Hyun Woong Kim

Innate Immune Signals in Autoimmune and Autoinflammatory Uveitis

Although traditionally the adaptive immune system has been viewed as the essential contributor to autoimmune diseases, the evidence implicating the innate immune system has grown considerably in recent years. Several multisystem inflammatory diseases affect the uvea and occur as a result of a mutation in a gene coding for a component of the innate immune system. Diseases associated with uveitis such as ankylosing spondylitis, sarcoidosis, Behcets disease and inflammatory bowel disease can best be conceptually understood by hypotheses that consider microbial infection and innate immunity as contributing factors.

Edema of the Photoreceptor Layer in Vogt-Koyanagi-Harada Disease Observed Using High-Resolution Optical Coherence Tomography

Purpose To evaluate the characteristics of fluid accumulation in the uveitic stage of Vogt-Koyanagi-Harada (VKH) disease using high resolution optical coherence tomography (OCT3). Methods Twenty-eight eyes in 14 patients with VKH disease were reviewed retrospectively. These 28 eyes were divided into 19 eyes with intraretinal fluid (C group) and 9 eyes without intraretinal fluid (N group). Changes in visual acuity and fluid accumulation observed using OCT were compared between the two groups. Results Visual acuity at the time of presentation was significantly worse in the C group than in the N group (p=0.005). The photoreceptor layer appeared to be double-layered due to a cystoid space in the C group. Layered structures and strands found in the cystoid space. Expanding sponge-form edema led to the development of a cystoid space in the photoreceptor layer. Intraretinal fluid resolved earlier than subretinal fluid. There were no observed differences in visual acuity between the two groups after four days of treatment. Conclusions Accumulation of intraretinal fluid was related to poor initial visual acuity, but not to final visual acuity. High resolution OCT findings indicate that edema of the photoreceptor layer participates in the development of a cystoid space.

Clinical Outcomes of Double Staining and Additional ILM Peeling during ERM Surgery

Purpose To assess the clinical outcomes in idiopathic epiretinal membrane (ERM) patients after vitrectomy and ERM removal with or without additional indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling. Methods The medical records of 43 patients with an idiopathic ERM that underwent vitrectomy and ERM removal between July 2007 and April 2010 were reviewed. The patients were divided into two groups: triamcinolone-assisted simple ERM peeling only (group A, n = 23) and triamcinolone-assisted ERM peeling followed by ICG staining and peeling of the remaining internal ILM (group B, n = 20). Results No difference was found between the two groups in terms of visual acuity, macular thickness, P1 amplitude or implicit time on multifocal-electroretinogram (mfERG) at six and 12 months postoperatively. In group B, ICG staining after ERM peeling demonstrated that the ILM had been removed together with the ERM in 12 eyes (60%), and all 12 eyes showed punctate retinal hemorrhages during ERM peeling. There was no recurrence of an ERM in either group. Conclusions Additional procedures involving ICG staining and ILM peeling during ERM surgery do not appear to have an additive effect on the clinical outcomes in terms of visual acuity, retinal function based on mfERG, or recurrence rate.

Effect of lipoic acid on expression of angiogenic factors in diabetic rat retina.

Background:  This study evaluated the effect of a lipoic acid on reactive oxygen species formation and the simultaneous changes of several angiogenic factors in an experimental diabetic rat retina.

