Long-term efficacy of infliximab on background vascular leakage in patients with Behçet's disease.

PURPOSE: To evaluate the effect of infliximab over the initial 4 years of treatment on inflammatory ocular attacks and background retinal/disc vascular leakage in patients with refractory uveoretinitis associated with Behçet's disease. METHODS: Clinical records of nine patients were retrospectively reviewed. The main outcomes analyzed were frequency of ocular inflammatory attacks, background retinal and disc vascular leakage as assessed by fluorescein angiography during periods of clinical quiescence, best-corrected visual acuity, and adverse effects. RESULTS: The median follow-up on infliximab was 50 months (range 48-58 months). Mean frequency of attacks decreased significantly in years 1, 2, 3, and 4 compared with the baseline 1-year period before infliximab use. Mean background retinal and disc vascular leakage scores also decreased significantly at the end of each 1-year period compared with baseline. Visual acuity improved or was unchanged at the end of 4 years in 17 of 18 eyes. No serious adverse effects were observed. CONCLUSION: Infliximab reduced the mean frequency of ocular attacks and mean background retinal/disc vascular leakage in a long-term sustained manner over 4 years of treatment in Behçet's disease patients.

Clinical features and visual outcomes of Japanese patients with scleritis.

PURPOSE: To analyse clinical features, systemic associations, treatment and visual outcomes in Japanese patients with scleritis. METHODS: Clinical records of 83 patients with scleritis who presented between 1998 and 2008 to the Ocular Inflammation Service of the Kyorin Eye Center, Tokyo, were reviewed. RESULTS: Of the 83 patients, 57 (69%) had diffuse anterior scleritis, 9 (11%) had nodular anterior scleritis, 8 (10%) had necrotising anterior scleritis and 9 (11%) had posterior scleritis. There was a slight predominance of women (55%) and unilateral disease (53%). Mean age at presentation was 51 years (range 12-82 years). Secondary ocular complications were observed in 78% of patients, including anterior uveitis in 25% and increased intraocular pressure in 40%. Investigation revealed a systemic disease association in 24 patients (29%), including six patients (7.2%) with tuberculosis and 18 patients (22%) with rheumatologic disease. Thirty-five patients (42%) received systemic corticosteroid treatment and 19 patients (23%) received immunosuppressive agents. All 17 patients with necrotising anterior scleritis or posterior scleritis were treated with oral corticosteroids and/or immunosuppressive drugs. Visual outcomes were generally good; however, poorer outcomes were observed in eyes with necrotising scleritis, mostly due to corneal ulceration or corneal opacification. CONCLUSIONS: A systemic disease association was identified in 29% of Japanese patients with scleritis. Roughly one-half of patients received oral corticosteroids and/or immunosuppressive drugs to control inflammation, with generally good visual outcomes.

Trans-Tenon's retrobulbar triamcinolone infusion for the treatment of uveitis.

AIM: To assess efficacy and complications of trans-Tenon's retrobulbar infusion of triamcinolone acetonide for posterior uveitic inflammation. METHODS: Non-randomised, uncontrolled, retrospective study of 51 eyes of 37 patients who underwent triamcinolone infusion for vitritis, cystoid macular oedema (CMO), or posterior retinal vasculitis using a long blunt cannula via an incision made through conjunctiva and Tenon's capsule. RESULTS: Overall clinical efficacy was 86%; 96% for vitritis, 82% for CMO, and 33% for posterior retinal vasculitis. Mean visual acuity improved within 1 month after triamcinolone infusion (p <0.05). Cataract progression and intraocular pressure elevation were observed in 31% and 27% of eyes, respectively. CONCLUSION: Trans-Tenon's retrobulbar triamcinolone infusion may be a safe and effective treatment for posterior uveitic inflammation.

[A case of choroidal hemangioma with bullous exudative retinal detachment treated successfully by transpupillary thermotherapy].

