Kihwang Lee

A prospective study of blood pressure and intraocular pressure changes in hypertensive and nonhypertensive patients after intravitreal bevacizumab injection.

Purpose: To evaluate the changes in blood pressure and intraocular pressure (IOP) in patients with and without hypertension after intravitreal bevacizumab (Avastin) injection. Methods: This study examined 135 (74 nonhypertensive vs. 61 hypertensive) consecutive patients treated with an intravitreal injection of 1.25 mg bevacizumab for retinal vascular diseases prospectively over a 6-month period. All the hypertensive patients were on medication, and only patients with controlled hypertension after consultation with cardiology specialists were included. Intraocular pressure and blood pressure were measured before and 30 minutes, 1 day, 1 week, 3 weeks, and then every month after the bevacizumab injection. Results: The mean baseline systolic and diastolic pressures were significantly higher in the hypertensive group (systolic P = 0.001, diastolic P = 0.023). None of the systolic and diastolic values after injection differed significantly from the baseline values in the hypertensive group. By contrast, the 30-minute systolic values were significantly higher than baseline (P < 0.05), and the 1-day diastolic values were lower than before injection in the nonhypertensive group (P < 0.05). The mean baseline IOP of the nonhypertensive and hypertensive groups was similar (P = 0.08). The mean IOP 30 minutes after injection was significantly higher than the baseline mean IOP (P < 0.05), and the mean IOPs at 1 day and 1 week were significantly lower than before injection in both groups (P < 0.05). Conclusion: Intravitreal bevacizumab injection is safe in terms of blood pressure and IOP in both hypertensive and nonhypertensive patients after 6 months of follow-up.

CHOROIDAL THICKNESS IN PATIENTS WITH CENTRAL SEROUS CHORIORETINOPATHY: Assessment of Haller and Sattler Layers.

Purpose: To investigate subfoveal choroidal thickness and subanalyze Haller and Sattler layers in eyes with central serous chorioretinopathy (CSC), uninvolved fellow eyes, and eyes of healthy controls using enhanced depth imaging optical coherence tomography. Methods: Ocular findings and clinical features of 31 eyes with CSC, 24 fellow eyes and eyes of 30 healthy controls were analyzed retrospectively from October, 2014 to March, 2015. Subfoveal choroidal thickness was measured using enhanced depth imaging optical coherence tomography, and the thicknesses of Haller and Sattler layers were analyzed. Results: Mean subfoveal choroidal thickness and mean thickness of Haller layer were significantly greater in CSC than in fellow eyes (P = 0.043 and P = 0.036, respectively) and in normal control eyes (P < 0.001 each), and those of fellow eyes in CSC patients were significantly thicker than those in normal control eyes (P = 0.018 and P = 0.017, respectively). The thickness of Sattler layer did not differ significantly among these groups (P = 0.519). Conclusion: Subfoveal choroidal thickness and the thickness of Haller layer were increased not only in affected but also in uninvolved fellow eyes of CSC patients. Nonvascular smooth muscle cells of the choroid may play a role in the pathophysiology of CSC, in response to increased sympathetic tone.

RAGE mediated intracellular Aβ uptake contributes to the breakdown of tight junction in retinal pigment epithelium

Intracellular amyloid beta (Aβ) has been implicated in neuronal cell death in Alzheimers disease (AD). Intracellular Aβ also contributes to tight junction breakdown of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD). Although Aβ is predominantly secreted from neuronal cells, the mechanism of Aβ transport into RPE remains to be fully elucidated. In this study, we demonstrated that intracellular Aβ was found concomitantly with the breakdown of tight junction in RPE after subretinal injection of Aβ into the mouse eye. We also presented evidence that receptor for advanced glycation end products (RAGE) contributed to endocytosis of Aβ in RPE. siRNA-mediated knockdown of RAGE prevented intracellular Aβ accumulation as well as subsequent tight junction breakdown in RPE. In addition, we found that RAGE-mediated p38 MAPK signaling contributed to endocytosis of Aβ. Blockade of RAGE/p38 MAPK signaling inhibited Aβ endocytosis, thereby preventing tight junction breakdown in RPE. These results implicate that intracellular Aβ contributes to the breakdown of tight junction in RPE via the RAGE/p38 MAPK-mediated endocytosis. Thus, we suggest that RAGE could be a potential therapeutic target for intracellular Aβ induced outer BRB breakdown in AMD.

Heparin nanogel-containing liposomes for intracellular RNase delivery

AbstractLiposomes containing nanogels (liponanogels) were fabricated by sonicating heparin-Pluronic (HP) nanogels with pegylated lipids for ribonuclease (RNase) delivery. Liponanogels with an average diameter of 316 nm were obtained and their spherical morphology was elucidated by atomic force microscopy (AFM). Confocal laser scanning microscopy (CLSM) revealed the core-shell structure of the liponanogels using two different fluorescent dyes, showing that HP nanogels were localized in the core of the liposomes. Interestingly, the hybridization of these two systems remedies the drawbacks of each system while they hold their strengths called “WIN-WIN effect”. When HP nanogels were used to encapsulate RNase in liponanogels, the loading of RNase was almost doubled as compared with the loading in liposomes without nanogels. Due to the presence of a lipid bilayer on the nanogels, the release of RNase was prolonged over 4 days whereas it was much faster (82% after 21 h) for bare HP nanogels. The cytotoxicity of the RNase-loaded liponanogels was much higher than that of free RNase because of the endocytic cellular uptake of the particles. We believe that these hybrid liponanogel systems can potentially be utilized for the hereditary diseases and targeted cancer therapy since they can efficiently load RNases and sustainly release in target cells.

Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Behçet's Disease

Behçets disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behçet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behçet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.

Antifibrotic Effect of Pirfenidone on Human Pterygium Fibroblasts

Abstract Objective: The effects of pirfenidone were investigated on cultured human pterygium fibroblasts (HPFs). Methods: HPFs were obtained from pterygium surgery and subjected to primary culture. After treatment with 0.5, 1.0 or 1.5 mg/mL pirfenidone, MTT and cell migration assays were performed, and procollagen secretion and TGF-β expression were measured by Western blotting and immunofluorescence analysis. Results: Pirfenidone had a significant inhibitory effect on HPF proliferation, migration and collagen synthesis. There were no differences between the cells treated with 0.5, 1.0 and 1.5 mg/mL pirfenidone and the controls in the MTT assay. After 48 h of treatment with 1.0 or 1.5 mg/mL pirfenidone, TGF-β expression was significantly decreased. Conclusions: These findings demonstrate that pirfenidone inhibits the proliferation, migration and procollagen secretion of HPFs at nontoxic concentrations by decreasing TGF-β expression. Thus, pirfenidone may be considered as a safe adjuvant for pterygium surgery to prevent recurrence.

Retinal artery occlusion in a healthy pregnant patient.

Purpose We report a case of branch retinal artery occlusion (BRAO) in a healthy pregnant woman. Methods A 29-year-old pregnant woman presented with decreased vision in her left eye. She had a pale retina with macular edema consistent with BRAO. An extensive workup was performed to determine an etiologic factor. All test results were within normal limits except for her factor VIII activity. Her visual acuity improved from finger counting to 20/30 over 2 months without any treatment. Results This case suggests that BRAO can occur in healthy patients without any systemic or ocular disorders. Conclusions BRAO can occur in healthy patients without any systemic or ocular disorders, despite an extensile evaluation.

β-Adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation

Pericytes (PCs) are crucial in maintaining the quiescence of endothelial cells (ECs) and the integrity of EC tight junctions. Especially in diabetic retinopathy (DR), PC loss is one of the early pathologic changes in capillaries of diabetic retinas. Thus, preventing PC loss is beneficial for attenuating vision impairment in patients with DR. Although many studies have revealed the mechanism of PC loss in retinas, little is known about the mechanisms that increase PC survival. We focused on the effect of β‐adrenergic receptor agonists (β‐agonists) on PC loss in diabetic retinas. In this study, β‐agonists increased the cell viability of PCs by increasing PC survival and proliferation. Mechanistically, β‐agonist‐induced protein kinase B activation in PCs reduced PC apoptosis in response to various stimuli. β2‐agonists more potently increased PC survival than β1‐agonists. β2‐Agonist reduced vascular leakage and PC loss in retinas of mice with streptozotocin‐induced diabetes. In cocultures of PCs and ECs, β2‐agonists restored the altered permeability and ZO‐1 expression in ECs induced by PC loss. We concluded that β‐agonists, especially β2‐agonists, increase PC survival, thereby preventing diabetes‐induced PC loss in retinas. These results provide a potential therapeutic benefit of β‐agonists for preventing PC loss in DR.—Yun, J.‐H., Jeong, H.‐S., Kim, K.‐J., Han, M. H., Lee, E. H., Lee, K., Cho, C.‐H. β‐Adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation. FASEB J. 32, 2324–2338 (2018). www.fasebj.org

PROTECTIVE EFFECTS OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS ON PROGRESSION OF DIABETIC RETINOPATHY IN PATIENTS WITH TYPE 2 DIABETES.

Purpose: To investigate the effects of dipeptidyl peptidase-4 (DPP4) inhibitors on the progression of diabetic retinopathy (DR) in patients with Type 2 diabetes based on the DR severity scale. Methods: The medical records of 82 patients with Type 2 diabetes enrolled from 2005 to 2015 were retrospectively reviewed. Fundus photographs were graded using Early Treatment Diabetic Retinopathy Study methods. The associations between baseline risk factors and progression of DR were investigated. Results: Seven of 28 patients treated with DPP4 inhibitors and 26 of 54 treated with other hypoglycemic agents showed progression of retinopathy, defined as one or more steps on the Early Treatment Diabetic Retinopathy Study scale (P = 0.043). Only treatment with DPP4 inhibitors significantly reduced the progression of DR in patients after propensity score matching (P = 0.009). Treatment with DPP4 inhibitors was associated with a lower risk of DR progression (P = 0.011). Conclusion: Treatment with DPP4 inhibitors was the independent protective factor against the progression of DR, aside from improving glycemic control. This is the first study to show the benefits of DPP4 inhibitors in reducing DR progression, and provides encouraging preliminary data for further evaluation of DPP4 inhibitors in the progression of DR in a randomized, double-blind, placebo-controlled trial.

Central retinal vein occlusion in an otherwise healthy child.

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