Macular Degeneration: Nishida K

Abe T, Yoshida M, Yoshioka Y, Wakusawa R, Tokita-Ishikawa Y, Seto H, Tamai M, Nishida K. · Division of Clinical Cell Therapy, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai, Japan. · Prog Retin Eye Res. · Pubmed #17324604 No free full text.

Abstract: The transplantation of different types of cells into the eye to treat retinal diseases has advanced in the past 20 years. One of the types of cells used for transplantation is the iris pigment epithelial (IPE) cell, because autologous IPE cells are easily obtained and their properties are similar to those of retinal pigment epithelial (RPE) cells and retinal cells. IPE cells are transplanted as; freshly isolated or cultured cells to replace defective or diseased RPE cells, genetically modified IPE cells for delivering target molecules to the retina or RPE, and retinal progenitor cells. IPE cells have also been transplanted for non-retinal disorders. The survival of the transplanted cells in the host is an important factor for the success of transplantation. Autologous IPE cells have been found in the transplanted subretinal space and were able to phagocytose rod outer segments even 6 months after transplantation. Allogeneic and xenogenic cells will not remain in the region longer than autologous cells. Allogenic cells transplanted into the subretinal space are rejected in humans. Thus, we have transplanted cultured autologous IPE cells in 56 patients with age-related macular degeneration. The long-term results (more than 2 years with a maximum of 8 years) showed that the visual acuity (VA) was significantly improved over the pre-transplantation VA, although a slight decrease of VA was observed 2 weeks after the transplantation. One patient showed a vasculitis-like lesion. IPE cells that were transduced with neurotrophic factors by plasmid or viral vectors have also been transplanted in animals. We have transduced several neurotrophic factor genes into IPE cells with a plasmid vector, adeno-associated virus, or adenovirus. Transplantation of these transduced IPE cells into the subretinal space rescued photoreceptor cells from several types of photoreceptor toxicities. In addition, transduction of a gene into the IPE cells suppressed the systemic dissemination of the viral genome. The neuroprotective effects of the IPE cells were different for the different types of neurotrophic factor, and some of the neurotrophic factors may enhance systemic immune reaction after transplantation. IPE cells have also been used as retinal progenital cells because they originate from the same cell lines that give rise to the neural retina and RPE cells. The transduction of the photoreceptor-related homeobox gene was reported to induce photoreceptor phenotypes in IPE cells. Furthermore, transplantations of IPE cells have been performed to treat central nervous system disorders. In this review, we summarize recent progress on IPE transplantation.

Shimura M, Nakazawa T, Yasuda K, Kunikata H, Shiono T, Nishida K. · Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Japan. · Acta Ophthalmol. · Pubmed #18039346 No free full text.

Abstract: PURPOSE: To investigate the relationship between vitreous levels of cytokines, including interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), and visual prognosis after pars plana vitrectomy (PPV) with arteriovenous sheathotomy in patients with branch retinal vein occlusion (BRVO) associated with macular oedema. METHODS: We studied 60 patients with logMAR visual acuity (VA) scores of < 0.3 and visual impairment secondary to BRVO-associated macular oedema. All patients underwent PPV with arteriovenous sheathotomy. At the time of PPV, vitreous samples were collected from the operated eye and vitreous levels of VEGF and IL-6 were measured. Best corrected VA (BCVA) (using a logMAR chart) and foveal thickness (FT) (using optical coherence tomography) were monitored for up to 6 months after PPV. RESULTS: Both BCVA and FT significantly improved after PPV. According to multiple regression analysis, both the improvement in BCVA and decrease in FT were closely related to the vitreous level of IL-6 but not to that of VEGF. The vitreous level of VEGF was strongly correlated with duration of BRVO. CONCLUSIONS: Both improvement in BCVA and decrease in FT were observed after PPV in BRVO patients with macular oedema. Interestingly, these visual prognoses strongly correlate with the vitreous level of IL-6, whereas the duration of BRVO strongly correlates with the vitreous level of VEGF.

Shimura M, Nakazawa T, Yasuda K, Nishida K. · Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Japan. · J Ocul Pharmacol Ther. · Pubmed #17593013 No free full text.