BACKGROUND: Choroidal hemangioma associated with bullous retinal detachment may be difficult to treat, due to varying results with conventional laser photocoagulation, radiotherapy, or surgical drainage. Here we report on a case of extensive bullous retinal detachment secondary to circumscribed choroidal hemangioma that was resolved after combined treatment with vitrectomy, silicone oil tamponade, and transpupillary thermotherapy. CASE: A 29-year-old woman presented with a large choroidal hemangioma in her right eye associated with serous retinal detachment. The tumor measured 8 disc diameters in size and was located in the inferotemporal macula, abutting the fovea. RESULTS: Laser photocoagulation of the tumor was unsuccessful in inducing absorption of subretinal fluid. Because of progressive bullous retinal detachment, surgery was performed consisting of external drainage of subretinal fluid, vitrectomy, endolaser photocoagulation of the tumor, and silicone oil tamponade. The silicone oil was removed four weeks postoperatively at which time almost complete resolution of the retinal detachment was observed. However, retinal detachment recurred eight weeks later, and transpupillary thermotherapy was then applied to the tumor. By four weeks after transpupillary thermotherapy, total reabsorption of subretinal fluid, visual acuity improvement, and decreased height of the choroidal hemangioma were noted. CONCLUSION: Transpupillary thermotherapy is an effective treatment for serous retinal detachment associated with choroidal hemangioma.

Evaluation of retinal damage induced by air/fluid exchange using a trypan blue inclusion test in rabbits.

PURPOSE: To investigate whether retina damaged in the process of air/fluid exchange could be visualized in situ using trypan blue staining. METHODS: Vitrectomy and air/fluid exchange with continuous air infusion for various periods of time was performed in adult pigmented rabbits, followed by injection of 0.4% trypan blue solution into the vitreous cavity. Retinal staining was evaluated intraoperatively under the operating microscope and by light microscopy after enucleation. RESULTS: Intraoperative examination showed localized trypan blue staining of areas of the retina opposite the infusion cannula. Light microscopy of the same areas revealed intranuclear trypan blue inclusion in the retina. CONCLUSION: Trypan blue staining allows for the immediate in situ evaluation of damage to the retina associated with air/fluid exchange and continuous air infusion in rabbit eyes.

Visual function after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy.

PURPOSE: To assess functional and anatomical outcomes after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy. METHODS: Foveal translocation with 360-degree retinotomy was performed in 11 eyes of 11 patients with myopic neovascular maculopathy. Ten eyes had simultaneous torsional muscle surgery with recession of the superior oblique muscle and tucking of the inferior oblique muscle. Silicone oil removal with or without intraocular lens implantation was performed 2 to 8 weeks after the primary procedure. Visual acuity, binocular function, and degree of cyclotorsion were assessed preoperatively and postoperatively. Angles of retinal and globe rotation, distance of foveal shift, and surgical complications were also investigated. RESULTS: With a mean postoperative follow-up of 6.2 months (range, 3 to 13 months), vision improved (greater than 0.2 logarithm of minimal angle of resolution [logMAR] units) in eight eyes, was unchanged in two eyes, and worsened (greater than 0.2 logMAR units) in 1 eye. Seven of 11 eyes (64%) had a final visual acuity of 20/50 or better. Five patients developed or maintained binocular fusion, four patients continued to have suppression, and two patients developed diplopia that was managed by spectacles with Fresnel prisms. Subjective cyclotorsion was less than 8 degrees in 10 eyes. Mean retinal and globe rotations were 23.4 degrees and 19.8 degrees, respectively. Average size of the choroidal neovascular membrane was 0.8 disk diameter, whereas the average distance of foveal shift was 1.5 disk diameter. After the primary procedure, three eyes developed retinal detachment, one eye macular hole, and one eye proliferative vitreoretinopathy. These complications were successfully managed by additional surgery. CONCLUSION: Foveal translocation with 360-degree retinotomy is effective in restoring vision in some patients with myopic neovascular maculopathy. Although the development of torsional diplopia is generally obviated by simultaneous extraocular muscle surgery, a relatively high incidence of surgical complications should be taken into account with this procedure.

Inhibition of experimental choroidal neovascularization by overexpression of tissue inhibitor of metalloproteinases-3 in retinal pigment epithelium cells.

