[Show abstract][Hide abstract] ABSTRACT: We report a case of a sympathetic ophthalmia that occurred after 23-gauge transconjunctival sutureless vitrectomy for a retinal detachment.
A 41-year-old Japanese woman underwent combined phacoemulsification with intraocular lens implantation and 23-gauge transconjunctival sutureless vitrectomy for a rhegmatogenous retinal detachment in the right eye. Endolaser photocoagulation and silicone oil tamponade were used to manage inferior retinal holes. Four weeks after the surgery, she returned with a 5-day history of reduced vision and metamorphopsia in her left eye. Slit-lamp examination showed a shallow anterior chamber in the right eye and moderate anterior uveitis bilaterally. Silicone oil bubbles and pigment dispersion were observed in the subconjunctival space adjacent to the right eye's superonasal sclerotomy site. Fundus examination showed multifocal serous retinal detachments in both eyes. A diagnosis of sympathetic ophthalmia was made and the patient was treated with intensive topical and systemic steroids. The subretinal fluid cleared in both eyes following treatment. Twelve months after the onset of inflammation, the patient's condition was stable on a combination of oral cyclosporine and topical steroids. Sunset glow retinal changes remain, but there has been no evidence of recurrent inflammation.
Sympathetic ophthalmia can develop after 23-gauge transconjunctival sutureless vitrectomy despite its smaller sclerotomy size. We recommend that special care should be taken to inspect for adequate closure of sclerotomy sites at the end of this operation.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the intraocular gas dynamics after 23-gauge transconjunctival sutureless vitrectomy (TSV) as compared with 20-gauge pars plana vitrectomy (PPV).
A consecutive series of 290 eyes that experienced 20-gauge or 23-gauge vitrectomy with 25% sulfur hexafluoride (SF6) gas tamponade were retrospectively reviewed. Intraocular gas bubble size on postoperative Day 1 and Gas50, the interval to dissipate to a 50% gas fill, were evaluated.
The mean intraocular bubble size on postoperative Day 1 was 92.0 ± 8.3% in the 20-gauge PPV cases and 83.8 ± 13.7% in the 23-gauge TSV cases (P < 0.001). The mean Gas50 was 8.6 ± 1.6 days in the 20-gauge PPV cases and 6.6 ± 2.2 days in the 23-gauge TSV cases (P < 0.001). Thorough peripheral vitrectomy and 23-gauge TSV were significantly associated with Gas50 ≤ 4 days (odds ratio, 4.62 and 16.8; P = 0.036 and P = 0.007, respectively). Among thoroughly vitrectomized eyes, 13 eyes treated with 23-gauge PPV with intraoperative suture placement at the sclerotomy sites had gas longevity comparative to those with 20-gauge PPV.
Eyes treated with 23-gauge TSV tend to have earlier gas disappearance or incomplete gas fill. Intraoperative suture placement would be a solution.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the long-term effects of photodynamic therapy (PDT) on different phenotypes of age-related macular degeneration (AMD): typical AMD (tAMD) and polypoidal choroidal vasculopathy (PCV).
A multicenter prospective study of 207 eyes of 201 patients (tAMD, 123 eyes; PCV, 84 eyes) treated with PDT. Sex, age, best-corrected visual acuity (BCVA), greatest linear dimension, and lesion type were evaluated for pretreatment factors. PDT frequency, BCVA at 30 months post-PDT, frequency of recurrence, and mean recurrence period were compared as posttreatment outcomes.
The 30 months post-PDT mean BCVA was significantly lower than the pre-PDT value in the tAMD group, but it remained unchanged in the PCV group. There was no difference in PDT frequency between the two groups. Multivariate analysis revealed that lesion type was the only predicting factor significantly associated with BCVA at 30 months post-PDT. The incidence of recurrence before 30 months post-PDT was not significantly different between the tAMD and PCV groups, whereas the mean duration of the PDT effect was significantly longer in the PCV group than in the tAMD group.
