Association between Sight-Threatening Eye Diseases and Death by Suicide in South Korea: A Nationwide Population-based Cohort Study.

PURPOSE: Although associations between visual impairment (VI) and suicide are posited, specific risks across the sight-threatening eye disease (STED) spectrum remain to be assessed. We determined whether individuals with STED die more often by suicide than do other people and assessed the temporal associations. DESIGN: A nationwide, population-based cohort study. PARTICIPANTS: All persons aged 40 years or older in South Korea from 2010 to 2020. METHODS: Persons diagnosed with STEDs (i.e., glaucoma, exudative age-related macular degeneration [AMD], or diabetic retinopathy [DR]) were identified in the Korean National Health Insurance (NHI) service database. Both NHI health checkup records and the National Disability Registration were used for coexisting severe VI. Death by suicide was defined as diagnostic codes as recorded in the Korea National Statistical Office. Incidence rate ratios (IRRs) were estimated by quasi-Poisson regressions and adjusted for sociodemographics, comorbidity, psychiatric diagnoses, and VI. The temporal relationship between time since first STED diagnosis and suicide risk was determined by identifying patients with STED newly diagnosed during the period from 2010 to 2011. MAIN OUTCOME MEASURES: The IRR of death by suicide in people with STED relative to those without. RESULTS: Of the 2.8 million people (45% male) observed for 24 300 969 person-years, 13 205 died by suicide. Among them, 34% (n = 4514) had a STED diagnosis, for a suicide rate of 69 per 100 000 person-years (95% confidence interval [CI], 67-72), relative to 51 per 100 000 person-years (95% CI, 50-52) for non-STED individuals. People with STED had an adjusted IRR of 1.33 (95% CI, 1.26-1.41) relative to those without. The largest excess adjusted IRR of suicide mortality was that for DR (1.40, 95% CI, 1.29-1.52). For exudative AMD, the adjusted IRR was 1.20 (95% CI, 1.04-1.39), whereas for glaucoma, the corresponding value was 1.09 (95% CI, 1.02-1.17). With coexisting severe VI, the IRR for any STED was 1.49 (95% CI, 1.29-1.73). The highest suicide hazard ratio was between 3 and 6 months postdiagnosis (5.33; 95% CI, 4.59-6.20). CONCLUSIONS: In South Korea between 2010 and 2020, a higher suicide rate was evident among those with diagnosed STED than for persons not so diagnosed. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Placebo Effect and Its Determinants in Ocular Hypotensive Therapy: Meta-analysis and Multiple Meta-regression Analysis.

TOPIC: The placebo effect and its potential determinants in ocular hypotensive therapy. CLINICAL RELEVANCE: The placebo effect has been studied and documented within a wide clinical context. It remains unclear whether placebo is effective in glaucoma treatment or, if so, which factors are determinative of effect size (ES). METHODS: Randomized controlled trials (RCTs) of topical ocular hypotensive therapy for patients with open-angle glaucoma or ocular hypertension, conducted through June 2, 2022, were included. First, a perceived placebo effect was measured as the overall intraocular pressure (IOP) change from the baseline. It was evaluated in terms of the ES (mean difference between the baseline and the end point) and then was compared with the ES, as obtained from the untreated control participant to obtain a true placebo effect. The primary outcome was ES based on 4 weeks of treatment. Meta-analysis-based statistical pooling was performed where appropriate, and 95% confidence intervals (CIs) were used for comparison. Potential placebo effect determinants were scrutinized using a multiple meta-regression model (PROSPERO identifier, CRD42022348098). RESULTS: A total of 40 RCTs (7829 eyes) with 33 placebo groups (2055 eyes) along with 7 untreated groups (1184 eyes) were included. Among placebo-controlled trials, placebo was determined to be effective in lowering IOP (ES, -1.30 mmHg; 95% CI, -1.75 to -0.84 mmHg). Using NMA, the ES for placebo was -2.27 mmHg (95% CI, -3.52 to -1.01 mmHg) greater than ES for untreated control participants.. According to the multiple meta-regression model, the active treatment ES was a significant factor to predict the amount of placebo effect. Placebo additionally lowered IOP by -0.45 mmHg per -1 mmHg of active treatment effect. Add-on study design and larger sample size also were associated with greater amount of placebo effect. No publication bias was evident in either a funnel plot or the Begg and Mazumdar adjusted rank correlation test results (P = 0.24). DISCUSSION: This meta-analysis indicated that placebo is effective in lowering IOP and is superior to the effect observed for the untreated control participants. However, caution is required in interpreting the results because of the small number of untreated controlled trials and potential bias from the lack of direct comparison between the placebo and untreated arms. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy and Safety of 8 Atropine Concentrations for Myopia Control in Children: A Network Meta-Analysis.

