蕪城 俊克

背景:両眼の内因性真菌性網膜下膿瘍を発症し,眼球内容物から,検索し得た範囲では本邦初のScedosporium prolificans(S.prolificans)が分離された症例を経験した.症例:74歳男性.急性骨髄性白血病の治療中に両眼の視力低下を自覚.眼科検査にて,矯正視力は右手動弁,左0.01.右眼は眼球突出,前房内炎症と虹彩新生血管があり,眼底は透見不能であった.左眼は黄斑を含む黄白色・不整円形の網膜下病巣を認めた.血液培養は陰性,C-reactive protein(CRP)とβ-Dグルカンの高値を認め,抗真菌薬と広域抗菌薬を全身投与した.右眼は初診2日後に光覚弁となり,診断を兼ねて眼球摘出した.網膜下病巣より真菌が培養され,S.prolificansと同定された.抗真菌薬の全身投与と,計16回の硝子体内注射で膿瘍は徐々に縮小した.初診から6か月目の左眼・矯正視力は0.1である.結論:S.prolificans眼内炎は難治とされているが,反復した抗真菌薬の硝子体内注射の併用が有効と考えられた.(著者抄録)

BACKGROUND: We report a case with bilateral endogenous fungal subretinal abscesses. To our knowledge, this is the first report from Japan in which Scedosporium prolificans (S. prolificans) was cultured from intraocular tissue. CASE: A 74-year-old man, receiving chemotherapy for acute myeloid leukemia, complained of visual loss in both eyes. Best-corrected visual acuity was hand motion in the right and 2/200 in the left eye. His right eye showed exophthalmos, inflammation in the anterior chamber and iris neovascularization. Funduscopy revealed no details as there was vitreous opacity in the right eye, and irregular round yellowish-white subretinal lesions involving the macula in the left eye. Blood culture was negative, and C-reactive protein (CRP) and β-D glucan titers were high. An antifungal drug and broad-spectrum antibiotics were initiated. Two days after the initial visit, right visual acuity had deteriorated to light perception. Enucleation of the right eye was performed for diagnosis and treatment. Fungi were cultured from the subretinal lesion, confirming a diagnosis of S. prolificans infection. After systemic administration and intravitreal injections of antifungal agents, the subretinal abscess in the left eye gradually diminished. At present, six months after the first visit, left visual acuity is 20/200. CONCLUSION: Although S. prolificans endophthalmitis can be intractable, this case suggests that repeated intravitreal antifungal agent injections can be effective.

PURPOSE: To investigate the frequencies of the diseases in the new patients with uveitis during 2007-2009 and compare them with previously-reported data from the University of Tokyo Hospital. METHODS: We retrospectively analyzed the clinical records of patients who visited the outpatient clinic from January 2007 to December 2009, and compared them with those of 1963-2006. RESULTS: During 2007-2009, 468 new patients visited our hospital. Definite diagnoses were made in 63.0%. Frequent diagnoses include sarcoidosis (9.4%), Vogt-Koyanagi-Harada (VKH) disease (7.9%), herpetic iritis (6.0%), Behçet's disease (5.6%), Posner-Schlossman syndrome (4.3%), HLA-B27-associated uveitis (3.0%), and intraocular malignant lymphoma (2.8%). Compared with our former findings, the ratios of sarcoidosis, herpetic iritis, CMV retinitis, Fuch's heterochromic iridocyclitis, acute retinal necrosis and intraocular lymphoma increased, while that of Behçet's disease decreased. CONCLUSIONS: Top three uveitis during 2007-2009 were sarcoidosis, VKH disease, herpetic iritis. Reduced frequency of Behçet's disease was one of the most prominent characteristics.

