Takeshi Tomomatsu

Role of the Polyol Pathway in High Glucose–Induced Apoptosis of Retinal Pericytes and Proliferation of Endothelial Cells

PURPOSE The selective degeneration of pericytes and the proliferation of endothelial cells (ECs) appear to be associated with microaneurysm formation, an initial deficit in the early stage of diabetic retinopathy. The preventive effect of aldose reductase (AR) inhibitor (ARI) for high glucose-induced pericyte loss and EC growth was investigated. METHODS The effect of high glucose (30 mM) exposure in the presence or absence of ARI for the cell growth of porcine pericytes and ECs was examined with the use of an in vitro coculture system to mimic the interaction between pericytes and ECs. To determine the role of transforming growth factor (TGF)-beta, its amount in culture media was measured, and the effects of the treatment of TGF-beta or neutralizing antibody on EC growth were examined. RESULTS Abundant expression of AR and increased levels of polyol and apoptosis induced by high glucose were observed in pericytes, but not in ECs. ECs overexpressing AR cultured in high-glucose medium showed decreased cell viability. The growth-inhibitory effect of ECs on coculture with pericytes was attenuated by exposure to a high glucose concentration. Biochemical assays disclosed that the levels of active TGF-beta in media were linked to EC growth. Supply of active TGF-beta to coculture medium containing 30 mM D-glucose restored the inhibitory activity on EC growth. CONCLUSIONS ARI rescued pericytes from high glucose-induced apoptosis and maintained the levels of TGF-beta, resulting in the prevention of cocultured EC growth.

Comparison of the Inverted Internal Limiting Membrane Flap Technique and the Internal Limiting Membrane Peeling for Macular Hole with Retinal Detachment

Purpose To evaluate the efficacy of the inverted internal limiting membrane (ILM) flap technique in vitrectomy for macular hole (MH) with retinal detachment (RD) compared with vitrectomy using ILM peeling. Methods A retrospective case series study was performed. Twenty-two eyes of 22 patients who underwent vitrectomy for MH with RD and followed-up more than 12 months after the surgery were included in this study. We retrospectively reviewed the medical records of patients who underwent vitrectomy with inverted ILM flap technique or vitrectomy with ILM peeling. Ten patients who had been treated vitrectomy with inverted ILM flap technique, and 12 patients who had been treated vitrectomy with ILM peeling were analyzed. We evaluated changes in best-corrected visual acuity (BCVA) before and after surgery, closing rates of MH, and retinal reattachment rates and compared between both groups. Results MH was closed and RD was reattached postoperatively in 9 eyes (90%) in the inverted ILM flap group. In the ILM peeling group, the MH was closed in 4 eyes (33.3%) and the retinas were reattached in 6 eyes (50%) after surgery. Significant improvement in BCVA after surgery (P = 0.0017) was only found in the inverted ILM flap group. Conclusions Higher rates of closed MH and retinal reattachment, and small but significant improvement in BCVA were found in the inverted ILM flap group. Based on our data, the inverted ILM flap technique may be useful in vitrectomy for MH with RD.

The effect of triamcinolone acetonide or bevacizumab on the levels of proinflammatory cytokines after retinal laser photocoagulation in pigmented rabbits.

Although laser photocoagulation is a gold standard for the treatment of retinal ischemic diseases, thermal burn induces the inflammation and the progression of macular edema. To prevent this complication, combination therapy using anti-vascular endothelial growth factor (VEGF) drugs or steroids is clinically utilized, however the mechanisms are still unclear. In this study, we aimed to evaluate the changes in inflammatory and angiogenic cytokine levels in aqueous humor and vitreous body after intravitreal injection of bevacizumab (IVB) or triamcinolone (IVTA), as well as sub-Tenon injection of triamcinolone (STTA) after retinal laser photocoagulation in rabbits. Pigmented rabbits were treated with retinal laser photocoagulation and divided into 4 groups, namely Control (no additional treatment), IVB, IVTA or STTA accordingly. Samples of vitreous and aqueous humor were collected on post-treatment days 0, 1, 7 and 14. The levels of intraocular VEGF, interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein-1 (MCP-1) were measured using an immunoassay. The levels of VEGF, IL-6, ICAM-1 and MCP-1 were significantly elevated 1 day after laser treatment. IVTA and STTA significantly reduced the increase in the levels of VEGF, IL-6, ICAM-1 and MCP-1, while IVB reduced that of VEGF only in aqueous humor and vitreous body. The protein amount in the aqueous humor transiently increased 1 day after laser, and was significantly prevented by IVTA or STTA but not IVB. Data showed that bevacizumab only reduced intraocular VEGF after laser, while triamcinolone suppressed both the expression of VEGF and proinflammatory cytokines. We propose that these cytokine profiles may play an important role in the pathogenesis of inflammation after photocoagulation and the underlying mechanism of treatment with anti-VEGF drug and steroids.

