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American Journal of Ophthalmology 03/2013; · 4.22 Impact Factor
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ABSTRACT: PURPOSE: To investigate the role of intravitreal injection of triamcinolone acetonide (IVTA) in preventing photoreceptor apoptosis in eyes with rhegmatogenous retinal detachment (RRD) by measuring cytokine levels in the aqueous humor before and after IVTA. DESIGN: Prospective, nonrandomized, interventional case series. METHODS: setting: Institutional. patients: Nineteen eyes of 19 consecutive patients with RRD. intervention: All 19 eyes underwent IVTA 1 day before 25-gauge vitrectomy. Seventeen eyes free of retinal vascular disease served as controls. main outcome measure: Both baseline and 1 day post-IVTA measurements were made of the relative concentrations of 15 soluble factors (3 cytokines, 7 chemokines, and 5 growth factors). The associations with clinical findings, including macular status, were then analyzed. RESULTS: Elevated monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1β (MIP-1β), and interferon γ-induced protein 10 (IP-10) in eyes with RRD were significantly reduced after IVTA. MCP-1 levels were significantly correlated with MIP-1β and IP-10 before and after IVTA. The decreases in MCP-1, MIP-1β, and IP-10 were also closely correlated to each other. Both before and after IVTA, MCP-1 was higher in eyes with macula-off RRD than in eyes with macula-on RRD. CONCLUSIONS: IVTA suppressed elevated levels of intraocular MCP-1, MIP-1β, and IP-10 in eyes with RRD. The decrease in the aqueous levels of each of these factors was significantly correlated with the others. In addition to MCP-1, MIP-1β and IP-10 might potentially be additional target molecules for RRD therapy.
American journal of ophthalmology 03/2013; · 3.83 Impact Factor
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ABSTRACT: To evaluate the efficacy of combined 25-gauge microincision vitrectomy surgery (MIVS) and toric intraocular lens (IOL) implantation with posterior capsulotomy.
Noncomparative, interventional case series performed at a single center. Twelve patients with vitreoretinal disease and cataracts, with preexisting regular corneal astigmatism greater than 1 diopter, underwent 25-gauge MIVS and toric IOL implantation with posterior capsulotomy.
The toric IOL was successfully implanted in each case. At 6 months postoperatively, mean axis rotation was 5.7° ± 3.1°. At 1 month postoperatively, mean uncorrected and best corrected visual acuity improved; the improvement was maintained after 6 months. The absolute residual refractive cylinder was significantly lower postoperatively than the pre-existing regular corneal cylinder (P = .003). There were no surgical complications except temporary posterior iris synechiae in one case.
Combined 25-gauge MIVS and toric IOL implantation with posterior capsulotomy is a practical and safe method to treat vitreoretinal disease and cataracts with pre-existing corneal astigmatism.[Ophthalmic Surg Lasers Imaging Retina. 2013;44:145-154].
Ophthalmic surgery, lasers & imaging retina. 03/2013; 44(2):145-54.
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ABSTRACT: We established a sustained vasohibin-1 (a 42-kDa protein), delivery device by a novel method using photopolymerization of a mixture of polyethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and collagen microparticles. We evaluated its effects in a model of rat laser-induced choroidal neovascularization (CNV) using a transscleral approach. We used variable concentrations of vasohibin-1 in the devices, and used an enzyme-linked immunosorbent assay and Western blotting to measure the released vasohibin-1 (0.31 nM/day when using the 10 μM vasohibin-1 delivery device [10VDD]). The released vasohibin-1 showed suppression activity comparable to native effects when evaluated using endothelial tube formation. We also used pelletized vasohibin-1 and fluorescein isothiocyanate-labeled 40 kDa dextran as controls. Strong fluorescein staining was observed on the sclera when the device was used for drug delivery, whereas pellet use produced strong staining in the conjunctiva and surrounding tissue, but not on the sclera. Vasohibin-1 was found in the sclera, choroid, retinal pigment epithelium (RPE), and neural retina after device implantation. Stronger immunoreactivity at the RPE and ganglion cell layers was observed than in other retinal regions. Significantly lower fluorescein angiography (FA) scores and smaller CNV areas in the flat mounts of RPE-choroid-sclera were observed for the 10VDD, VDD (1 μM vasohibin-1 delivery device), and vasohibin-1 intravitreal direct injection (0.24 μM) groups when compared to the pellet, non-vasohibin-1 delivery device, and intravitreal vehicle injection groups. Choroidal neovascularization can be treated with transscleral sustained protein delivery using our novel device. We offer a safer sustained protein release for treatment of retinal disease using the transscleral approach.