PURPOSE: To investigate the clinical features of psoriatic uveitis in Japanese patients. METHODS: Clinical features of 13 consecutive patients with psoriatic uveitis treated at our facility were retrospectively examined using medical records. In this study, we collected data about psoriasis type, uveitis laterality, onset type, HLA types, visual acuity, ocular inflammation localization, anterior segment findings, funduscopy findings, complications, recurrence, and medical treatments for uveitis and skin diseases. RESULTS: The cohort comprised ten males and three females (43.6 ± 7.1 years old), and types of psoriasis included psoriasis vulgaris (seven cases), psoriatic arthritis (four cases), pustular psoriasis (three cases) and psoriatic erythroderma (one case). Two cases represented complicated cases of pustular psoriasis and psoriatic arthritis. Seven cases were unilateral, and six cases were bilateral. All cases had acute non-granulomatous anterior uveitis, whereas panuveitis occurred in one case. Furthermore, macular edema and vascular leakage on fluorescein angiography occurred in four cases, and hyperemic disc occurred in two cases. Recurrence occurred in nine cases. In addition to topical corticosteroid treatment, eight cases underwent oral immunosuppressive treatment or biologics. All six cases undergoing HLA typing were HLA-A2 positive. CONCLUSIONS: Cases of psoriatic uveitis in Japan appear to present with acute non-granulomatous uveitis; other symptoms may include macular edema, retinal vasculitis, or hyperemic disc.

Behçet's disease (BD), a multi-organ inflammatory disorder, is associated with the presence of the human leukocyte antigen (HLA) HLA-B*51 allele in many ethnic groups. The possible antigen involvement of the major histocompatibility complex class I chain related gene A transmembrane (MICA-TM) nonapeptide (AAAAAIFVI) has been reported in BD symptomatic patients. This peptide has also been detected in HLA-A*26:01 positive patients. To investigate the link of BD with these two specific HLA alleles, molecular dynamics (MD) simulations were applied on the MICA-TM nonapeptide binding to the two BD-associated HLA alleles in comparison with the two non-BD-associated HLA alleles (B*35:01 and A*11:01). The MD simulations were applied on the four HLA/MICA-TM peptide complexes in aqueous solution. As a result, stabilization for the incoming MICA-TM was found to be predominantly contributed from van der Waals interactions. The P2/P3 residue close to the N-terminal and the P9 residue at the C-terminal of the MICA-TM nonapeptide served as the anchor for the peptide accommodated at the binding groove of the BD associated HLAs. The MM/PBSA free energy calculation predicted a stronger binding of the HLA/peptide complexes for the BD-associated HLA alleles than for the non-BD-associated ones, with a ranked binding strength of B*51:01 > B*35:01 and A*26:01 > A*11:01. Thus, the HLAs associated with BD pathogenesis expose the binding efficiency with the MICA-TM nonapeptide tighter than the non-associated HLA alleles. In addition, the residues 70, 73, 99, 146, 147 and 159 of the two BD-associated HLAs provided the conserved interaction for the MICA-TM peptide binding.

Purpose: To report a case of acute retinal vasculitis in whom polymerase chain reaction (PCR) was useful in the diagnosis. Case: A 28-year-old female presented with acute impairment of vision in the right eye. She was at 9 months of pregnancy. Findings: Corrected visual acuity was 0.5 right and 1.2 left. The right eye showed signs of inflammation in the anterior chamber, vitreous opacity, and retinal vasculitis. Aqueous humor was positive for herpes simplex virus (HSV) by PCR. She was treated by systemic acyclovir.

PURPOSE: Candida albicans subretinal abscess is extremely rare. To our knowledge, only one unilateral case has been reported. Herein, we report one bilateral case. Mixed bacterial infection was also suspected based on broad-range real-time polymerase chain reaction. METHODS: A 64-year-old man being treated with oral corticosteroids for interstitial pneumonia visited us for visual loss in the left eye. Best corrected visual acuity (BCVA) was 20/20 in the right eye and 8/200 in the left eye. Funduscopy revealed round yellowish-white subretinal lesions with retinal hemorrhage in both eyes. RESULTS: Broad-range polymerase chain reaction of the vitreous fluid from the left eye showed a high copy count of bacterial 16s ribosome RNA. Despite large doses of antibiotics, the abscess expanded and vision decreased to light perception in the left eye. Exenteration of the left eye was performed followed by microscopic examination showing Gram-negative bacilli, and C. albicans was also cultured. Antibiotics and the maximum doses of antifungal drugs were administered. However, the abscess in the right eye expanded, and BCVA decreased to 2/200. Vitrectomy and silicone oil tamponade were performed. Vitreous fluid culture revealed C. albicans. At 16 months follow-up, BCVA was stable at 4/200 with healing of the subretinal abscess under silicone oil. CONCLUSION: Since C. albicans subretinal abscess is extremely rare and there was a concurrent mixed bacterial infection, diagnostic procedures in our bilateral case were more complicated than usual. C. albicans infection should be included in the differential diagnosis of subretinal abscesses.

