The Correlation between Waist Circumference and the Pro-Inflammatory Adipokines in Diabetic Retinopathy of Type 2 Diabetes Patients.

Central obesity is one of the major risk factors for type 2 diabetes mellitus (DM), and the most common complication of DM is diabetic retinopathy. However, the exact relationship between obesity and DR remains unknown. In this study, we evaluate the effect of obesity on DR by comparing the aqueous humor-derived adipokines. For the analysis, 37 DR patients and 29 non-DR-patients participated. To evaluate the obesity of the patients, body mass index (BMI) and waist circumference (WC) were used. By comparing the concentrations of adipokines obtained from the aqueous humor of the two groups, the relationship between DR and adipokines was analyzed. In addition, by analyzing the correlation between obesity and adipokines in patients, the relationship between central obesity and DR was finally confirmed. The WC was significantly higher in patients than in the non-patient group. The concentrations of all adipokines compared in this study were significantly higher in the DR group than in the non-DM group (p < 0.05). Among them, adiponectin, leptin, TNF-α, Factor D (adipsin), lipocalin-2 (NGAL), Serpin E1 (PAI-1), and CXCL8 (IL-8) were confirmed to have a positive correlation with central obesity (defined as WC). These findings suggest that central obesity is strongly associated with the risk of DR.

Effect of Photobiomodulation in Suppression of Oxidative Stress on Retinal Pigment Epithelium.

As the world undergoes aging, the number of age-related diseases has increased. One of them is disease related to retinal pigment epithelium (RPE) degeneration, such as age-related macular degeneration, causing vision loss without physical damage in the ocular system. It is the leading cause of blindness, with no cure. Although the exact pathogenesis is still unknown, the research shows that oxidative stress is one of the risk factors. Various molecules have been reported as anti-oxidative materials; however, the disease has not yet been conquered. Here, we would like to introduce photobiomodulation (PBM). PBM is a non-invasive treatment based on red and near-infrared light and has been used to cure various diseases by regulating cellular functions. Furthermore, recent studies showed its antioxidant effect, and due to this reason, PBM is arising as a new treatment for ocular disease. In this study, we confirm the antioxidant effect of PBM in retinal pigment epithelium via an RPE model with hypoxia. The function of RPE is protected by PBM against damage from hypoxia. Furthermore, we observed the protective mechanism of PBM by its suppression effect on reactive oxygen species generation. These results indicate that PBM shows great potential to cure RPE degeneration to help patients with blindness.

Molecular Mechanisms of Retinal Pigment Epithelium Dysfunction in Age-Related Macular Degeneration.

The retinal pigment epithelium (RPE), situated upon Bruch's membrane, plays multiple roles in the ocular system by interacting with photoreceptors and. Therefore, dysfunction of the RPE causes diseases related to vision loss, such as age-related macular degeneration (AMD). Despite AMD being a global cause of blindness, the pathogenesis remains unclear. Understanding the pathogenesis of AMD is the first step for its prevention and treatment. This review summarizes the common pathways of RPE dysfunction and their effect in AMD. Potential treatment strategies for AMD based on targeting the RPE have also been discussed.

Maturation and Protection Effect of Retinal Tissue-Derived Bioink for 3D Cell Printing Technology.

Retinal degeneration is a leading cause of incurable vision loss and blindness. The increasing incidence of retinal degeneration has triggered research into the development of in vitro retinal models for drug development and retinal alternatives for transplantation. However, the complex retinal structure and the retinal microenvironment pose serious challenges. Although 3D cell printing technology has been widely used in tissue engineering, including in vitro model development and regeneration medicine, currently available bioinks are insufficient to recapitulate the complex extracellular matrix environment of the retina. Therefore, in this study, we developed a retinal decellularized extracellular matrix (RdECM) from the porcine retina and evaluated its characteristics. The RdECM conserved the ECM components from the native retina without cellular components. Then, we mixed the RdECM with collagen to form a bioink and confirmed its suitability for 3D cell printing. We further studied the effect of the RdECM bioink on the differentiation of Muller cells. The retinal protective effect of the RdECM bioink was confirmed through a retinal degeneration animal model. Thus, we believe that the RdECM bioink is a promising candidate for retinal tissue engineering.