TOPIC: Comparative efficacy and safety of different concentrations of atropine for myopia control. CLINICAL RELEVANCE: Atropine is known to be an effective intervention to delay myopia progression. Nonetheless, no well-supported evidence exists yet to rank the clinical outcomes of various concentrations of atropine. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on April 14, 2021. We selected studies involving atropine treatment of at least 1 year's duration for myopia control in children. We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) and compared 8 atropine concentrations (1% to 0.01%). We ranked the atropine concentrations for the corresponding outcomes by P score (estimate of probability of being best treatment). Our primary outcomes were mean annual changes in refraction (diopters/year) and axial length (AXL; millimeters/year). We extracted data on the proportion of eyes showing myopia progression and safety outcomes (photopic and mesopic pupil diameter, accommodation amplitude, and distance and near best-corrected visual acuity [BCVA]). RESULTS: Thirty pairwise comparisons from 16 RCTs (3272 participants) were obtained. Our NMA ranked the 1%, 0.5%, and 0.05% atropine concentrations as the 3 most beneficial for myopia control, as assessed for both primary outcomes: 1% atropine (mean differences compared with control: refraction, 0.81 [95% confidence interval (CI), 0.58-1.04]; AXL, -0.35 [-0.46 to -0.25]); 0.5% atropine (mean differences compared with control: refraction, 0.70 [95% CI, 0.40-1.00]; AXL, -0.23 [-0.38 to -0.07]); 0.05% atropine (mean differences compared with control: refraction, 0.62 [95% CI, 0.17-1.07]; AXL, -0.25 [-0.44 to -0.06]). In terms of myopia control as assessed by relative risk (RR) for overall myopia progression, 0.05% was ranked as the most beneficial concentration (RR, 0.39 [95% CI, 0.27-0.57]). The risk for adverse effects tended to rise as the atropine concentration was increased, although this tendency was not evident for distance BCVA. No valid network was formed for near BCVA. DISCUSSION: The ranking probability for efficacy was not proportional to dose (i.e., 0.05% atropine was comparable with that of high-dose atropine [1% and 0.5%]), although those for pupil size and accommodation amplitude were dose related.

Interventions for Glaucoma Medication Adherence Improvement: A Network Meta-analysis of Randomized Controlled Trials.

TOPIC: Comparative effectiveness of interventions to improve glaucoma medication adherence. CLINICAL RELEVANCE: High adherence to ocular hypotensive therapy is essential for prevention of visual impairment in glaucoma patients. Various types of intervention for adherence enhancement have been proposed, although there is still no firm evidence of their relative efficacies. METHODS: We searched PubMed, EMBASE, Scopus, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on November 30, 2021. Randomized controlled trials (RCTs) entailing interventions for improved adherence to ocular hypotensive therapy were identified. A network meta-analysis (NMA) was performed, and the following 11 interventions (single category or combinations of categories) were compared: (1) standard of care ([SOC] control), (2) short message service, (3) telephone call, (4) device reminder, (5) motivational interview, (6) multimedia education, (7) physician education, (8) provision of own medical records, (9) incentives, (10) tailored care, and (11) enhanced SOC. The primary outcome was the postintervention mean adherence score. The standardized mean differences (SMDs) were analyzed, and the effectiveness was ranked by P-score (probability of being best treatment). We appraised trials using the Cochrane risk-of-bias tool for RCTs. Confidence of results was assessed by Confidence in Network Meta-analysis. RESULTS: We obtained data for 19 RCTs (4981 participants). Tailored care, as inclusive of face-to-face needs assessment and a personalized care plan, was superior to SOC in improving adherence (SMD, 1.28; 95% confidence interval [CI], 0.08-2.48; P-score, 0.810). Multifaceted interventions that included tailored care showed further adherence improvement: tailored care + multimedia education (SMD, 1.44; 95% CI, 0.20-2.67; 0.850) and tailored care + multimedia education + device reminder (SMD, 1.61; 95% CI, 0.75-2.47; 0.914). The ranking of the remaining interventions by P-scores was as follows: incentives (0.606), short message service (0.535), enhanced SOC (0.458), multimedia education (0.430), device reminder (0.429), telephone call (0.401), provision of own medical records (0.391), physician education (0.281), SOC (0.230), and motivational interview (0.165). CONCLUSIONS: The NMA indicated that tailored care can improve adherence to glaucoma medication compared with SOC. A multifaceted approach might yield additional improvements.

Macular sector-wise decision tree model for the prediction of parafoveal scotoma not detected by 24-2 visual field test.