PURPOSE: It has been suggested thatSairei-to (TJ114), a traditional Japanese herbal medicine, has immunomodulatory activities. To evaluate the effects of TJ114 on uveitis, we examined the effectiveness of oral administration in a murine model of experimental autoimmune uveitis (EAU). METHODS: Murine EAU was induced by subcutaneous injection of human inter-photoreceptor retinoid-binding protein (IRBP) peptide mixed with complete Freund's adjuvant. In the TJ114-treated group, 2 g/kg was administrated orally from 0 to 20 days after immunization. Clinical scoring, histopathological scoring of EAU, cell proliferation, cytokine assessment, and adoptive transfer experiment of splenic T cells into naïve mice were performed. RESULTS: EAU development occurred in 32 of 38 mice (86 %) in the untreated group and 12 of 33 (36 %) in the TJ114-treated group. The clinical scores for EAU in the vehicle-treated and TJ114-treated groups were 1.56 ± 1.65 and 0.59 ± 0.63 respectively, at 14 days after immunization (p < 0.01, Mann-Whitney U-test), and 2.26 ± 1.56 and 0.75 ± 1.31 respectively at 21 days (p < 0.001, Mann-Whitney U-test), while the histopathological scores at 21 days were 1.47 ± 1.42 and 0.54 ± 0.84 respectively (p < 0.01, Mann-Whitney U-test). Interferon (IFN)-γ and tumor necrosis factor (TNF)-α production by cervical lymph node cells obtained from the TJ114-treated group were significantly reduced as compared with those from the vehicle-treated group (p < 0.01, Student's unpaired t-test). Moreover, the levels of C-C motif chemokine 2 (CCL2) and IFN-γ were significantly reduced in splenocytes of TJ114-treated mice as compared with the vehicle-treated group (p < 0.01, Student's unpaired t-test). Mice that received adoptive transfer of splenic T cells from TJ114-treated EAU mice caused significantly lower severity of EAU compared to those that received from vehicle-treated EAU mice. CONCLUSION: Oral administration of TJ114 has an inhibitory effect on a murine model of EAU, possibly via reduction in cytokine production by helper type-1 T cells.

BACKGROUND: We describe a HLA-B27-positive Japanese man with recurrent severe anterior uveitis OU and ankylosing spondylitis (AS) who was successfully treated with infliximab. CASE: A 25-year-old HLA-B27-positive Japanese man presented with recurrent anterior uveitis OU. The symptoms were consistent with typical HLA-B27-associated uveitis, whereas the subsequent course, which consisted of frequent episodes of recurrent severe anterior uveitis, was atypical. Although the patient was treated with intensive topical corticosteroids, cycloplegic treatment, sub-Tenon triamcinolone acetonide injections, systemic corticosteroids and immunosuppressive agents, recurrence of the anterior uveitis persisted. Over 8 years there were 14 documented episodes of recurrent anterior uveitis OD and 10 OSs. At age 33, the patient was diagnosed with AS after a radiographic examination. We began infusions of infliximab (2.5 mg/kg) at 0, 2 and 6 weeks, and then every 8 weeks thereafter. The recurrent uveitis disappeared, and the immunosuppressive agents and oral corticosteroids were tapered and discontinued without relapse. All drugs other than infliximab were successfully stopped in October 2010. During the follow-up period, there were no adverse events. CONCLUSION: A case of severe recurrent anterior uveitis OU in a patient with AS with infliximab was successfully treated. This is the first report describing the efficacy of infliximab in AS-associated uveitis in Japan.

