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BackgroundDiabetic macular edema (DME), a leading cause of blindness, requires treatment with costly drugs, such as anti–vascular endothelial growth factor (VEGF) agents. The prolonged use of these effective but expensive drugs results in an incremental economic burden for patients with DME compared with those with diabetes mellitus (DM) without DME. However, there are no studies on the long-term patient-centered economic burden of DME after reimbursement for anti-VEGFs. ObjectiveThis retrospective cohort study aims to estimate the 3-year patient-centered economic burden of DME compared with DM without DME, using the Common Data Model. MethodsWe used medical data from 1,903,603 patients (2003-2020), transformed and validated using the Observational Medical Outcomes Partnership Common Data Model from Seoul National University Bundang Hospital. We defined the group with DME as patients aged >18 years with nonproliferative diabetic retinopathy and intravitreal anti-VEGF or steroid prescriptions. As control, we defined the group with DM without DME as patients aged >18 years with DM or diabetic retinopathy without intravitreal anti-VEGF or steroid prescriptions. Propensity score matching, performed using a regularized logistic regression with a Laplace prior, addressed selection bias. We estimated direct medical costs over 3 years categorized into total costs, reimbursement costs, nonreimbursement costs, out-of-pocket costs, and costs covered by insurance, as well as healthcare resource utilization. An exponential conditional model and a count model estimated unbiased incremental patient-centered economic burden using generalized linear models and a zero-inflation model. ResultsIn a cohort of 454 patients with DME matched with 1640 patients with DM, the economic burden of DME was significantly higher than that of DM, with total costs over 3 years being 2.09 (95% CI 1.78-2.47) times higher. Reimbursement costs were 1.89 (95% CI 1.57-2.28) times higher in the group with DME than with the group with DM, while nonreimbursement costs were 2.54 (95% CI 2.12-3.06) times higher. Out-of-pocket costs and costs covered by insurance were also higher by a factor of 2.11 (95% CI 1.58-2.59) and a factor of 2.01 (95% CI 1.85-2.42), respectively. Patients with DME had a significantly higher number of outpatient (1.87-fold) and inpatient (1.99-fold) visits compared with those with DM (P

Abstract The aim of this study was to introduce novel vector field analysis for the quantitative measurement of retinal displacement after epiretinal membrane (ERM) removal. We developed a novel framework to measure retinal displacement from retinal fundus images as follows: (1) rigid registration of preoperative retinal fundus images in reference to postoperative retinal fundus images, (2) extraction of retinal vessel segmentation masks from these retinal fundus images, (3) non-rigid registration of preoperative vessel masks in reference to postoperative vessel masks, and (4) calculation of the transformation matrix required for non-rigid registration for each pixel. These pixel-wise vector field results were summarized according to predefined 24 sectors after standardization. We applied this framework to 20 patients who underwent ERM removal to obtain their retinal displacement vector fields between retinal fundus images taken preoperatively and at postoperative 1, 4, 10, and 22 months. The mean direction of displacement vectors was in the nasal direction. The mean standardized magnitudes of retinal displacement between preoperative and postoperative 1 month, postoperative 1 and 4, 4 and 10, and 10 and 22 months were 38.6, 14.9, 7.6, and 5.4, respectively. In conclusion, the proposed method provides a computerized, reproducible, and scalable way to analyze structural changes in the retina with a powerful visualization tool. Retinal structural changes were mostly concentrated in the early postoperative period and tended to move nasally.

Abstract Congenital and infantile (CI) cataract is one of the most important and preventable cause of blindness in children, but the incidence has not been studied in Korea. We collected data from the national claims database of the National Health Insurance Service of Korea from 2002 through 2019. We identified children who underwent cataract surgery within the age of 5 years, and cumulative incidence rates were calculated for each of the three age criteria. 989 patients out of 4,221,459 births underwent surgery with CI cataract during the period. The cumulative incidence rates per 10,000 births were 1.60 (0–1 years), 2.38 (0–3 years), and 2.95 (0–5 years), respectively. The incidence peaked in the 2007 birth cohort, which coincides with the start of the national screening program for infants/children. Primary intraocular lens implantation was performed in 439 patients (44%). Strabismus and glaucoma requiring surgery occurred in 291 patients (29.4%) and 32 patients (3.2%), respectively, within 8 years after cataract surgery. The incidence rates of CI cataract in Korea appear to be comparable to previous studies in other regions. The early screening program for infants may reduce delayed diagnosis and increase the proportion of patients undergoing surgery at a critical time for visual development.

Abstract To compare the efficacy of scleral buckling with adjuvant pneumatic retinopexy (SB with PR) and scleral buckling (SB) alone for primary rhegmatogenous retinal detachment (RRD). This retrospective and comparative study included patients who underwent SB with PR (n = 88) or SB alone (n = 161) for primary RRD. The primary anatomical success rate for SB with PR was 81.8%, whereas that for SB alone was 80.7% (P = 0.836). Among patients who achieved primary anatomical success, those in the SB with PR group showed postoperative epiretinal membrane (ERM) formation more frequently than those in the SB alone group (11 of 72 [15.3%] vs. 6 of 130 [4.6%]) (P = 0.009). The mean time to subretinal fluid absorption was not significantly different between the SB with PR and SB alone groups (11.2 ± 6.2 vs. 11.4 ± 5.8 months, P = 0.881). In the SB with PR group, retinal detachment involving ≥ three quadrants was a significant risk factor for surgical failure (hazard ratio, 3.04; P = 0.041). Adjuvant pneumatic retinopexy does not provide additional benefit in improving the surgical outcomes of SB for primary RRD repair.

Abstract This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was − 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment.

Abstract As retinitis pigmentosa (RP) is chronic and progressive, the chronological sequence of microvascular changes is important for understanding its pathophysiology. We aimed to investigate retinal and choroidal microvascular changes according to the RP stages. The stages of RP were classified into three stages according to the integrity and width of the inner segment ellipsoid zone: early, ≥ 2500 μm; moderate,

Abstract When medical genetic syndromes are influenced by allelic hierarchies, mutant alleles have distinct effects on clinical phenotypes. Genotype–phenotype correlations for Usher syndrome type 2 (USH2) suggest that the USH2A gene exhibits an allelic hierarchy. Here, we analyzed the phenotypes and genotypes of 16 South Korean patients with USH2A biallelic variants to investigate an allelic hierarchy from audiological and ophthalmological perspectives. Using whole exome and genome sequencing, 18 mutant alleles, including 4 novel alleles, were identified and implicated in USH2A-related disorders. Truncated alleles were linked to earlier onset of subjective hearing loss and more severe thresholds; biallelic truncated alleles had more severe effects. Truncated alleles were also associated with retinal structure degeneration and severe functional deterioration. However, younger patients (aged

Abstract Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ( $$P \, < \, 1.19\times {10}^{-8}$$ P < 1.19 × 10 − 8 ). Substantial genetic sharing between PCV and typical nAMD is noted (r g = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; $$P=1.05\times {10}^{-6}$$ P = 1.05 × 10 − 6 ) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.