PDT may have some advantages for PCV patients, but not for tAMD patients. However, as PCV often recurred 12 months post-PDT, long-term observation after the treatment is crucial.
Japanese Journal of Ophthalmology 11/2009; 53(6):593-7. DOI:10.1007/s10384-009-0741-0 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to evaluate the effects of photodynamic therapy (PDT) on different phenotypes of age-related macular degenerations (AMD): typical AMD (tAMD) and polypoidal choroidal vasculopathy (PCV).
246 eyes from 242 patients (tAMD: 139, PCV: 107 eyes) were recruited. Gender, age, best-corrected visual acuity (BCVA) before treatment, greatest linear dimension before treatment, lesion phenotype and PDT frequency were evaluated for predicting the BCVA at 12 months after PDT using stepwise multiple regression analyses. Additionally, 125 eyes with tAMD and 97 eyes with PCV followed up for more than 12 months after the final PDT were compared for the recurrence period.
In the stepwise analysis, a younger age, better pretreatment BCVA, lower PDT frequency, lesions with PCV and a smaller pretreatment greatest linear dimension were all significantly beneficial for a better BCVA at 12 months after PDT. PCV showed a significantly lower PDT frequency and greater improvement in the BCVA than tAMD. The recurrence period of PCV was significantly later than that of tAMD.
The phenotype of AMD is significantly correlated with its prognosis after PDT. PCV showed a significantly better response to PDT in terms of BCVA improvement and effect durability.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effects of intravitreal injection of tissue plasminogen activator (tPA) on central retinal vein occlusion(CRVO) associated with diabetic retinopathy (DR).
A retrospective study of 42 eyes of 42 patients(mean age: 68 years, female/male = 20/22, 5 eyes associated with DR) with macular edema caused by CRVO treated with tPA. Best corrected visual acuity (BVCA or logarithm of the minimal angle of resolution: logMAR), macular thickness was mea sured by optical coherence tomography (OCT), and several variables were evaluated.
The mean logMAR and macular thickness improved significantly in the DR (-) group, but, no significant changes were observed in the DR (+) group. Post-operative posterior vitreous detachment (PVD) developed in 62% of the DR (-) group and none of the DR (+) group.
There may be no beneficial effects of intravitreal tPA on CRVO associated with diabetic retinopathy.
[Show abstract][Hide abstract] ABSTRACT: We studied the suppressant effect of kallidinogenase on retinal vascular permeability and vascular endothelial growth factor (VEGF) in diabetic rats. Diabetes was induced by intravenously injecting streptozotocin (60 mg/kg body weight) dissolved in citrate buffer. Kallidinogenase (7 microg/kg/day) was injected intravenously once daily for 21 days. The retinal vascular permeability was estimated from the amount of fluorescent dye leaking into the retina after administration of fluorescein isothiocyanate-conjugated dextran. VEGF in intraocular fluids was quantified by an enzyme-linked immunosorbent assay. The amounts of nitrite and nitrate in the retina were quantified by a fluorescence method using 2,3-diaminonaphthalene. Retinal vascular permeability in the diabetic control group was about 5.5 times higher than in the normal control group (P<0.001). Kallidinogenase suppressed the increased retinal vascular permeability. In the diabetic control group, the VEGF level was three times that of the normal control group (diabetic control group, 160+/-12 pg/ml; normal control group, 54+/-9 pg/ml; P<0.001). The VEGF concentration in the kallidinogenase-treated group was 120+/-12 pg/ml (P<0.05). In the diabetic control group, the amounts of nitrite and nitrate in the retina were lower by about 2.6-fold, compared with the normal control group (P<0.05). Kallidinogenase almost normalized the decreases in nitrite and nitrate in the retina. The current study showed beneficial effects of kallidinogenase on increased retinal vascular permeability and VEGF in diabetic rats, suggesting that kallidinogenase may be effective for simple retinopathy in patients with diabetes.