Therapeutic Efficacy of Autologous Platelet Concentrate Injection on Macular Holes with High Myopia, Large Macular Holes, or Recurrent Macular Holes: A Multicenter Randomized Controlled Trial.

We aimed to evaluate the anatomical and functional outcomes of pars-plana vitrectomy (PPV) with or without autologous platelet concentrate (APC) injection in patients with recurrent macular holes (MHs), large MHs, or MHs with high myopia. This multicenter, prospective, interventional randomized controlled trial was conducted from March 2017 to April 2020. Participants were randomly allocated to a PPV group or a PPV+APC group. All participants underwent standard 25-gauge PPV, and eyes in the PPV+APC group underwent PPV with intravitreal APC injection before air-gas exchange. A total of 117 patients were enrolled (PPV group: n = 59, PPV+APC group: n = 58). Hole closure was achieved in 47 participants (79.7%) in the PPV group and 52 participants (89.7%) in the PPV+APC group. There were no between-group differences in the anatomical closure rate or functional outcomes including best-corrected visual acuity, metamorphopsia, pattern-reversal visual evoked potential, or Visual Function Questionnaire-25 score. The use of APC injection does not improve the anatomical and functional outcomes of surgery for large MHs, recurrent MHs, or MHs with high myopia. The adjunctive use of APC can be considered in selected cases because it is not inferior to conventional MH surgery, is relatively simple to perform, and is not affected by the surgeon's skill.

Development of 3D Printed Bruch's Membrane-Mimetic Substance for the Maturation of Retinal Pigment Epithelial Cells.

Retinal pigment epithelium (RPE) is a monolayer of the pigmented cells that lies on the thin extracellular matrix called Bruch's membrane. This monolayer is the main component of the outer blood-retinal barrier (BRB), which plays a multifunctional role. Due to their crucial roles, the damage of this epithelium causes a wide range of diseases related to retinal degeneration including age-related macular degeneration, retinitis pigmentosa, and Stargardt disease. Unfortunately, there is presently no cure for these diseases. Clinically implantable RPE for humans is under development, and there is no practical examination platform for drug development. Here, we developed porcine Bruch's membrane-derived bioink (BM-ECM). Compared to conventional laminin, the RPE cells on BM-ECM showed enhanced functionality of RPE. Furthermore, we developed the Bruch's membrane-mimetic substrate (BMS) via the integration of BM-ECM and 3D printing technology, which revealed structure and extracellular matrix components similar to those of natural Bruch's membrane. The developed BMS facilitated the appropriate functions of RPE, including barrier and clearance functions, the secretion of anti-angiogenic growth factors, and enzyme formation for phototransduction. Moreover, it could be used as a basement frame for RPE transplantation. We established BMS using 3D printing technology to grow RPE cells with functions that could be used for an in vitro model and RPE transplantation.

3D printing of drug-loaded multi-shell rods for local delivery of bevacizumab and dexamethasone: A synergetic therapy for retinal vascular diseases.

The clinical therapy for retinal vascular diseases requires repeated intravitreal injections of drugs owing to their short half-life, which imposes health and economic burdens on patients. Therefore, it is necessary to develop an advanced drug delivery system that can prolong the drug activity and minimize secondary complications. In this study, we developed a core/shell drug-loaded rod (drug rod) to deliver two types of drugs (bevacizumab (BEV) and dexamethasone (DEX)) from a single implant. The coaxial printing technique allowed BEV and DEX to be released with different kinetics at the same site by using a polymeric shell and a hydrogel core, respectively. The suggested printing technique facilitates the production of drug rods with various dimensions and drug concentrations, and the multi-layered design allows to adjust the release profile of dual drug-delivery system. The rod was injected in rat vitreous less invasively using a small-gauge needle. Further, we validated the efficacy of the implanted drug rods in inhibiting inflammatory responses and long-term suppression of neovascularization compared to the conventional intravitreal injection of BEV in animal model, indicating that the drug rods can be an alternative therapeutic approach for the treatment of various types of retinal vascular diseases.

Ocular Manifestations of Biopsy-Proven Pulmonary Sarcoidosis in Korea.