BackgroundExudative age-related macular degeneration (AMD), one of the leading causes of blindness, requires expensive drugs such as anti–vascular endothelial growth factor (VEGF) agents. The long-term regular use of effective but expensive drugs causes an economic burden for patients with exudative AMD. However, there are no studies on the long-term patient-centered economic burden of exudative AMD after reimbursement of anti-VEGFs. ObjectiveThis study aimed to evaluate the patient-centered economic burden of exudative AMD for 2 years, including nonreimbursement and out-of-pocket costs, compared with nonexudative AMD using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). MethodsThis retrospective cohort study was conducted using the OMOP CDM, which included 2,006,478 patients who visited Seoul National University Bundang Hospital from June 2003 to July 2019. We defined the exudative AMD group as patients aged >50 years with a diagnosis of exudative AMD and a prescription for anti-VEGFs or verteporfin. The control group was defined as patients aged >50 years without a diagnosis of exudative AMD or a prescription for anti-VEGFs or verteporfin. To adjust for selection bias, controls were matched by propensity scores using regularized logistic regression with a Laplace prior. We measured any medical cost occurring in the hospital as the economic burden of exudative AMD during a 2-year follow-up period using 4 categories: total medical cost, reimbursement cost, nonreimbursement cost, and out-of-pocket cost. To estimate the average cost by adjusting the confounding variable and overcoming the positive skewness of costs, we used an exponential conditional model with a generalized linear model. ResultsWe identified 931 patients with exudative AMD and matched 783 (84.1%) with 2918 patients with nonexudative AMD. In the exponential conditional model, the total medical, reimbursement, nonreimbursement, and out-of-pocket incremental costs were estimated at US $3426, US $3130, US $366, and US $561, respectively, in the first year and US $1829, US $1461, US $373, and US $507, respectively, in the second year. All incremental costs in the exudative AMD group were 1.89 to 4.25 and 3.50 to 5.09 times higher in the first and second year, respectively, than those in the control group (P

Abstract The identification of abnormal findings manifested in retinal fundus images and diagnosis of ophthalmic diseases are essential to the management of potentially vision-threatening eye conditions. Recently, deep learning-based computer-aided diagnosis systems (CADs) have demonstrated their potential to reduce reading time and discrepancy amongst readers. However, the obscure reasoning of deep neural networks (DNNs) has been the leading cause to reluctance in its clinical use as CAD systems. Here, we present a novel architectural and algorithmic design of DNNs to comprehensively identify 15 abnormal retinal findings and diagnose 8 major ophthalmic diseases from macula-centered fundus images with the accuracy comparable to experts. We then define a notion of counterfactual attribution ratio (CAR) which luminates the system’s diagnostic reasoning, representing how each abnormal finding contributed to its diagnostic prediction. By using CAR, we show that both quantitative and qualitative interpretation and interactive adjustment of the CAD result can be achieved. A comparison of the model’s CAR with experts’ finding-disease diagnosis correlation confirms that the proposed model identifies the relationship between findings and diseases similarly as ophthalmologists do.

Abstract Background Evaluate the visual outcomes of Ahmed glaucoma valve implantation (AGVI) in patients with neovascular glaucoma (NVG) who underwent diabetic vitrectomy and suggest appropriate AGVI timing. Methods Medical records of patients who underwent AGVI due to NVG after diabetic vitrectomy were reviewed. Successful intraocular pressure (IOP) control was defined as an IOP between 6 and 21 mmHg. Visual outcome was compared before NVG diagnosis and after AGVI, and the “favorable” visual outcome was defined as a postoperative deterioration in BCVA of less than 0.3 logMAR units compared to those before the development of NVG. Various factors including surgical timing were evaluated to identify the risk factors associated with unfavorable visual outcome. Results A total of 35 eyes were enrolled and divided into group 1(medically uncontrolled NVG group, IOP more than 30mmHg, 16 eyes) and group 2(NVG group responded well to the initial non-surgical treatment but eventually required AGVI, 19 eyes). Despite the favorable rate of normalization of post-AGVI IOP (85.7%), 43.8% in Group 1 and 26.3% in Group 2 showed unfavorable visual outcomes. In group 1, delayed surgical timing more than 1 week from the NVG diagnosis showed a significant association with unfavorable visual outcomes (P = 0.041). In group 2, poor patient compliance (follow up loss, refuse surgery) was the main factor of unfavorable visual outcomes. Conclusion When NVG occurs in patients with proliferative diabetic retinopathy after vitrectomy, physicians should be cautious not to delay the surgical intervention, especially in patients with IOP of 30 or more despite non-surgical treatment. Early AGVI within six days might be necessary to preserve useful vision in these patients.

Abstract The single nucleotide polymorphisms (SNPs) of complement factor H (CFH) gene are well-known genetic risk factors for age-related macular degeneration (AMD). To identify whether the measurement of plasma protein concentrations of CFH variants using the multiple reaction monitoring (MRM) assay can determine the genotypes of CFH SNP rs1061170 and rs800292, 120 patients with AMD and 26 controls were included in this study. The number of cases were TT:TC:CC = 121:24:1 in CFH SNP Y402H and GG:AG:AA = 72:57:17 in CFH SNP I62V. Plasma concentrations of tryptic peptides were measured using the MRM assay, and tyrosine/histidine (Y/H) and valine/isoleucine (V/I) CFH variant protein ratios were obtained. To discriminate the genotypes by the plasma protein ratios, cut-off values were set for Y/H ratios (TT: > 4.428; TC: 1.00–4.428; CC: 1.09; AG: 0.0089–1.08; AA:

Abstract Background To compare the efficacy of intraoperative localized and 360-degree laser photocoagulation in 23-gauge limited pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Methods This retrospective, comparative, consecutive, interventional study included 155 eyes of 155 patients who underwent primary repair of RRD utilizing 23-gauge PPV with at least six months of follow up. Medical records were retrospectively reviewed, and the corresponding demographic data, preoperative ophthalmic features, surgical management, and postoperative course were recorded. Main outcome measures included single surgery anatomical success, pre- and post-operative visual acuity, and complications. Results Eighty-three patients (group A) received localized laser photocoagulation in PPV, while the remaining 72 patients (group B) received underwent circumferential 360-degree laser photocoagulation in PPV. Two skilled-surgeons performed all the surgeries, and 23-gauge PPV instrumentation, a wide-angle viewing system, endolaser photocoagulation, and gas tamponade were used in each case. No significant difference was identified in baseline characteristics. The single surgery anatomical success rate was 96.4 % in group A, and 95.8 % in group B, showing no significant difference (p = 1.00). Primary anatomical failure was caused by re-detachment due to break in 2 eyes in each group (no new break 1 eye, new break 1eye in group A, 2 eyes with no new break in group B), and proliferative vitreoretinopathy in 1 eye in each group. Other complications were epiretinal membrane in 7 eyes (3 in group A, 4 in group B), and macular hole in 1 eye in group B. There were no differences in pre- and post-operative best-corrected visual acuity (BCVA) as well as BCVA improvement (p=0.144, p=0.866 and p=0.263, respectively). Conclusion Localized laser photocoagulation showed no difference in anatomic and visual outcome in RRD patients, when compared with 360-degree laser photocoagulation in limited PPV. Routine circumferential 360-degree laser photocoagulation may not be necessary in vitrectomy surgery for primary rhegmatogenous retinal detachment without severe PVR.