European journal of pharmacology 03/2009; 606(1-3):187-90. DOI:10.1016/j.ejphar.2009.01.027 · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We described three cases of macular holes with an epiretinal membrane that developed after triamcinolone-assisted vitrectomy for proliferative diabetic retinopathy (PDR).
[Show abstract][Hide abstract] ABSTRACT: Purpose: To investigate the efficacy of intravitreal injection of triamcinolone acetonide (TA) for treatment of cystoid foveal edema (CFE) associated with Coats' disease.
Methods and Patient: A 32-year-old man with a 28-month history of Coats' disease received an intravitreal TA injection (4 mg) in the right eye.
Results: Visual acuity improved from 20/200 to 20/50, and foveal thickness decreased from 701 μm to 216 μm 45 days after treatment.
Conclusion: Intravitreal TA injection might temporarily improve visual acuity in eyes with CFE associated with Coats' disease.
[Show abstract][Hide abstract] ABSTRACT: To detect the prognostic factors associated with initial reattachment after primary pars plana vitrectomy (PPV) with gas tamponade for retinal detachment attributable to macular hole (MHRD).
Retrospective, multicenter, interventional case series.
This study included 49 eyes of 48 patients with MHRD in high myopia (axial length more than 28.0 mm). All eyes underwent PPV with gas tamponade. We retrospectively reviewed the medical records and performed univariate analysis to detect the presence of any difference between eyes with a successful initial reattachment and those that failed. We performed multivariate logistic regression analysis to assess the influence of each preoperative factor on initial success.
Success rate of initial reattachment was 69%. Postoperative best-corrected visual acuity (BCVA) of 34 eyes with initial success was significantly better than those of 15 eyes with initial failure (P < .05); preoperative BCVA was not significantly different (P = .43). The axial length of eyes with initial success (29.26 +/- 0.94 mm) was shorter than that of eyes with initial failure (30.04 +/- 1.49 mm) with borderline significance (P = .049). There were no significant differences noted for other factors such as use of ILM peeling (P = .43) or type of tamponade gas (P = .99). Multiple logistic regression analysis using preoperative factors indicated that only axial length was significantly associated with initial success (odds ratio, 0.49; 95% confidence interval, 0.26 to 0.93; P < .05).
Initial reattachment is important for visual prognosis, and axial length is a prognostic factor for initial reattachment after PPV with gas tamponade for MHRD in high myopia.
American Journal of Ophthalmology 06/2008; 146(2):198-204. DOI:10.1016/j.ajo.2008.04.022 · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effects of posterior vitreous detachment (PVD) in macular edema associated with central retinal vein occlusion (CRVO) treated with intravitreal tissue plasminogen activator (tPA).
The authors conducted a retrospective study of 36 eyes of 36 patients with macular edema by CRVO treated with intravitreal tPA. In 16 of 21 eyes without pretreatment PVD, PVD developed after the treatment. Multiple linear regression analysis was used to evaluate the correlation between logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) changes and several variables.
The VA and macular thickness significantly improved after treatment. The pretreatment logMAR VA (R = 0.646; P < 0.0001), PVD development after tPA (R = -0.303; P = 0.025), and age (R = 0.255; P = 0.050) correlated with the logMAR VA at final visit. The greater improvement in logMAR VA was correlated only with PVD development (R = 0.467; P = 0.0041). Macular thickness in the eyes with PVD development was significantly less than without PVD development at the 6-month visit and the end of follow-up.
The findings suggest that PVD development after intravitreal tPA may partly contribute to the resolution of macular edema and a better VA outcome.
