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Abstract This study evaluated changes in retinal sensitivity (RS) during aflibercept treatment in neovascular age-related macular degeneration (nAMD) patients with good vision. Treatment-naive nAMD patients with visual acuity better than 20/40 were treated with an aflibercept loading regiment, and RS was measured using the MAIA microperimetry device. The study examined RS differences based on visit, region, adjacent local pathology, outer retinal changes and optical coherence tomography angiography (OCTA) data were investigated. Twelve patients completed the protocol. Mean RS improved from 17.9 (3.9) µm at baseline to 20.4 (4.7) µm at final visit, while best-corrected visual acuity (BCVA) did not change. (P = 0.041) RS at baseline is worst in the presence of intraretinal fluid (IRF) and improved after treatment for all retinal pathologies except IRF. RS improvement occurred even with initial outer retinal damage. A Linear mixed model showed subretinal hyperreflective material, baseline IRF height, outer retinal integrity, fibrovascular pigment epithelial detachment height, and local choroidal vascular index as factors associated with RS. In conclusion, RS improved with aflibercept treatment in nAMD eyes with good initial visual acuity, despite no change in BCVA, except when IRF was present.

Objective Although central serous chorioretinopathy (CSC) treatment using selective retinal therapy (SRT) has presented favourable outcomes, no long-term studies with a real-world clinical practice regimen have been conducted.Methods and analysis We performed a long-term assessment of CSC treatment using SRT with real-time feedback (RTF) technology. 50 patients (53 eyes) with CSC and more than a 1-month symptom duration were recruited and treated with SRT using a 1.7 µs pulse width, 527 nm neodymium-doped yttrium lithium fluoride (Nd:YLF) laser equipped with an RTF system.Results After 6 months of treatment, complete subretinal fluid resolution was achieved in 62% of the eyes. The mean best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution, mean±SD) improved slightly from 0.15±0.18 at baseline to 0.12±0.21 at 6 months (p=0.062). The central retinal thickness (CRT; mean±SD) was reduced significantly from 350.6±100.1 µm at baseline to 268.2±70.6 µm at 6 months (p

AIM: To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor (VEGF) injections to treat neovascular age-related macular degeneration (nAMD) with subretinal fluid (SRF) and pigment epithelial detachment (PED). METHODS: This prospective study included eyes with nAMD previously treated with as-needed anti-VEGF injections. The patients were treated with six monthly intravitreal injections of ranibizumab. Quantitative volumetric segmentation analyses of the SRF and PED were performed. The main outcome measures included best-corrected visual acuity (BCVA), and SRF and PED volumes. RESULTS: Twenty eyes of 20 patients were included in this study. At the 6-month follow-up, BCVA and PED volume did not change significantly (P=0.110 and 0.999, respectively) but the mean SRF volume decreased from 0.53±0.82 mm3 at baseline to 0.08±0.23 mm3 (P=0.002). The absorption rate of the SRF volume was negatively correlated with the duration of previous anti-VEGF treatment (P=0.029). Seven of the 20 eyes (35%) showed a fluid-free macula and significant improvement in BCVA (P=0.036) by month 6. CONCLUSION: Quantifying the SRF can precisely determine the patient's responsiveness to anti-VEGF treatment of nAMD.

Abstract We investigated the associations between retinal vascular geometric measurements and idiopathic epiretinal membrane (ERM). Whether changes in retinal vascular geometry are independent of systemic cardiovascular risk factors was also evaluated. This retrospective, cross sectional study included 98 patients with idiopathic ERM, and 99 healthy age-matched controls. Quantitative retinal vascular parameters were measured from digital retinal fundus photographs using a semi-automated computer-assisted program. Multivariate logistic regression analyses were performed to evaluate associations between retinal vascular geometric parameters and the presence of idiopathic ERM after adjusting for systemic cardiovascular risk factors. There was no significant difference in the baseline characteristics of the two groups, except that the ERM group had a higher proportion of females than the control group. In multivariate regression analyses, female sex (odds ratio [OR] 0.402; 95% CI 0.196–0.802; P = 0.011), wider retinal venular caliber (OR 16.852; 95% CI 5.384–58.997; P