Abstract The optimal treatment of submacular hemorrhage (SMH) following neovascular age-related macular degeneration (nAMD) is controversial. This study aimed to compare visual outcomes of conservative versus active surgical treatment. Two hundred thirty-six eyes of 236 patients with SMH (≥ 1 disc diameter) were stratified into four groups: observation (n = 21); anti-vascular endothelial growth factor (VEGF) monotherapy (n = 161); non-surgical gas tamponade (n = 31); and subretinal surgery (n = 23). The primary outcome was best-corrected visual acuity (BCVA) at 12 months. The baseline BCVAs of the observation, anti-VEGF monotherapy, non-surgical gas tamponade, and subretinal surgery groups were 1.50 ± 0.70, 1.09 ± 0.70, 1.31 ± 0.83, and 1.62 ± 0.77 logarithm of minimal angle resolution (LogMAR), respectively. The mean BCVAs at 12 months were 1.39 ± 0.84, 0.90 ± 0.83, 1.35 ± 0.88, and 1.44 ± 0.91 LogMAR, respectively. After adjusting for age, baseline BCVA, SMH size, and the number of intravitreal anti-VEGF injections before SMH, the mean BCVA showed no significant difference among treatments at 12 months (P = 0.204). The anti-VEGF monotherapy group showed better mean BCVA significantly at 3 months (P

Purpose: To investigate the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP).Design: We conducted a retrospective, multicenter, observational cohort study.Participants: We reviewed the medical records of 42 patients with RHO-associated RP of 36 families who visited 4 hospitals in Korea.Methods: Patients with molecular confirmation of pathogenic variants of the RHO gene were included. The patients were divided into two subgroups: the generalized and sector RP groups. A central visual field of the better-seeing eye of

IntroductionThis single-center retrospective cohort study investigated the incidence rate and risk factors for the discontinuation of anti-vascular endothelial growth factor (VEGF) injections and retreatment in typical neovascular age-related macular degeneration (tnAMD) and polypoidal choroidal vasculopathy (PCV) in the real-world setting.MethodsA total of 488 eyes with either tnAMD (n = 334) or PCV (n = 154) followed up for ≥3 years were analyzed. The discontinuation of treatment was defined as the cessation of anti-VEGF injections for 1 year or longer. Eyes with discontinuing treatment were subdivided into group A: eyes with stable responses (complete or incomplete resolution) and group B: those with no expectation of visual gain or poor response. The proportion and median time of discontinuation of treatment or retreatment were analyzed. The visual prognosis and the associated risk factors for the discontinuation of treatment or retreatment were also investigated.ResultsThe mean follow-up period was 8.1 ± 3.4 years. Of 488 eyes, discontinuation of the treatment occurred in 322 eyes (66.0%), and the median time to discontinuation was 1.5 years after the initial injection. Of 297 eyes with discontinuation of treatment excluding 25 eyes with vitrectomy or photodynamic therapy after the discontinuation of the injection, 277 eyes belonged to group A and the remaining 20 eyes belonged to group B. Of the 277 eyes discontinuing treatment with a stable response, 185 eyes (66.8%) were given retreatment. The median time to retreatment was 3.3 years after the discontinuation of the injections. PCV and the lower annual number of injections were the significant factors associated with discontinuation. Younger age, male gender, and PCV were the significant factors for the retreatment.ConclusionOur long-term real-world study showed that two-thirds of eyes with neovascular age-related macular degeneration (nAMD) had the discontinuation of the anti-VEGF injections and two-thirds of eyes discontinuing treatment with stable responses experienced retreatment. Long-term follow-up and regular monitoring are needed to detect the recurrence.

Abstract Despite many studies, optimal treatment sequences or intervals are still questionable in retinal vein occlusion (RVO) macular edema. The aim of this study was to examine the real-world treatment patterns of RVO macular edema. A retrospective analysis of the Observational Medical Outcomes Partnership Common Data Model, a distributed research network, of four large tertiary referral centers (n = 9,202,032) identified 3286 eligible. We visualized treatment pathways (prescription volume and treatment sequence) with sunburst and Sankey diagrams. We calculated the average number of intravitreal injections per patient in the first and second years to evaluate the treatment intensities. Bevacizumab was the most popular first-line drug (80.9%), followed by triamcinolone (15.1%) and dexamethasone (2.28%). Triamcinolone was the most popular drug (8.88%), followed by dexamethasone (6.08%) in patients who began treatment with anti-vascular endothelial growth factor (VEGF) agents. The average number of all intravitreal injections per person decreased in the second year compared with the first year. The average number of injections per person in the first year increased throughout the study. Bevacizumab was the most popular first-line drug and steroids were considered the most common as second-line drugs in patients first treated with anti-VEGF agents. Intensive treatment patterns may cause an increase in intravitreal injections.

Abstract Central serous chorioretinopathy (CSC) is one of the most common macular diseases that can reduce the quality of life of patients. This study aimed to build a deep learning-based classification model using multiple spectral domain optical coherence tomography (SD-OCT) images together to diagnose CSC. Our proposed system contains two modules: single-image prediction (SIP) and a final decision (FD) classifier. A total of 7425 SD-OCT images from 297 participants (109 acute CSC, 106 chronic CSC, 82 normal) were included. In the fivefold cross validation test, our model showed an average accuracy of 94.2%. Compared to other end-to-end models, for example, a 3D convolutional neural network (CNN) model and a CNN-long short-term memory (CNN-LSTM) model, the proposed system showed more than 10% higher accuracy. In the experiments comparing the proposed model and ophthalmologists, our model showed higher accuracy than experts in distinguishing between acute, chronic, and normal cases. Our results show that an automated deep learning-based model could play a supplementary role alongside ophthalmologists in the diagnosis and management of CSC. In particular, the proposed model seems clinically applicable because it can classify CSCs using multiple OCT images simultaneously.

Abstract Purpose To evaluate the necessity and safety of primary posterior capsulotomy during phaco-vitrectomy for idiopathic epiretinal membrane (ERM). Setting Seoul National University Bundang Hospital, Seongnam, Korea. Design Retrospective consecutive cohort analysis. Methods This study enrolled 219 patients (228 eyes) who underwent combined 25-gauge phaco-vitrectomy for idiopathic ERM and cataract, divided into capsulotomy (−) group (152 eyes, 144 patients) and capsulotomy (+) group (76 eyes, 75 patients). The main outcomes were rate of posterior capsular opacity (PCO) occurrence and postoperative complications. Ophthalmic examinations were performed at baseline, 1, 3, 6, and 12 months postoperatively. Results PCO only occurred in capsulotomy (−) group (20 eyes, 13.2%), with mean onset of 10.59 months. Visually-significant PCO that needed Nd:YAG posterior capsulotomy was present in 9 eyes (45.0% of PCO eyes). The rate of cystoid macular edema (CME) was higher in capsulotomy (+) group (6.6% vs. 15.8%, p = 0.026) with longer duration (1.50 vs. 3.36 months, p = 0.019). Female sex and posterior capsulotomy were significant risk factors for CME occurrence (p

Abstract Central serous chorioretinopathy (CSC) is the fourth most common retinopathy and can reduce quality of life. CSC is assessed using optical coherence tomography (OCT), but deep learning systems have not been used to classify CSC subtypes. This study aimed to build a deep learning system model to distinguish CSC subtypes using a convolutional neural network (CNN). We enrolled 435 patients with CSC from a single tertiary center between January 2015 and January 2020. Data from spectral domain OCT (SD-OCT) images of the patients were analyzed using a deep CNN. Five-fold cross-validation was employed to evaluate the model’s ability to discriminate acute, non-resolving, inactive, and chronic atrophic CSC. We compared the performances of the proposed model, Resnet-50, Inception-V3, and eight ophthalmologists. Overall, 3209 SD-OCT images were included. The proposed model showed an average cross-validation accuracy of 70.0% (95% confidence interval [CI], 0.676–0.718) and the highest test accuracy was 73.5%. Additional evaluation in an independent set of 104 patients demonstrated the reliable performance of the proposed model (accuracy: 76.8%). Our model could classify CSC subtypes with high accuracy. Thus, automated deep learning systems could be useful in the classification and management of CSC.