Intraocular infestation with Thelazia callipaeda

To the EditorIn their recently published manuscript, Kim and colleagues[1] describe a case of human intraocular infestation byworms. The authors erroneously identify the nematodecollected in the conjunctiva as Thelazia callipaeda (Spiru-rida: Thelaziidae). However, the morphological identifica-tion of T. callipaeda adult nematodes relies on evidence ofthe presence of a buccal capsule with the internal marginseverted and subdivided by excavations into six festoons andthe mouth opening with a hexagonal profile. These mor-phological features clearly differ from those of the nema-tode in the figure presented by Kim and colleagues [1]. Theauthors also state that the life cycle of T. callipaeda remainsunclear and discuss the possibility of human infectionthrough the skin or by drinking untreated water. It isimportant for physicians and ophthalmologists who may notbe experts in parasitology to realize that, similarly to othermembers of the Thelaziidae, and at a higher taxonomicallevel of the order Spirurida, T. callipaeda is transmittedonly by secretophagous flies [2]. T. callipaeda develops thefirst to third infective stages of larvae within its body andthese are then deposited into the eyes of receptive hostswhen flies feed on lachrymal secretions.The lack of knowledge of this helminth’s infestation isprobably due to the fact that, until the last decade, the bodyof literature on this nematode was published in languagesother than English (mainly Chinese) and thus it was notaccessible to a great part of the western scientific commu-nity. This nematode was commonly known as the ‘‘orientaleye-worm’’ because of its distribution in Asian countrieswhere it is still frequently reported as being responsible forthelaziosis in humans, carnivores (dogs, cats and foxes) andrabbits, causing mild to severe clinical signs (includingepiphora, conjunctivitis, keratitis and/or even cornealulcers) [2]. The little attention medical researchers tend topay human thelaziosis may also be attributable to the dif-ficulties in its clinical diagnosis and differentiation fromallergic conjunctivitis, particularly when small numbers ofadult or larval stages are present in affected patients. Overthe last decades, however, infestation by T. callipaeda hasgained the interest of the scientific community and there isevidence of its spreading throughout Europe, with a highprevalence (up to 60%) in dogs being recorded in someareas of southern Italy [2]. In the same areas the frequencyof wolves, beech martens, brown hares and wild cats asdefinitive hosts for T. callipaeda has been recently dem-onstrated. In addition, there is evidence for its occurrence indogs in France, Germany and Switzerland. Recently, thefirst four cases of human thelaziosis in Europe have alsobeen diagnosed [3]. Correct knowledge of the biology ofT. callipaeda is, therefore, pivotal in addressing the pre-vention of human thelaziosis (e.g., use of nets to protectchildren while sleeping, keeping their faces and eyes clean).Domenico OtrantoDepartment of Veterinary Public Healthand Animal SciencesFaculty of Veterinary Medicine of BariStrada Provinciale per Casamassima km 370010 Valenzano (Bari), ItalyReferences

A case of cystoid macular edema associated with Paclitaxel chemotherapy.

We encountered a patient with cystoid macular edema (CME) secondary to paclitaxel use. A 57-year-old man presented with gradual decreased bilateral vision. His chemotherapeutic regimen consisted of bevacizumab, paclitaxel (175 mg/m2 for 5 months), and carboplatin. Optical coherence tomography imaging revealed bilateral CME greater than 500 µm. However, one year later, visual acuity was improved, best-corrected Snellen visual acuity was 40 / 80 in each eye, and CME was spontaneously improved. Our study confirmed that macular edema associated with paclitaxel use shows spontaneous resolution and improvement of visual acuity after a change of chemotherapeutic regimen.

The Clinical Features of Macular Pucker Formation after Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment Repair

Purpose To investigate the incidence and predisposing factors of macular pucker formation after pars plana vitrectomy in patients who developed primary rhegmatogenous retinal detachment. Methods We retrospectively reviewed a consecutive series of 284 eyes in 284 patients who underwent primary retinal detachment repair by pars plana vitrectomy alone between January 1, 2009 and December 31, 2010. Patients with a history of retinal surgery or another visually significant ocular problem were excluded. Results Postoperatively, of the 264 eyes that completed at least six months of follow-up, 16 (6.1%) eyes developed obvious macular pucker at clinical examination. Of these 16 eyes, ten (70.0%) underwent repeat vitrectomy with membrane peeling for macular pucker removal during the follow-up period. The mean time from primary vitrectomy for the retinal reattachment to the secondary vitrectomy with membrane peeling for macular pucker was 7.9 months. The mean improvement in vision after membrane peeling surgery was 0.37 (logarithm of the minimum angle of resolution). Using an independent t-test, chi-square test, and Mann-Whitney U-test, we found that the number or size of retinal break and vitreous hemorrhage could be significant risk factors of macular pucker. Conclusions In our study, 6.1% of eyes which underwent pars plana vitrectomy alone for primary retinal detachment developed a postoperative macular epiretinal membrane. Multiple or large retinal breaks and postoperative vitreous hemorrhage were related to macular pucker formation. Overall, the 70.0% of eyes which underwent secondary vitrectomy with membrane peeling for removal of macular pucker showed a favorable visual outcome.