PURPOSE: To examine the factors associated with anatomic and visual outcomes in Japanese patients with acute retinal necrosis (ARN). METHODS: One hundred four patients with ARN who were followed for more than 1 year at nine referral centers were reviewed. Retinal involvement at initial presentation was classified into four groups: zone 1 (posterior pole, n = 22), zone 2 (midperiphery, n = 54), zone 3 (periphery, n = 25), and unknown (n = 3). Forty-eight eyes underwent prophylactic vitrectomy before development of retinal detachment (vitrectomy group); 56 eyes were treated conventionally without prophylactic vitrectomy (observation group). RESULTS: The retina was attached in 28 of 48 eyes (58.3 %) in the vitrectomy group and 42 of 56 eyes (75.0 %) in the observation group at the final visit (P = 0.071). At 1 year, 56 eyes (53.8 %) had a best-corrected visual acuity (BCVA) of 20/200 or worse. Multivariate logistic regression analyses identified zone 1 disease (odds ratio = 4.983) and optic nerve involvement (odds ratio = 5.084) as significantly associated with BCVA of 20/200 or worse. Among the zone 3 eyes, significantly (P = 0.012) more eyes in the observation group than in the vitrectomy group had an attached retina. CONCLUSIONS: Prophylactic vitrectomy did not improve the final BCVA in any eyes. Zone 3 eyes had better outcomes without prophylactic vitrectomy.

PURPOSE: To examine the factors affecting the efficacy of infliximab (IFX) as a treatment for uveitis in Behçet's disease. METHODS: Clinical records of 29 patients with refractory uveoretinitis were examined retrospectively for the period between 6 months before the initiation of IFX therapy to 12 months thereafter. The patients were divided into two groups based on the absence (Group 1) or occurrence (Group 2) of ocular inflammatory attacks during the observation period after IFX therapy, and the clinical records of the groups were compared RESULTS: The mean age at onset of ocular inflammation in Group 1 patients (n = 17) was lower than that in Group 2 patients (n = 12) (p = 0.023). Compared to Group 2 patients, the period from onset to IFX therapy in Group 1 was longer (p = 0.037), and the frequency of ocular inflammatory attacks before IFX therapy was lower (p = 0.013). The rates of ocular fundus attacks before IFX therapy were 0.82 ± 0.28 in Group 1 and 0.96 ± 0.10 in Group 2 (p = 0.040). Three of 33 (9.1 %) eyes in Group 1 and nine of 24 eyes (37.5 %) in Group 2 had an improved best-corrected visual acuity of >0.2 logarithm of the minimal angle resolution (p < 0.01). CONCLUSIONS: Patients in Group 1 tended to have fewer intraocular attacks (fewer fundus attacks in particular) prior to IFX therapy and have a longer period from onset of intraocular inflammation to IFX therapy. The improvement of the BCVA in Group 2 tended to be better.

PURPOSE: Sarcoidosis is a heterogeneous and multisystem granulomatous disorder. The etiology still is uncertain, but the disease currently is thought to be triggered by various genetic as well as environmental factors. Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene located in close proximity to the HLA-DRB1 gene was reported. The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles. METHODS: In our study, 11 single nucleotide polymorphisms (rs28362677, rs2076533, rs2076530, rs2076529, rs2294881, rs3763304, rs2076523, rs28362682, rs3806156, rs9268499, rs3763317), including the functional rs2076530 (G > A) of the BTNL2 gene, and HLA-DRB1 and -DQB1 alleles, were genotyped in 237 Japanese patients diagnosed with sarcoidosis and 287 healthy Japanese control subjects. RESULTS: In the patient group, the HLA-DRB1*08:03 (P = 6.15 × 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530_A (P = 6.90 × 10(-6), OR = 1.84) were associated with disease susceptibility. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium between BTNL2 rs2076530_A and HLA-DRB1*08:03, our results suggested that the risk-bearing allele of these two loci interact negatively. No significant differences were observed in allele frequencies for alleles in patients with ocular and other systemic sarcoidosis. CONCLUSIONS: Our studies implicated that the HLA-DRB1 allele is a major contributing genetic factor in the development of sarcoidosis in Japan. However, further studies are needed to verify how HLA or BTNL2 alleles confer the disease phenotype, severity of sarcoidosis.