ProblemLow-quality fundus images with complex degredation can cause costly re-examinations of patients or inaccurate clinical diagnosis.AimThis study aims to create an automatic fundus macular image enhancement framework to improve low-quality fundus images and remove complex image degradation.MethodWe propose a new deep learning-based model that automatically enhances low-quality retinal fundus images that suffer from complex degradation. We collected a dataset, comprising 1068 pairs of high-quality (HQ) and low-quality (LQ) fundus images from the Kangbuk Samsung Hospital's health screening program and ophthalmology department from 2017 to 2019. Then, we used these dataset to develop data augmentation methods to simulate major aspects of retinal image degradation and to propose a customized convolutional neural network (CNN) architecture to enhance LQ images, depending on the nature of the degradation. Peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), r-value (linear index of fuzziness), and proportion of ungradable fundus photographs before and after the enhancement process are calculated to assess the performance of proposed model. A comparative evaluation is conducted on an external database and four different open-source databases.ResultsThe results of the evaluation on the external test dataset showed an significant increase in PSNR and SSIM compared with the original LQ images. Moreover, PSNR and SSIM increased by over 4 dB and 0.04, respectively compared with the previous state-of-the-art methods (P < 0.05). The proportion of ungradable fundus photographs decreased from 42.6% to 26.4% (P = 0.012).ConclusionOur enhancement process improves LQ fundus images that suffer from complex degradation significantly. Moreover our customized CNN achieved improved performance over the existing state-of-the-art methods. Overall, our framework can have a clinical impact on reducing re-examinations and improving the accuracy of diagnosis.

Abstract It has been known that retinal vein occlusion (RVO) is associated with chronic kidney disease, especially end-stage renal disease (ESRD). However, little is known about the effect of kidney transplantation (KT) on RVO incidence in ESRD patients. This study aimed to compare the incidence of RVO in KT recipients (n = 10,498), matched ESRD patients (n = 10,498), and healthy controls (HCs, n = 10,498), using a long-term population-based cohort. The incidence of RVO was 2.74, 5.68, and 1.02 per 1000 patient-years, for the KT group, the ESRD group, and the HCs group, respectively. Adjusted hazard ratios for RVO development compared to the HCs group, were 1.53 and 3.21, in the KT group and the ESRD group, respectively. In the KT group, multivariable regression analysis indicated that an age over 50, a Charlson Comorbidity Index score over 4, and a history of desensitization therapy were associated with an increased risk of RVO. In summary, KT recipients have a lower risk for development of RVO than ESRD patients treated with dialysis. However, the risk is still higher compared to healthy people who have normal kidney functions.

Abstract Background To date, no genetic analysis of inherited retinal disease (IRD) using whole-exome sequencing (WES) has been conducted in a large-scale Korean cohort. The aim of this study was to characterise the genetic profile of IRD patients in Korea using WES. Methods We performed comprehensive molecular testing in 168 unrelated Korean IRD patients using WES. The potential pathogenicity of candidate variants was assessed using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology variant interpretation guidelines, in silico prediction tools, published literature, and compatibility with known phenotypes or inheritance patterns. Results Causative variants were detected in 86/168 (51.2%) IRD patients, including 58/107 (54.2%) with retinitis pigmentosa, 7/15 (46.7%) with cone and cone-rod dystrophy, 2/3 (66.6%) with Usher syndrome, 1/2 (50.0%) with congenital stationary night blindness, 2/2 (100.0%) with Leber congenital amaurosis, 1/1 (100.0%) with Bietti crystalline dystrophy, 1/1 (100.0%) with Joubert syndrome, 9/10 (90.0%) with Stargardt macular dystrophy, 1/10 (10.0%) with vitelliform macular dystrophy, 1/11 (9.1%) with other forms of macular dystrophy, and 3/4 (75.0%) with choroideraemia. USH2A, ABCA4, and EYS were the most common causative genes associated with IRD. For retinitis pigmentosa, variants of USH2A and EYS were the most common causative gene mutations. Conclusions This study demonstrated the distribution of causative genetic mutations in Korean IRD patients. The data will serve as a reference for future genetic screening and development of treatment modalities for Korean IRD patients.

