Pathological Features of Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats.

OBJECTIVE: The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele (obesity gene) of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. We studied the pathologic features of diabetic retinopathy (DR) in this animal. METHODS: The eyes of SDT fatty, SDT (controls), and Sprague Dawley (SD) rats (normal controls) were enucleated at 8, 16, 24, 32, and 40 weeks of age (n = 5-6 for each rat type at each age). The retinal thicknesses, numbers of retinal folds, and choroidal thicknesses were evaluated. Immunostaining for glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was performed. Quantitative analyses of the immunopositive regions were performed using a cell-counting algorithm. RESULTS: The retinas tended to be thicker in the SDT fatty rats and SDT rats than in the SD rats; the choroids tended to be thicker in the SDT fatty rats than in the SD rats. The retinal folds in the SDT fatty rats developed earlier and were more severe than in the SDT rats. Quantitative analyses showed that the GFAP- and VEGF-positive regions in the retinas of the SDT fatty rats were significantly larger than those of the SDT rats. CONCLUSIONS: SDT fatty rats developed more severe DR earlier than the SDT rats. The SDT fatty rats might be useful as a type 2 diabetes animal model to study DR.

Risk factors and clinical signs of severe Acanthamoeba keratitis.

PURPOSE: To determine risk factors and clinical signs for severe Acanthamoeba keratitis (AK) by comparing severe cases with mild cases with good prognosis. PATIENTS AND METHODS: We reviewed medical records of ten cases of AK (five males and five females) referred to our hospital and classified cases into two groups. One eye that required therapeutic keratoplasty and three eyes with a poor visual acuity (<0.2) on last visit were included in the severe group. Six eyes that had good prognosis with a visual acuity of 1.2 on last visit were classified as mild group. We compared patients' age, the time required for diagnosis, visual acuity on first visit, the history of steroid eye drops use, and other clinical findings. RESULTS: The average age of the severe group was older than the mild group (P=0.04). The duration between onset and diagnosis of AK and visual acuity on first visit was not statistically different. A history of steroid eye drop use was found in four eyes of the severe group (100%) and four eyes of the mild group (67%). Keratoprecipitates were found in all severe group eyes and one mild group eye during follow-up (P=0.01). One case in the severe group was diagnosed with diabetes mellitus at initial examination. We detected Staphylococcus epidermis by palpebral conjunctival culture in one case of the severe group. CONCLUSION: Aging may be a possible risk factor for severe AK. The presence of keratoprecipitates is a possible sign of severe AK. Attention is also required in patients with comorbidities such as diabetes mellitus and bacterial infection.

Clinicopathological features of epiretinal membranes in eyes filled with silicone oil.

PURPOSE: The aim of this case series was to clarify the clinicopathological features of epiretinal membranes (ERMs) that developed in eyes after silicone oil (SO) tamponade to treat rhegmatog-enous retinal detachments (RRDs). PATIENTS AND METHODS: In the Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, patients with idiopathic ERMs (23 eyes) and ERMs in eyes filled with SO (SO ERMs) after vitreous surgery to treat RRDs (nine eyes) were enrolled from July 2012 to March 2014. ERM tissues obtained intraoperatively were examined histopathologically. Besides the main outcome measure of the pathological findings of the ERM tissues, other outcome measures included the preoperative findings on optical coherence tomography (OCT) images and the surgical findings. RESULTS: Eight (89%) of nine eyes with SO ERMs had bilayered membranes composed of a firm layer on the retinal side with glial cells and extracellular matrix and a fragile sponge-like layer on the vitreous side. The sponge-like layer was composed of emulsified SO surrounded by macrophages. Quantitative analysis showed that the areas with cluster of differentiation 68 (CD68)-positive macrophages identified by immunohistochemistry in eyes with SO ERMs were significantly (P<0.001) larger than those in eyes with idiopathic ERMs. The findings on OCT images were consistent with the pathological features of the SO ERMs. Surgical removal of the SO ERMs was difficult because the sponge-like layer was fragile, and the underlying retina was also fragile due to inflammation. CONCLUSION: SO ERMs are bilayered membranes. Long-standing emulsified SO formed a sponge-like layer and SO (foreign body)-induced granulation and caused retinal inflammation in these eyes, making surgical removal difficult. A preoperative OCT examination is necessary to identify SO ERMs.