We report a case of bilateral iridocyclitis accompanied by bacterial meningitis in an immunocompetent patient. Case report. A 48 year-old healthy female visited our hospital with strong headache, fever, bilateral hyperemia, and blurred vision in both eyes. A slit-lamp examination revealed moderate cells and flare in the anterior chamber of both eyes, with fine keratoprecipitates. There were no obvious inflammatory changes in the vitreous, retina, and optic disc of both eyes. Elevation of peripheral blood white blood cells, C-reactive protein, and an elevated number of cerebrospinal fluid (CSF) cells suggested bacterial meningitis. The patient was admitted to our hospital and received intravenous antibiotics. Finally, a CSF culture revealed infection with gram-positive rods, suspected Listeria monocytogenes, confirming bacterial meningitis. For iridocyclitis, we prescribed betamethasone eyedrops and 0.5 % tropicamide eyedrops with intravenous adminstration of systemic antibiotics. 3 days later, her headache and bilateral hyperemia disappeared. This case is better described as sterile reactive uveitis rather than endogenous bacterial endophthalmitis, because bilateral anterior uveitis was resolved without chronic uveitis, iris atrophy, and vitreous opacity. When clinicians see patients with meningitis and bilateral anterior uveitis, sterile reactive uveitis should be considered in the differential diagnosis of uveitis.

PURPOSE: Several recent studies suggest that some chemokines/chemokine receptors are involved in choroidal neovascularization (CNV). CXCR3 was the focus of the present study because microarray analysis for murine laser-induced CNV model showed the increased expression of CXCR3. The purpose of this study was to evaluate the effect of CXCR3 on CNV. METHODS: Microarray analysis was performed for the mouse eyes with laser-induced CNV. CXCR3 expressions on the CNV were evaluated by immunohistochemistry and real-time RT-PCR. CNV was compared between CXCR3-deficient mice and wild-type mice, between mice treated with anti-CXCR3/anti-IP-10 neutralizing antibody and mice treated with control IgG. Macrophage recruitment into CNV was also investigated. Ocular expressions of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), C-C chemokine ligand-2 (CCL2), and complement component-3 (C3) were evaluated by real-time PCR. RESULTS: Microarray analysis and real-time RT-PCR revealed the elevation of CXCR3 and IP-10 in laser-treated mouse eyes compared with control eyes. Immunohistochemistry showed CXCR3 expression on the endothelial cells of CNV. Laser-induced CNV of CXCR3-deficient mice was significantly larger, with greater leakage in fluorescein angiography, and with greater macrophage-infiltration compared with wild-type mice (P < 0.01). Intravitreal injection of anti-CXCR3/anti-IP-10 neutralizing antibody exacerbated CNV. The CCL2 expression in the laser-treated eyes of CXCR3-deficient mice was higher than in those of wild-type mice (P < 0.05), whereas VEGF, PEDF, and C3 showed no differences. CONCLUSIONS: These results suggested that CXCR3 expressed on CNV could have an angiostatic effect on it.

Although intraocular pressure (IOP) is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG) termed normal tension glaucoma (NTG), which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS). We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value = 7.40× 10(-8), odds ratio (OR)= 2.00 with 95% confidence interval (CI) 1.55-2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p = 4.96 × 10(-11), OR= 2.13 with 95% CI 1.69-2.68). The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG), the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.

PURPOSE: To investigate whether interleukin 10 (IL10) gene polymorphisms are associated with the development of sarcoidosis in Japanese patients. METHODS: Two hundred and eighty-eight Japanese sarcoidosis patients and 310 Japanese healthy controls were recruited. We genotyped 9 single-nucleotide polymorphisms in IL10 and assessed the allelic diversity between cases and controls. RESULTS: No significant differences in the frequency of IL10 alleles, genotypes, and haplotypes in the sarcoidosis cases compared to the controls were detected. CONCLUSIONS: Our results suggest that IL10 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.

BACKGROUND: Most intraocular metastatic tumors occur in the uveal tract, while isolated metastasis to the optic nerve is rarely found. We report a case of metastasis to the optic disc from primary lung cancer, diagnosed from biopsy findings obtained during a vitrectomy. PATIENT AND METHODS: A 69-year-old male presented with gradual visual impairment due to a milky white tumour that extended from the optic disc into the vitreous cavity. A systemic examination revealed primary squamous cell lung cancer. RESULTS: A biopsy specimen was obtained from the optic disc tumor during a vitrectomy, which led to a diagnosis of metastasis from lung cancer. Despite courses of chemotherapy and radiotherapy, the patient died of brain metastasis. DISCUSSION: There are few reports of secondary optic disc tumors and pathological biopsy findings are rare. When a milky white tumor is observed extending from the optic disc, a possible differential diagnosis is metastatic neoplasm.