PLoS ONE 01/2013; 8(3):e58580. · 4.09 Impact Factor
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ABSTRACT: To evaluate the efficacy of combined 25-gauge microincision vitrectomy surgery, intraocular lens (IOL) implantation, and posterior capsulotomy.
Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Comparative case series.
The medical records of eyes that had 25-gauge microincision vitrectomy and IOL implantation without posterior capsulotomy (June 2009 to May 2010) or with posterior capsulotomy (June 2010 to May 2011) were reviewed. Outcomes measured were corrected distance visual acuity (CDVA) at 1 and 6 months, the rate of neodymium:YAG (Nd:YAG) laser capsulotomies for postoperative posterior capsule opacification (PCO), and the rate of surgical complications.
The records of 343 eyes were reviewed; 136 eyes did not have a posterior capsulotomy, and 207 eyes had a posterior capsulotomy. There was a significant difference in the rate of Nd:YAG capsulotomy between the no-capsulotomy group (18 eyes, 13.2%) and the capsulotomy group (2 eyes, 1.0%) (P<.01). The mean CDVA improved postoperatively in both groups (P<.01); in 20 patients with postoperative PCO, the mean CDVA improved after Nd:YAG capsulotomy (P<.05). Intraoperatively, gas leaked into the anterior chamber in 5 (6.3%) of 79 eyes in the capsulotomy group that required fluid-air exchange.
Combined 25-gauge microincision vitrectomy, IOL implantation, and posterior capsulotomy was safe and reduced the need for postoperative Nd:YAG capsulotomy. Posterior capsulotomy should be performed with caution in eyes that are expected to require intraoperative fluid-air exchange.
Journal of cataract and refractive surgery 09/2012; 38(9):1602-7. · 2.75 Impact Factor
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Ahmed Y Shanab,
Toru Nakazawa,
Morin Ryu,
Yuji Tanaka,
Noriko Himori,
Keiko Taguchi,
Masayuki Yasuda,
Ryo Watanabe,
Jiro Takano,
Takaomi Saido,
Naoko Minegishi,
Toshio Miyata, Toshiaki Abe,
Masayuki Yamamoto
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ABSTRACT: To describe how a high fat diet (HFD) and hyperglycemia initiate a sequence of calpain activation and oxidative stress associated with neuro-degenerative changes in diabetic retinopathy (DR), hyperglycemia was induced with streptozotocin in mice lacking the gene for calpastatin (CAST KO), and in mice lacking the gene for the transcription factor NF-E2 related factor 2 (Nrf2 KO). All animals were fed a HFD. Retinal ganglion cell (RGC) density was estimated by labeling with fluorogold and immunohistochemistry. A potent calpain inhibitor, SNJ-1945, was administered daily until the animals were sacrificed. In vitro, oxidative stress-induced RGC loss was evaluated in a high glucose culture medium with and without SNJ-1945. Retinal mRNA of calpain-1 and calpain-2 was measured by quantitative RT-PCR. Pre-apoptotic substrates of cleaved α-fodrin and synaptophysin protein were quantified by immunoblot analysis. Axonal damage was examined in transverse sections of the optic nerve. A HFD and hyperglycemia significantly increased RGC and axonal degeneration 3weeks into the experiment. Levels of cleaved α-fodrin were increased. In the CAST KO mice, the neurotoxicity was augmented significantly. Gene manipulation of CAST and orally administered SNJ-1945 successfully modified calpain levels in the retina and prevented RGC death. In vitro, a high-glucose culture of retinal cells without antioxidants showed more RGC death than that with antioxidant treatment. The expression of synaptophysin was significantly suppressed by SNJ-1945 treatment. These results suggest that calpain plays a crucial role in metabolic-induced RGC degeneration caused by hyperglycemia and oxidative stress. Antioxidant and calpain inhibition offers important opportunities for future neuroprotective treatment against RGC death in various metabolic stress-induced diseases including DR.
