genomic analyses of the shared genes indicate their modulation of critical physiological processes in human cells, including those occurring in the mitochondria, nucleus, and cellular membranes. Most of the shared genes indicated a potential modulation of metabolic processes in human cells and tissues. Furthermore, human protein-protein interaction network analyses revealed that some of the shared genes, especially MTCH2, NDUFS3, and PTPMT1, as well as SPI1 and MYBPC3, may function concordantly. The modulation of their expressions may be related to metabolic dysfunction and pathogenic processes. CONCLUSION: Our study identified a shared genetic architecture between AD and glaucoma, which may explain their shared features in epidemiology and pathophysiology. The potential involvement of these shared genes in molecular and cellular processes reflects the "inter-organ crosstalk" between AD and glaucoma. These results may serve as a genetic basis for the development of innovative and effective therapeutics for AD, glaucoma, and other neurodegenerative diseases.
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ItemMyopia Control Effect of Repeated Low- Level Red-Light Therapy in Chinese Children A Controlled Clinical Trial(ELSEVIER SCIENCE INC, 2023-02)PURPOSE: Repeated low-level red-light (RLRL) therapy is an emerging treatment for myopia control. Nevertheless, previous studies are limited by open-label design. Our study aimed to assess the efficacy and safety of RLRL therapy in controlling myopia progression compared to a sham device with only 10% of the original power. DESIGN: Randomized, double-blind, controlled clinical trial. PARTICIPANTS: A total of 112 Chinese children aged 7 to 12 years with myopia of at least -0.50 diopter (D), astigmatism of 1.50 D or less, and anisometropia of 1.50 D or less. METHODS: Participants were assigned randomly in a 1:1 ratio to the RLRL group or the sham device control group, following a schedule of 3 minutes per session, twice daily, with an interval between sessions of at least 4 hours. The RLRL therapy was provided by a desktop red-light therapy device and administered at home. The sham device was the same device but with only 10% of the original device's power. Cycloplegic refraction and axial length (AL) were measured at baseline and 6 months. MAIN OUTCOME MEASURES: Changes in cycloplegic spherical equivalence refraction (SER) and AL between 2 groups were compared using a generalized estimating equation (GEE). RESULTS: A total of 111 children were included in the analysis (n = 56 in the RLRL group and n = 55 in the sham device control group). The mean SER change over 6 months was 0.06 ± 0.30 D in the RLRL group and -0.11 ± 0.33 D in the sham device control group (P = 0.003), with respective mean increases in AL of 0.02 ± 0.11 mm and 0.13 ± 0.10 mm (P < 0.001). In the multivariate GEE models, children in the RLRL group showed less myopia progression and axial elongation than those in the sham device control group (SER: coefficient, 0.167 D; 95% confidence interval [CI], 0.050-0.283 D; P = 0.005; AL: coefficient, -0.101 mm; 95% CI, -0.139 to -0.062 mm; P < 0.001). No treatment-related adverse events were reported. CONCLUSIONS: In myopic children, RLRL therapy with 100% power significantly reduced myopia progression over 6 months compared with those treated with a sham device of 10% original power. The RLRL treatment was well tolerated without treatment-related adverse effects.