PURPOSE: Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas, with varied clinical manifestations. The common etiology of sarcoidosis is uncertain, but it is thought to be triggered by an exogenous antigenic stimulus, such as some bacterial proteins. Toll-like receptors (TLRs) recognize microbial components and elicit innate as well as adaptive immune responses. It has been reported that polymorphisms in TLR2 might be important in a small group of Caucasian sarcoidosis patients. The present study aimed to establish whether these findings are relevant to the Japanese population. METHODS: We genotyped 5 single-nucleotide polymorphisms (SNPs) in TLR2 and assessed the allelic diversity between 257 Japanese sarcoidosis patients and 193 Japanese healthy controls. RESULTS: No significant differences in the frequency of TLR2 alleles and haplotypes in the sarcoidosis cases were found in comparison with the controls. However, marginal associations were observed for TLR2 at rs3804099 and rs3804100 in sarcoidosis patients with cutaneous manifestations. CONCLUSIONS: Our results suggest that TLR2 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.

Objective. Behcet&apos;s disease (BD) is known to be associated with HLA-B*51, especially HLA-B*5101, in many different ethnic groups. Recently, several HLA-A or -B alleles have been proposed as possible candidate genes for BD in addition to HLA-B*5101. To investigate those associations, we studied HLA-A and -B alleles in Japanese ocular BD patients and the association of possible susceptibility HLA genes with visual prognosis. Methods. Eighty-eight Japanese BD patients with uveitis and 104 healthy controls were enrolled for analyses of HLA-A and B alleles. Statistical analysis was performed with Fisher&apos;s exact test and odds ratio (OR). Association of the possible susceptible HLA gene and visual prognosis was also examined. Results. The phenotype frequency (PF) of HLA-A*2601 was significantly higher in the patients (37.5%) than the controls (14.4%) (pc=0.00529, OR=3.56), especially in patients without HLA-B*510.1 (57.4% vs. 14.1%, pc=4.58x10(-6), OR=8.21). In contrast, the PF of HLA-A*2601 was not increased in patients with HLA-B*5101 (14.6% vs. 15.8%). Also, the PF in patients possessing HLA-A*2601 or HLA-B*5101 was increased up to 77.3%. Interestingly, the PF of HLA-A*2601 was significantly associated with poor visual prognosis corresponding to visual acuity of 0.1 or less in the worse eye (p=0.0262). Conclusion. Our results indicate that HLA-A*2601 is possibly associated with ocular BD, independent of HLA-B*5101, indicating that HLA-A*2601 is an additional susceptibility allele candidate of ocular BD in Japan. HLA-A*2601 would also be a possible marker for poor visual prognosis.

BACKGROUND: Recent publications have suggested considerable improvements in the clinical outcomes of ocular Behcet's disease (BD) patients. However, the long-term time course of clinical ocular features of BD in recent cases remains largely unknown. In this study, we investigated annual time-course changes of best-corrected visual acuity (BCVA) during ocular convalescent stages, as well as annual frequency of ocular attacks during the initial 10 years of follow-up in patients with BD. METHODS: We studied 75 eyes in 39 patients (31 men, eight women) with BD, who were referred to our hospital between 1980 and 1996 within 1 year after the initial ocular attack and followed them up continuously for more than 10 years. The clinical courses of BCVA at the ocular convalescent stage from the onset of ocular disease were retrospectively examined, and the numbers of ocular attacks per eye per year were determined. RESULTS: Mean BCVA was 0.59 at 1 year, 0.31 at 3 years, and 0.12 at 10 years from the onset of ocular disease, while the numbers of ocular attacks per eye were 4.1 +/- 3.1 at 1 year, 2.2 +/- 1.9 at 5 years, and 1.4 +/- 1.8 at 10 years. Ocular attacks were still observed in 33 eyes (45%) of 21 patients (54%) with BD even after 10 years. Final BCVA in 42 eyes (56%) became lower than 0.5. The major reasons for poor visual prognosis were macular atrophy (41%) and chorioretinal atrophy (26%). CONCLUSIONS: The decline of BVCA continued, and nearly half the patients still suffered from ocular attacks at 10 years after the onset of ocular BD.