Neurobiology of Disease 08/2012; 48(3):556-67. · 5.40 Impact Factor
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ABSTRACT: A 32-year-old man had dysgenesis of the corpus callosum associated with iris nevi and conjunctival malignant melanoma. Iris
lesions revealed intrastromal proliferation of melanocytes accompanied by surface plaque. Epithelioid and spindle cells with
pigmentation, positive for the melanoma marker HMB-45 and S-100 protein, were observed in the conjunctival lesion by histologic
examination. These findings may suggest an underlying neoplastic potential of melanocytes.
Annals of Ophthalmology 04/2012; 34(3):237-239. · 0.16 Impact Factor
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ABSTRACT: To determine whether intravitreal vasohibin-1 will reduce the grade of the choroidal neovascularization in monkey eyes.
Choroidal neovascularizations were induced in 12 monkey eyes by laser photocoagulation. Three monkeys were evaluated for the safety of the vasohibin-1 injections, 6 monkeys for the effects of a single injection, and 3 monkeys for repeated injections of vasohibin-1. Ophthalmoscopy, fluorescein angiography, focal electroretinograms, and optical coherence tomography were used for the evaluations. The level of vascular endothelial growth factor in the aqueous was determined by enzyme-linked immunosorbent assay. Immunohistochemistry was performed.
An intravitreal injection of 10 μg of vasohibin-1 induced mild intraocular inflammation. Eyes with an intravitreal injection of 0.1 μg and 1.0 μg of vasohibin-1 had significant less fluorescein leakage from the choroidal neovascularizations and larger amplitude focal electroretinograms than that of vehicle-injected eyes. Similar results were obtained by repeated injections of 0.1 μg of vasohibin-1. Immunohistochemistry showed that vasohibin-1 was expressed mainly in the endothelial cells within the choroidal neovascularizations. The vascular endothelial growth factor level was not significantly altered by intravitreal vasohibin-1.
The reduction of the laser-induced choroidal neovascularizations and preservation of macular function in monkey by intravitreal vasohibin-1 suggest that it should be considered for suppressing choroidal neovascularizations in humans.
Retina (Philadelphia, Pa.) 02/2012; 32(6):1204-13. · 2.93 Impact Factor
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Advances in experimental medicine and biology 01/2012; 723:305-10. · 1.09 Impact Factor
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ABSTRACT: This is a report of a case of choroidal excavation accompanied by polypoidal choroidal vasculopathy (PCV) and retinal pigment epithelium detachment (PED).
A 57-year-old Japanese woman who had begun complaining of metamorphopsia in her left eye 7 months earlier underwent spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (IA), as well as a routine ophthalmological examination.
The patient's intraocular pressure, visual acuity, and visual field were within normal range. Ophthalmoscopy revealed a serous macular detachment, soft drusen, exudates, and a reddish-orange elevated lesion in the macula of the left eye. The right eye was normal. SD-OCT revealed two lesions in the left eye. One was a PED accompanied by a notch sign, and the other was a choroidal excavation. Additionally, FA revealed a window defect in the PED, and IA showed typical PCV. Three monthly injections of antivascular endothelial growth factor preserved visual acuity, but failed to have any visible effect on the lesion during the 6-month follow up period.
This is the first report of choroidal excavation accompanied by PED and PCV. The data suggest that choroidal excavation may be associated with various changes that have not been previously reported. Careful observation of such cases may therefore be necessary.
Clinical Ophthalmology 01/2012; 6:1373-6.
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ABSTRACT: The authors examined the feasibility of performing 25- and 23-gauge micro-incision vitrectomy surgery (MIVS) for a giant retinal tear.
The medical records of 12 eyes of 11 patients with giant retinal tear who underwent MIVS using perfluorocarbon liquids were reviewed. All patients were observed for at least 6 months postoperatively.