Vogt-Koyanagi-Harada Disease Associated with Influenza A Virus Infection.

We herein report a case of a 31-year-old Japanese man who simultaneously had a positive influenza A virus antigen test result and Vogt-Koyanagi-Harada disease (VKHD), demonstrated by both diffuse multiple early hyperfluorescent points on fluorescein fundus photography and serous retinal detachments on optical coherence tomography. He had meningitis. It was difficult to determine whether the main cause of meningitis was influenza A or VKHD. After initial treatment with peramivir for influenza A and then methylprednisolone pulse with subsequent corticosteroid therapy for VKHD, his symptoms improved gradually. These findings suggest that influenza A virus infection contributes to the onset or exacerbation of VKHD.

Diabetic Retinal and Choroidal Edema in SDT Rats.

We evaluated the features of diabetic retinal and choroidal edema in Spontaneously Diabetic Torii (SDT) rats. We measured the retinal and choroidal thicknesses in normal Sprague-Dawley (SD) rats (n = 9) and SDT rats (n = 8). The eyes were enucleated 40 weeks later after they were diagnosed with diabetes, and 4-micron sections were cut for conventional histopathologic studies. The mean retinal and choroidal thicknesses were significantly thicker in the SDT rats than in the normal SD rats. The choroidal thickness was correlated strongly with the retinal thickness in both rat models. Diabetic retinopathy (DR) and diabetic choroidopathy appeared as edema in the SDT rats. The retinal thickness was correlated strongly with the choroidal thickness in the SDT rats, which is an ideal animal model of both DR and choroidopathy.

Relationship between variations in posterior vitreous detachment and visual prognosis in idiopathic epiretinal membranes.

PURPOSE: To clarify the relationship between variations in posterior vitreous detachments (PVDs) and visual prognoses in idiopathic epiretinal membranes (ERMs). METHODS: In this retrospective, observational, and consecutive case series, we observed variations in PVDs in 37 patients (mean age, 65.7±11.0 years) with ERMs and followed them for 2 years. Three PVD types were found biomicroscopically: no PVD, complete PVD with collapse (C-PVD with collapse), and partial PVD without shrinkage, with persistent vitreous attachment to the macula through the premacular hole of the posterior hyaloid membrane (P-PVD without shrinkage [M]). The best-corrected visual acuity (BCVA) was measured and converted to the logarithm of the minimum angle of resolution (logMAR) BCVA at the first visit and 2 years later. RESULTS: No PVD was observed in 16 of the 37 eyes (mean age, 61.3±11.3 years), C-PVD with collapse in 11 of the 37 eyes (mean age, 69.1±9.9 years), and P-PVD without shrinkage (M) in 10 of the 37 eyes (mean age, 69.3±10.9 years). The logMAR BCVA at the first visit was the worst in the P-PVD without shrinkage (M) group (0.22±0.35) compared with the no-PVD group (-0.019±0.07; P<0.01) and the C-PVD group (0.029±0.08; P<0.05). The logMAR BCVA 2 years later was also worst in the P-PVD without shrinkage (M) group (0.39±0.35) compared with the no-PVD group (0.04±0.13) and the C-PVD with collapse group (0.03±0.09; P<0.05 for both comparisons). The change in the logMAR BCVA over the 2-year follow-up period was worst in the P-PVD without shrinkage (M) group (0.17±0.23) compared with the no-PVD group (0.06±0.14) and the C-PVD with collapse group (0.0009±0.09; P<0.05 for both comparisons). CONCLUSION: Cases with an ERM with a P-PVD without shrinkage (M) had a worse visual prognosis than those with an ERM with no PVD and C-PVD with collapse.

Candidemia from an upper urinary tract infection complicated by candida endophthalmitis.