BACKGROUND: Development of a macular sector-wise decision tree model (DTM) for the prediction of parafoveal scotoma. METHODS: This prospective study enrolled 126 patients with early-stage open-angle glaucoma (mean deviation ≥-6 decibels) without the signs of parafoveal scotoma on the 24-2 visual field (VF) test (i.e., any abnormalities at the four innermost points). Based on the central 36 points of the 10-2 pattern deviation plot, patients were classified as being with or without 10-2 parafoveal scotoma. For the discrimination of patients from those without 10-2 parafoveal scotoma, a macular ganglion cell-inner plexiform layer (mGCIPL) sector-wise DTM analysis was performed. RESULTS: Among 126 eyes without 24-2 parafoveal scotoma, 10-2 parafoveal scotoma was detected in 77 (61.1%) eyes. The balanced accuracy of DTM was best in the inferotemporal sector (0.9286; 95% CI, 0.7458-0.9697) and worst in the inferior sector (0.8373; 0.6484-0.9204). DTM revealed that even in the absence of VF abnormalities at the innermost 4 points on the 24-2 test, (1) 10-2 parafoveal scotoma should be strongly suspected when the adjacent 24-2 perifoveal point in the correlated sector is abnormal; (2) if the 24-2 perifoveal point is normal, and if the probability colour codes of the correlated mGCIPL sector are green, the probability of 10-2 parafoveal scotoma is very low. CONCLUSIONS: In clinical practice, the evaluation of the 24-2 perifoveal test points along with the probability colour codes of mGCIPL can be a useful decision-support tool in determining whether 10-2 tests are needed for a given patient.

Explaining the Rationale of Deep Learning Glaucoma Decisions with Adversarial Examples.

PURPOSE: To illustrate what is inside the so-called black box of deep learning models (DLMs) so that clinicians can have greater confidence in the conclusions of artificial intelligence by evaluating adversarial explanation on its ability to explain the rationale of DLM decisions for glaucoma and glaucoma-related findings. Adversarial explanation generates adversarial examples (AEs), or images that have been changed to gain or lose pathologic characteristic-specific traits, to explain the DLM's rationale. DESIGN: Evaluation of explanation methods for DLMs. PARTICIPANTS: Health screening participants (n = 1653) at the Seoul National University Hospital Health Promotion Center, Seoul, Republic of Korea. METHODS: We trained DLMs for referable glaucoma (RG), increased cup-to-disc ratio (ICDR), disc rim narrowing (DRN), and retinal nerve fiber layer defect (RNFLD) using 6430 retinal fundus images. Surveys consisting of explanations using AE and gradient-weighted class activation mapping (GradCAM), a conventional heatmap-based explanation method, were generated for 400 pathologic and healthy patient eyes. For each method, board-trained glaucoma specialists rated location explainability, the ability to pinpoint decision-relevant areas in the image, and rationale explainability, the ability to inform the user on the model's reasoning for the decision based on pathologic features. Scores were compared by paired Wilcoxon signed-rank test. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivities, and specificities of DLMs; visualization of clinical pathologic changes of AEs; and survey scores for locational and rationale explainability. RESULTS: The AUCs were 0.90, 0.99, 0.95, and 0.79 and sensitivities were 0.79, 1.00, 0.82, and 0.55 at 0.90 specificity for RG, ICDR, DRN, and RNFLD DLMs, respectively. Generated AEs showed valid clinical feature changes, and survey results for location explainability were 3.94 ± 1.33 and 2.55 ± 1.24 using AEs and GradCAMs, respectively, of a possible maximum score of 5 points. The scores for rationale explainability were 3.97 ± 1.31 and 2.10 ± 1.25 for AEs and GradCAM, respectively. Adversarial example provided significantly better explainability than GradCAM. CONCLUSIONS: Adversarial explanation increased the explainability over GradCAM, a conventional heatmap-based explanation method. Adversarial explanation may help medical professionals understand more clearly the rationale of DLMs when using them for clinical decisions.

Ten Years and Beyond Longitudinal Change of ß-Zone Parapapillary Atrophy: Comparison of Primary Open-Angle Glaucoma with Normal Eyes.