Abstract: PURPOSE: This study compares the effect of topical diclofenac with that of betamethasone against postoperative cystoid macular edema (CME) following cataract surgery in patients with non- and mild nonproliferative diabetic retinopathy. METHODS: Forty-six (46) consecutive patients with mild nonproliferative- or nondiabetic retinopathy who had bilateral and symmetrical cataracts underwent uncomplicated cataract surgery in both eyes (92 eyes in total). Postoperatively, topical diclofenac was applied 4 times daily for 1 eye, and topical betamethasone 4 times daily for the other eye in each patient. Best corrected logMAR visual acuity (BCVA), averaged foveal thickness (FT) as measured by optical coherence tomography (OCT), and intraocular pressure (IOP) were monitored preoperatively, and also postoperatively at 1 day and 1, 4, and 8 weeks. RESULTS: VA in both the diclofenac- and betamethasone-treated eyes significantly improved following the cataract surgery; however, no statistical difference of VA was noted between the diclofenac- and betamethasone-treated eyes throughout the observational period (before and after the surgery until 8 weeks postoperatively). FT in both eyes increased after the cataract surgery. FT in the diclofenac-treated eyes did not increase 1 week after surgery, but gradually increased at week 4 and week 8. In contrast, the FT in the betamethasone-treated eyes increased during 1-8 weeks postoperatively. IOP in the diclofenac-treated eyes decreased with time, but IOP in the betamethasone-treated eyes showed no change throughout the observational period. CONCLUSIONS: Postoperative macular thickening following cataract surgery in patients with non- or mild nonproliferative-diabetic retinopathy cannot be fully suppressed by either topical diclofenac or betamethasone. Nonetheless, diclofenac protected against an early event of postoperative CME and also a decrease of IOP.

Wakusawa R, Abe T, Sato H, Yoshida M, Kunikata H, Sato Y, Nishida K. · Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Miyagi, Japan. · Am J Ophthalmol. · Pubmed #18486097 No free full text.

Abstract: PURPOSE: To determine whether vasohibin, an antiangiogenic factor produced by vascular endothelial cells, is expressed in the choroidal neovascular (CNV) membranes obtained from human eyes with age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective, interventional case series. METHODS: The medical charts of 21 eyes of 21 patients with AMD or PCV who underwent surgical removal of the CNV membrane were reviewed. The removed tissues were immunostained for von Willebrand Factor (vWF), vascular endothelial growth factor (VEGF), and vasohibin. The levels of the messenger ribonucleic acid of VEGF, VEGFR2, and vasohibin were determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) from the CNV membranes excised from nine AMD and nine PCV patients. RESULTS: The patients were divided into three groups; four patients were placed in the most active group (Group H), 13 in the less active group (Group E), and four in the nonactive group (Group S). Immunohistochemistry showed that vasohibin, vWF, and VEGF were expressed in the vascular endothelial cells in the CNV membranes and in the polypoidal vessels. RT-PCR showed that there was a strong correlation between the level of expression of VEGFR2 and vasohibin (P = .0002). Eyes with a lower vasohibin-to-VEGF ratio tended to have larger subretinal hemorrhages or vitreous hemorrhages, whereas eyes with higher vasohibin-to-VEGF ratio had subretinal fibrosislike lesions. Statistical analysis of the vasohibin-to-VEGF ratio among the three groups was significant (P = .0209). CONCLUSIONS: Vasohibin is expressed in human CNV membranes. Our results indicate that the vasohibin-to-VEGF ratio may be related with the activity of the CNV.

Shimura M, Nakazawa T, Yasuda K, Shiono T, Iida T, Sakamoto T, Nishida K. · Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Miyagi, Japan. · Am J Ophthalmol. · Pubmed #18328456 No free full text.

Abstract: PURPOSE: To compare the effect of an intravitreal injection of bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, with that of triamcinolone acetonide, a corticosteroid for reduction of diabetic macular edema (DME). DESIGN: Prospective, comparative interventional case series. METHODS: Twenty-eight eyes of 14 patients with bilateral DME participated in this study. In each patient, one eye received an intravitreal injection of 4 mg triamcinolone acetonide and the other eye received 1.25 mg bevacizumab. The clinical course of best-corrected visual acuity (VA) with a logarithm of the minimum angle of resolution chart and averaged foveal thickness using optical coherence tomography was monitored for up to 24 weeks after the injection. RESULTS: Before the injection, foveal thickness and VA were 522.3 +/- 91.3 microm and 0.64 +/- 0.28 microm in the triamcinolone-injected eye, and 527.6 +/- 78.8 microm and 0.61 +/- 0.18 microm in the bevacizumab-injected eye, respectively; there was no significant difference between the eyes. One week after the injection, both eyes showed significant regression of macular edema. The triamcinolone-injected eye (342.6 +/- 85.5 microm and 0.33 +/- 0.21 microm) showed significantly better results than the bevacizumab-injected eye (397.6 +/- 103.0 microm and 0.37 +/- 0.17 microm). However, both eyes showed the recurrence of macular edema with time, even at 24 weeks. Triamcinolone (410.4 +/- 82.4 microm and 0.47 +/- 0.25 microm) kept better results than bevacizumab (501.6 +/- 92.5 microm and 0.61 +/- 0.17 microm). CONCLUSIONS: With the generally used concentration, intravitreal injection of triamcinolone acetonide showed better results in reducing DME and in the improvement of VA than that of bevacizumab, suggesting that the pathogenesis of DME is not only attributable to VEGF-dependency, but is also attributable to other mechanisms suppressed by corticosteroid.