A 51-year-old Japanese woman developed candidemia as an outpatient secondary to a Candida albicans upper urinary tract infection complicated by previously undiagnosed type 2 diabetes mellitus with poor glycemic control and ureterolithiasis. The patient did not have any risk factors typically associated with candidemia, such as an indwelling vascular catheter, parenteral nutrition or broad-spectrum antibiotic use. During the clinical course, her condition was complicated by unilateral candida endophthalmitis, which progressed despite the administration of systemic antifungal agents and ultimately required vitreous surgery. The etiology of candidemia in this patient and the reason she developed progressive ocular symptoms after starting antifungal treatment are reviewed.

Effect of ranirestat, a new aldose reductase inhibitor, on diabetic retinopathy in SDT rats.

PURPOSE: To evaluate the effect of ranirestat, a new aldose reductase inhibitor (ARI), on diabetic retinopathy (DR) in Spontaneously Diabetic Torii (SDT) rats. METHODS: The animals were divided into six groups, normal Sprague-Dawley rats (n = 8), untreated SDT rats (n = 9), ranirestat-treated SDT rats (0.1, 1.0, and 10 mg/kg/day, n = 7, 8, and 6, resp.), and epalrestat-treated SDT rats (100 mg/kg/day, n = 7). Treated rats received oral ranirestat or epalrestat once daily for 40 weeks after the onset of diabetes. After the eyes were enucleated, the retinal thickness and the area of stained glial fibrillary acidic protein (GFAP) were measured. RESULTS: The retinas in the untreated group were significantly thicker than those in the normal and ranirestat-treated (0.1, 1.0, and 10 mg/kg/day) groups. The immunostained area of GFAP in the untreated group was significantly larger than that in the normal and ranirestat-treated (1.0 and 10 mg/kg/day) groups. There were no significant differences between the untreated group and epalrestat-treated group in the retinal thickness and the area of stained GFAP. CONCLUSION: Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress DR and have a neuroprotective effect on diabetic retinas.

Effects of long-term treatment with ranirestat, a potent aldose reductase inhibitor, on diabetic cataract and neuropathy in spontaneously diabetic torii rats.

We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN) in spontaneously diabetic Torii (SDT) rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg) or epalrestat (100 mg/kg) for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal) to 3 (mature cataract). The combined scores (0-6) from both lenses represented the total for each animal. DN was assessed by measuring the motor nerve conduction velocity (MNCV) in the sciatic nerve. Sorbitol and fructose levels were measured in the lens and sciatic nerve 40 weeks after diabetes onset. Cataracts developed more in untreated rats than normal rats (P < 0.01). Ranirestat significantly (P < 0.01) inhibited rapid cataract development; epalrestat did not. Ranirestat significantly reversed the MNCV decrease (40.7 ± 0.6 m/s) in SDT rats dose-dependently (P < 0.01). Epalrestat also reversed the prevented MNCV decrease (P < 0.05). Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 ± 0.10 nmol/g), which ranirestat significantly suppressed dose-dependently, (P < 0.05, <0.01, and <0.01); epalrestat did not. Ranirestat prevents DN and cataract; epalrestat prevents DN only.

Blunt needle revision with viscoelastic materials via the anterior chamber for early failed filtering blebs after trabeculectomy.

PURPOSE: To report a new technique of blunt needle revision with viscoelastic materials via the anterior chamber for the treatment of early failed filtering blebs and elevated intraocular pressure after trabeculectomy, in which digital ocular massage and laser suture lysis have been ineffective. METHODS: A 27-gauge blunt needle attached to a syringe containing viscoelastic material was inserted into the anterior chamber from the inferior paracentesis. The needle tip was inserted into the subscleral flap space from the filtering fistula at the anterior chamber side, and the scleral flap was lifted bluntly. The needle tip was then inserted into the subconjunctival space where the viscoelastic agent was injected and the adhesion between the sclera and conjunctiva was separated bluntly. Blunt needle revision via the anterior chamber was performed 14 times in six eyes of six patients at Saitama Medical Center, Jichi Medical University from January 2007 to May 2009. All procedures were performed within 1 month after trabeculectomy. RESULTS: The intraocular pressure remained 21 mmHg or lower for more than 6 months in three of six eyes. Slight bleeding from the iris occurred in one of the 14 procedures, and hypotony (intraocular pressure below 5 mmHg) occurred in one of the 14 procedures. No serious complications developed. CONCLUSION: Blunt needle revision via the anterior chamber for early failed filtering blebs is a new, simple, and safe procedure.