PURPOSE: To investigate the difference in longitudinal change of ß-zone parapapillary atrophy (PPA) between eyes with primary open-angle glaucoma (POAG) and normal eyes. DESIGN: Longitudinal, observation study. PARTICIPANTS: A total of 153 eyes with POAG and 105 normal eyes. METHODS: Participants were followed for 10 years or more, with disc photography performed every year. The topographic parameters of ß-zone PPA (area, maximal radial extent, angular extent around disc) were measured. The factors associated with the enlargement of ß-zone PPA parameters were assessed by odds ratio (OR) using multivariable logistic regression. MAIN OUTCOME MEASURES: Enlargement of ß-zone PPA parameters and associated factors. RESULTS: Over the course of the average 11.6±1.3-year follow-up period, enlargement of ß-zone PPA was detected in 66.7% of POAG eyes and in 26.7% of normal eyes. Increment of all PPA parameters was significantly more common in cases of POAG than in normal eyes (all P < 0.001). The spatial distribution of maximal radial extent at baseline and final examination was significantly different between the 2 groups: POAG eyes; inferotemporal versus normal eyes; temporal (chi-square = 26.549, P < 0.001, chi-square = 19.320, P = 0.004, respectively). The widening of radial extent was significantly associated with older age (OR, 1.036; P = 0.010) and the presence of glaucoma (OR, 2.599; P = 0.002). The increment of angular extent was associated with the presence of glaucoma (OR, 12.167; P = 0.017) and optic disc hemorrhage (OR, 3.266; P = 0.019). CONCLUSIONS: The pattern of ß-zone PPA change differed between POAG and normal eyes during a follow-up of 10 years or more. The enlargement of PPA occurred more frequently in POAG than in normal eyes. The widening of radial extent was associated with older age and glaucoma, whereas the increment of angular extent was associated with glaucomatous damage.

Twenty-four-Hour Intraocular Pressure-Related Patterns from Contact Lens Sensors in Normal-Tension Glaucoma and Healthy Eyes: The Exploring Nyctohemeral Intraocular pressure related pattern for Glaucoma Management (ENIGMA) Study.

PURPOSE: To investigate 24-hour nyctohemeral intraocular pressure (IOP)-related patterns with contact lens sensors (CLSs) in eyes with primary open-angle glaucoma (POAG) with normal baseline IOP (i.e., normal-tension glaucoma [NTG]) and healthy controls. DESIGN: Prospective, case-control study. PARTICIPANTS: Thirty eyes of 30 patients with NTG, who had had a wash-out period for their IOP-lowering treatment, and 20 eyes of 20 healthy volunteer subjects. METHODS: Patients and subjects were hospitalized for the purposes of 24-hour CLS (SENSIMED Triggerfish; Sensimed AG, Lausanne, Switzerland) measurement. The IOP-related patterns during wake and sleep times over the course of the 24 hours were compared between the 2 groups. The 24-hour ambulatory blood pressure and posture were monitored simultaneously. A generalized linear model was used to find the factors associated with NTG. MAIN OUTCOME MEASURES: The IOP-related patterns, including mean and standard deviation (SD) of measurements, amplitude of cosine-fit curve, acrophase (signal peak), and bathyphase (signal trough) values (millivolt equivalents [mVEq]). RESULTS: The SDs of the 24-hour CLS measurements were significantly greater in NTG eyes than in healthy controls (112.51±26.90 vs. 85.18±29.61 mVEq, P = 0.002). The amplitudes of cosine-fit curve (141.88±39.96 vs. 106.08±41.49 mVEq, P = 0.004) and acrophase values (277.74±129.80 vs. 190.58±127.88 mVEq, P = 0.024), mostly measured during nocturnal period, were significantly greater in NTG eyes than in healthy controls. The NTG subjects slept longer in the lateral decubitus posture than the healthy controls (199.1±137.8 vs. 113.2±86.2 minutes, P = 0.009). In the multivariable generalized linear model, the greater amplitude of cosine-fit curve (ß = 0.218, P = 0.012) and greater time of decubitus posture during sleep (ß = 0.180, P = 0.004) were found to be significantly associated with NTG. CONCLUSIONS: Continuous monitoring of 24-hour IOP-related values with CLS can be useful for assessment of glaucoma risk, especially for patients with NTG whose IOP appears to be in the normal range. Fluctuation of 24-hour IOP-related values and posture during sleep time might be associated with NTG.

Temporal Raphe Sign for Discrimination of Glaucoma from Optic Neuropathy in Eyes with Macular Ganglion Cell-Inner Plexiform Layer Thinning.