PURPOSE: To evaluate the feasibility of introducing exogenous tissue inhibitor of metalloproteinases-3 gene into the rat retinal pigment epithelium using hemagglutinating virus of Japan liposomes and to assess the effect of tissue inhibitor of metalloproteinases-3 overexpression in retinal pigment epithelium cells on the formation of experimental choroidal neovascularization. METHODS: Hemagglutinating virus of Japan liposomes containing hemagglutin epitope-tagged tissue inhibitor of metalloproteinases-3 gene were injected into the subretinal space in rat eyes. Localization of oligonucleotides was evaluated by fluorescence microscopy. Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression was assessed by reverse transcribed polymerase chain reaction. Exogenous tissue inhibitor of metalloproteinases-3 protein expression was visualized by immunostaining with monoclonal antibody 12CA5 against the hemagglutin epitope. Three days after transfection of tissue inhibitor of metalloproteinases-3 gene into retinal pigment epithelium cells, intense laser photocoagulation was performed and the incidence of choroidal neovascularization was assessed by fluorescein fundus angiography. RESULTS: Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression in the choroid and retina was detected on day 3. The efficiency of tissue inhibitor of metalloproteinases-3 gene transfection into retinal pigment epithelium cells was greatest on day 7 and decreased gradually thereafter. The incidence of choroidal neovascularization in tissue inhibitor of metalloproteinases-3 gene-transfected eyes was markedly decreased compared with controls. CONCLUSIONS: This study shows that tissue inhibitor of metalloproteinases-3 gene can be transferred into rat retinal pigment epithelium using the hemagglutinating virus of Japan-liposome method and that tissue inhibitor of metalloproteinases-3 gene overexpression can inhibit development of experimental choroidal neovascularization. This method may represent a future treatment modality for human macular degeneration associated with choroidal neovascularization.

Drug therapy in Behçet's disease.

Behçet's disease is one of the most difficult forms of uveitis to treat. Variety in disease presentation and severity, as well as regional differences in standard of care, demand a tailor-made approach. Anterior segment inflammation generally responds to topical corticosteroids. However, the onset of posterior segment inflammation usually requires the advancement of treatment to periocular injections and/or oral administration of corticosteroids. Cyclosporin, either alone or in combination with corticosteroids, is considered in refractory patients. Other immunosuppressive drugs, such as azathioprine and chlorambucil, may be considered in difficult cases. Finally, preliminary results suggest efficacy with the immunomodulatory agent interferon alfa, although further clinical trials are necessary to evaluate safety and efficacy.

X-linked retinoschisis with point mutations in the XLRS1 gene.

BACKGROUND: X-linked retinoschisis (XLRS) is a relatively rare vitreoretinal dystrophy that causes visual loss in young men. Recently, a gene responsible for this disease, designated XLRS1, was identified, and several deleterious gene mutations were reported. OBJECTIVE: To analyze Japanese patients clinically diagnosed as having XLRS formutational changes in the XLRS1 gene. METHODS: Ten patients with XLRS underwent full ophthalmologic examination, including slitlamp biomicroscopy and dilated funduscopy. Genomic DNA was isolated from leukocytes, and all exons of the XLRS1 gene were amplified by polymerase chain reaction and analyzed using a direct sequencing method. RESULTS: Point mutations in the XLRS1 gene were identified in all 10 patients. The mutations were identical in each of 2 pairs of brothers. Six of the point mutations represented missense mutations, 1 was a nonsense mutation, and 1 was a frameshift mutation. Five of the mutations are newly reported herein. CONCLUSIONS: The discovery of new point mutations in this study increases the available information regarding the spectrum of genetic abnormalities and clinical manifestations of XLRS. However, the limited data failed to reveal a correlation between mutation and disease phenotype. CLINICAL RELEVANCE: Identification of mutations in the XLRS1 gene and expanded information on clinical manifestations will facilitate early diagnosis, appropriate early therapy, and genetic counseling regarding the prognosis of XLRS.

The role of costimulatory molecules B7-1 and B7-2 in mice with experimental autoimmune uveoretinitis.