PURPOSE: To investigate the clinical features and ocular manifestations of biopsy-proven pulmonary sarcoidosis in Korea. METHODS: 55 patients diagnosed with pulmonary sarcoidosis by bronchoscopic or excisional biopsy were included. By retrospective clinical chart review, we investigated features of uveitis, ocular and systemic treatments, visual acuity, angiotensin-converting enzyme level, chest radiography, and pulmonary function tests. Clinical features were analyzed by presence of uveitis, site of biopsy, and first manifested sign of sarcoidosis. RESULTS: The group with uveitis (n = 39) presented with higher systemic (71.8%) and immunosuppressive treatment rates (35.9%) than the group without uveitis (31.3%, 0%, resp.) (P = 0.007, P = 0.005, resp.). There were no significant differences in clinical features, including systemic treatment rate, by type of biopsy. Of 39 patients with uveitis, the group with ocular manifestation as a first sign of sarcoidosis showed higher systemic and immunosuppressive treatment rates (88.9%, 55.6%) compared to the group with pulmonary manifestation as a first sign (57.1%, 19.0%) (P = 0.037, P = 0.018, resp.). CONCLUSIONS: In patients with biopsy-proven pulmonary sarcoidosis, the presence of ocular involvement and uveitis as a first sign could be significant factors associated with higher systemic treatment rate, especially with immunosuppressive agents. Biopsy site determined by location and size had no influence on clinical features.

Patterns of ocular toxoplasmosis presenting at a tertiary eye care center in Korean patients.

The objective of this study was to describe demographic and clinical features of ocular toxoplasmosis (OT) in Korean patients compared to those in other countries.This retrospective study comprised 46 patients diagnosed with OT. All participants were recruited at the uveitis clinic in Seoul St. Mary's Hospital.The mean age of patients was 54 years. Of 46 patients, 31 (67.4%) were females. Of all patients, 24 (52.2%) had definite eating history of wild boar meat or deer blood while 5 (10.9%) had history of close contact with cats. The most common forms of OT were vitritis (91.3%) combined with retinochoroiditis (65.2%). Active retinochoroidal lesion was located at the peripheral retina in 18 (39.1%) patients, central retina in 8 (17.4%) patients, and peripapillary retina in 4 (8.7%) patients. Seven (15.2%) cases were clinically diagnosed with typical OT without serologic evidence. Thirty-nine (84.8%) had serum IgG for toxoplasmosis. However, only 8 (17.4%) had serum IgM. In 65.2% of patients, there was no complication after treatment. The most common ocular complication was macular scar (8.7%).The present study provides demographic and clinical characteristics of OT in Korea, a low endemic area of Toxoplasma gondii. Acquired infection is the major cause of OT in Korea. Even though Korea is a low endemic area of Toxoplasma gondii, OT is a preventable and common cause of acquired infectious uveitis.

Postoperative changes in the retinal thickness and volume after vitrectomy for epiretinal membrane and internal limiting membrane peeling.

The aim of the study was to investigate the thickness and volume profiles of each retinal layer in postoperative patients with epiretinal membranes.Twenty-four patients who underwent pars plana vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane were included. The best corrected visual acuity, thickness, and volume were recorded from the medical records through a retrospective review. Spectral domain optical coherence tomography was used to measure the average thickness and volume of each retinal layer before surgery and 6 months postoperatively.All 24 patients were monitored for 60 months after surgery. In all Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, the thickness and volume of the retinal nerve fiber layer and the inner retinal layer decreased significantly. In contrast, the thickness and volume of the ganglion cell layer, inner nuclear layer, inner plexiform layer, and outer plexiform layer only decreased in some ETDRS subfields. Finally, there was no significant change in the thickness or volume of the outer nuclear layer (ONL), retinal pigment epithelium (RPE), and photoreceptor layers in all ETDRS subfields.The thickness and volume of the inner retina layer decreased significantly after pars plana vitrectomy using ILM peeling. However, there was no significant change in the thickness and volume of the outer retinal layers (ONL, RPE, and photoreceptor) after surgery.

Effect of age and sex on retinal layer thickness and volume in normal eyes.