Abstract Background To determine the 12-year incidence of and trends in rhegmatogenous retinal detachment (RRD) requiring surgery in Korea. Methods This was a nationwide, population-based, retrospective study. We identified 53,179 patients with incident RRD requiring surgery using the Korean National Health Claims Database from 2004 to 2015. We estimated the crude incidence rates and age- and sex-standardized incidence rates per 100,000 person-years in each year during the study period. A joinpoint regression analysis was performed to determine the trend. Results The average annual incidence rate was 9.78 (95% CI: 9.70–9.86). Male patients showed an incidence rate (10.68 [95% CI: 10.57–10.80]) 1.20 times that of female patients (8.87 [95% CI: 8.76–8.98]). The incidence showed a bimodal distribution; the highest peak was in the 60–64 year age group (23.77 [95% CI: 23.18–24.35]) and the second peak was in the 20–24 year age group (7.68 [95% CI: 7.41–7.95]). An increasing trend of RRD incidence was observed in the total population throughout the study period using joinpoint analysis (annual percentage change [APC], 2.05; 95% CI: 0.7–3.4). The increasing trend was more prominent among individuals aged under 50 years (APC, 3.44; 95% CI: 2.3–4.6), while among those aged 50 years or above, the increasing incidence was observed only in male patients. Conclusions In Korea, the incidence of RRD has increased recently. People in the

AIM: To evaluate the long-term effect and safety of focal laser photocoagulation treatment in eyes with polypoidal choroidal vasculopathy (PCV). METHODS: Medical records of 13 eyes of 13 patients with PCV were followed-up for more than 2y after focal laser photocoagulation treatment. The patients were diagnosed with PCV using indocyanine green angiography, and eyes with other comorbid ocular diseases were excluded. The measurement outcomes of the study were the post-treatment regression and recurrence of polyps, complications, and changes in visual acuities. Paired t-test was performed to compare visual outcome before and after the treatment. RESULTS: The mean age of the 13 patients was 70.2±5.5y, and the follow-up period was 72.3±31.0 (range, 25-118)mo. Three eyes had juxtafoveal polyps and 10 eyes had extrafoveal polyps. Of the 13 eyes, 9 eyes (69.2%) had regression of polyps 1.7±1.2 (range, 0.9-4)mo after focal laser photocoagulation. Five eyes (55.6%) showed recurrence of polyps during the follow-up periods, and the recurrence period was 12.8±18.9 (range, 1.9-48)mo. Mild subretinal hemorrhage occurred in two eyes (15.4%) 27 and 72d after laser treatment, respectively. There were no statistically significant differences in visual acuities at baseline; 1, 2, 3y post-treatment (all P>0.05); and last follow-up (0.63±0.5, 0.73±0.70, 0.67±0.57, 0.75±0.7, and 0.95±0.8 logMAR, respectively). CONCLUSION: Focal laser photocoagulation is beneficial for early regression of polyps in eyes with PCV and does not result in significant submacular hemorrhage during the long-term follow-up. Furthermore, it can be primarily considered in eyes with PCV with extrafoveal or juxtafoveal polyps to regress risky polyps as well as to maintain visual acuity without serious hemorrhagic complications.

Abstract To evaluate the long-term outcomes of ranibizumab (RBZ) vs. aflibercept (AFL) in treatment-naïve eyes with typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). This multicenter, retrospective, matched-cohort analysis was conducted on data up to 4 years of follow-ups. The primary outcome was the visual acuity (VA) change from baseline. The secondary outcomes included the number of injections, proportion of eyes without a yearly injection, and the number of eyes with treatment switching. Subgroup analyses were performed for typical nAMD and PCV. Typical nAMD was defined as nAMD other than PCV. We included VA-matched 215 eyes of 209 patients (131 and 84 eyes with RBZ and AFL, respectively). The crude mean VA changes from baseline were + 6.7 vs. + 2.6, + 2.1 vs. − 0.4, − 1.3 vs. − 1.8, and − 2.2 vs. − 5.0 letters in the RBZ and AFL groups, at 1, 2, 3, and 4 years, respectively (p > 0.05). The adjusted predicted VA by linear mixed model, proportion of eyes stratified by VA, and the survival curve for significant vision loss were comparable during the 4-year follow-up (p > 0.05). The mean number of injections were similar between the RBZ and AFL groups (2.9 vs. 3.0, respectively, p = 0.692). The subgroup analysis for typical nAMD and PCV showed similar results between the groups. The visual outcomes did not differ between RBZ and AFL during 4 years with comparable numbers of injections. Our study reflects the long-term, real-world clinical practice and treatment pattern of two treatments for typical nAMD and PCV.

BackgroundIn 2021, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) validated a new equation for estimated glomerular filtration rate (eGFR). However, this new equation is not ethnic-specific, and prevalence of CKD in Asians is known to differ from other ethnicities. This study evaluates the impact of the 2009 and 2021 creatinine-based eGFR equations on the prevalence of CKD in multiple Asian cohorts.MethodsEight population-based studies from China, India, Russia (Asian), Singapore and South Korea provided individual-level data (n = 67,233). GFR was estimated using both the 2009 CKD-EPI equation developed using creatinine, age, sex, and race (eGFRcr [2009, ASR]) and the 2021 CKD-EPI equation developed without race (eGFRcr [2021, AS]). CKD was defined as an estimated glomerular filtration rate (eGFR)

Abstract This cross-sectional study aimed to build a deep learning model for detecting neovascular age-related macular degeneration (AMD) and to distinguish retinal angiomatous proliferation (RAP) from polypoidal choroidal vasculopathy (PCV) using a convolutional neural network (CNN). Patients from a single tertiary center were enrolled from January 2014 to January 2020. Spectral-domain optical coherence tomography (SD-OCT) images of patients with RAP or PCV and a control group were analyzed with a deep CNN. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were used to evaluate the model’s ability to distinguish RAP from PCV. The performances of the new model, the VGG-16, Resnet-50, Inception, and eight ophthalmologists were compared. A total of 3951 SD-OCT images from 314 participants (229 AMD, 85 normal controls) were analyzed. In distinguishing the PCV and RAP cases, the proposed model showed an accuracy, sensitivity, and specificity of 89.1%, 89.4%, and 88.8%, respectively, with an AUROC of 95.3% (95% CI 0.727–0.852). The proposed model showed better diagnostic performance than VGG-16, Resnet-50, and Inception-V3 and comparable performance with the eight ophthalmologists. The novel model performed well when distinguishing between PCV and RAP. Thus, automated deep learning systems may support ophthalmologists in distinguishing RAP from PCV.

Abstract Background Although ophthalmic devices have made remarkable progress and are widely used, most lack standardization of both image review and results reporting systems, making interoperability unachievable. We developed and validated new software for extracting, transforming, and storing information from report images produced by ophthalmic examination devices to generate standardized, structured, and interoperable information to assist ophthalmologists in eye clinics. Results We selected report images derived from optical coherence tomography (OCT). The new software consists of three parts: (1) The Area Explorer, which determines whether the designated area in the configuration file contains numeric values or tomographic images; (2) The Value Reader, which converts images to text according to ophthalmic measurements; and (3) The Finding Classifier, which classifies pathologic findings from tomographic images included in the report. After assessment of Value Reader accuracy by human experts, all report images were converted and stored in a database. We applied the Value Reader, which achieved 99.67% accuracy, to a total of 433,175 OCT report images acquired in a single tertiary hospital from 07/04/2006 to 08/31/2019. The Finding Classifier provided pathologic findings (e.g., macular edema and subretinal fluid) and disease activity. Patient longitudinal data could be easily reviewed to document changes in measurements over time. The final results were loaded into a common data model (CDM), and the cropped tomographic images were loaded into the Picture Archive Communication System. Conclusions The newly developed software extracts valuable information from OCT images and may be extended to other types of report image files produced by medical devices. Furthermore, powerful databases such as the CDM may be implemented or augmented by adding the information captured through our program.

