Takaki Sato

Effect of Hypoxia on Susceptibility of RGC-5 Cells to Nitric Oxide

PURPOSE To determine whether retinal neurons become more susceptible to injury by nitric oxide (NO) under hypoxic conditions. METHODS Cells from the RGC-5 line were exposed to different concentrations (0.1-100 microM) of S-nitroso-N-acetyl-penicillamine (SNAP), an NO donor, under normoxic and hypoxic (1.0% O(2)) conditions with 5.5 mM glucose or with no glucose. In some experiments, carboxy-PTIO, a scavenger of NO, was added with SNAP. The SNAP-induced cell injury was determined by the WST-8 assay and by the assessment of phosphatidylserine externalization and changes in hypodiploid DNAs. Alterations of mitochondrial membrane potential, superoxide anion formation, cellular adenosine triphosphate (ATP) contents, and caspase activity were also determined after exposure to SNAP. RESULTS Exposure of RGC-5 cells to SNAP (100 microM) significantly decreased the number of living cells cultured under hypoxic conditions with or without glucose. Coadministration of carboxy-PTIO (1.0 microM) suppressed SNAP-induced cell death. SNAP-induced cell death of cells cultured under hypoxia with glucose was accompanied by increased expression of phosphatidylserine and hypodiploid DNAs. These findings indicated that death was mediated in part by apoptosis. In addition, loss of mitochondrial membrane potential, increase of superoxide formation, and activation of caspase was observed. Cyclosporine A, TEMPOL, and Z-VAD-FMK suppressed cell death. On the other hand, SNAP depleted the ATP contents of cells cultured under hypoxia without glucose, causing mainly necrotic cell death. CONCLUSIONS These results indicate that RGC-5 cells become susceptible to SNAP under hypoxic conditions in which NO may have greater impact on mitochondrial function.

Treatment of massive subretinal hematoma associated with age-related macular degeneration using vitrectomy with intentional giant tear.

The purpose of this study was to report the surgical outcomes after creating a 120° intentional giant retinal tear for use in removing hemorrhage and subretinal proliferative tissue in patients with polypoidal choroidal vasculopathy (PCV) or age-related macular degeneration (ARMD). This study involved 12 eyes of 12 patients (10 eyes: PCV, 2 eyes: ARMD). After removal of the lens in phakic eyes, we performed a vitrectomy with artificial posterior vitreous detachment. Subsequently, a 120° intentional giant retinal tear was created in the temporal periphery, the retina was then turned, and the subretinal hemorrhage and proliferative tissue were removed. In order to preserve as much of the retinal pigment epithelium (RPE) as possible, we used a bimanual technique under direct visualization. After stretching the retina by use of perfluorocarbon liquid (PFCL), we performed endophotocoagulation around the tear followed by PFCL/silicone oil exchange. Except for 1 eye in which extensive loss of the RPE occurred, the fundus findings and the visual acuity (VA) improved in all patients. In addition, postoperative VA improved to ≥20/50 in 3 eyes in which the macular RPE was preserved. This surgical procedure is an effective treatment for PCV or ARMD patients with extensive subretinal hemorrhage and proliferative tissue.

Vitrectomy for Tractional Retinal Detachment with Twin Retinal Capillary Hemangiomas in a Patient with Von Hippel-Lindau Disease: A Case Report.

Purpose: The purpose of this study was to report a case of Von Hippel-Lindau disease (VHL) with twin retinal capillary hemangiomas that was successfully treated by vitreous surgery for tractional retinal detachment following laser photocoagulation. Case: A 44-year-old male presented at our university hospital after noticing decreased visual acuity in his right eye. The patient had previously undergone multiple operations for cerebellar, thoracic, and lumbar spine hemangioblastomas when he was approximately 19 years old. Upon initial examination, ocular findings revealed twin connected retinal capillary hemangiomas around the temporal upper area of the patient’s right eye. The patient was subsequently diagnosed with VHL based on his medical history and current observations of the ocular fundus. Tractional retinal detachment had occurred as the result of the formation of proliferative membranes following laser photocoagulation. The patient underwent vitreous surgery to treat the tractional retinal detachment, resulting in a successful postoperative outcome. Conclusion: The findings of this study show the possibility that proliferative changes and tractional retinal detachment can arise following photocoagulation for retinal capillary hemangiomas in patients with VHL.

