Purpose The purpose of this study was to analyze the effects of systemic and ocular profiles on subfoveal choroidal thickness (SFChT) in treatment-naïve eyes with diabetic retinopathy (DR). Methods This study included patients with treatment-naïve DR. They underwent routine laboratory evaluations, including complete blood cell count, liver function tests, kidney function tests, and urinalysis for macroalbuminuria. The systemic and ocular factors associated with the change in SFChT in DR were analyzed. Results A total of 136 eyes from 136 patients with diabetes and 30 eyes from 30 age-matched healthy controls were recruited. Generalized linear model analyses showed that the SFChT in treatment-naïve eyes with DR was positively associated with the DR grade and estimated glomerular filtration rate (eGFR; P = 0.001) and negatively associated with age (P < 0.001) and serum phosphorus levels (P = 0.001). Treatment-naïve eyes with proliferative DR (PDR; 313.4 ± 9.0 µm) or severe nonproliferative DR (NPDR; 299.7 ± 9.7 µm) had thicker choroid than eyes with mild to moderate NPDR (251.7 ± 11.1 µm) or no DR (231.2 ± 14.5 µm) after adjusting for age, eGFR, and phosphorus levels. Conclusions Choroid is affected by renal function and the grade of DR in patients with diabetes. Advanced retinopathy is associated with choroidal thickening, and the severity of concomitant renal disease is associated with choroidal thinning.

We analyzed and compared the sensitivity of choroidal neovascularization (CNV) detection according to CNV type in patients with active neovascular age-related macular degeneration (AMD) using swept-source optical coherence tomography (OCT) angiography (OCTA). A retrospective chart review was performed in patients with neovascular AMD. OCTA images were classified into three groups: GroupA(well-circumscribed vascular complex); Group B (moderately circumscribed vascular complex); and Group C (poorly circumscribed vascular complex), according to CNV appearance. Demographic characteristics, OCT parameters, neovascularization subtypes, and OCTA image quality were analyzed to determine the effect on visualization of the neovascular complex. A total of 130 patients with CNV secondary to active neovascular AMD were analyzed. Among them, 52 eyes from 47 patients were included in the study. Eighteen eyes (34.6%) were classified into Group A, 24 (46.2%) into Group B, and 10 (19.2%) into Group C. Statistical analysis showed no significant differences in demographic characteristics or OCT parameters between the three groups. Overall sensitivity of active CNV detection was 80.7% (42/52 eyes). In 73.5% (25/34) of eyes with type 1 CNV (sub-retinal pigment epithelial type), 100.0% (9/9) of eyes with type 2 CNV (sub-retinal type), and 88.9% (8/9) of eyes with type 3 CNV (retinal angiomatous proliferation type), the vascular complex was well visualized on OCTA. OCTA provides adequate noninvasive imaging of CNV in patients with neovascular AMD, which may assist in CNV diagnosis and activity monitoring. In particular, type 2 CNV was well detected in OCTA in comparison with type 1 and type 3 CNV.

PurposeTo develop a new classification system for vitreomacular traction (VMT) syndrome according to spectral-domain optical coherence tomography (SD-OCT) imaging and to investigate the clinical course of VMT patients.MethodsThis study included 68 eyes of 68 consecutive patients who were followed with observation or treated with vitrectomy for idiopathic VMT. Eyes were classified into one of three groups according to SD-OCT findings: group A (foveal pseudocyst, which was defined as the formation of cystoid cavity located in the inner part of the central fovea along with foveal thickening), group B (parafoveal retinoschisis, which was defined as intraretinal cysts or clefts along with no apparent foveal thickening), and group C (outer retinal dehiscence at the fovea, which is sometimes accompanied by foveal thinning). The minimum required follow-up period was 1year. Clinical course and anatomical and functional outcomes were compared among the groups.ResultsTwenty-seven eyes (39.7%) were included in group A, 22 eyes (32.4%) were included in group B, and 19 eyes (27.9%) were included in group C. Among the 24 eyes that were managed by observation, a significantly larger percentage of patients in group A (6/10 [60%]) exhibited more spontaneous resolution of VMT compared with those in groups B (9.1%) or C (0%) (P=0.010). In the 44 eyes that were managed with vitrectomy, a significantly larger percentage of patients in group C (4/16 [25%]) experienced subsequent full-thickness macular hole development following vitrectomy compared with those in groups B (0%) or C (0%) (P=0.014). The percentage of patients with photoreceptor inner segment/outer segment disruption was significantly reduced in group A after vitrectomy, with group C exhibiting the lowest recovery rate. Postoperatively, group A experienced a significantly better visual outcome than group C (P=0.021).ConclusionsA novel configuration system offering insight into the clinical course of VMT is proposed. According to this system, anatomical and functional outcomes were favorable in group A and worse in group C.