An intraoperative re-attachment was achieved in 12 eyes (100%) and 11 eyes (92%) remained attached without intraocular tamponade. Silicone oil was used in 9 of 12 eyes and removed 2 weeks after the initial vitrectomy except in one eye. The postoperative retinal complications included macular pucker in two eyes, subretinal perfluorocarbon liquid in two eyes, retinal folds in one eye, cystoid macular edema in one eye, and redetachment due to proliferative vitreoretinopathy in one eye.
Although the study had a short follow-up period, primary MIVS appears to be safe and feasible for giant retinal tear surgery.
Ophthalmic Surgery Lasers and Imaging 09/2011; 42(6):487-92. · 0.62 Impact Factor
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ABSTRACT: To determine the incidence of difficulty in inserting a 25- and 23-gauge trocar cannula (DITC) during 25- or 23-gauge micro-incision vitrectomy surgery (MIVS).
Retrospective, consecutive, interventional case series performed by a single surgeon at a single centre. We defined a DITC as the condition where at least 1 trocar cannula could not be inserted into the vitreous at the beginning of MIVS. The incidence of DITC was calculated from 1,525 eyes, and the pre-operative demographics of the DITC cases were compared to those of the non-DITC cases.
The incidence of DITC for all cases was 0.6% (9 of 1,525 eyes). Overall, there were 242 eyes with a retinal detachment (RD), and 8 of the 9 eyes with DITC had an RD with an incidence of 3.3% (8 of 242 RD eyes). Seven of these 8 eyes had a total RD, 4 also had a choroidal detachment, 4 eyes were also myopic (>-8.0 dpt, high myopia), and 6 of the 8 eyes were hypotonic (<8 mm Hg). The DITC cases had larger RDs (p<0.0001), a higher incidence of choroidal detachment (p<0.0001), higher myopia (p=0.0204) and hypotony (p=0.0003) than the non-DITC eyes with an RD.
A large RD, a choroidal detachment, high myopia and hypotony are significant risk factors for DITC. We recommend that MIVS should be performed cautiously for eyes with these risk factors.
Ophthalmologica 09/2011; 226(4):198-204. · 1.42 Impact Factor
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American journal of ophthalmology 09/2011; 152(3):499-500. · 3.83 Impact Factor
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American journal of ophthalmology 08/2011; 152(2):326. · 3.83 Impact Factor
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ABSTRACT: To describe a technique for suturing a dislocated intraocular lens (IOL) with 25-gauge (G) instruments.
Non-comparative interventional case series performed at a single center. Five patients with a dislocated IOL underwent 25-G transconjunctival sutureless vitrectomy (25G-TSV) with a temporary externalization of the haptics to fixate the IOL. Three IOLs enclosed in the lens capsule were dislocated into the vitreous and removed from the capsule with 25G-TSV using perfluorocarbon liquid. The best-corrected visual acuity and surgical complications resulting from this technique were recorded.
In all cases, the IOL was fixed stably and remained well positioned. The visual acuity was improved or maintained in all cases. There were no intraoperative or postoperative complications except for one eye with a postoperative iris capture of the sutured IOL.
Findings indicate that 25G-TSV is a practical and safe method for fixating a dislocated IOL.
Ophthalmic Surgery Lasers and Imaging 05/2011; 42(4):297-301. · 0.62 Impact Factor
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ABSTRACT: A transscleral drug-delivery device, designed for the administration of protein-type drugs, that consists of a drug reservoir covered with a controlled-release membrane was manufactured and tested. The controlled-release membrane is made of photopolymerized polyethylene glycol dimethacrylate (PEGDM) that contains interconnected collagen microparticles (COLs), which are the routes for drug permeation. The results showed that the release of 40-kDa FITC-dextran (FD40) was dependent on the COL concentration, which indicated that FD40 travelled through the membrane-embedded COLs. Additionally, the sustained-release drug formulations, FD40-loaded COLs and FD40-loaded COLs pelletized with PEGDM, fine-tuned the release of FD40. Capsules filled with COLs that contained recombinant human brain-derived neurotrophic factor (rhBDNF) released bioactive rhBDNF in a manner dependent on the membrane COL concentration, as was found for FD40 release. When capsules were sutured onto sclerae of rabbit eyes, FD40 was found to spread to the retinal pigment epithelium. Implantation of the device was easy, and it did not damage the eye tissues. In conclusion, our capsule is easily modified to accommodate different release rates for protein-type drugs by altering the membrane COL composition and/or drug formulation and can be implanted and removed with minor surgery. The device thus has great potential as a conduit for continuous, controlled drug release.