Progression of nuclear sclerosis based on changes in refractive values after lens-sparing vitrectomy in proliferative diabetic retinopathy

Background Nuclear sclerosis (NS) based on the Emery–Little classification and refractive values after lens-sparing vitrectomy was compared between proliferative diabetic retinopathy (DR) patients and nondiabetic patients. Methods Progression of NS based on the Emery–Little classification and changes in refractive values were compared between 13 proliferative DR patients (14 eyes, DR group) and 14 nondiabetic patients (14 eyes, non-DR group) who underwent lens-sparing vitrectomy. All patients revealed grade I NS based on the Emery–Little classification. Mean patient age and refractive value just after surgery were 56.07 years and −0.33 diopters (D) in the DR group, and 57.06 years and −0.96 D in the non-DR group. Results The Emery–Little classification in the DR group at 6 and 24 months postoperative were grade I (13 eyes)/grade II (one eye) and grade I (eleven eyes)/grade II (three eyes), respectively. Mean refractive values in the DR group at 6, 12, and 24 months postoperative were +0.28 D, +0.27 D, and +0.37 D, respectively. The Emery–Little classification in the non-DR group at 6 and 24 months (or preoperative for patients undergoing cataract surgery) were grade I (five eyes)/grade II (eight eyes) and grade I (zero eyes)/grade II (eight eyes)/grade III (five eyes), respectively. The mean refractive value in the non-DR group at 6 months postoperative was −3.20 D. All eyes exhibited myopic changes and progression of NS. Conclusion The findings of this study show that the progression of NS postvitrectomy is mild, even for DR patients 50 years of age or older, thus suggesting the need to reconsider the indications for simultaneous cataract surgery with vitrectomy.

A case of Alagille syndrome complicated by intraocular lens subluxation and rhegmatogenous retinal detachment.

This case report describes a case of Alagille syndrome with developing intraocular lens subluxation and rhegmatogenous retinal detachment 4 years after cataract surgery. A 15-year-old female patient with Alagille syndrome-associated cataracts in both eyes underwent phacoemulsification aspiration and intraocular lens implantation. Four years postoperative, intraocular lens subluxation developed in her left eye. For treatment, extraction of the dislocated intraocular lens, anterior vitrectomy, and intraocular lens fixation was performed. Three weeks later, the patient developed rhegmatogenous retinal detachment, which was well-treated by pars plana vitrectomy. Cataract surgery needs to be performed carefully in patients with Alagille syndrome due to the weakness of the zonule of Zinn. Careful postoperative observation is necessary for patients with Alagille syndrome who have undergone intraocular surgery in order to facilitate early detection of a possible rhegmatogenous retinal detachment.

A comparison of sex steroid concentration levels in the vitreous and serum of patients with vitreoretinal diseases

The purpose of this study was to compare steroid hormone concentration levels in the vitreous and serum of vitreoretinal disease patients to elucidate the possibility of neurosteroid production in the retina. Serum and vitreous samples were collected from vitrectomy patients, and estradiol (E2) and testosterone (T) concentrations were measured using electro-chemiluminescence immunoassay. We measured E2 in epiretinal membrane (ERM, n = 14), macular hole (MH, n = 18), proliferative diabetic retinopathy (PDR, n = 20), and retinal detachment (RD, n = 19) cases, and T in ERM (n = 14), MH (n = 17), PDR (n = 13), and RD (n = 17) cases. No statistically significant age differences existed among the groups. Mean respective E2 concentrations (pg/ml) in the male/female vitreous were ERM: 6.67±4.04/18.82±7.10, MH: 10.3±7.02/17.00±4.8, PDR: 4.2±3.05/15.83±3.46, and RD: 10.00±4.58/16.06±4.57, while those in serum were ERM: 31.67±5.51/5.82±1.08, MH: 21.00±8.89/7.53±3.2, PDR: 29.20±7.07/12.75±10.62, and RD: 24.33±6.51/7.5±4.42. E2 concentrations were significantly higher (P<0.001) in the male serum than vitreous, yet significantly higher in the female vitreous than serum. Mean respective T concentrations (ng/ml) in the male/female vitreous were ERM: 0.15±0.03/0.15±0.01, MH: 0.15±0.01/0.15±0.01, PDR: 0.15±0.03/0.16±0.12, and RD: 0.14±0.01/0.17±0.08, while those in serum were ERM: 4.54±1.46/0.16±0.01, MH: 8.04±2.29/0.16±0.10, PDR: 5.14±1.54/0.22±0.11, and RD: 3.24±0.75/0.17±0.10. T concentrations were high in the male serum, yet extremely low in the male and female vitreous and female serum. High concentrations of E2 were found in the vitreous, and women, in particular, exhibited significantly higher concentrations in the vitreous than in the serum. This finding suggests the possibility that in vitreoretinal disease cases, the synthesis of E2 is increased locally only in female eyes.