[Show abstract][Hide abstract] ABSTRACT: Diabetic retinopathy is a leading cause of visual disturbance in adults. In proliferative diabetic retinopathy, ischemia-induced pathologic growth of new blood vessels often causes catastrophic loss of vision. Besides VEGF, the existence of another potent ischemia-induced angiogenic factor is postulated. Since ischemia-inducible erythropoietin (Epo) has recently been identified its angiogenic properties, we investigated its potential role during retinal angiogenesis in proliferative diabetic retinopathy (PDR). The vitreous Epo level in patients with PDR was significantly higher than that in nondiabetic patients. Multivariate logistic regression analyses indicated that Epo and VEGF were independently associated with PDR and that Epo was more strongly associated with PDR than VEGF. Blockade of Epo inhibits retinal neovascularization in vivo, and inhibits endothelial cell proliferation response to PDR vitreous in vitro. Our data provide strong evidence that erythropoietin is a potent retinal angiogenic factor independent of VEGF and is capable of stimulating ischemia-induced retinal angiogenesis in proliferative diabetic retinopathy. Inhibition of such molecular mechanisms in the retinal angiogenesis could be a new therapeutical strategy in halting or preventing pathologic angiogenesis in diabetic retinopathy.
Diabetes Research and Clinical Practice 10/2007; 77 Suppl 1(3):S62-4. DOI:10.1016/j.diabres.2007.01.035 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the potential beneficial effects of gliclazide and other sulphonylureas on ischemia-induced retinal neovascularization. To produce an animal model of oxygen-induced ischemic retinopathy, 7-day-old (P7) mice were exposed to a 75% oxygen environment for 5 days. On their return to ambient air at P12, these mice were then treated with gliclazide, glibenclamide, glimepiride, or N-acetylcysteine. Gliclazide, but not glibenclamide or glimepiride, markedly suppresses retinal neovascularization. N-Acetylcysteine, however, only moderately suppresses retinal neovascularization. The number of neovascular nuclei in the retinal cross sections decreased by 29% in the gliclazide-treated mice (P<0.05 vs control). The induction of VEGF mRNA expression at P13 is significantly suppressed in the gliclazide group, relative to the control group (-44%, P<0.05). The VEGF protein expression levels at P15 were also suppressed in the gliclazide group (-43%, P<0.01). The 8-isoprostane production levels at P15 were suppressed in both the gliclazide group (-20%, P<0.05) and the N-acetylcysteine-treated group (-31%, P<0.01). Gliclazide inhibits ischemia-induced retinal neovascularization, and this is likely to be mediated in part through the downregulation of VEGF and the suppression of oxidative stress.
Free Radical Biology and Medicine 08/2007; 43(3):454-61. DOI:10.1016/j.freeradbiomed.2007.04.030 · 5.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypertension is known to exacerbate diabetic complications, such as retinopathy and nephropathy. Apoptosis of retinal vascular pericytes has been well established as the earliest conceivable change in diabetic retinopathy. In this study, we investigated the contribution of cyclic stretch, which mimics a hypertensive state to pericyte apoptosis. A 48-hour cyclic stretch induced DNA fragmentation in porcine retinal pericytes and increased the number of TUNEL+ cells at a pathophysiologically relevant extension level (10%/60 cycles per minute). Stretch also increased intracellular reactive oxygen species generation and increased c-Jun NH(2)-terminal kinase phosphorylation in a time- and magnitude-dependent manner, which were reduced by the nicotinamide-adenine dinucleotide phosphate oxidase inhibitor diphenylene iodonium or dominant-negative protein kinase C-delta. Stretch activated protein kinase C-delta and increased its association with p47phox. Stretch induced cleavage of caspase-9 and -3 and increased caspase-3 activity. Protein kinase C-delta or c-Jun NH(2)-terminal kinase inhibition normalized stretch-induced caspase-3 activity and prevented stretch-induced apoptosis. These data indicate that cyclic stretch induces apoptosis in porcine retinal pericytes by activation of the reactive oxygen species-c-Jun NH(2)-terminal kinase-caspase cascades, suggesting a novel molecular mechanism to explain the exacerbation of early diabetic retinopathy by concomitant hypertension.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the integrity of photoreceptors in macular edema (ME) associated with branch retinal vein occlusion after intravitreal tissue plasminogen activator.