Background: Group-based trajectory modelling (GBTM) has recently been explored internationally as an improved approach to measuring medication adherence (MA) by differentiating between alternative temporal patterns of nonadherence. To build on this international research, we use the method to identify temporal patterns of medication adherence to antidepressants, bisphosphonates or statins, and their associations with patient characteristics. Objectives: The objectives include identification of MA types using GBTM, exploration of features and associated patient characteristics of each MA type, and identification of the advantages of GBTM compared to the traditional proportion of days covered (PDC) measure. Data and methods: We used 45 and Up Study survey data which contains information about demographics, family, health, diet, work and lifestyle of 267,153 participants aged at least 45 years across New South Wales, Australia. This data was linked to participant records of medication use, outpatient and inpatient care, and death. Our study participants initiated use of antidepressants (9287 participants), bisphosphonates (1660 participants) or statins (10,242 participants) during 2012–2016. MA types were identified from 180-day patterns of medication use for antidepressants and 360-day patterns for bisphosphonates and statins. Multinomial and binomial logistic regressions were performed to estimate participant characteristics associated with GBTM MA and PDC MA, respectively. Results: Three GBTM MA types were identified for antidepressants and six for bisphosphonates and statins. For all three medications, MA types included: almost fully adherent; decreasing adherence and early discontinuation. The additional nonadherent types for bisphosphonates and statins were improved adherence, low adherence and later discontinuation. Participant characteristics impacting GBTM MA and PDC MA were consistent. However, several associations were uniquely found for GBTM MA as compared to PDC MA. Conclusion: GBTM permits clinicians, policy-makers and researchers to differentiate between alternative nonadherence patterns, allowing them to better identify patients at risk of poor adherence and tailor interventions accordingly.

AIM: To describe the clinical features and multimodal images of unilateral foveomacular retinitis in young Korean soldiers. METHODS: Ten patients having foveomacular retinitis were included. Fluorescein angiography, fundus autofluorescence (FAF), infrared reflectance (IR), and spectral-domain optical coherence tomography (SD-OCT) were analyzed. RESULTS: All patients were young males experienced insidious visual decline without exposure to bright light. Initial and final vision ranged from hand movement to 20/20 (median 20/200) and 20/2000 to 20/20 (median 20/500), respectively. Vision decreased in 6 patients while improved in two. Typical macular abnormality was yellow granular spots. SD-OCT showed ellipsoid zone (EZ) or interdigitation zone (IZ) disruption of fovea. The degree of EZ/IZ damage correlated with vision. Lesions were clearly visualized through IR and matched with SD-OCT findings. CONCLUSION: This is the first case series of foveomacular retinitis diagnosed with multimodal imaging. Foveomacular retinitis should be suspected in sudden unilateral visual decline especially in young soldiers. SD-OCT is the most important diagnostic modality.

BackgroundDepression, osteoporosis, and cardiovascular disease impose a heavy economic burden on society. Understanding economic impacts of suboptimal use of medication due to nonadherence and non-persistence (non-MAP) for these conditions is important for clinical practice and health policy-making.ObjectiveThis systematic literature review aims to assess the impact of non-MAP to antidepressants, bisphosphonates and statins on healthcare resource utilisation and healthcare cost (HRUHC), and to assess how these impacts differ across medication classes.MethodsA systematic literature review and an aggregate meta-analysis were performed. Using the search protocol developed, PubMed, Cochrane Library, ClinicalTrials.gov, JSTOR and EconLit were searched for articles that explored the relationship between non-MAP and HRUHC (i.e., use of hospital, visit to healthcare service providers other than hospital, and healthcare cost components including medical cost and pharmacy cost) published from November 2004 to April 2021. Inverse-variance meta-analysis was used to assess the relationship between non-MAP and HRUHC when reported for at least two different populations.ResultsScreening 1,123 articles left 10, seven and 13 articles on antidepressants, bisphosphonates, and statins, respectively. Of those, 27 were rated of good quality, three fair and none poor using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. In general, non-MAP was positively associated with HRUHC for all three medication classes and most prominently for bisphosphonates, although the relationships differed across HRUHC components and medication classes. The meta-analysis found that non-MAP was associated with increased hospital cost (26%, p = 0.02), outpatient cost (10%, p = 0.01), and total medical cost excluding pharmacy cost (12%, pConclusionsThis systematic literature review is the first to compare the impact of non-MAP on HRUHC across medications for three prevalent conditions, depression, osteoporosis and cardiovascular disease. Positive relationships between non-MAP and HRUHC highlight inefficiencies within the healthcare system related to non-MAP, suggesting a need to reduce non-MAP in a cost-effective way.

OBJECTIVES The aim of this study was to evaluate the real-world incidence of endophthalmitis after intravitreal anti-vascular endothelial growth factor (VEGF) injections using data from the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). METHODS Patients with endophthalmitis that developed within 6 weeks after intravitreal anti-VEGF injections were identified in 3 large OMOP CDM databases. RESULTS We identified 23,490 patients who received 128,123 intravitreal anti-VEGF injections. The incidence rates of endophthalmitis were 15.75 per 10,000 patients and 2.97 per 10,000 injections. The incidence rates of endophthalmitis for bevacizumab, ranibizumab, and aflibercept (per 10,000 injections) were 3.64, 1.39, and 0.76, respectively. The annual incidence has remained below 5.00 per 10,000 injections since 2011 despite the increasing number of intravitreal anti-VEGF injections. Bevacizumab presented a higher incidence rate for endophthalmitis than ranibizumab and aflibercept (incidence rate ratio, 3.17; p=0.021). CONCLUSIONS The incidence of endophthalmitis after intravitreal anti-VEGF injections has stabilized since 2011 despite the explosive increase in anti-VEGF injections. The off-label use of bevacizumab accounted for its disproportionately high incidence of endophthalmitis. The OMOP CDM, which includes off-label uses, laboratory data, and a scalable standardized database, could provide a novel strategy to reveal real-world evidence, especially in ophthalmology.

Abstract Background The exudative age-related macular degeneration (AMD) causes considerable healthcare costs for patients and healthcare system, which are expected to grow as the population ages. The objective of this study was to assess the incremental economic burden of exudative AMD by comparing total healthcare costs between the exudative AMD group and non-AMD group to understand economic burden related to exudative AMD. Methods This retrospective cohort study used the National Health Insurance Service database including the entire Korean population. Exudative AMD group included individuals with at least one claim for ranibizumab and one claim using the registration code for exudative AMD (V201). Non-AMD group was defined as individuals without any claims regarding the diagnostic code of H35.3 or ranibizumab. The exudative AMD group and non-AMD group were matched using a propensity-score model. Incremental healthcare resource utilization and healthcare costs were measured during a one-year follow-up by employing econometric models: ordinary least squares (OLS) with log transformation and heteroscedastic retransformation; and generalized linear model (GLM) with a log link function and gamma distribution. Results A total of 7119 exudative AMD patients were matched to 7119 non-AMD patients. The number of outpatient visits was higher in the exudative AMD group (P-value

Purpose: To evaluate light exposure from microscope versus intracameral illuminations to patient's and surgeon's retina during cataract surgery. Methods: Thirty consecutive patients who had cataract surgery using microscope and intracameral illuminations. At the point of the ocular of an operating microscope, optical illuminance and irradiance from the microscope illumination (60, 40, 20% intensity) and the intracameral illumination (60% intensity) were measured using a light meter and a spectrometer at a pause after lens capsule polishing in cataract surgery. Results: Average illuminance (lux) was 1.46, 0.66, 0.27, and 0.1 from 60%, 40%, 20% intensity microscope illuminations and 60% intracameral illumination. Average total spectral irradiance (μW/cm2) was 1.25, 0.65, 0.26, and 0.03 from 60%, 40%, 20% intensity microscope illuminations and 60% intracameral illumination. Conclusion: Microscope ocular illuminance and irradiance during cataract surgery were higher in the microscope illumination than in the intracameral illumination. It suggests that light exposure reaching patient's and surgeon's retina during cataract surgery is lower in the intracameral illumination than in the microscope illumination.