Retrospective review of 13 eyes that had undergone pars plana vitrectomy (PPV) for vitreomacular traction (VMT) syndrome in retinitis pigmentosa (RP) and had a postoperative follow-up period ≥9mo in order to evaluate whether it is necessary to treat VMT in RP by vitrectomy. The 13 RP eyes suffering from VMT were evaluated by means of best corrected visual acuity (BCVA), anterior and posterior binocular examination, spectral-domain optical coherence tomography (SD-OCT) before and after operation. We detected that although vitrectomy could improve the macular morphology in some RP patients with VMT, visual outcomes might be limited and unpredicted most likely because of the long-standing retinal dysfunction, but the vitrectomy is necessary in order to remain or improve the central vision in some cases.

Abstract Background Anterior uveitis is the most common extra-articular manifestation of ankylosing spondylitis (AS). AS-related anterior uveitis frequently presents as acute, recurrent iridocyclitis; therefore, AS is often initially suspected by an ophthalmologist, not by a rheumatologist. In this study, we aimed to investigate the relationship between the recurrence of anterior uveitis and the subsequent incidence of AS. Methods From a national sample cohort, 10,483 patients with new-onset uveitis between 2004 and 2013 and 52415 matched control subjects who had never experienced uveitis were selected. Among the patients with new-onset uveitis, a subpopulation of patients with recurrent uveitis, defined as a minimum 120-day reported interval between consecutive claims of uveitis (based on diagnostic codes) treated with local or systemic steroids or immune-modulating drugs, was identified. The incidence rates of AS were calculated according to the number of episodes of uveitis, and the incidence rate ratios (IRRs) were derived on the basis of the incidence rate in the control group. Results The incidence rate per 100,000 person-years of AS after the first uveitis episode was 121.5, whereas the incidence in the control group was 16.9 (IRR, 7.40; 95% CI, 4.99–10.98); after the second uveitis episode, the IRR increased to 17.71 (95% CI, 10.44–30.06). In male and female patients with recurrent uveitis, the incidence rates of AS were 284.1 and 268.7 per 100,000 person-years, respectively. In patients aged under 40 years, the IRR of the recurrent uveitis group was 46.78 (95% CI, 19.61–111.61). In patients aged over 59 years, AS incidence in the recurrent uveitis group did not differ from that in the control group. Conclusions The risk of subsequent AS increased with the number of episodes of anterior uveitis. This quantitative evidence could contribute to the establishment of a rationale for ancillary workup for possible systemic associations in patients with recurrent uveitis.

Abstract Background To investigate whether genetic risk variants for age-related macular degeneration (AMD) are associated with response to intravitreal anti-vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) patients. Methods This prospective cohort study included 95 treatment-naïve patients that underwent anti-VEGF treatment for PCV for 12 months. Patients were genotyped for 10 single nucleotide polymorphisms in eight AMD-relevant genes. Genotypic association with visual and anatomic outcome measures at 12 months after initial treatment, including mean change in best-corrected visual acuity (BCVA) and total foveal thickness, visual gain of ≥ 15 letters, dry status on optical coherence tomography (OCT), pigment epithelial detachment (PED) regression on OCT, polyp regression on indocyanine green angiography, and injection numbers, were investigated using regression models with adjustment for non-genetic covariates under additive genetic model. Results In 81 patients who completed 12-month anti-VEGF monotherapy without photodynamic therapy, significant pharmacogenetic association was found between ARMS2 rs10490924 and PED regression on OCT. Proportions of PED regression were 26.4% for TT, 45.7% for TG, and 63.6% for GG genotype, showing additive effect of G allele for higher chance of PED regression (OR, 2.96; 95% CI, 1.38–6.36; corrected P = 0.043). For entire 95 patients, no significant association was found between candidate polymorphisms and receiving photodynamic therapy within 12 months. Conclusions In PCV patients, ARMS2 rs10490924 showed association with anatomic therapeutic response to anti-VEGF, suggesting pharmacogenetic relationship.