PURPOSE: To evaluate the potential of the temporal raphe sign on the macular ganglion cell-inner plexiform layer (mGCIPL) thickness map for discriminating glaucomatous from nonglaucomatous optic neuropathy (NGON) in eyes with mGCIPL thinning. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 175 eyes of 175 patients with mGCIPL thinning on Cirrus (Carl Zeiss Meditec, Dublin, CA) high-definition OCT were retrospectively included. Glaucoma specialists and neuro-ophthalmology specialists evaluated the patients' medical records for diagnosis of glaucomatous optic neuropathy (GON) or NGON. Finally, by consensus, 67 eyes with GON and 73 eyes with NGON were enrolled. METHODS: A positive temporal raphe sign was declared in patients in whom there was a straight line longer than one-half of the length between the inner and outer annulus in the temporal elliptical area of the mGCIPL thickness map. Decision tree analysis was performed to formulate a diagnostic model. MAIN OUTCOME MEASURES: Area under receiver operating characteristic curve (AUC) with sensitivity and specificity. RESULTS: The temporal raphe sign was observed in 61 of 67 GON eyes (91.0%), but in only 21 of 73 NGON eyes (28.8%) (P < 0.001; chi-square test). On this basis, the diagnostic ability of the temporal raphe sign for discriminating GON from NGON was judged to be good (AUC, 0.811; 95% confidence interval, 0.749-0.874; sensitivity, 91.0%; specificity, 71.2%). The diagnostic performance of the decision tree-based model (AUC 0.879; 95% confidence interval, 0.824-0.933; sensitivity, 88.1%; specificity, 87.7%) was better than that of the temporal raphe sign or the relative afferent pupillary defect (RAPD) alone (P = 0.005, P < 0.001, respectively; DeLong's test). The decision tree model revealed the following: (1) If the temporal raphe sign is positive and the RAPD is absent, the case should be diagnosed as GON; (2) if the temporal raphe sign is absent regardless of the presence or absence of the RAPD, or both the temporal raphe sign and the RAPD are present, the case should be diagnosed as NGON. CONCLUSIONS: In clinical practice, determining whether the temporal raphe sign appears on OCT macular scans can be a useful tool for discrimination of glaucomatous from nonglaucomatous mGCIPL thinning.

Baseline Lamina Cribrosa Curvature and Subsequent Visual Field Progression Rate in Primary Open-Angle Glaucoma.

PURPOSE: To investigate the relationship between the degree of posterior bowing of the lamina cribrosa (LC) at baseline and the rate of subsequent visual field (VF) progression in eyes with primary open-angle glaucoma (POAG). DESIGN: Prospective, observational study. PARTICIPANTS: One hundred one early-stage (VF mean deviation [MD], -5.0 to -0.01 dB) POAG eyes that met the following conditions: (1) follow-up longer than 3.5 years, (2) more than 5 reliable standard automated perimetry tests, and (3) medically well-controlled intraocular pressure during follow-up. METHODS: All participants underwent swept-source OCT scanning of the LC at baseline. The area enclosed by a vertical line at the anterior laminar insertion, anterior LC plane, and reference plane of Bruch's membrane opening (BMO) was divided by D (distance between the 2 cross-points made by vertical lines drawn from the anterior laminar insertion to the reference plane of BMO) to approximate the LC depth (LCD). The difference between the LCD and mean anterior laminar insertion depth was defined as the LC curvature index (LCCI). To consider the steepness of the LC curve, the adjusted LCCI (aLCCI) was calculated as LCCI divided by D and multiplied by 100. The mean LCD (mLCD), mean LCCI (mLCCI), and mean aLCCI (maLCCI) were computed by averaging the measurements on 12 radial scans. The subsequent MD slope and associated factors were analyzed. MAIN OUTCOME MEASURES: Lamina cribrosa parameters and subsequent MD slope. RESULTS: The participants' mean baseline MD was -3.8 ± 3.4 dB. The mean baseline mLCD, mLCCI, and maLCCI were 419.0 ± 111.2 µm, 76.4 ± 29.0 µm, and 4.8 ± 1.9, respectively. A greater MD slope was associated with a greater baseline maLCCI (P < 0.001). We found a statistically significant breakpoint for the maLCCI (4.12) above which a larger maLCCI showed a steeper MD slope (P < 0.001). Analysis by age revealed that significantly more VF progression with maLCCI changes occurred in the relatively younger group (≤69 years; P = 0.043). CONCLUSIONS: The baseline maLCCI showed a significant correlation with the rate of subsequent VF deterioration. This suggests that, in POAG eyes with greater posterior bowing of the LC, the axons of retinal ganglion cells may be more vulnerable to further glaucomatous injury.

Amino-Functionalized Mesoporous Silica Particles for Ocular Delivery of Brimonidine.

To treat glaucoma, conventional eye drops are often prescribed. However, the eye drops have limited effectiveness as a result of low drug bioavailability due to their rapid clearance from the preocular space. To resolve this, we proposed amino-functionalized mesoporous silica (AMS) particles as delivery carriers of the glaucoma drug, brimonidine. Because of the presence of mesopores, brimonidine (BMD) could be encapsulated in the AMS with a loading amount of 41.73 µg/mg (i.e., drug loading capacity of about 4.17%) to give the BMD-AMS, which could release the drug in a sustained manner over 8 h. BMD-AMS was also shown to be mucoadhesive due to the presence of both hydroxyl and amino groups in the surface, allowing for formation of hydrogen bonds and an ionic complex with the mucin, respectively. Therefore, when topically administered to rabbit eyes in vivo, BMD-AMS could reside in the preocular space for up to 12 h because of its adherence to the mucous layer. To assess in vivo efficacy, we examined the variance in intraocular pressure (IOP) and brimonidine concentration in the aqueous humor (AH) after applying BMD-AMS to the eye, which was compared with that induced by Alphagan P, the marketed brimonidine eye drops. For BMD-AMS, the duration in the decrease in IOP and the area under the drug concentration in the AH-time curve (AUC) were 12 h and 2.68 µg·h/mL, respectively, which were about twice as large as those obtained with Alphagan P; this finding indicated enhanced ocular bioavailability of brimonidine with BMD-AMS.