BACKGROUND: Onset of experimental autoimmune uveoretinitis (EAU) is believed to involve a CD4-positive type 1 T helper cell (Th1) immune response, with inhibition involving a Th2 immune response. Development of Th1 and Th2 responses involves the participation of the costimulatory molecules B7-1 and B7-2, respectively. The purpose of this study was to investigate the role of B7-1 and B7-2 in the EAU model in mice. METHODS: B10.A mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) and given daily intraperitoneal injections of either phosphate-buffered saline (control), mouse monoclonal antibody (mAb) to B7-1, mAb to B7-2, or mAb to both B7-1 and B7-2. Eyes were evaluated by histopathological criteria and cytokines were assayed in culture medium of IRBP-stimulated lymphocytes. Cellular immune responses were measured by cell proliferation assay under IRBP stimulation. RESULTS: Rates of EAU onset were 5/10 (50%) for control mice, 1/9 (11%) for mice treated with anti-B7-1 mAb, 5/6 (83%) for mice treated with anti-B7-2 mAb, and 2/6 (33%) for mice treated with both anti-B7-1 and anti-B7-2 mAb. Mean histopathological severity scores were 2. 4+/-0.8, 1.0+/-0, 2.6+/-1.0, and 1.0+/-0, respectively. Production of IL-5 was significantly increased in mice treated with anti-B7-1 mAb, while IFN-gamma was increased in mice treated with anti-B7-2 mAb. Spleen cell proliferation was significantly reduced in mice treated with anti-B7-1 mAb. CONCLUSIONS: These results suggest that the costimulatory molecules B7-1 and B7-2, via their influence on generating Th1 and Th2 immune responses, play an important role in the clinical outcome of EAU in mice immunized with IRBP.

Analysis of vitrectomy for idiopathic macular hole by optical coherence tomography.

PURPOSE: To evaluate foveal structure after vitrectomy for idiopathic macular hole in relation to postoperative visual outcome. METHODS: Optical coherence tomography was performed postoperatively to assess retinal thickness at the foveal center in patients who underwent vitrectomy, posterior hyaloid membrane removal, and perfluoropropane gas tamponade for idiopathic macular hole. Thirty-seven eyes of 36 patients documented to have achieved anatomic hole closure by optical coherence tomography were included in the study. RESULTS: Increased visual acuity significantly correlated with greater foveal thickness assessed at a median of 5 months postoperatively (Spearman analysis; R = .453, P = .005). CONCLUSION: Visual outcome after anatomic closure of macular holes by vitrectomy is closely related to the structure of the center of the fovea postoperatively.

T-cell-mediated immune responses in alloepithelial rejection after murine keratoepithelioplasty.

PURPOSE: To evaluate the role of delayed-type hypersensitivity (DTH) and cytotoxic T-lymphocyte (CTL) responses on alloepithelial rejection in a murine keratoepithelioplasty model. METHODS: C3H/He mouse corneal lenticules were grafted around the limbus in BALB/c mice, and alloepithelial rejection was assessed by microscopic evaluation. The relation between rejection scores and DTH or CTL responses to donor antigens was assessed by Spearman correlation analysis. Suppression of DTH responses by induction of anterior chamber-associated immune deviation (ACAID) was used to evaluate the contribution of DTH responses to allograft rejection. CTL responses were evaluated by in vitro and in vivo depletion of CD4+ or CD8+ cells. RESULTS: DTH responses, which developed 2 weeks postoperatively, correlated significantly with rejection scores (correlation coefficient r = 0.55). ACAID induction by anterior chamber inoculation of C3H/He splenocytes significantly suppressed allospecific DTH responses and alloepithelial rejection. While allospecific CTL responses also developed 2 weeks postoperatively and increased by 4 weeks, CTL responses did not exhibit positive correlation with rejection scores (r = -0.36, P = 0.076). The CTL responses were mediated exclusively by CD8+ cells. Although in vivo depletion of CD8+ cells abolished the induction of CTL responses, it did not prevent allograft rejection. Immunohistochemistry showed infiltration of CD4+ and CD8+ cells into the alloepithelium. Positive staining for interferon gamma but not interleukin 4 further implicated the participation of a DTH response. CONCLUSIONS: Allograft rejection after keratoepithelioplasty appears to be mediated primarily by DTH responses, with CTL responses playing only a minor role perhaps in modifying the development of rejection.