Purpose To evaluate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for treatment of neovascular age-related macular degeneration (nAMD) in vitrectomized eyes. Methods The medical records were reviewed of nAMD patients treated with anti-VEGF agents who previously underwent pars plana vitrectomy (PPV). PPV was performed with complete posterior vitreous detachment induction. Results A total of 44 eyes from 44 patients were included. The mean central foveal thickness (CFT) was 478.50 ± 156.93 μm at baseline, 414.25 ± 143.55 μm (86.6% of baseline) at 1 month after first injection (P < 0.001), and 386.75 ± 141.45 μm (80.8% of baseline) after monthly multiple injections (2.30 ± 1.07; range, 1–5) (P < 0.001). The mean logarithm of the minimum angle of resolution best-corrected visual acuity visual acuity (BCVA) was 0.85 ± 0.57 at baseline, 0.86 ± 0.63 after the first injection, and 0.84 ± 0.64 after monthly multiple injections. BCVA improved in 39.5% at 1 month after first injection and 45.2% at 1 month after monthly multiple injections. In the subgroup analysis, CFT of eyes with the posterior capsule decreased significantly to 85.8% and 79.8% of baseline values at 1 month after the first injection and after monthly multiple injections, respectively. CFT of eyes without the posterior capsule decreased to 91.6% and 87.4% of baseline values at 1 month after the first injection and after monthly multiple injections, respectively, without statistical significance. Conclusion Monthly injections of Intravitreal anti-VEGF agents induced favorable anatomical improvement and vision maintenance in vitrectomized eyes with nAMD.

Abstract Background To identify novel biomarkers related to the pathogenesis of dry age-related macular degeneration (AMD), we adopted a human retinal pigment epithelial (RPE) cell culture model that mimics some features of dry AMD including the accumulation of intra- and sub-RPE deposits. Then, we investigated the aqueous humor (AH) proteome using a data-independent acquisition method (sequential window acquisition of all theoretical fragment ion mass spectrometry) for dry AMD patients and controls. Methods After uniformly pigmented polarized monolayers of human fetal primary RPE (hfRPE) cells were established, the cells were exposed to 4-hydroxy-2-nonenal (4-HNE), followed by Western blotting, immunofluorescence analysis and ELISA of cells or conditioned media for several proteins of interest. Data-dependent acquisition for identification of the AH proteome and SWATH-based mass spectrometry were performed for 11 dry AMD patients according to their phenotypes (including soft drusen and reticular pseudodrusen [RPD]) and 2 controls (3 groups). Results Increased intra- and sub-RPE deposits were observed in 4-HNE-treated hfRPE cells compared with control cultures based on APOA1, cathepsin D, and clusterin immunoreactivity. Additionally, the differential abundance of proteins in apical and basal chambers with or without 4-HNE treatment confirmed the polarized secretion of proteins from hfRPE cells. A total of 119 proteins were quantified in dry AMD patients and controls by SWATH-MS. Sixty-five proteins exhibited significantly altered abundance among the three groups. A two-dimensional principal component analysis plot was generated to identify typical proteins related to the pathogenesis of dry AMD. Among the identified proteins, eight proteins, including APOA1, CFHR2, and CLUS, were previously considered major components or regulators of drusen. Three proteins (SERPINA4, LUM, and KERA proteins) have not been previously described as components of drusen or as being related to dry AMD. Interestingly, the LUM and KERA proteins, which are related to extracellular matrix organization, were upregulated in both RPD and soft drusen. Conclusions Differential protein expression in the AH between patients with drusen and RPD was quantified using SWATH-MS in the present study. Detailed proteomic analyses of dry AMD patients might provide insights into the in vivo biology of drusen and RPD.

Abstract Background Interface fluid syndrome (IFS) is an unusual complication after laser-assisted in-situ keratomileusis (LASIK). We report the first case of IFS after uncomplicated phacotrabeculectomy in a patient who had undergone LASIK 10 years previously. This case emphasizes the importance of intraocular pressure (IOP) interpretation in eyes that have undergone LASIK. Case presentation A 30-year-old woman with a history of LASIK surgery presented to glaucoma clinic due to uncontrolled IOP despite of maximally tolerable medical treatment. After receiving phacotrabeculectomy, IOP decreased to 3 mmHg on the first postoperative day, but again increased up to 21 mmHg and a diffuse corneal edema with cloudy flap interface was demonstrated by slit-lamp microscopy. Corneal edema was sustained even after the IOP was lowered to 14 mmHg. Spectral-domain optical coherence tomography scanning of the cornea revealed a diffuse, thin fluid pocket in the corneal interface. After laser lysis of the scleral flap sutures, IOP was further decreased to 9 mmHg and interface fluid was resolved. Conclusion IFS should be considered as a possible cause of postoperative corneal edema despite of low IOP in the eyes that underwent LASIK surgery. Additional IOP lowering may be helpful for resolving the corneal edema.

Abstract Vision loss can occur in eyes with blunt ocular trauma, but the causes have not been elucidated fully. We encountered cases of retinal pigment epithelium (RPE) sequelae following blunt ocular trauma associated with permanent vision loss in our cohort of patients with blunt ocular trauma. In this multicentre retrospective cohort study on 129 patients with retinal abnormalities caused by acute blunt ocular trauma, we investigated the incidence of RPE sequelae and evaluated associated factors and visual outcomes. RPE sequelae, which typically presented as hyperpigmentation within well-demarcated hypopigmented lesions, occurred in 29 (22.5%) patients within 1 month of trauma. Optical coherence tomography (OCT) revealed complete photoreceptor loss over the abnormal RPE. Final visual outcomes were significantly different between eyes with and without RPE sequelae. Logistic regression analysis revealed a significant association between the presence of subretinal fluid and RPE sequelae. In conclusion, RPE sequelae occurred in approximately 20% of patients with blunt ocular trauma and was associated with permanent photoreceptor defects and visual loss. Clinical evaluation using OCT may help predict RPE sequelae and visual outcomes in eyes with blunt trauma.

We investigated the presence of cerebral small vessel disease (SVD) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) compared to control subjects without NAION to identify the association between NAION and cerebral SVD. We retrospectively reviewed the cases of 63 patients with NAION and 2749 control subjects without any neurologic and ocular diseases including NAION who underwent careful medical interviews, ophthalmic examinations, and magnetic resonance imaging (MRI) studies of the brain. We assessed and compared the degree of cerebral SVD on the MRIs. The patients with NAION presented with cerebral SVD more frequently than controls (68% versus 37%, respectively, p

ObjectivesTo investigate the characteristics and temporal changes in visual field defects (VFDs) in eyes with acute central retinal artery occlusion (CRAO).DesignRetrospective, observational case series.MethodsA total of 119 patients diagnosed with acute non-arteritic CRAO through examination with Goldmann perimetry were included among the patients who visited Seoul National University Bundang Hospital between January 2009 and December 2016. They were treated with either conservative treatments or intra-arterial thrombolysis (IAT). The baseline features and temporal changes of visual field examination results and the association with clinical parameters including visual acuity, optical coherence tomography (OCT) findings, and the CRAO stages.ResultsAll of the 119 patients showed visual field defect and suffered unilateral acute CRAO. We observed five characteristic VFDs: peripheral constriction only (8%), paracentral scotoma (3%), central and cecocentral scotoma (19%), temporal island (59%), and no visual field (10%). Severe VFDs were associated with severe CRAO stages, poor baseline BCVA, delayed retinal arterial perfusion, and severe retinal morphologic changes on OCT. We found improvements in the visual field in 39% of all cases during the follow-up periods. Mild CRAO stages, good baseline BCVA, mild retinal morphologic changes, and mild initial VFDs were significantly associated with visual field improvement.ConclusionsThe five characteristic types of VFDs and their improvement in eyes with CRAO are associated with baseline features related to the severity of retinal ischemia. We suggest that the underlying mechanisms of VFDs involve the balance between the retinal arterial perfusion and the ischemic vulnerability of each retinal area.