PurposeVitreous vitamin C, as an anti-oxidant, is responsible for regulating oxygen tension and oxidative stress in the eye. Oxidative stress and retinal ischemia are implicated in the development of proliferative diabetic retinopathy (PDR). In this study, we aimed to determine whether vitreous level of vitamin C is compromised in patients with PDR and to investigate the association of diabetic macular ischemia and vitamin C.MethodsThis prospective study enrolled forty patients who underwent pars plana vitrectomy for the treatment of PDR (PDR group, n = 20) and idiopathic epiretinal membrane (control group, n = 20). Serum, aqueous humor, and the vitreous were collected for the analysis of vitamin C level by HPLC. Diabetic macular ischemia (DMI) in PDR group was evaluated with fluorescein angiography (FA).ResultsPDR patients (60.4 ± 2.1 y) were younger than non-diabetic control patients (67.4 ± 1.2 y). Serum, aqueous, and vitreous levels of vitamin C in PDR were 38.7%, 22.5%, and 11.1% of non-diabetic control group, respectively. All PDR patients had DMI (grade 1: 25%, grade 2: 30%, grade 3: 30%, grade 4: 15%). DMI grade was inversely correlated with the level of vitreous vitamin C (r = -0.546, P = 0.019), not with HbA1C, serum, or aqueous vitamin C level. In addition, the level of vitreous vitamin C (4.5 ± 2.6 μg/ml) in high DMI group (Gr 3 &4) was lower than that (31.0 ± 9.1 μg/ml) in low DMI group (Gr 1&2) (P = 0.015).ConclusionsVitreous level of vitamin C in PDR patients showed a tenfold decrease, which was associated with the degree of macular ischemia. This suggests that vitreous vitamin C depletion may cause macula ischemia in PDR patients.

Purpose: The promotion of educators is challenged by the lack of accepted standards to evaluate the quality and impact of educational activities. Traditionally, promotion is related to research productivity. This study developed an evaluation tool for educational performance of medical school faculty using educator portfolios (EPs). Methods: Design principles and quantitative items for EPs were developed in a consensus workshop. These principles were tested in a simulation and revised based on feedback. The changes of total educational activities following introduction of the system were analyzed. Results: A total of 71% faculty members answered the simulation of the system and the score distributed widely (mean±standard deviation, 65.43±68.64). The introduction of new system significantly increased the total educational activities, especially in assistant professors. Conclusion: The authors offer comprehensive and practical tool for enhancing educational participation of faculty members. Further research for development of qualitative evaluation systems is needed.

Oxidative stress has been implicated as critical pathogenic factors contributing to the etiology of diabetic retinopathy and other retinal diseases. This study investigated antioxidative effect of ascorbic acid and astaxanthin on ARPE-19 cells within an oxidative stress model induced by common biological sources of reactive oxygen species (ROS). Hydrogen peroxide (H2O2) at concentrations of 0.1–0.8 mM and 20–100 mJ/cm2 of ultraviolet B (UVB) were treated to ARPE-19 cells. Cell viability and intracellular ROS level changes were measured. With the sublethal and lethal dose of each inducers, 0–750 μM of ascorbic acid and 0–40 μM of astaxanthin were treated to examine antioxidative effect on the model. Ascorbic acid at concentrations of 500 and 750 μM increased the cell viability not only in the UVB model but also in the H2O2 model, but 20 and 40 μM of astaxanthin only did so in the UVB model. The combination of ascorbic acid and astaxanthin showed better antioxidative effect compared to each drug alone, suggesting a synergistic effect.