Clinical Features of Japanese Patients with Central Retinal Vein Occlusion Complicated by Normal-Tension Glaucoma: A Retrospective Study

Purpose: The association of central retinal vein occlusion (CRVO) with primary open-angle glaucoma (POAG) or ocular hypertension has been reported, and lowering intraocular pressure (IOP) helps to improve the retinal circulation in eyes with CRVO. However, the clinical features of CRVOs with normal-tension glaucoma (NTG) are not well known. Therefore, we investigated Japanese CRVO patients with NTG. Methods: We retrospectively investigated 234 CRVO patients over 5 years, with follow-ups of more than 12 months, and evaluated the prevalence of glaucoma. Results: Of the 234 CRVO patients, 18 (7.7%) were diagnosed with NTGs (n = 10) or POAGs (n = 8). Seven POAG (87.5%) and 3 NTG (30%) patients had systemic hypertension. At the initial CRVO evaluation, 6 NTGs showed a significantly increased IOP; mean IOP was 13.3 mm Hg before CRVO, 16.2 mm Hg at CRVO, and 13.5 mm Hg at the final visit. Conclusions: The proportion of NTGs with systemic hypertension was low. IOP of NTG patients was significantly elevated at the initial CRVO evaluation, even in the presence of anti-glaucoma drugs.

A Case of Proliferative Diabetic Retinopathy with HIV Infection in Which HAART Possibly Influenced the Prognosis of Visual Function

Background: We report on a patient with proliferative diabetic retinopathy (PDR) and human immunodeficiency virus (HIV) infection who exhibited extremely active PDR followed by a rapid onset of blindness in the right eye. The progression of visual disturbance in the patient’s left eye was slowed after starting highly active anti-retroviral therapy (HAART), and vision in that eye was rescued after vitrectomy. Case Report: A 72-year-old male developed pneumocystis carinii pneumonia stemming from an HIV infection and began HAART at the Department of Hematology, Osaka Medical College, Takatsuki City, Japan. Prior to HAART, the patient had shown rapidly progressing retinopathy in the right eye accompanied by vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma, ultimately leading to early-onset blindness. After starting HAART, the progression of the retinopathy in the left eye became slower compared to the right eye, with corrected visual acuity improving to 0.6 after vitrectomy, despite being accompanied by vitreous hemorrhage. The patient’s overall condition has remained stable following the operation, and the condition of the ocular fundus in the left eye has also settled. Conclusion: Significant differences were found in the progression rate of PDR with HIV infection between before and after starting HAART. Our findings suggest that early administration of HAART to HIV patients with diabetic retinopathy is crucial for maintaining visual function.

A Case of a Vitreomacular Traction- Associated Macular Microhole in an Eye with Focal Choroidal Excavation

Purpose: It was the aim of this study to report a case of a vitreomacular traction-associated macular microhole (MMH) in an eye with focal choroidal excavation (FCE) detected by spectral-domain optical coherence tomography (SD-OCT). Patients and Methods: A 38-year-old Japanese female presented to our clinic complaining of metamorphopsia in her left eye. The patient then underwent SD-OCT as well as a routine ophthalmological examination. She had a previous history of a macular hole in her right eye that had been successfully treated by pars plana vitrectomy. Results: Upon initial examination, her best-corrected visual acuity was 20/25 in the left eye with a refractive error of -10.25 diopters. Examination by SD-OCT revealed an MMH with an outer retinal defect adjacent to the FCE. SD-OCT also revealed an intraretinal cystoid space in the macula with vitreous attachment around the foveal center. Conclusions: The findings of this report show that variable changes are likely to be associated with FCE. However, the etiology of FCE has yet to be fully elucidated and careful observation is necessary in cases of FCE.

Vitrectomy for Proliferative Diabetic Retinopathy Associated with Klinefelter Syndrome.

Introduction: We encountered a patient with Klinefelter syndrome (KS) who experienced poor outcomes after vitrectomy for proliferative diabetic retinopathy (PDR). Case: A 44-year-old male with poorly controlled diabetes was diagnosed with KS by chromosome analysis. Ocular findings revealed severe PDR complicated with extensive preretinal hemorrhages and traction retinal detachment in his left eye, and pars plana vitrectomy was subsequently performed for treatment. Results: A clotting hemorrhage developed during surgery and proved difficult to control. Due to postoperative bleeding and redetachment, the vitrectomy was repeated. At the second operation, we performed a silicone oil tamponade; however, the retina was redetached under the silicone oil, and the light perception vision ultimately disappeared. Conclusion: The patient, despite showing increased blood coagulability due to diabetes, presented severe coagulopathy, likely related to KS. In patients with KS and severe PDR, the potential difficulty of vitrectomy should always be kept in mind.