[This corrects the article DOI: 10.1371/journal.pone.0209118.].

In this study, Retina-RPE-Choroid-Sclera (RCS) and RPE-Choroid-Sclera (CS) were prepared by scraping them off neural retina, and using the Ussing chamber we measured the average time–concentration values in the acceptor chamber across five isolated rabbit tissues for each drug molecule. We determined the outward direction permeability of the RCS and CS and calculated the neural retina permeability. The permeability coefficients of RCS and CS were as follows: ganciclovir, 13.78 ± 5.82 and 23.22 ± 9.74; brimonidine, 15.34 ± 7.64 and 31.56 ± 12.46; bevacizumab, 0.0136 ± 0.0059 and 0.0612 ± 0.0264 (×10−6 cm/s). The calculated permeability coefficients of the neural retina were as follows: ganciclovir, 33.89 ± 12.64; brimonidine, 29.83 ± 11.58; bevacizumab, 0.0205 ± 0.0074 (×10−6 cm/s). Between brimonidine and ganciclovir, lipophilic brimonidine presented better RCS and CS permeability, whereas ganciclovir showed better calculated neural retinal permeability. The large molecular weight drug bevacizumab demonstrated a much lower permeability than brimonidine and ganciclovir. In conclusion, the ophthalmic drug permeability of RCS and CS is affected by the molecular weight and lipophilicity, and influences the intravitreal half-life.

PurposeTo analyze the associations of retinal and choroidal thickness on enhanced-depth imaging optical coherence tomography (EDI-OCT) with clinical, ophthalmic and genetic factors in the normal elderly population (aged 65 years or older).MethodsIn this prospective, population-based cohort study, people aged 65 years or older were enrolled in the baseline study of the Korean Longitudinal Study on Health and Aging (KLoSHA) Eye Study. All participants underwent spectral domain-OCT scan using the EDI technique. A topographic map of the retina was obtained and subfoveal choroidal thickness (SFCT) was measured manually. Blood samples from all subjects were genotyped for major age-related macular degeneration (AMD)-associated single nucleotide polymorphisms (SNPs) the major AMD-associated SNPs; CFH Y402H rs1061170, CFH I62V rs800292, ARMS2 A69S rs10490924. A statistical analysis was conducted to compare the retinal thickness, choroidal thickness, and AMD risk genotypes.ResultsAmong the three hundred eighty people enrolled, the mean age was 76.6 years (range 65-99 years). Factors that showed correlation with either tomographic retinal parameters, retinal nerve fiber layer, or SFCT, were age and gender. Significant age-related decrease in thickness was observed in the RNFL, mean central thickness (MCT) and SFCT. Gender differences existed in central foveolar thickness (CFT) and MCT, where it was thicker in men. While chorioretinal parameters were not related with other genotypes, CFH rs1061170 risk genotype was significantly associated with thin SFCT. The group containing the AMD- risk allele (CT) had a 14.7% reduction in the SFCT compared to the non-risk TT group.ConclusionsIn addition to the well-known association with AMD, CFH rs1061170 is a significant genetic risk factor associated with choroidal thinning in normal eyes of the elderly population. Such findings may provide further insight into the pathogenesis of age-related macular degeneration as well as normal aging. In addition, our study provides the first normative data on retinal and choroidal thickness in population-based aged groups with a mean age over seventy-five.

PURPOSE:To determine whether ocular motor cranial nerve (CN) palsy raises the risk of subsequent stroke in the general population. METHODS:We investigated the association between ocular motor CN palsy and occurrence of stroke using the National Health Insurance Service-National Sample Cohort database from 2002 to 2013. We included individuals aged ≥ 20 years on January 1st, 2004, and excluded those having any paralytic strabismus, disorders in binocular movement, diplopia and any cerebrovascular diseases before entering the cohort. Incident ocular motor CN palsy was identified by diagnostic codes for third, fourth, and sixth nerve palsies. To determine the effect of incident ocular motor CN palsy on the occurrence of subsequent stroke, we used time-varying covariate Cox regression models. Model 1 included only incident third, fourth, and sixth nerve palsies as a time-varying covariate. Model 2 included Model 1 and defined demographic information. Model 3 included Model 2, comorbidity, co-medication, and the Charlson index score. RESULTS:Among 727,689 individuals in the cohort, 1,633 patients developed ocular motor CN palsy and 17,657 patients suffered stroke. Cox regression models showed that development of ocular motor CN palsy was associated with an increased risk of subsequent stroke (hazard ratio [HR] = 4.65; 95% confidence intervals [CIs], 3.74-5.80 in Model 1), and the results were consistent even after adjusting for demographic factors and confounders in Model 2 and 3. Men, older age, and individuals not living in Seoul/Incheon area were associated with an increased risk of stroke, while individuals with higher income were associated with decreased risk of stroke in both Model 2 and 3. Sensitivity analyses using propensity score-based matching produced similar results in all three Models (HR = 1.95; 95% CI, 1.55-2.46 in Model 1, HR = 1.91; 95% CI, 1.52-2.41 in Model 2, and HR = 1.63; 95% CI, 1.29-2.06 in Model 3). CONCLUSIONS:The occurrence of ocular motor CN palsy is a significant risk factor of subsequent stroke even after adjusting for demographic factors and confounders in the general population. Physicians may need to educate patients with ocular motor CN palsy regarding the higher risk of future stroke.

PURPOSE:We aimed to investigate the prevalence of diabetic retinopathy (DR) in patients with diabetic foot ulcer (DFU) and elucidate the association between DR and DFU severities and their shared risk factors. METHODS:A retrospective review was conducted on DFU patients who underwent ophthalmic and vascular examinations within 6 months; 100 type 2 diabetic patients with DFU were included. The medical records of 2496 type 2 diabetic patients without DFU served as control data. DR prevalence and severity were assessed in DFU patients. DFU patients were compared with the control group regarding each clinical variable. Additionally, DFU patients were divided into two groups according to DR severity and compared. RESULTS:Out of 100 DFU patients, 90 patients (90%) had DR and 55 (55%) had proliferative DR (PDR). There was no significant association between DR and DFU severities (R = 0.034, p = 0.734). A multivariable analysis comparing type 2 diabetic patients with and without DFUs showed that the presence of DR [OR, 226.12; 95% confidence interval (CI), 58.07-880.49; p < 0.001] and proliferative DR [OR, 306.27; 95% CI, 64.35-1457.80; p < 0.001), higher HbA1c (%, OR, 1.97, 95% CI, 1.46-2.67; p < 0.001), higher serum creatinine (mg/dL, OR, 1.62, 95% CI, 1.06-2.50; p = 0.027), older age (years, OR, 1.12; 95% CI, 1.06-1.17; p < 0.001), higher pulse pressure (mmHg, OR, 1.03; 95% CI, 1.00-1.06; p = 0.025), lower cholesterol (mg/dL, OR, 0.94; 95% CI, 0.92-0.97; p < 0.001), lower BMI (kg/m2, OR, 0.87, 95% CI, 0.75-1.00; p = 0.044) and lower hematocrit (%, OR, 0.80, 95% CI, 0.74-0.87; p < 0.001) were associated with DFUs. In a subgroup analysis of DFU patients, the PDR group had a longer duration of diabetes mellitus, higher serum BUN, and higher serum creatinine than the non-PDR group. In the multivariable analysis, only higher serum creatinine was associated with PDR in DFU patients (OR, 1.37; 95% CI, 1.05-1.78; p = 0.021). CONCLUSIONS:Diabetic retinopathy is prevalent in patients with DFU and about half of DFU patients had PDR. No significant association was found in terms of the severity of these two diabetic complications. To prevent blindness, patients with DFU, and especially those with high serum creatinine, should undergo retinal examinations for timely PDR diagnosis and management.