PURPOSE:This study evaluated changes in choroidal vascularity after half-fluence photodynamic therapy (HF-PDT) in patients with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (SS-OCT) en face imaging. METHODS:This retrospective comparative case series included 50 eyes of 25 patients with unilateral CSC who underwent HF-PDT and 50 age-and sex-matched normal healthy control eyes. En face SS-OCT images of the choriocapillaris, Sattler's layer, and Haller's layer were converted into binary images. The vascular proportions were defined as the percentage of the area of vascular lumen against the area of the 3.0-mm-diameter circular area. The main outcome measures were the vascular proportions before HF-PDT and at 6 weeks, 6 months, and 12 months after HF-PDT. RESULTS:At baseline, the vascular proportions in the CSC eyes were significantly greater than those in the control eyes in all layers (choriocapillaris: 51.8% ± 15.5% vs. 41.3 ± 18.7%, P = 0.018; Sattler's: 58.6% ± 13.4% vs. 49.7% ± 15.7%, P = 0.017; Haller's: 65.3% ± 15.3% vs. 53.0% ± 13.4%, P = 0.001). In the CSC eyes, the vascular proportion in the choriocapillaris significantly decreased at 6 weeks (36.6% ± 16.9%, P < 0.001), 6 months (34.0% ± 12.3%, P < 0.001), and 12 months (34.8% ± 17.6%, P < 0.001) after HF-PDT compared with baseline. The vascular proportions in Sattler's and Haller's layers did not show a significant decrease at 6 weeks (Sattler's: 49.7% ± 17.3%, P = 0.052 and Haller's: 58.3% ± 12.9%, P = 0.558) but decreased significantly at 6 months (Sattler's: 48.9% ± 12.4%, P < 0.001 and Haller's: 57.7% ± 15.7%, P = 0.027) and 12 months after HF-PDT from the baseline values (Sattler's: 45.8% ± 10.4%, P < 0.001 and Haller's: 56.8% ± 15.7%, P < 0.001). CONCLUSION:After HF-PDT, the choriocapillaris showed the earliest decrease in vascular proportion of en face images, Sattler's and Haller's layers showed later decreases. The temporal differences in the response of each layer may reflect the pathophysiology of CSC and the therapeutic mechanism of HF-PDT.

BackgroundTo evaluate the efficacy of intravitreal ranibizumab for subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD) with combined severe diabetic retinopathy (DR).MethodsThis retrospective, interventional case series included eleven patients (mean age, 70.09 years; range, 54 to 83 years) with at least severe non-proliferative DR and subfoveal CNV secondary to AMD. Each subject was treated with intravitreal injections of 0.5 mg ranibizumab. The primary outcomes included change in best-corrected visual acuity and central subfield thickness (CST) on optical coherence tomography (OCT).ResultsThe mean follow-up time was 16.7±14 months (range, 6 to 31 months). Mean visual acuity improved from 1.21±0.80 logarithm of the minimum angle of resolution (logMAR) to 1.0±0.6 logMAR (P=0.107), 0.95±0.62 logMAR (P=0.044), 1.10±0.68 logMAR (P=0.296), and 1.13±0.66 logMAR (P=0.838) at 1, 3, 6, and 12 months after injection, respectively. Eight patients (72.7%) gained or maintained vision (mean 0.32 logMAR), whereas three patients (27.3%) lost more than one line of vision (mean 0.51 logMAR). The mean OCT CST was 343.9±134.6 µm at baseline, and the mean CST at 1, 3, 6, 12 months after the injection was 367.8±172.1 (P=0.864), 346.2±246.2 (P=0.857), 342±194.1 (P=0.551), and 294.2±108.3 µm (P=0.621), respectively.ConclusionIntravitreal ranibizumab injection can be considered to be a therapy for the stabilization of subfoveal CNV secondary to AMD with combined severe DR. However, these patients might exhibit limited visual improvement after treatment.

Purpose. To demonstrate the long-term effectiveness of vitrectomy for intermediate uveitis (IU) and to determine whether complete control of inflammation before vitrectomy is necessary. Methods. This retrospective study included 66 eyes of 66 patients with IU who underwent vitrectomy for vitreoretinal complications. Eyes were followed for at least 12 months after vitrectomy. The degree of inflammation control and visual acuity were compared before and after vitrectomy. These parameters were compared according to the presence of complete inflammation control before surgery. Results. The indications of vitrectomy included epiretinal membrane (26 eyes), vitreous opacity (21 eyes), and tractional retinal detachment (12 eyes), among others. Uveitic attacks did not occur in 44 of the 66 patients after vitrectomy. The numbers of uveitis attacks, local steroid injections, and systemic medications significantly decreased, and vision meaningfully improved after vitrectomy. These parameters did not differ significantly, regardless of the presence of preoperative inflammation. Conclusions. This study showed that vitrectomy is a good modality to manage vitreoretinal complications associated with IU, even if complete control of intraocular inflammation is not achieved before vitrectomy.

Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p

A 53-year-old woman presented with complaints of blurred vision in the left eye. She had been treated for recurrent non-functioning pituitary adenoma (NFPA). A vitreous biopsy followed by histopathologic examination showed the presence of Candida albicans. Meanwhile, Cushing׳s disease was diagnosed and gamma knife surgery was performed. Vitrectomy and antifungal treatment improved ocular infection and inflammation. Herein, we describe the first case of C. albicans endophthalmitis in a patient with NFPA evolving into Cushing׳s disease.

Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR.

IL-22 is a pro- and anti-inflammatory cytokine that is mainly produced by T cells and NK cells. Recent studies have reported the increased number of IL-22 producing T cells in patients with autoimmune noninfectious uveitis; however, the correlation between IL-22 and uveitis remains unclear. In this study, we aimed to determine the specific role of IL-22 and its receptor in the pathogenesis of uveitis. Serum concentration of IL-22 was significantly increased in uveitis patients. IL-22Rα was expressed in the retinal pigment epithelial cell line, ARPE-19. To examine the effect of IL-22, ARPE-19 was treated with recombinant IL-22. The proliferation of ARPE-19 and the production of monocyte chemoattractant protein (MCP)-1 from ARPE-19 were clearly elevated. IL-22 induced MCP-1 which facilitated the migration of inflammatory cells. Moreover, IL-22 increased the IL-22Rα expression in ARPE-19 through the activation of PI3K/Akt. Experimental animal models of uveitis induced by interphotoreceptor retinoid binding protein 1-20 (IRBP1-20) exhibited elevation of hyperplasia RPE and IL-22 production. When CD4+ T cells from the uveitis patients were stimulated with IRBP1-20, the production of IL-22 definitely increased. In addition, we examine the regulatory role of cysteamine, which has an anti-inflammatory role in the cornea, in uveitis through the down-regulation of IL-22Rα expression. Cysteamine effectively suppressed the IRBP1-20-induced IL-22Rα expression and prevented the development of IRBP1-20-induced uveitis in the experimental animal model. These finding suggest that IL-22 and its receptor have a crucial role in the development and pathogenesis of uveitis by facilitating inflammatory cell infiltration, and that cysteamine may be a useful therapeutic drug in treating uveitis by down-regulating IL-22Rα expression in RPE.

Purpose. To evaluate the real-world efficacy and safety of the dexamethasone implant (DEX implant) in patients with diabetic macular edema (DME). Methods. Retrospective, multicenter, and noncomparative study of DME patients who were treated with at least one DEX implant. A total of 186 eyes from 165 patients were included. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and number of retreatments were collected. Data at baseline and monthly for 6 months were analyzed. Results. The average baseline BCVA and CRT were 0.60 LogMAR and 491.6 μm, respectively. The mean BCVA improved until 3 months and then decreased up to 6 months of follow-up (0.53, 0.49, and 0.55 LogMAR at 1, 3, and 6 months; p=0.001,

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.

This study investigated the effect of Melissa officinalis extract on laser-induced choroidal neovascularization (CNV) in a rat model. The mechanism by which M. officinalis extract acted was also investigated.Experimental CNV was induced by laser photocoagulation in Brown Norway rats. An active fraction of the Melissa leaf extract was orally administered (50 or 100 mg/kg/day) beginning 3 days before laser photocoagulation and ending 14 days after laser photocoagulation. Optical coherence tomography and fluorescein angiography were performed in vivo to evaluate the thickness and leakage of CNV. Choroidal flat mount and histological analysis were conducted to observe the CNV in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 expression were measured in retinal and choroidal-scleral lysates 7 days after laser injury. Moreover, the effect of M. officinalis extract on tertiary-butylhydroperoxide (t-BH)-induced VEGF secretion and mRNA levels of VEGF, MMP-2, and MMP-9 were evaluated in human retinal epithelial cells (ARPE-19) as well as in human umbilical vein endothelial cells (HUVECs).The CNV thickness in M. officinalis-treated rats was significantly lower than in vehicle-treated rats by histological analysis. The CNV thickness was 33.93±7.64 µm in the high-dose group (P