Biomaterials 03/2011; 32(7):1950-6. · 7.40 Impact Factor
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ABSTRACT: To determine whether polymorphisms in the ARMS2 (LOC387715) gene and the lysyl oxidase-like 1 (LOXL1) gene are associated with age-related macular degeneration (AMD) in Japanese patients.
Clinically relevant laboratory investigation.
Forty-one unrelated Japanese subjects with dry AMD, 50 subjects with exudative (wet) AMD, and 60 subjects with polypoidal choroidal vasculopathy (PCV) were studied. The single nucleotide polymorphisms (SNPs), p.Ala69Ser of the ARMS2 gene and p.Arg141Leu of the LOXL1 gene, were amplified by polymerase chain reaction, directly sequenced, and genotyped.
For the ARMS2 gene, the genotype frequency of the p.Ala69Ser single nucleotide polymorphism in eyes with dry AMD was not significantly different from that in the controls (P = .04), but the frequency was significantly higher in the exudative AMD group (P = 3.1 × 10(-8)) and PCV group (P = 6.9 × 10(-3)). For the LOXL1 gene, the genotype frequency of the p.Arg141Leu single nucleotide polymorphism was not statistically higher in the dry AMD and PCV groups than in the control group (dry AMD, P = .05; PCV, P = .16), but was statistically higher in the exudative AMD group (P = 6.8 × 10(-3)). Regression analyses showed significant associations between the ARMS2 gene and LOXL1 gene in patients with exudative AMD.
The p.Ala69Ser polymorphism of the ARMS2 gene is strongly associated with exudative AMD and PCV and is associated marginally with dry AMD. The polymorphisms in the LOXL1 gene did not predispose the individual to dry AMD and PCV. These findings suggest that there is a significant association between the ARMS2 gene and LOXL1 gene in exudative AMD.
American journal of ophthalmology 03/2011; 151(3):550-6.e1. · 3.83 Impact Factor
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Ryosuke Wakusawa, Toshiaki Abe,
Hajime Sato,
Hikaru Sonoda,
Masaaki Sato,
Yuuichi Mitsuda,
Tomoaki Takakura,
Tomi Fukushima,
Hideyuki Onami,
Nobuhiro Nagai,
Yumi Ishikawa,
Kohji Nishida,
Yasufumi Sato
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ABSTRACT: PURPOSE. To determine the expression of vasohibin-1 during the development of experimentally induced choroidal neovascularization (CNV) and to investigate the effect of vasohibin-1 on the generation of CNV. METHODS. CNV lesions were induced in the eyes of wild-type (WT) and vasohibin-1 knockout (KO) mice by laser photocoagulation. The expression of vasohibin-1, vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR1), VEGFR2, and pigment epithelial-derived factor (PEDF) was determined by semiquantitative reverse transcription-polymerase chain reaction. The expression of vasohibin-1 was also examined by immunohistochemistry with anti-CD68, anti-alpha smooth muscle actin (αSMA), anti-cytokeratin, and anti-CD31. Vasohibin-1 was injected into the vitreous and the activity and size of the CNV were determined by fluorescein angiography and in choroidal flat mounts. RESULTS. Vasohibin-1 was detected not only in CD31-positive endothelial cells but also in CD68-positive macrophages and αSMA-positive retinal pigment epithelial cells. Strong vasohibin-1 expression was observed at day 28, when the CNV lesions had regressed by histologic examination. The vasohibin-1 level was significantly decreased at day 14 and increased at day 28 after laser application. Significantly less VEGFR2 expression was observed on day 4 after vasohibin-1. The expression of PEDF was not significantly changed by vasohibin-1 injection. Vasohibin-1 injection significantly suppressed the CNV, with no adverse side effects. The CNV lesions in the vasohibin-1-KO mice were significantly larger than those in the WT mice. CONCLUSIONS. The endogenous expression of vasohibin-1 is associated with the natural course of the development of CNV. Intravitreal injections of vasohibin-1 may be a method for inhibiting CNV.