Retrospective, interventional case series.
Nineteen eyes with ME by branch retinal vein occlusion were treated with intravitreal tissue plasminogen activator injection. We assessed visual acuity (VA) and the presence or absence in the fovea of a third high reflectance band (HRB) by optical coherence tomography at the final visit.
No differences were found in age, preoperative VA, and foveal thickness between the groups with or without the third HRB. After treatment, the mean VA improved significantly (P < .05) in both groups. At the final visit, the mean VA in the group without HRB was significantly poorer than the group with HRB (P = .0042); foveal thickness did not differ between the groups.
The integrity of the third HRB in the fovea is associated with VA after the resolution of ME.
American Journal of Ophthalmology 01/2007; 143(1):171-3. DOI:10.1016/j.ajo.2006.08.030 · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetic retinopathy (DR) is an angiogenic disease that leads to severe visual loss. However, adequate animal models of vitreoretinal neovascularization in proliferative diabetic retinopathy (PDR) have not yet been described. The purpose of this study was to develop a novel ex vivo system for assessing vitreoretinal angiogenic processes that originate from both quiescent and mature vessels that could be observed with time-sequential imaging.
The retinas of 7- to 8-week-old mice were cultured for 4 days, with or without several growth factors with novel procedures, and immunohistochemistry was performed. The retinas from Tie2-GFP mice were cultured with vascular endothelial growth factor (VEGF), and time-sequential imaging of vitreoretinal angiogenesis was acquired.
Vascular sprouts were induced by both VEGF and placenta growth factor, but not by insulin-like growth factor-1, basic fibroblast growth factor or angiopoietin-2. In explants with or without VEGF, perivascular mural cells were dissociated from endothelial cells, which is an important step during angiogenesis and in the progression of DR. Furthermore, use of time-lapse observations of retinal neovascularization events visualized that the first step in vascular sprout emergence from quiescent vessels was a single cell extension. The leading edges of a sprouting endothelial cell extended and retracted in a sequential manner. From newly formed vessels, additional vascular sprouts then emerged and new vessels fused to each other, resulting in vascular branching.
Time-lapse imaging of this system visualized the dynamic process in vitreoretinal neovascularization from quiescent and mature vessels.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy of intravitreal tissue plasminogen activator (tPA) injection for branch retinal vein occlusion (BRVO).
Retrospective, interventional case series.
Seventeen eyes presenting with macular edema caused by BRVO were treated with an intravitreal tPA (Monteplase, 40 k IU) injection. We assessed the visual acuity (VA) and foveal thickness measured with optical coherence tomography.
The mean duration of symptoms before surgery was 3.6 +/- 3.8 weeks. The mean logMAR VA significantly improved from 0.603 +/- 0.327 at baseline to 0.388 +/- 0.248 (P < .01) at one month and 0.359 +/- 0.319 (P < .05) at six months. The mean foveal thickness significantly decreased from 738 +/- 156 microm at baseline to 454 +/- 213 microm (P < .001) at one month and 253 +/- 164 microm (P < .001) six months.
Intravitreal tPA injection may be an effective treatment for resolving macular edema and improving the VA in BRVO.