Temporal Relation between Macular Ganglion Cell-Inner Plexiform Layer Loss and Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma.

PURPOSE: To investigate the temporal relationship between inferior macular ganglion cell-inner plexiform layer (mGCIPL) loss and corresponding peripapillary retinal nerve fiber layer (pRNFL) defect on the optical coherence tomography (OCT) deviation map in glaucoma. DESIGN: Retrospective, observational study. PARTICIPANTS: A total of 151 patients with early-stage glaucoma (visual field [VF] mean deviation between -1.5 and -5.5 decibels [dB]). METHODS: Spectral-domain OCT mGCIPL and pRNFL deviation maps were obtained for the baseline (from January 2012 to August 2012) and again for the follow-up (from January 2015 to August 2015). An integrated deviation map thereafter was merged by vascular landmark-guided superimposition of mGCIPL and pRNFL deviation maps onto RNFL imagery. On the basis of an earlier schematic model, the inferotemporal peripapillary area was divided into (1) the macular vulnerability zone (MVZ) and (2) the inferoinferior portion. MAIN OUTCOME MEASURES: Temporal sequence of inferior mGCIPL loss and corresponding pRNFL (i.e., pRNFL in MVZ) defect on integrated deviation map. RESULTS: At baseline, 99 (65.6%) of the 151 eyes showed inferior mGCIPL loss. In addition, 112 eyes (74.2%) and 5 eyes (3.3%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. At the 3-year follow-up, 112 (74.2%) of the eyes showed inferior mGCIPL loss, whereas 123 eyes (81.5%) and 25 eyes (16.6%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. Ninety-four eyes initially showed inferior mGCIPL loss without pRNFL defect in the MVZ; among them, 19 (20.2%) subsequently showed defect during the 3-year follow-up interval. Meanwhile, among the 52 eyes without preexisting inferior mGCIPL loss, only 1 (1.9%; P < 0.001) developed a pRNFL defect in the MVZ during the 3-year follow-up interval. CONCLUSIONS: In eyes with early glaucoma, mGCIPL change is frequently detected before corresponding pRNFL change. This could be the result of a superior sensitivity of mGCIPL deviation map that allows detection of an abnormality in the mGCIPL thickness earlier. In this light, OCT pRNFL analysis alone likely would overlook macular damage. Macular OCT imaging should be included in the imaging algorithm for the serial observation of patients with glaucoma.

Preservative-Free Fixed Combination of Tafluprost 0.0015% and Timolol 0.5% for Treatment-Naive Patients with Open-Angle Glaucoma.

PURPOSE: To assess efficacy, safety, and tolerability of the preservative-free (PF) fixed-dose combination (FC) of tafluprost 0.0015%/timolol 0.5% (PF tafluprost/timolol FC) in treatments-naive patients with primary open-angle glaucoma (POAG). METHODS: This was a retrospective, real-world clinical practice setting study that included 107 eyes of 107 subjects with POAG who had never been treated for glaucoma. All subjects were received PF tafluprost/timolol FC once daily. Intraocular pressure (IOP) levels were documented for each eye at the untreated baseline and up to 6 months after the initiation of medical treatment. All adverse events, including ocular and systemic adverse reactions, were recorded. Additionally, the reasons for medication discontinuations were thoroughly documented. RESULTS: A total of 32 POAG patients with high-baseline IOP (>21 mmHg) and 75 with normal-baseline IOP were included in the study. The subjects' baseline mean age was 62.4 ± 8.7 years (range, 26.0-85.0 years); among them, 42 were female (39.3%). Mean IOP at baseline for all patients was 18.6 ± 4.3 mmHg. The mean IOP at 6 months was 12.6 ± 4.7 mmHg, representing a significant decrease compared to the baseline (-32%, p < 0.001). In POAG patients with high-baseline IOP, mean IOP was significantly lowered from 28.0 ± 5.7 mmHg at baseline to 18.0 ± 5.5 mmHg (-35%, p < 0.001); in patients with normal-baseline IOP, from 14.6 ± 3.4 mmHg at baseline to 10.3 ± 4.1 mmHg (-29%, p < 0.001). PF tafluprost/timolol FC was well-tolerated and safe. After 6 months, 97.2% of all patients remained on therapy. CONCLUSIONS: In this real-world observational study, once-daily treatment with PF tafluprost/timolol FC demonstrated clinically relevant and statistically significant efficacy, as well as safety and good tolerability, in treatment-naive patients diagnosed with POAG.