PURPOSE: We report a case of Candida albicans endophthalmitis with subretinal abscess formation in a patient who underwent liver transplantation. METHODS: Case report. RESULTS: A 51-year-old Japanese woman complained of deep pain and ciliary injection in her right eye. Three months prior, the patient had undergone liver transplantation for cirrhosis caused by hepatitis C. A slit-lamp examination revealed intense anterior chamber inflammation with hypopyon and fundoscopy showed a yellowish-white subretinal mass lesion in the inferior peripheral fundus. Systemic and topical antibiotics did not prevent further progression of the infection. The patient underwent pars plana vitrectomy treatment three times and a histopathological study of a vitreous specimen revealed C. albicans to be the causative organism. CONCLUSION: A subretinal abscess, previously reported in Nocardia, Pseudomonas, Staphylococcus, and Aspergillus infection cases, can also occur in patients infected with Candida. Therefore, Candida infection should be considered as a potential cause of subretinal abscess in organ transplant recipients.

PURPOSE: Toll-like receptors (TLRs) are pattern-recognition receptors that play an important role in innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR4 recognizes lipopolysaccharides of Gram-negative bacteria. Genetic polymorphisms within the TLR4 gene have been reported to be associated with various inflammatory diseases; therefore, TLR4 appears to be a susceptibility gene for sarcoidosis. Although sarcoidosis has various clinical manifestations, its association with uveitis is more common in Japan than in other countries. The aim of this study was to investigate whether TLR4 polymorphisms were associated with sarcoidosis-related uveitis in a Japanese population. METHODS: Two hundred twenty-three patients with sarcoidosis and 206 healthy control subjects were recruited at seven sites in Japan. Eight single-nucleotide polymorphisms (SNPs) in TLR4 were genotyped with a TaqMan assay, and allelic and phenotypic diversity were assessed in affected and control subjects. RESULTS: We found no association with susceptibility to sarcoid-related uveitis for any of the SNPs analyzed. Strong linkage disequilibrium was observed among all the SNPs analyzed (D'>/=0.78), which were located in one haplotype block. CONCLUSION: TLR4 polymorphisms do not play an important role in the development of uveitis in Japanese patients with sarcoidosis.

PURPOSE: To analyse clinical outcomes of trabeculectomy with mitomycin C (MMC) in eyes with uveitic glaucoma (UG) with inactive uveitis and compare them to those in eyes with primary open-angle glaucoma (POAG). DESIGN: Retrospective non-randomized comparative interventional case series. METHODS: A total of 53 eyes with UG and 80 eyes with POAG that received MMC trabeculectomy as an initial ocular surgery with average follow-up of 5.4 years were reviewed retrospectively. The intraocular pressure (IOP) control and persistence of filtering bleb were analysed using the Kaplan-Meier life-table method based on two definitions of successful IOP control, ie complete success (IOP<or=15 mm Hg without anti-glaucoma medications) and qualified success (IOP<or=15 mm Hg with topical anti-glaucoma medications). The incidences of postoperative complications were also examined. RESULTS: Complete success rate for postoperative IOP control at 5 years after trabeculectomy was 57.1+/-7.5% (mean+/-SE) in UG, being comparable to that in POAG (53.7+/-6.1%), and those of qualified success was 64.7+/-7.0 and 65.9+/-5.5% (P=0.60 and 0.53) respectively. Persistence of filtrating blebs was shorter in UG than in POAG (P=0.031). Postoperative inflammation in UG was associated with worse postoperative IOP control and loss of filtering bleb (P=0.027 and 0.021). Postoperative long-standing ocular hypotony was more frequent in UG (P=0.0063). CONCLUSIONS: An MMC trabeculectomy for UG with inactive uveitis as an initial ocular surgery had IOP control comparable to that for POAG, suggesting that pre-existing uveitis itself is not a risk factor for failure of a filtering surgery.

BACKGROUND AND OBJECTIVES: It is essential to have a clear understanding of the present condition of cardiopulmonary resuscitation (CPR) training courses and the associated problems. The present study was performed to identify the current conditions of CPR training in Japanese high schools and the attitudes of students toward CPR. METHODS AND RESULTS: We distributed a questionnaire study to the students of 12 cooperating high schools regarding their willingness to perform CPR in 5 hypothetical scenarios of cardiopulmonary arrest: a stranger, a trauma patient, a child, an elderly person, and a relative. Between February and March 2006, a total of 3316 questionnaires were completed. Across all scenarios, only 27% of respondents from general high schools reported willingness to perform chest compression (CC) plus mouth-to-mouth ventilation (MMV), and 31% reported willingness to perform CC alone. Fifty-nine percent of students had previous CPR training, and only 35% were willing to perform CC plus MMV. Most of the respondents who reported that they would decline to perform full CPR, stated that poor knowledge and/or fear of incomplete performance of CPR were deciding factors. CONCLUSIONS: Japanese high school students are reluctant to perform CC plus MMV, despite having received training. The present educational system in Japan has limitations in encouraging high school students to perform CC plus MMV.