Comparative study of combined bevacizumab/targeted photocoagulation vs bevacizumab alone for macular oedema in ischaemic branch retinal vein occlusions

To investigate whether targeted retinal photocoagulation (TRP) of peripheral non‐perfused areas (NPAs) could prevent the recurrence of macular oedema (ME) due to branch retinal vein occlusion (BRVO) after intravitreal bevacizumab injection (IVB).

Anterior capsule contraction and flare intensity in the early stages after cataract surgery in eyes with diabetic retinopathy

Purpose To evaluate the changes and relationship in the area of the anterior capsule opening (ACO) and anterior inflammation during the early stages after cataract surgery in diabetic patients with or without diabetic retinopathy (DR). Setting Department of Ophthalmology, University of Fukui, Fukui, Japan. Design Case‐control study. Methods This study comprised diabetic patients without DR (non‐DR group), diabetic patients with nonproliferative DR (DR group), and patients without diabetes mellitus (DM) (non‐DM group) who had cataract surgery. The ACO area and aqueous flare intensity were measured using the EAS‐1000 device and a laser flare–cell meter, respectively, 1 day, 1 week, and 1 and 3 months after surgery. Results The percentage of anterior capsule contraction (ACC) was significantly higher in the DR group than in the non‐DR and non‐DM groups 1 week and 1 and 3 months postoperatively (P<.01, Turkey‐Kramer test). The aqueous flare intensity was significantly greater in the DR group than in the non‐DR and non‐DM groups 1 day, 1 week, and 1 and 3 months postoperatively (P<.01). Ordinary least‐squares regression analysis showed a significant positive correlation between aqueous flare intensity at 1 week and ACC 3 months after surgery in the non‐DR group (P=.0178, R2 = 0.173) and the DR group (P=.0018, R2 = 0.308). Conclusion Greater anterior flare levels 1 week after cataract surgery contributed to the extensive postoperative contraction of the ACO in diabetic patients, particularly those with DR. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Aldose reductase inhibitor counteracts the attenuated adhesion of human corneal epithelial cells induced by high glucose through modulation of MMP-10 expression

AIMS We investigated the preventive effect of aldose reductase inhibitor (ARI) on the adhesion of SV40-transformed human corneal epithelial cells (HCECs) exposed to high glucose, and the underlying mechanism focusing on the role of matrix metalloproteinase (MMP)-10. METHODS HCECs were cultured in medium containing a normal (5.5 mM) or high (31.2 mM) concentration of D-glucose in the presence or absence of ARI, fidarestat. Cell attachment ability was evaluated by short-term adhesion assay. The levels of intracellular polyol were measured by liquid-gas chromatography. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR), and Western blotting were used to determine the expression levels. RESULTS Decreased attachment activity and increased accumulation of polyol induced by exposure to high glucose were abrogated by ARI. Supply of recombinant MMP-10 decreased integrin alpha3beta1-expression and cell adhesion. The expression level of MMP-10 was enhanced at both protein and mRNA levels by exposure to high glucose, while that of integrin alpha3beta1 was decreased at the protein level, but remained unchanged at the mRNA level. These alterations in the expression levels of MMP-10 and integrin alpha3beta1 were normalized by ARI. CONCLUSIONS ARI counteracts the decreased adhesion of HCECs induced by high glucose exposure, through the modulation of the expression of MMP-10.

Changes in Matrix Metalloproteinases in Diabetes Patients' Tears After Vitrectomy and the Relationship With Corneal Epithelial Disorder.

PURPOSE Previous studies indicate involvement of matrix metalloproteinases (MMPs) in the pathogenesis of diabetic keratopathy. To evaluate MMP levels in the tears of patients with diabetes, we investigated changes in MMP levels during perioperative periods and clarify the relationship with corneal epithelial disorders following vitrectomy. METHODS Matrix metalloproteinase levels in tears were measured by multiplex bead array in patients with or without diabetes who were scheduled for vitrectomy. Twenty-two patients with diabetes and proliferative diabetic retinopathy, and 20 patients with epiretinal membrane or macular hole (control group), were recruited. Changes in MMP levels during perioperative periods and the relationship with corneal epithelial disorders after vitrectomy were analyzed. RESULTS The levels of MMP-2, -9, and -10 at 1 day after surgery in the diabetic group were significantly higher than in the control group. At 1 week after surgery, MMP-10 levels in the diabetic group were significantly higher than in the control group. After vitrectomy, corneal epithelial disorders occurred in six patients in the diabetic group but not in the control group. In the diabetic group, MMP-10 levels in tears of patients with corneal epithelial disorders were significantly higher than those in patients without corneal epithelial disorders. CONCLUSIONS The MMP concentration in tears of patients with diabetes was higher than in nondiabetic patients after vitrectomy. High MMP-10 levels were observed in patients with diabetes and corneal epithelial disorders after vitrectomy. Aberrant levels of MMP-10 may cause corneal epithelial disorder after vitrectomy.