Microbial keratitis in the subtropical region of Korea: a comprehensive 12-year retrospective review at a single referral center.

OBJECTIVES: To investigate the epidemiological characteristics and clinical outcomes of culture-proven bacterial and fungal keratitis at a single tertiary referral centre on Jeju Island, South Korea. DESIGN: A retrospective study design. SETTING: Data from a solitary referral centre on Jeju Island spanning January 2011 to December 2022. PARTICIPANTS: Among the 245 patients clinically diagnosed with infectious microbial keratitis, 110 individuals had culture-positive results. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the identification of causative microbial profiles and epidemiological characteristics, while the secondary outcome was the correlation of these factors with treatment outcomes. RESULTS: Of 245 patients, 110 (44.9%) had culture-positive infectious keratitis, showing 69 bacterial, 32 fungal, 4 superimposed bacterial and 5 cases with coinfection by bacteria and fungus. The most common pathogen was Pseudomonas species in 14.4% of the bacterial keratitis cases, followed by Staphylococcus epidermidis (9%), Staphylococcus aureus (8%) and Moraxella species (7%). The total treatment success rate for bacterial keratitis was 67.5%. The frequency of methicillin-resistant Staphylococcus on Jeju Island did increase during the study period. Fusarium species had the highest incidence at 22.2%, followed by Candida (16.7%) and Colletotrichum species (11.1%). 56.7% of fungal keratitis patients were successfully treated. An initial large corneal lesion (>3 mm) showed a statistically significant association with treatment failure. CONCLUSION: The incidence of Moraxella and Colletotrichum species in our study was higher than that reported in other districts with different climates and environments. The results reported here reflect the unique environmental features of Jeju Island, characterised by high humidity and temperatures.

Visual Impairment and Suicide Risk: A Systematic Review and Meta-Analysis.

Importance: Suicide is a substantial public health concern that involves various recognized contributing factors. Sensory impairments, specifically visual impairment, are deemed potential risk factors. Nonetheless, comprehensive information about associated risk levels and underlying determinants remains limited. Objective: To investigate the association between visual impairment and different aspects of suicide, including the assessment of risk levels and exploration of potential contributing factors. Data Sources: An electronic search was performed in the PubMed, EMBASE, Scopus, and Cochrane Library databases from their inception to February 8, 2024. Study Selection: All published studies were considered without restrictions on study design, publication date, or language. Data Extraction and Synthesis: Two independent reviewers extracted the published data using a standardized procedure in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Random-effects meta-analyses were used to estimate pooled effect sizes. Multiple meta-regression analyses were conducted to identify potential factors contributing to the association between visual impairment and the risk of suicide. Main Outcomes and Measures: The primary outcome measure was the odds ratio (OR) of suicidal behavior (including suicide attempt and suicide death) for individuals with visual impairment compared with those without. The secondary outcome measures were the pooled ORs of suicidal ideation and suicide death, respectively. Results: A total of 31 population-based studies with 5 692 769 unique individuals (mean [SD] age, 48.4 [8.5] years; 2 965 933 females [52%]) were included. For 17 studies (5 602 285 individuals) that evaluated suicidal behavior, the pooled OR was 2.49 (95% CI, 1.71-3.63). For 21 studies (611 899 individuals) that assessed suicidal ideation, the pooled OR was 2.01 (95% CI, 1.62-2.50). For 8 studies (5 067 113 individuals) investigating the association between visual impairment and suicide death, the pooled OR was 1.89 (95% CI, 1.32-2.71). The multiple meta-regression model identified age group as a predictive factor associated with suicidal behavior, with the studies included suggesting that adolescents were at the highest risk. While this analysis showed moderate heterogeneity for suicide death, high heterogeneity was observed for suicidal behavior and suicidal ideation. Conclusions and Relevance: The findings of this systematic review and meta-analysis support the association between visual impairment and increased risk of suicidal tendencies. The risk differed by age group, with a pronounced risk observed among adolescents.

Trends in Childhood Glaucoma Prevalence and Incidence in South Korea, 2002-2019: A Nationwide Population-Based Study.