Clarifying the mechanism of idiopathic macular hole development in fellow eyes using spectral-domain optical coherence tomography.

BACKGROUND: To clarify the mechanism of idiopathic macular hole development, we evaluated the vitreoretinal relationship in fellow eyes of those with a macular hole and normal eyes using spectral-domain optical coherence tomography. Thirty-one fellow eyes and 34 normal volunteer eyes without a posterior vitreous detachment (PVD) were included. RESULTS: WE CLASSIFIED SIX VITREOMACULAR RELATIONSHIPS: type 1, no PVD, five fellow eyes (16.1%) and nine control eyes (26.5%); type 2, shallow PVD with perifoveal vitreous attachment, seven fellow eyes (22.6%) and 19 control eyes (55.9%); type 3, shallow PVD with pinpoint foveal vitreous traction, seven fellow eyes (22.6%) and no control eyes (0%), type 4a; shallow PVD with a round defect in the posterior vitreous cortex over the perifoveal area with vitreous attachment to the perifoveal area, two fellow eyes (6.5%) and one control eye (2.9%); type 4b, shallow PVD with a round defect in the posterior vitreous cortex over the perifoveal area without vitreous attachment to the perifoveal area, no fellow eyes (0%) and one control eye (2.9%); type 5a, shallow PVD with no pseudo-operculum, no fellow eyes (0%) and four control eyes (11.8%); type 5b, shallow PVD with a pseudo-operculum, four fellow eyes (12.9%) and no control eyes (0%); and type 6, biomicroscopically relevant PVD, six fellow eyes (19.4%). CONCLUSION: Types 3 and 5b developed only in fellow eyes. Type 2 developed most often in normal eyes and seemed to cause less foveal stress. Type 3 may show the basic pathogenesis of macular holes. Progression of type 5b after type 3 induces abortion of developing macular holes.

Surgical results of pars plana vitrectomy combined with pars plana lensectomy with anterior capsule preservation, endophotocoagulation, and silicon oil tamponade for neovascular glaucoma.

PURPOSE: To report on pars plana vitrectomy (PPV) combined with pars plana lensectomy (PPL) with a preserved anterior capsule, panretinal endophotocoagulation (EPC) throughout the pars plana, and silicon oil (SO) tamponade (PPV + PPL + EPC + SO tamponade) for neovascular glaucoma (NVG). METHODS: Thirteen eyes with NVG were treated. Ten eyes also underwent SO removal and intraocular lens (IOL) implantation (SO removal + IOL). Intraocular pressure (IOP), number of medications, and visual acuity were evaluated at the first visit, immediately before and 3 months after the procedure, 3 months after SO removal + IOL, and 1 year after the procedure. RESULTS: At the first visit, immediately before and 3 months after the procedure, 3 months after SO removal + IOL, and 1 year after the procedure, the IOPs were 29 ± 19, 23 ± 12, 13 ± 5, 17 ± 10, and 17 ± 6 mmHg; numbers of medications, 0.7 ± 1.4, 2.1 ± 2.0, 0.6 ± 0.7, 1.2 ± 1.2, and 1.6 ± 1.6; and best-corrected visual acuities converted to logarithm of the minimum angle of resolution (BCVA logMAR), 0.96 ± 0.96, 1.27 ± 0.80, 1.67 ± 0.91, 1.37 ± 0.89, and 1.90 ± 1.44, respectively. No severe hypotony or phthisis bulbi developed within 1 year after the procedure. The success rates (IOP ≤ 21 mmHg and sustained light perception) were 92.3% after 3 months and 69.2% after 1 year. CONCLUSION: PPV + PPL + EPC + SO tamponade might have prevented acute increases of vascular endothelial growth factor and inflammatory cytokine production postoperatively and resulted in good vision in patients with NVG.