Shimura M, Nakazawa T, Yasuda K, Shiono T, Nishida K. · Department of Ophthalmology, NTT East Japan Tohoku Hospital, 2-29-1, Yamato, Wakabayashi, Sendai, Miyagi 984-8560, Japan. · Br J Ophthalmol. · Pubmed #17077114 No free full text.

Abstract: AIM: To prospectively evaluate the efficacy of subtenon injection of triamcinolone acetonide (TA) before laser grid pattern photocoagulation (G-PC) for the treatment of diffuse diabetic macular oedema (DDME). METHODS: 42 eyes of 37 consecutive patients with DDME were studied. 1 week before G-PC, 21 eyes received TA subtenon injection, and the other eyes served as control. The clinical course of visual acuity (VA) and foveal thickness (FT) was monitored for up to 24 weeks after G-PC. Mean deviation (MD) of perimetry with 30-2 program on Humphrey Perimeter (Zeiss-Humphrey, Dublin, California, USA) was also measured. The average laser intensity was recorded. RESULTS: After TA injection, FT and VA were improved, and subsequent G-PC maintained the improvement for up to 24 weeks without recurrence of diffuse diabetic macular oedema. In contrast, G-PC without TA injection induced transient worsening of FT and VA, then both were gradually improved. At 24 weeks after G-PC, MD in the TA-injected eyes was better than those in control. The required laser intensity in TA-injected eyes was less than that for control. CONCLUSION: Subtenon injection of TA prior to G-PC allows for treatment with a lower intensity of laser spots and also prevents the decrease in central visual field sensitivity, all of which have clinical advantages for G-PC.

Fukui T, Yamamoto S, Nakano K, Tsujikawa M, Morimura H, Nishida K, Ohguro N, Fujikado T, Irifune M, Kuniyoshi K, Okada AA, Hirakata A, Miyake Y, Tano Y. · Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan. · Invest Ophthalmol Vis Sci. · Pubmed #12202497 links to  free full text

Abstract: PURPOSE: To evaluate photoreceptor cell-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) gene mutations in Japanese patients with Stargardt disease (STGD) and the correlation of these mutations to clinical phenotypes. METHODS: Serum was obtained from 10 unrelated Japanese patients with STGD and 96 unrelated Japanese patients with autosomal recessive retinitis pigmentosa (arRP). All 50 ABCA4 gene exons of the patients with STGD were screened for mutations by a combination of single-strand conformation polymorphism analysis and polymerase chain reaction (PCR) direct-sequencing techniques. By restriction enzyme digestion, primer extension analysis, and PCR direct sequencing techniques, the patients with arRP were screened for three segregated, presumably null ABCA4 gene mutations observed in Japanese patients with STGD. RESULTS: Three novel, presumably null mutations of the ABCA4 gene, IVS7-45_952delinsTCTGACC, IVS12+2T-->G, and 1894delA, were identified. The Arg2149stop mutation that had been found in a white patient with STGD in a prior study was also found in a Japanese patient. Two arRP-affected siblings and two unrelated patients with STGD were found to be homozygous for the same IVS12+2T-->G mutation, and three other arRP-affected siblings were carriers of the IVS12+2T-->G mutation and/or the IVS7-45_952delinsTCTGACC mutation. These three siblings with arRP showed only atrophic degeneration in the macula early after the onset of the disease, and STGD had been diagnosed. CONCLUSIONS: Three novel ABCA4 gene mutations were identified in Japanese patients with STGD and arRP. Mutations in the ABCA4 gene can cause panretinal degeneration that changes its clinical appearance from STGD to arRP over time.