PURPOSE:To investigate reproducible surgical techniques to optimize the long-term safety of liquid crystal polymer (LCP)-based retinal prosthesis implantation.METHODS:An LCP-based retinal prosthesis is fabricated monolithically on a single-body LCP substrate with all components, including the package and electrode array. We implanted the electrode array into the suprachoroidal space and anchored the package and transition part to the sclera in rabbits (n = 11). The safety profile was assessed upon the completion of the surgery and postoperatively.RESULTS:The surgical procedures for implantation of the entire system were easily performed in nine eyes (81.8%) without any intraoperative complications. In the other two eyes (18.2%), surgical complications related to electrode insertion, including optic nerve damage and retinal tear, arose. In 10 eyes (90.9%), the devices were well tolerated for at least 3 months. However, in most eyes (nine; 81.8%), two complications began to appear after 3 months, postoperatively, including conjunctival erosion or dehiscence over the package or transition part. The electrode arrays were maintained safely in the suprachoroidal space after surgery without any complications, regardless of the status of the extraocular components in all cases except two intraoperative complications.CONCLUSIONS:We established safe and reproducible surgical techniques for implantation of our LCP-based retinal prosthesis into the suprachoroidal space. Although issues related to surgical technique or device configuration were identified, further technical solutions would improve the long-term safety of device implantation.TRANSLATIONAL RELEVANCE:This study presents successful implantation of LCP-based retinal prosthesis. The technical solutions will permit an optimization of surgical techniques.

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.

Purpose: To identify factors associated with the recovery of foveal photoreceptor disruption in eyes with an impending macular hole (MH) with vitreomacular traction syndrome after surgery.Methods: This study comprised 33 consecutive patients who underwent vitrectomy for Stage 1 impending macular hole with disrupted photoreceptor inner segment/outer segment (IS/OS) layer and were followed up for a minimum of 1 year after surgery. Preoperative optical coherence tomography (OCT) parameters were compared between eyes that achieved complete restoration of the IS/OS layer (Group A) and those that did not (Group B). Postoperative serial changes in best-corrected visual acuity (BCVA) and IS/OS disrupted length were also investigated.Results: Smooth and symmetric foveolar contour was restored in 29 eyes (87.9%). Complete recovery of IS/OS disruption was observed in 11 of 33 cases (33.3%, Group A). Group A exhibited a larger percentage of foveal pseudocysts (54.5% vs. 13.6%, P = 0.033) and a smaller mean aperture size (102.1 +/- 182.1 mu m vs. 241.5 +/- 163.8 mu m, P = 0.031) than Group B. Postoperatively, Group A revealed a significantly better visual outcome than Group Be, which was the same as Group B, but with the four eyes that developed a full-thickness macular hole excluded.Conclusion: Restoration of the foveal photoreceptor layer was more likely to occur in eyes with a foveal pseudocyst and smaller aperture size.