American Journal of Ophthalmology 08/2006; 142(2):318-20. DOI:10.1016/j.ajo.2006.02.039 · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Eph receptor/ephrin system is a recently discovered regulator of vascular development during embryogenesis. Activation of EphA2, one of the Eph receptors, reportedly suppresses cell proliferation and adhesion in a wide range of cell types, including vascular endothelial cells. Vascular endothelial growth factor (VEGF) plays a primary role in both pathological angiogenesis and abnormal vascular leakage in diabetic retinopathy. In the study described herein, we demonstrated that EphA2 stimulation by ephrinA1 in cultured bovine retinal endothelial cells inhibits VEGF-induced VEGFR2 receptor phosphorylation and its downstream signaling cascades, including PKC (protein kinase C)-ERK (extracellular signal-regulated kinase) 1/2 and Akt. This inhibition resulted in the reduction of VEGF-induced angiogenic cell activity, including migration, tube formation, and cellular proliferation. These inhibitory effects were further confirmed in animal models. Intraocular injection of ephrinA1 suppressed ischemic retinal neovascularization in a dose-dependent manner in a mouse model. At a dose of 125 ng/eye, the inhibition was 36.0 +/- 14.9% (P < 0.001). EphrinA1 also inhibited VEGF-induced retinal vascular permeability in a rat model by 46.0 +/- 10.0% (P < 0.05). These findings suggest a novel therapeutic potential for EphA2/ephrinA1 in the treatment of neovascularization and vasopermeability abnormalities in diabetic retinopathy.
American Journal Of Pathology 01/2006; 168(1):331-9. DOI:10.2353/ajpath.2006.050435 · 4.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oxidative stress activates various signal transduction pathways, including Jun N-terminal kinase (JNK) and its substrates, that induce apoptosis. We reported here the role of angiopoietin-1 (Ang1), which is a prosurvival factor in endothelial cells, during endothelial cell damage induced by oxidative stress. Hydrogen peroxide (H2O2) increased apoptosis of endothelial cells through JNK activation, whereas Ang1 inhibited H2O2-induced apoptosis and concomitant JNK phosphorylation. The inhibition of H2O2-induced JNK phosphorylation was reversed by inhibitors of phosphatidylinositol (PI) 3-kinase and dominant-negative Akt, and constitutively active-Akt attenuated JNK phosphorylation without Ang1. These data suggested that Ang1-dependent Akt phosphorylation through PI 3-kinase leads to the inhibition of JNK phosphorylation. H2O2-induced phosphorylation of SAPK/Erk kinase (SEK1) at Thr261, which is an upstream regulator of JNK, was also attenuated by Ang1-dependent activation of the PI 3-kinase/Akt pathway. In addition, Ang1 induced SEK1 phosphorylation at Ser80, suggesting the existence of an additional signal transduction pathway through which Ang1 attenuates JNK phosphorylation. These results demonstrated that Ang1 attenuates H2O2-induced SEK1/JNK phosphorylation through the PI 3-kinase/Akt pathway and inhibits the apoptosis of endothelial cells to oxidative stress.
[Show abstract][Hide abstract] ABSTRACT: To determine the expression of connective tissue growth factor (CTGF) in choroidal neovascularization.
Surgically excised choroidal neovascular membranes (CNVMs) were obtained at vitrectomy from eight eyes with age-related macular degeneration, five eyes with high myopia, and two eyes with angioid streaks. Light microscopic immunohistochemical analysis was performed to detect CTGF, transforming growth factor beta 1 (TGF-beta1), vascular endothelial growth factor (VEGF), pancytokeratin, and smooth muscle actin (SMA).
CNVMs were classified by fibrotic status as cellular CNVM, moderate fibrous CNVM, and extensive fibrous CNVM. CTGF expression was found in vascular cells, stromal cells, and retinal pigment epithelium (RPE) cells. For the stromal cells, fibroblastlike cells were most strongly positive for CTGF. CTGF immunoreactivity in the stroma was stronger in the fibrous CNVMs than in the cellular CNVMs. Immunohistochemical analysis of serial sections revealed colocalization of CTGF with TGF-beta1 and VEGF; colocalization of CTGF with pancytokeratin and SMA was also found.
Our findings suggest that transdifferentiated RPE cells and vascular cells possess remarkable CTGF expression in CNVMs. This expression of CTGF may stimulate fibroblasts to produce extracellular matrix and may promote angiogenesis in vascular cells. Colocalized TGF-beta1 and VEGF may also contribute the upregulation of CTGF.