Relationship between lenticular power and refractive error in children with hyperopia

Objectives To evaluate the contribution of axial length, and lenticular and corneal power to the spherical equivalent refractive error in children with hyperopia between 3 and 13 years of age, using noncontact optical biometry. Methods There were 62 children between 3 and 13 years of age with hyperopia (+2 diopters [D] or more) who underwent automated refraction measurement with cycloplegia, to measure spherical equivalent refractive error and corneal power. Axial length was measured using an optic biometer that does not require contact with the cornea. The refractive power of the lens was calculated using the Sanders-Retzlaff-Kraff formula. Single regression analysis was used to evaluate the correlation among the optical parameters. Results There was a significant positive correlation between age and axial length (P = 0.0014); however, the degree of hyperopia did not decrease with aging (P = 0.59). There was a significant negative correlation between age and the refractive power of the lens (P = 0.0001) but not that of the cornea (P = 0.43). A significant negative correlation was observed between the degree of hyperopia and lenticular power (P < 0.0001). Conclusion Although this study is small scale and cross sectional, the analysis, using noncontact biometry, showed that lenticular power was negatively correlated with refractive error and age, indicating that lower lens power may contribute to the degree of hyperopia.

Randomized Clinical Trial for Early Postoperative Complications of Ex-PRESS Implantation versus Trabeculectomy: Complications Postoperatively of Ex-PRESS versus Trabeculectomy Study (CPETS).

We compared early postoperative complications between trabeculectomy and Ex-PRESS implantation. Enrolled patients with 39 primary open-angle or 25 exfoliative glaucoma were randomly assigned to receive trabeculectomy (trabeculectomy group) or Ex-PRESS implantation (Ex-PRESS group). Primary outcomes were early postoperative complications, including postoperative anterior chamber inflammation, frequencies of hyphema, flat anterior chamber, choroidal detachment, hypotonic maculopathy, and the change of visual acuity. The postoperative flare values in trabeculectomy group were higher than those in the Ex-PRESS group (overall, P = 0.004; and 10 days, P = 0.02). Hyphema occurred significantly more frequently in the trabeculectomy group (P = 0.0025). There were no significant differences of the other primary outcomes between the two groups. Additionally, duration of anterior chamber opening was significantly shorter in the Ex-PRESS group (P = 0.0002) and the eyes that had iris contact with Ex-PRESS tube had significantly shallower anterior chambers than did the eyes without the iris contact (P = 0.013). The Ex-PRESS implantation prevented early postoperative inflammation and hyphema in the anterior chamber and shortened the duration of anterior chamber opening. Iris contact with the Ex-PRESS tube occurred more frequently in eyes with open-angle glaucoma and shallow anterior chambers.

Large capsulorhexis with implantation of a 7.0 mm optic intraocular lens during cataract surgery in patients with diabetes mellitus.

Purpose To evaluate the efficacy of a large capsulorhexis and intraocular lens (IOL) in obtaining a larger anterior capsule opening after cataract surgery in patients with diabetes mellitus (DM). Setting Department of Ophthalmology, University of Fukui, Fukui, Japan. Design Prospective clinical trial. Methods Patients with DM had bilateral cataract surgery with a 2.8 or 3.0 mm scleral incision, a capsulorhexis with a diameter of approximately 5.0 or 6.0 mm, and implantation of a 6.0 mm optic (Eternity X‐60) or 7.0 mm optic (Eternity X‐70) IOL. The anterior capsule opening area, aqueous flare intensity, surgically induced astigmatism (SIA), corneal endothelial cell density (ECD), and central corneal thickness (CCT) were measured 1 day, 1 week, and 1, 3, and 6 months after surgery. Results Thirty‐one patients (62 eyes) with DM were enrolled. At all postoperative timepoints, the anterior capsule opening was significantly larger in eyes with the 7.0 mm optic IOL than in eyes with the 6.0 mm optic IOL (P<.05, Mann‐Whitney U test). There were no significant differences in postoperative aqueous flare intensity, SIA, ECD, or CCT based on the size of the capsulorhexis and IOL. Conclusion A larger capsulorhexis and implantation of a 7.0 mm IOL resulted in a larger anterior capsule opening after cataract surgery in patients with DM. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.