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 Our purpose was to evaluate the anatomical and functional changes in retinae of rabbit eyes following monocular intravitreal injection of sodium iodate (SI).Methods Twenty albino rabbits were divided into four groups and underwent monocular intravitreal injection with four different doses of SI (0.1, 0.2, 0.4, and 0.8 mg). Before and for 28 days after injection, the eyes were examined using fundus photography, optical coherence tomography (OCT), and electroretinography (ERG). At postinjection days 2, 7, and 28, the eyes were enucleated and underwent histological examination.Results On fundus examination, no distinct retinal changes were seen in any group except the 0.8-mg group, which showed chorioretinal vascular attenuation. In 0.1 and 0.2-mg groups, no significant anatomical changes were found except transient hyperreflective dots over the vitreoretinal interface on OCT. In 0.4 and 0.8-mg groups, disruption of the ellipsoid zone and diffuse retinal swelling were observed in the early period on OCT. In the 0.4-mg group, the outer retina was significantly destroyed at day 28, whereas the inner retina was relatively preserved. In the 0.8-mg group, the entire retina was destroyed irreversibly. The b-wave of ERG was reduced immediately in all groups, which recovered fully (0.1- and 0.2-mg groups), partially (0.4-mg group), or never (0.8-mg group). No structural or functional abnormalities were found in the fellow control eyes.Conclusions Retinal degeneration following intravitreal injection of SI appears to be dose dependent; retinal damage is reversible at low doses but irreversible at high doses. At a certain dose, the outer retina may be preferably ablated.

Objective. The aim of this study is to evaluate the long-term reliability of a recently presented liquid crystal polymer (LCP)-based retinal prosthesis in vitro as well as in vivo. Because an all-polymer implant introduces another intrinsic leak type due to gas permeation, for which the traditional helium leak test for metallic packages was not designed to quantify, a new method to investigate its durability is required. Approach. We designed and carried out a series of reliability tests specifically for all-polymer implants by quantitatively investigating moisture ingress through various pathways of the polymer surface, and the polymer-polymer and polymer-metal adhesions. Moisture permeation through the bulk material was estimated by analytic calculation, while water ingress through the adhesively sealed LCP-LCP and LCP-metal interfaces was investigated using the separate parts of an electrode array and a package in an accelerated aging condition. In vivo tests were done in rabbits to examine the long-term biocompatibility and implantation stability by fundus observation and optical coherence tomography (OCT) imaging. Main results. The analytic calculation estimated good barrier properties of the LCP. Samples of the LCP-based electrode array failed after 114 days in 87 degrees C saline as a result of water penetration through the LCP-metal interface. An eye-conformable LCP package survived for 87 days in an accelerated condition at 87 degrees C. The in vivo results confirmed that no adverse effects were observed around the retina 2.5 years after the implantation of the device. Significance. These long-term evaluation results show the potential for the chronic use of LCP-based biomedical implants to provide an alternative to traditional metallic packages.

Comparison of Choroidal Hyperpermeability Change after Photodynamic Therapy and Ranibizumab for Chronic Central Serous Chorioretinopathy 김정아1⋅신주영1⋅배소현2⋅안지윤3⋅정 흠1⋅허장원1 Jeong Ah Kim, MD, Joo Young Shin, MD, So Hyun Bae, MD, Jee Yun Ahn, MD, Hum Chung, MD, Jang Won Heo, MD, PhD 서울대학교 의과대학 서울대학교병원 안과학교실, 한림대학교 의과대학 강동성심병원 안과학교실, 서울특별시보라매병원 안과 Department of Ophthalmology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea Department of Ophthalmology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea

In order to provide high-quality visual information to patients who have implanted retinal prosthetic devices, the number of microelectrodes should be large. As the number of microelectrodes is increased, the dimensions of each microelectrode must be decreased, which in turn results in an increased microelectrode interface impedance and decreased injection current dynamic range. In order to improve the trade-off envelope between the number of microelectrodes and the current injection characteristics, a 3D microelectrode structure can be used as an alternative. In this paper, the electrical characteristics of 2D and 3D Au microelectrodes were investigated. In order to examine the effects of the structural difference, 2D and 3D Au microelectrodes with different base areas but similar effective surface areas were fabricated and evaluated. Interface impedances were measured and similar dynamic ranges were obtained for both 2D and 3D Au microelectrodes. These results indicate that more electrodes can be implemented in the same area if 3D designs are used. Furthermore, the 3D Au microelectrodes showed substantially enhanced electrical durability characteristics against over-injected stimulation currents, withstanding electrical currents that are much larger than the limit measured for 2D microelectrodes of similar area. This enhanced electrical durability property of 3D Au microelectrodes is a new finding in microelectrode research, and makes 3D microelectrodes very desirable devices.