PRCIS: This nationwide analysis identified the prevalence and incidence of childhood glaucoma for an 18-year period. The prevalence and incidence of primary congenital glaucoma showed increasing trends. Juvenile open angle glaucoma, meanwhile, showed a decreasing tendency. PURPOSE: We aimed to determine the trends in the prevalence and incidence of childhood glaucoma in the entire population of South Korea. PATIENTS AND METHODS: A nationwide retrospective cohort study was performed with an age-specific and sex-specific population of South Korea. The Korean National Health Insurance Service claims database for 2002 to 2019 was accessed to identify cases of ophthalmologist-confirmed primary childhood glaucoma [ie, primary congenital glaucoma (PCG) and juvenile open angle glaucoma (JOAG)]. Incidence for PCG was estimated for a same-birth-year population, while that for JOAG was estimated using age-specific and sex-specific population figures. To verify the glaucoma cases, we also analyzed the diagnostic codes as well as any information on medication prescriptions and/or ocular-surgery history. RESULTS: During the 18-year observational period, totals of 505 and 7538 patients were diagnosed with PCG and JOAG, respectively. The mean prevalences of PCG and JOAG were 3.96±0.72 and 14.17±5.18, respectively. The prevalence of PCG showed an overall increasing trend during the study period, but the pattern was not significant ( ß =0.049, P =0.143); that of JOAG, meanwhile, showed a significant decreasing tendency ( ß =-0.713, P =0.001). PCG prevalence showed no difference between urban and rural areas, but JOAG showed a higher prevalence in rural areas ( P <0.001). As for mean incidence, the rates for PCG and JOAG were 1.54±0.49 and 5.02±1.95 (per 100,000 person-years), respectively, and were higher in males ( P <0.001 and P =0.013). CONCLUSION: This study identified childhood glaucoma prevalence and incidence in a general population of East Asian ethnicity. This data could help to promote a better understanding of the typical epidemiological features and clinical courses of childhood glaucoma patients.

Incidence of and Risk Factors for Fellow-Eye Involvement in Sturge-Weber Syndrome Children With Unilateral Glaucoma.

PRCIS: Among children with unilateral glaucoma associated with Sturge-Weber syndrome (SWS), 7 of 47 demonstrated involvement in the fellow eye, and that group had had earlier first-eye surgery relative to the noninvolvement group. PURPOSE: The aim of this study was to determine the incidence of and risk factors for fellow-eye involvement in children with unilateral SWS-associated glaucoma. MATERIALS AND METHODS: Children diagnosed with a unilateral facial port-wine stain and ipsilateral glaucoma before the age of 5 and followed up for at least 5 years were enrolled. The incidence rates of fellow-eye glaucoma involvement were estimated per 100 person-years, and factors associated with a higher incidence of fellow-eye involvement were investigated. RESULTS: A total of 47 children [24 (51.1%) girls] with unilateral SWS-associated glaucoma were included. All of them had facial port-wine stain involving ophthalmic division of the trigeminal nerve, and 18 (38.3%) had neurological comorbidities. The mean age at glaucoma diagnosis was 0.8±1.2 years [range, 0.08 (1 mo)-4.0 y]. Over a median follow-up of 8.4 years, glaucoma was diagnosed in the fellow eye of 7 of the children (14.9%; incidence rate of 1.8 per 100 person-years), 6 of whom were girls ( P =0.097) and 5 of whom were diagnosed before the age of 4 years ( P =0.508). The fellow-eye-involvement group showed significantly higher mean follow-up intraocular pressure in the fellow eye, older age at first-eye surgery (both P <0.005), and higher frequency of choroidal hemangioma both at first onset and in fellow eyes ( P =0.026 and 0.019, respectively). CONCLUSIONS: In this cohort of SWS children diagnosed with unilateral glaucoma, the risk of fellow-eye involvement was higher in girls, within the first 4 years, and in cases with choroidal hemangioma. The fellow-eye-involved children underwent surgery on the first eye earlier than those without fellow-eye involvement.

Clinical Significance of Optic Disc Hemorrhage Size in Visual Field Progression in Glaucoma.

PURPOSE: To investigate the correlation between optic disc hemorrhage (DH) size and glaucoma progression. DESIGN: A retrospective observational cohort study METHODS:   SETTING: A single tertiary hospital in South Korea STUDY POPULATION: Two hundred and fifty (250) open-angle glaucoma (OAG) patients with DH. Participants were followed for 5 years or longer, with a minimum of 5 visual field (VF) tests. OBSERVATION PROCEDURE: The DH area was calculated by comparing the pixel numbers of the DH area with the disc area based on optical coherence tomography (OCT). For recurrent DH cases, we calculated the average DH area. DH size was classified as large or small based on the median value. Rates of mean deviation (MD) loss were determined using guided progression analysis (GPA). Univariable and multivariable regression analyses were performed to identify significant predictors of MD loss. MAIN OUTCOME MEASURES: DH size and longitudinal VF progression RESULTS: The mean follow-up period was 11.1 ± 3.6 years. The group with large DH showed faster global MD loss relative to the group with small DH (-0.51±0.48 dB/y vs -0.36 ± 0.42 dB/y, P = .01). In the multivariable model, mean DH size, maximum DH size, and initial MD were all significantly associated with the overall rate of MD loss (all P < .05). CONCLUSIONS: DH size was associated with the rate of VF deterioration. Eyes with larger DH showed more pronounced VF progression.