Simvastatin suppresses expression of angiogenic factors in the retinas of rats with streptozotocin-induced diabetes

BackgroundAngiogenic factors such as vascular endothelial growth factor (VEGF), erythropoietin, and angiopoietin play important roles in the pathophysiology of diabetic retinopathy. Increased amounts of reactive oxygen species (ROS) are also known to associated with diabetic retinopathy and VEGF expression. This study evaluated the effect of a simvastatin on ROS generation and the changes in various angiogenic factors in the retinas of diabetic rats.MethodsThe rats were divided into normal, diabetes mellitus (DM), and simvastatin-treated groups (each group, n = 10). Diabetes was induced by intraperitoneal injection of streptozotocin into 20 Sprague–Dawley rats. After diabetic induction, simvastatin (5mg/kg) was administered orally to ten rats. The expression levels of VEGF, erythropoietin, angiopoietin 1 and 2, and NADPH oxidase were examined in rat retinas by RT-PCR and Western blot. Superoxide formation was examined by dihydroethidium (DHE) staining.ResultsDHE analysis revealed increased superoxide formation in the retinas of the diabetic group, which was decreased in the group treated with simvastatin. Western blot analysis showed that NADPH oxidase levels were decreased in the diabetic group and remained normal in the simvastatin-treated group. Simvastatin treatment blocked hyperglycemia-induced increases in VEGF, angiopoietin 2 and erythropoietin levels, as demonstrated by RT-PCR and Western blot analysis.ConclusionsSimvastatin treatment led to suppression of superoxide formation and decreased expression of VEGF, angiopoietin 2 and erythropoietin in diabetic rat retinas.

Enalapril alters expression of key growth factors in experimental diabetic retinopathy.

Purpose: Angiogenic factors such as vascular endothelial growth factor (VEGF), erythropoietin, and angiopoietin play important roles in the development of diabetic retinopathy. However, the suppression of a single factor does not inhibit angiogenesis completely. This study simultaneously evaluated the expression of several angiogenic factors in the retinas of diabetes-induced rats and determined the effects of an angiotensin-converting enzyme inhibitor (enalapril) on the expression of angiogenic factors. Methods: Diabetes was chemically induced by injecting 14 of 21 Sprague-Dawley rats with streptozotocin. After induction of diabetes, enalapril (10 mg/kg) was administered orally to seven rats. The rats were divided into normal, diabetes mellitus (DM), and enalapril-treated groups (each group, n = 7). The eyeballs were removed at 8 weeks after the induction of diabetes, and the retinal expression of VEGF, the signal transducer and activator of transcription (STAT)3/5, erythropoietin, and angiopoietin were examined using immunohistochemistry, RT-PCR, and Western blotting. Results: RT-PCR revealed that the expression of VEGF, VEGF receptors, STAT3, erythropoietin, erythropoietin receptor, STAT5, angiopoietin 2, and Tie2 mRNA increased in the DM group, whereas angiopoietin 1 expression decreased. The enalapril-treated group showed no increase in mRNA expression of angiogenic factors. Immunohistochemical staining and Western blotting showed that the expression of VEGF, STAT3, and erythropoietin receptor proteins increased in the DM group but not in the enalapril-treated group. Erythropoietin and angiopoietin proteins were not detected by immunohistochemical staining or Western blotting. STAT5 protein expression was detected only in the DM group using immunohistochemical staining and Western blotting. The mRNA expression of the angiogenic factors VEGF, erythropoietin, and angiopoietin 2 increased in the DM group but not in the enalapril-treated group. In contrast, angiopoietin 1 mRNA expression decreased in the DM group. Conclusions: Enalapril treatment prevented increased angiogenic factor levels in the retinas of experimentally induced diabetic rats.

Combined Treatment of Photodynamic Therapy and Bevacizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

Purpose To evaluate the outcome of a combined photodynamic therapy and intravitreal injection of bevacizumab in choroidal neovascularization secondary to age-related macular degeneration. Methods Photodynamic therapy (PDT) was administered to 28 eyes followed by 3 consecutive bevacizumab injections. Patients were followed-up for more than 12 months. At baseline, 1, 3, 6, and 12 months post PDT, visual acuity (VA) and central macular thickness were measured using optical coherence tomography. Results The mean VA was significantly improved from logarithm of the minimal angle of resolution 0.86 at baseline to 0.69 at 1 month (p = 0.011), 0.63 at 3 months (p = 0.003), 0.64 at 6 months (p = 0.004) and 0.60 at 12 months (p < 0.001). Central macular thickness decreased significantly from 328.3 µm at baseline to 230.0 µm at 6 months and 229.9 µm at 1 year (p < 0.001). Reinjection mean number was 0.4 for 6 months and 0.8 for 12 months. By 1 year, retreatment was performed in 10 eyes (36%). Conclusions PDT combined with three consecutive intraviteal bevacizumab injections was effective in improving VA and reducing central macular thickness.