To investigate the incidence and risk factors of the no-reflow phenomenon in central retinal artery occlusion (CRAO) patients and to determine its effects on visual and anatomic outcomes.In 102 eyes with CRAO in which arterial recanalization was obtained within 1 week from baseline, fluorescein angiography images obtained at baseline and 1 week were retrospectively reviewed. The no-reflow phenomenon in the retina was defined as macular capillary nonperfusion following arterial recanalization on fluorescein angiographs. We investigated the incidence and risk factors for the no-reflow phenomenon and compared the anatomical and visual outcomes between eyes with and without the phenomenon.Among the 102 CRAO eyes with arterial recanalization, 39 exhibited the no-reflow phenomenon, resulting in an incidence of 38.2%. The incidence among the eyes with treatment-induced and spontaneous recanalization was 43.4% and 15.8%, respectively, and it increased with the CRAO stage. CRAO stage and increased central macular thickness were risk factors for the phenomenon, with an odds ratio of 4.47 [95% confidence interval (CI), 1.19-16.8; P = 0.027] and 1.69 (95% CI, 1.12-2.55; P = 0.012) per 100-μm increase, respectively. The visual outcome was significantly poorer and retinal atrophy and photoreceptor disruption was greater in eyes with the no-reflow phenomenon than in those without.The no-reflow phenomenon may occur after arterial recanalization in approximately one-third of CRAO patients and can affect anatomical and visual outcomes. This phenomenon may provide an additional explanation regarding the permanent retinal damage and vision loss in eyes with CRAO.

To investigate the association of genetic and environmental factors, and their interactions in Korean patients with exudative age-related macular degeneration (AMD).A total of 314 robustly characterized exudative AMD patients, including 111 PCV (polypoidal choroidal vasculopathy) and 154 typical choroidal neovascularization (CNV), and 395 control subjects without any evidence of AMD were enrolled. Full ophthalmologic examinations including fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were done, according to which patients were divided into either PCV or typical CNV. Standardized questionnaires were used to collect information regarding underlying systemic diseases, dietary habits, smoking history and body mass index (BMI). A total of 86 SNPs from 31 candidate genes were analyzed. Genotype association and logistic regression analyses were done and stepwise regression models to best predict disease for each AMD subtype were constructed.Age, spherical equivalent, myopia, and ever smoking were associated with exudative AMD. Age, hypertension, hyperlipidemia, spherical equivalent, and myopia were risk factors for typical CNV, while increased education and ever smoking were significantly associated with PCV (p

To investigate the incidence of retinal vein occlusion (RVO) in pregnant women and in the subpopulation of pregnant women with pre-eclampsia/eclampsia compared to that in the age-matched general female population to determine if there is increased risk of RVO in pregnancy.Nationwide population-based retrospective study using data entered into the Korean national health claims database from 2007 to 2011.Of the incident RVO cases in the database, RVO cases that occurred during the pregnancy-associated period, which spanned a 52-week period from 40-weeks-before to 12-weeks-after childbirth, were identified. Of these cases, the presence of pre-eclampsia/eclampsia was determined.The standardized incidence ratios (SIRs) of RVO in the general pregnant population and in the pregnant population with pre-eclampsia/eclampsia were determined with respect to the age-matched general female population.Pregnancy-related RVO was identified in 33 cases from the 1.8 million women who experience childbirth during the study period, while the expected number of cases calculated by the direct standardization to the age-matched general population was 113. Of the 33 patients, 12 patients (36.4%) had pre-eclampsia or eclampsia. The SIR for the general pregnant population in reference to the age-matched general female population was 0.29 (95% CI, 0.20-0.41). In contrast, the SIR for the pregnant population with pre-eclampsia/eclampsia in reference to the age-matched general female population and the age-matched general pregnant population was 67.50 (95% CI, 34.88-117.92) and 246.50 (95% CI, 127.37-430.59), respectively.The results suggest that pre-eclampsia/eclampsia is a risk factor for RVO, while pregnancy itself may not be a risk factor for RVO.

PURPOSE: To investigate the clinical features, clinical course of granuloma, serologic findings, treatment outcome, and probable infection sources in adult patients with ocular toxocariasis (OT). METHODS: In this retrospective cohort study, we examined 101 adult patients diagnosed clinically and serologically with OT. Serial fundus photographs and spectral domain optical coherence tomography images of all the patients were reviewed. A clinic-based case-control study on pet ownership, occupation, and raw meat ingestion history was performed to investigate the possible infection sources. RESULTS: Among the patients diagnosed clinically and serologically with OT, 69.6% showed elevated immunoglobulin E (IgE) levels. Granuloma in OT involved all retinal layers and several vitreoretinal comorbidities were noted depending on the location of granuloma: posterior pole granuloma was associated with epiretinal membrane and retinal nerve fiber layer defects, whereas peripheral granuloma was associated with vitreous opacity. Intraocular migration of granuloma was observed in 15 of 93 patients (16.1%). Treatment with albendazole (400 mg twice a day for 2 weeks) and corticosteroids (oral prednisolone; 0.5-1 mg/kg/day) resulted in comparable outcomes to patients on corticosteroid monotherapy; however, the 6-month recurrence rate in patients treated with combined therapy (17.4%) was significantly lower than that in patients treated with corticosteroid monotherapy (54.5%, P=0.045). Ingestion of raw cow liver (80.8%) or meat (71.2%) was significantly more common in OT patients than healthy controls. CONCLUSIONS: Our study discusses the diagnosis, treatment, and prevention strategies for OT. Evaluation of total IgE, in addition to anti-toxocara antibody, can assist in the serologic diagnosis of OT. Combined albendazole and corticosteroid therapy may reduce intraocular inflammation and recurrence. Migrating feature of granuloma is clinically important and may further suggest the diagnosis of OT. Clinicians need to carefully examine comorbid conditions for OT. OT may be associated with ingestion of uncooked meat, especially raw cow liver, in adult patients.

PURPOSE: To define the incidence and demographic characteristics of rhegmatogenous retinal detachment (RRD) requiring surgery in Korea. DESIGN: Nationwide population-based retrospective study. METHODS: Patients who underwent surgery for RRD from 2007 to 2011 were retrospectively identified using the diagnostic code for RRD and the surgical codes for retinal detachment surgeries in the national claim database. The average incidence rate of RRD during the 5-year period was estimated using the population data of the 2010 Census in Korea. RESULTS: A total of 24,928 surgically treated RRD cases were identified. The average incidence of surgery requiring RRD was 10.39 cases per 100,000 person-years [95% confidence interval (CI), 10.26-10.52). The incidence in men (11.32 cases per 100,000 person-years; 95% CI: 11.13-11.51) was significantly higher than that in women (9.47 cases per 100,000 person-years; 95% CI: 9.29-9.64) (p