Investigative ophthalmology & visual science 02/2011; 52(6):3272-80. · 3.43 Impact Factor
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ABSTRACT: To report the preoperative best-corrected visual acuity (BCVA) and foveal thickness (FT) values that lead to a postoperative decimal BCVA of ≥1.0 after surgical removal of an idiopathic epiretinal membrane (ERM).
This is a retrospective case series of 73 eyes that underwent surgery for removal of an idiopathic ERM. All eyes had been treated by a single surgeon using a 25-gauge transconjunctival sutureless vitrectomy and indocyanine green-assisted internal limiting membrane peel. The BCVA and FT were measured at baseline and 6 months postoperatively.
A postoperative decimal BCVA ≥ 1.0 was obtained in eyes with a preoperative decimal BCVA ≥ 0.3 but not in those with a preoperative decimal BCVA ≤ 0.2. The incidence of obtaining a postoperative decimal BCVA ≥ 1.0 was significantly (P = 0.002) higher in eyes with a preoperative decimal BCVA ≥ 0.5 (50%) than in eyes with a preoperative decimal BCVA < 0.5 (11%). Additionally, a postoperative decimal BCVA of ≥ 1.0 was obtained in 51% of the eyes that had a preoperative FT < 400 μm, compared with only 21% of eyes with a preoperative FT ≥ 400 μm (P = 0.01). The incidence of obtaining a postoperative decimal BCVA ≥ 1.0 was significantly higher in eyes with preoperative decimal BCVA ≥ 0.5 and FT < 400 μm (60%) than in eyes with preoperative decimal BCVA ≥ 0.5 and FT ≥ 400 μm (20%; P = 0.03) or preoperative BCVA < 0.5 and FT ≥ 400 μm (7%; P < 0.001).
These findings indicate that eyes with both preoperative BCVA ≥ 0.5 and FT < 400 μm have a significantly better chance of obtaining a postoperative decimal BCVA ≥ 1.0 following idiopathic ERM removal.
Clinical Ophthalmology 01/2011; 5:147-54.
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Morin Ryu,
Toru Nakazawa,
Takami Akagi,
Tatsuhide Tanaka,
Ryou Watanabe,
Masayuki Yasuda,
Noriko Himori,
Kazuichi Maruyama,
Toshihide Yamashita, Toshiaki Abe,
Mitsuru Akashi,
Kohji Nishida
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ABSTRACT: To investigate the potential of nanoparticles (NPs) composed of poly(γ-glutamic acid) conjugated with l-phenylalanine (γ-PGA-Phe NPs) for the treatment of retinal diseases, γ-PGA-Phe NPs (200nm) were tested with macrophages and microglia in vitro or by intravitreal administration into normal or pathological rat eyes. The anti-inflammatory effects of the NPs containing dexamethasone (DEX-NPs) were examined using qRT-PCR in vitro by counting activated microglia and Fluorogold-labeled retinal ganglion cells in the retinas under excitotoxicity or by counting TUNEL (+) photoreceptors in the detached retinas. The NPs were taken up efficiently by cultured macrophages or microglia. At day 7, 60-80% of the diffuse signal remained in the cytoplasm of these cells. In normal rat eyes, the NPs did not accumulate in the retinas and no inflammatory cells were recruited. Conversely, under pathological conditions, the NPs were localized in activated CD11b-positive cells in the retina. DEX-NPs suppressed the expression of TNFα and MCP-1 in cultured macrophages or microglia, the activation of microglia, the loss of retinal ganglion cells (RGCs) in excitotoxic retinas, and the number of TUNEL (+) photoreceptors in detached retinas. These data suggest that γ-PGA-Phe NPs can be a powerful tool for suppressing inflammatory cells in pathological conditions in the retina.
Journal of Controlled Release 12/2010; 151(1):65-73. · 5.73 Impact Factor