Differential interference contrast microscopy is designed to image unstained and transparent specimens by enhancing the contrast resulting from the Nomarski prism-effected optical path difference. Retinitis pigmentosa, one of the most common inherited retinal diseases, is characterized by progressive loss of photoreceptors. In this study, Differential interference contrast microscopy was evaluated as a new and simple application for observation of the retinal photoreceptor layer and retinitis pigmentosa diagnostics and monitoring. Retinal tissues of Royal College of Surgeons rats and retinal-degeneration mice, both well-established animal models for the disease, were prepared as flatmounts and histological sections representing different elapsed times since the occurrence of the disease. Under the microscopy, the retinal flatmounts showed that the mosaic pattern of the photoreceptor layer was irregular and partly collapsed at the early stage of retinitis pigmentosa, and, by the advanced stage, amorphous. The histological sections, similarly, showed thinning of the photoreceptor layer at the early stage and loss of the outer nuclear layer by the advanced stage. To count and compare the number of photoreceptors in the normal and early-retinitis pigmentosa-stage tissues, an automated cell-counting program designed with MATLAB, a numerical computing language, using a morphological reconstruction method, was applied to the differential interference contrast microscopic images. The number of cells significantly decreased, on average, from 282 to 143 cells for the Royal College of Surgeons rats and from 255 to 170 for the retinal-degeneration mouse. We successfully demonstrated the potential of the differential interference contrast microscopy technique's application to the diagnosis and monitoring of RP.

Behçet’s disease (BD) is a chronic recurrent systemic inflammatory disorder of unknown etiology characterized by oral and genital ulcerations, skin lesions, and uveitis. The ocular involvement of BD, or Behçet’s uveitis (BU), is characterized by panuveitis or posterior uveitis with occlusive retinal vasculitis and tends to be more recurrent and sight threatening than other endogenous autoimmune uveitides, despite aggressive immunosuppression. Although pathogenesis of BD is unclear, researches have revealed that immunological aberrations may be the cornerstone of BD development. General hypothesis of BD pathogenesis is that inflammatory response is initiated by infectious agents or autoantigens in patients with predisposing genetic factors and perpetuated by both innate and acquired immunity. In addition, a network of immune mediators plays a substantial role in the inflammatory cascade. Recently, we found that the immunopathogenesis of BU is distinct from other autoimmune uveitides regarding intraocular effector cell profiles, maturation markers of dendritic cells, and the cytokine/chemokine environment. In addition, accumulating evidence indicates the involvement of Th17 cells in BD and BU. Recent studies on genetics and biologics therapies in refractory BU also support the immunological association with the pathogenesis of BU. In this review, we provide an overview of novel findings regarding the immunopathogenesis of BU.

PURPOSE: Studies that analyzed single nucleotide polymorphisms (SNP) in various genes have shown that genetic factors are strongly associated with age-related macular degeneration (AMD) susceptibility. Copy number variation (CNV) may be an additional type of genetic variation that contributes to AMD pathogenesis. This study investigated CNV in 4 AMD-relevant genes in Korean AMD patients and control subjects. METHODS: Four CNV candidate regions located in AMD-relevant genes (VEGFA, ARMS2/HTRA1, CFH and VLDLR), were selected based on the outcomes of our previous study which elucidated common CNVs in the Asian populations. Real-time PCR based TaqMan Copy Number Assays were performed on CNV candidates in 273 AMD patients and 257 control subjects. RESULTS: The predicted copy number (PCN, 0, 1, 2 or 3+) of each region was called using the CopyCaller program. All candidate genes except ARMS2/HTRA1 showed CNV in at least one individual, in which losses of VEGFA and VLDLR represent novel findings in the Asian population. When the frequencies of PCN were compared, only the gain in VLDLR showed significant differences between AMD patients and control subjects (p = 0.025). Comparisons of the raw copy values (RCV) revealed that 3 of 4 candidate genes showed significant differences (2.03 vs. 1.92 for VEGFA, p