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ItemAchieving Inner Aqueous Drain in Glaucoma Secondary to Iridocorneal Endothelial Syndrome: One Year Results of Penetrating Canaloplasty.(Elsevier BV, 2022-11)PURPOSES: To report the efficacy of a bleb-independent penetrating canaloplasty in the management of glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE). DESIGN: Prospective, non-comparative clinical study. METHODS: Penetrating canaloplasty was performed on 35 eyes from 35 patients with GS-ICE and medically uncontrolled intraocular pressure (IOP) between January 2018 and April 2020. Patients were followed up at 1 week, months 1, 3, 6, 12 postoperatively, and semi-annually thereafter. The IOP, anti-glaucoma medication, and surgery-related complications were recorded. Surgical success was defined as IOP ≥ 5 mmHg and ≤ 21 mmHg without (complete success) or with/without (qualified success) IOP-lowering medication. RESULTS: A total of 29 eyes (82.9%) had 360° catheterization and successfully received penetrating canaloplasty. Of these eyes, 24 (82.8%) achieved qualified success and 22 (75.9%) achieved qualified success at 12 months after surgery. The mean IOP decreased from 39.5 ± 11.8 mmHg on 2.9 ± 1.0 medications before surgery to 16.6 ± 5.3 mmHg (P < .001) on 0.2 ± 0.6 medications (P < .001) at 12 months postoperatively, respectively. Hyphema (37.9%), transient hypotony (34.5%), and transient postoperative IOP elevation (≥ 30 mmHg, 17.9%) were the most commonly observed early complications at the 1 week and 1 month visits. From 1 month and beyond, all treated eyes showed no obvious bleb at the operation quadrant. CONCLUSIONS: Penetrating canaloplasty rescued the inner aqueous outflow in ICE eyes and demonstrated acceptable success in IOP control with few complications, providing a new option for the management of GS-ICE.
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ItemTime Outdoors in Reducing Myopia(ELSEVIER SCIENCE INC, 2022-11)PURPOSE: To evaluate the efficacy of time outdoors per school day over 2 years on myopia onset and shift. DESIGN: A prospective, cluster-randomized, examiner-masked, 3-arm trial. PARTICIPANTS: A total of 6295 students aged 6 to 9 years from 24 primary schools in Shanghai, China, stratified and randomized by school in a 1:1:1 ratio to control (n = 2037), test I (n = 2329), or test II (n = 1929) group. METHODS: An additional 40 or 80 minutes of outdoor time was allocated to each school day for test I and II groups. Children in the control group continued their habitual outdoor time. Objective monitoring of outdoor and indoor time and light intensity each day was measured with a wrist-worn wearable during the second-year follow-up. MAIN OUTCOME MEASURES: The 2-year cumulative incidence of myopia (defined as cycloplegic spherical equivalent [SE] of ≤-0.5 diopters [D] in the right eye) among the students without myopia at baseline and changes in SE and axial length (AL) after 2 years. RESULTS: The unadjusted 2-year cumulative incidence of myopia was 24.9%, 20.6%, and 23.8% for control, test I, and II groups, respectively. The adjusted incidence decreased by 16% (incidence risk ratio [IRR], 0.84; 95% confidence interval [CI], 0.72-0.99; P = 0.035) in test I and 11% (IRR = 0.89; 95% CI, 0.79-0.99; P = 0.041) in test II when compared with the control group. The test groups showed less myopic shift and axial elongation compared with the control group (test I: -0.84 D and 0.55 mm, test II: -0.91 D and 0.57 mm, control: -1.04 D and 0.65 mm). There was no significant difference in the adjusted incidence of myopia and myopic shift between the 2 test groups. The test groups had similar outdoor time and light intensity (test I: 127 ± 30 minutes/day and 3557 ± 970 lux/minute; test II: 127 ± 26 minutes/day and 3662 ± 803 lux/minute) but significantly more outdoor time and higher light intensity compared with the control group (106 ± 27 minutes/day and 2984 ± 806 lux/minute). Daily outdoor time of 120 to 150 minutes at 5000 lux/minutes or cumulative outdoor light intensity of 600 000 to 750 000 lux significantly reduced the IRR by 15%～ 24%. CONCLUSIONS: Increasing outdoor time reduced the risk of myopia onset and myopic shifts, especially in nonmyopic children. The protective effect of outdoor time was related to the duration of exposure and light intensity. The dose-response effect between test I and test II was not observed probably because of insufficient outdoor time achieved in the test groups, which suggests that proper monitoring on the compliance on outdoor intervention is critical if one wants to see the protective effect.