The aim of the study was to evaluate the effect of sex and age on the thickness of the retinal layer in normal eyes using spectral-domain optical coherence tomography (SD-OCT).Fifty healthy subjects between the ages of 20 and 80 had their retinal layers measured using SD-OCT at Seoul St. Mary's Hospital. Mean thickness and volume were measured for 9 retinal layers in the fovea, the pericentral ring, and the peripheral ring. The differences of sex- and age-related thickness and volume in each retinal layer were analyzed.The retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer plexiform layer (OPL) were thinnest in the fovea area, whereas the outer nuclear layer (ONL), photoreceptor layer (PHL), and retinal pigment epithelium (RPE) were thickest at similar locations. Mean thickness of the RNFL, GCL, IPL, and OPL was significantly greater in men than women. However, mean thickness of the ONL was greater in women than in men. When compared between patients < 30 years and > 60 years of age, the thickness and volume of peripheral RNFL, GCL, and pericentral and peripheral IPL were significantly larger in the younger group than the older group. Conversely, the thickness and volume of foveal INL and IR were larger in the older group than in the younger group.The thickness and volume of the retinal layer in normal eyes significantly vary depending on age and sex. These results should be considered when evaluating layer analysis in retinal disease.

A comparison of the Plusoptix S09 with an autorefractometer of noncycloplegics and cycloplegics in children.

The aim of the study is to compare outcome measures of refractive error obtained using the Plusoptix S09 photorefractor and an autorefractometer of noncycloplegics and cycloplegics in children.We reviewed the medical records of 40 patients (77 eyes) who were classified using 2 methods. The patients were first assigned to 2 groups consisting of 11 eyes with ≥+3.0 D and 66 eyes with <+3.0 D, and then to 2 groups of 12 and 65 eyes with cycloplegic and noncycloplegic refraction of spherical powers ≥+2.0 D and <+2.0 D, respectively. We compared the outcome measures of refractive error using the Plusoptix S09 photorefractor and an autorefractometer of noncycloplegics and cycloplegics.There was no statistically significant difference between the Plusoptix S09 photorefractor and cycloplegic autorefractometer in the spherical power and spherical equivalent. In contrast, there was a statistically significant difference between the Plusoptix S09 photorefractor and noncycloplegic autorefractometer (P < 0.001). There was a statistically significant difference between the spherical equivalent of the Plusoptix S09 photorefractor and cycloplegic autorefractometer in children with hyperopia ≥+3.0D and with cycloplegic and noncycloplegic refraction of spherical power ≥+2.0 D. We also found a significant difference between the outcomes of the Plusoptix S09 photorefractor and cycloplegic autorefractometer in the spherical power and spherical equivalent for children with hyperopia ≥+3.0 D.The refractive error of the Plusoptix S09 photorefractor was similar to that of the cycloplegic autorefractometer, in contrast to the noncycloplegic autorefractometer. However, the Plusoptix S09 photorefractor is an inaccurate tool to estimate the refractive errors of children with moderate hyperopia.

Anti-TNFα Treatment for HLA-B27-Positive Ankylosing Spondylitis-Related Uveitis.

PURPOSE: To assess the long-term efficacy of the most widely used anti-tumor necrosis factor alpha (TNFα) agents for treatment of HLA-B27-positive ankylosing spondylitis (AS)-related uveitis. DESIGN: Retrospective cohort study. METHODS: The medical records of 143 patients with HLA-B27-positive AS who visited Seoul St. Mary's Hospital and were taking an anti-TNFα agent for at least 1 year were studied. Subjects were divided into 3 groups according to anti-TNFα treatment: Group 1 (infliximab, 66), Group 2 (adalimumab, 45), and Group 3 (etanercept, 32). RESULTS: Mean age was 41.0 ± 13.0 years, and 97 patients (67.8%) were male. Mean follow-up period was 70.6 ± 37.9 months. In cases of active ocular inflammation at the onset of anti-TNFα treatment, patients showed improved activity of uveitis after 24.0 ± 15.0 days (Group 1), 17.9 ± 6.0 days (Group 2), and 25.9 ± 18.0 days (Group 3). After the anti-TNFα treatment, 71 of 94 patients (32 [76.2%] in Group 1, 26 [78.8%] in Group 2, and 13 [68.4%] in Group 3) remained without uveitis relapse. A reduction in the number of systemic medications was achieved in 129 patients (90.2%). Twenty-eight cases of minor side effects were observed, and 4 cases were tuberculosis leading to discontinuation of anti-TNFα treatment. CONCLUSIONS: Infliximab, adalimumab, and etanercept were effective for treating and reducing the number of uveitis relapses in HLA-B27-positive AS. However, the risk of serious infections was noted, so ophthalmologists should consider the possibility that prolonged use of biologic agents may result in systemic side effects.