Nature Communications 6: Article number: 6063 (2015); Published 28 January 2015; Updated 30 March 2015. The financial support for this Article was not fully acknowledged. The Acknowledgements should have included the following: This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014055007), Ministry of Education, Science and Technology (2012004585), and by the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111345).

BACKGROUND:To compare the long-term efficacy of ranibizumab versus bevacizumab for myopic choroidal neovascularization (CNV).METHODS:This was a retrospective, multicenter, comparative, non-randomized study of 64 consecutive patients with myopic CNV treated with ranibizumab (22 patients) or bevacizumab (42 patients). Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography were evaluated before and after treatment. All the patients were followed for at least 12 months.RESULTS:BCVA (logarithm of the minimal angle of resolution) improved from 0.63 ± 0.30 to 0.43 ± 0.27, 0.41 ± 0.37, 0.40 ± 0.39, 0.39 ± 0.43, and 0.39 ± 0.42 at 1, 2, 3, 6, and 12 months after treatment in the ranibizumab group, and from 0.67 ± 0.28 to 0.52 ± 0.31, 0.49 ± 0.31, 0.47 ± 0.31, 0.42 ± 0.32, and 0.46 ± 0.43 in the bevacizumab group (all P < 0.05 compared with baseline BCVA in each group). CFT decreased by 20.21%, 19.58%, and 22.43% from the baseline 304 ± 76 μm at 3, 6, and 12 months after treatment in the former group, and by 15.20%, 15.67%, and 15.56% from the baseline 297 ± 62 μm in the latter group (all P < 0.05 compared with baseline CFT in each group). BCVA improvement and CFT reduction did not statistically differ when compared at the same periods from treatment between 2 groups. Neither ocular nor systemic safety problems appeared during follow up.CONCLUSIONS:This study showed a similar functional and anatomical improvement after treatment of ranibizumab and bevacizumab for myopic CNV over a 12-month follow-up period.

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:We examined the epidemiological association between systemic diseases and age-related macular degeneration (AMD) in the general Korean population.METHODS:This cross-sectional study involved nationally representative data obtained from the 2008 to 2011 Korea National Health and Nutrition Examination Surveys. A total of 14,352 subjects aged ≥40 years participated in standardized health interviews regarding physician-diagnosis of several systemic diseases as well as physical examinations, including fundus photography for the evaluation of AMD.RESULTS:The overall prevalence rates of early, late, and any AMD were 6.0%, 0.6%, and 6.6%, respectively. In univariate logistic regression analyses adjusted for age and sex as well as smoking in late AMD, any AMD and late AMD were less prevalent among diabetic patients and more prevalent in participants with a history of liver cancer. A history of liver cirrhosis was associated with a higher prevalence of any AMD. In the final multivariate model, the associated factors for any AMD included age (odds ratio [OR], 1.09), the presence of diabetes mellitus (DM; OR, 0.74), and a history of liver cancer (OR, 4.32). Factors associated with late AMD included age (OR, 1.09), ever-smoking history (OR, 2.45), the presence of DM (OR, 0.22), and a history of liver cancer (OR, 12.51). The presence of diabetic retinopathy was associated with a lower prevalence of any AMD (OR, 0.35).CONCLUSIONS:When adjusted for confounders, any AMD and late AMD were less prevalent in diabetic patients. In contrast, a history of liver cancer was associated with a higher prevalence of any AMD and late AMD.