The Association of Metabolic Syndrome with Diabetic Retinopathy: The Korean National Health and Nutrition Examination Survey 2008-2012.

AIMS: To explore gender differences and associations between metabolic syndrome (MetS) and its components, and diabetic retinopathy (DR) in Korean adults aged 40 years and older with diabetes. METHODS: We analyzed data from the Korean National Health and Nutrition Examination Surveys (2008-2012). In total, 2,576 type 2 diabetic participants, aged 40 and older, were evaluated. Seven standard retinal fundus photographs were obtained after pupil dilation in both eyes. DR was graded using the modified Airlie House classification system. Vision-threatening diabetic retinopathy (VTDR) included proliferative diabetic retinopathy and clinically significant macular edema. MetS was defined according to the Joint Interim Statement, proposed in 2009, by the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. Multivariate logistic regression analysis was used to assess the relationship between MetS and its individual components with DR and VTDR. RESULTS: After controlling for confounders, MetS was not associated with DR in men or women. Moreover, the risk for DR or VTDR did not increase with increasing MetS components. However, high waist circumference was significantly inversely associated with VTDR (adjusted odds ratio = 0.36; 95% confidence interval = 0.14-0.93) only in men. CONCLUSIONS: MetS was not associated with DR or VTDR in a Korean diabetic population. However, among MetS components, it seems that abdominal obesity was inversely associated with VTDR in Korean diabetic men.

VITREORETINAL COMPLICATIONS AFTER PENETRATING KERATOPLASTY.

PURPOSE: To evaluate the time, incidence, and visual outcome of vitreoretinal complications after penetrating keratoplasty (PK). METHODS: A retrospective chart review of 1,594 eyes that underwent PK was conducted. Preoperative characteristics, visual significance, and postoperative vitreoretinal complications were analyzed. RESULTS: The incidence of vitreoretinal complications after PK was 3.3% (52/1,594). The mean follow-up period was 38.5 ± 29.8 months. The mean time for vitreoretinal complications to occur was 4.8 months. The most common vitreoretinal complication was vitreous hemorrhage (0.75%), and others included choroidal detachment (0.7%), endophthalmitis (0.6%), and retinal detachment (0.5%). Majority of vitreous hemorrhage, endophthalmitis, and choroidal detachment occurred within 1 month postoperatively, but most cases of cystoid macular edema and epiretinal membrane occurred after 3 months. At follow-up after PK, the mean corrected distance visual acuity was worse among eyes that experienced vitreoretinal complications compared with eyes that did not (P = 0.013). CONCLUSION: Vitreoretinal complications after PK occurred in a significant percentage, resulting in persistent reduction of corrected distance visual acuity. Given this, it is of particular importance to control intraoperative and postoperative intraocular pressure, infection, and inflammation which will contribute to decrease in the incidence of vitreoretinal complications after PK.

A case of corneal cystinosis in a patient with rickets and chronic renal failure.

A 22-year-old man diagnosed with nephropathic cystinosis at the age of 4 years was found to have progressive bilateral corneal crystal deposition. He presented with severe photophobia and decreased visual acuity. Ocular cystinosis was diagnosed on observing the typical crystals. Optical coherence tomography showed multiple areas of stromal hyperreflectivity due to crystal deposits within the corneal stroma. Ex vivo transmission electron microscopy of the cornea showed pathognomonic crystal deposits in corneal stromal keratocytes. Using polymerase chain reaction sequencing of the entire coding region, we identified five gene mutations, including two unreported mutations.