目的:内因性真菌性眼内炎を発症した後,自傷行為が関与したと思われる角膜潰瘍,眼内炎を繰り返し,ミュンヒハウゼン症候群が疑われた症例を経験したので報告する.症例:44歳,女性.2000年10月に右眼に内因性真菌性眼内炎を発症,硝子体切除術で軽快したが,その後,医学的に説明のつかない角膜潰瘍および眼内炎を繰り返して失明に至った.経過中,自傷行為の物的証拠が発見され,術後に繰り返された角膜潰瘍および眼内炎には自傷行為が関与していると考えられた.精神科医のカルテ診察によりミュンヒハウゼン症候群が疑われたが,患者は精神科受診を拒否し続けた.結論:このような症例に対しては,眼科的治療だけでなく精神科的ケアをも念頭におき対応する必要があると考えられた(著者抄録)

PURPOSE: To report recurrent fungal endophthalmitis which developed after endogenous fungal endophthalmitis. The patient was suspected to be suffering from Munchausen syndrome. CASE: A 44-year-old woman contracted endogenous fungal endophthalmitis in her right eye in October 2000. After the endophthalmitis was healed by vitrectomy, corneal ulcer and endophthalmitis repeatedly occurred in the eye from an unknown cause. The patient finally lost the sight of her right eye. The corneal ulcer and endophthalmitis resulted from self-injury for which we found material evidence in the course of the treatment. Munchausen's syndrome was suspected but the patient persistently refused to see a psychiatrist. CONCLUSION: We must be prepared to provide mental and psychiatric care in addition to ophthalmological treatment for such a case.

Purpose: To report elevation of serum creatine phosphokinase (CK) following systemic colchicine in 6 cases of Behçet's disease. Cases: This study comprised 5 males and one female. The ages ranged from 28 to 64 years, average 44 yeas. Behçet's disease was of complete type in 4 cases and incomplete in 2. All the patients were receiving 1 mg of peroral colchicine. Five were receiving cyclosporin. Two were reiving anti-TNFα. Results: Patients complained of symptoms simulating myopathy, including weakness of muscles, myalgia, numbness, and loss of body weight. These symptoms disappeared after decrease or withdrawal of colchicine within a few weeks. Conclusion: Myopathy is a liability during treatment of Behçet's disease with peroral colchicine. Its early detection is advocated through attention to subjective symptoms and repeated hematological examination.

PURPOSE: It is still unknown which metabolite of isopropyl unoprostone is responsible for reducing intraocular pressure. This study was carried out to measure intraocular metabolites of isopropyl unoprostone in the aqueous humor of primate and human eyes. METHODS: Nine monkeys were randomly divided into three groups, all of which received isopropyl unoprostone. In group I, the drug was scheduled to be instilled at 0 hr, in group II at 1 hr, and in group III at 2 hr, prior to aqueous humor aspiration in order to determine metabolite concentration. Furthermore, 27 patients scheduled for cataract surgery and intraocular lens implantation were divided into five groups that received isopropyl unoprostone. In group A, the drug was scheduled to be instilled at 0 hr, in group B at 1 hr, in group C at 2 hr, in group D at 3 hr, and in group E at 4 hr, prior to surgery. At the beginning of the operation, the aqueous humor was aspirated. Metabolites of isopropyl unoprostone in the aqueous humor were determined by high-performance liquid chromatography. RESULTS: M1 (3-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]propionic acid) (unoprostone free acid) and M2 ((Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]hept-5-enoic acid), an intraocular oxidized metabolite of isopropyl unoprostone, were measured. M1:M2 in monkeys was respectively 0:0 ng/ml in group I, 150.2 +/- 45.1:9.5 +/- 1.7 (p < 0.05) in group II, and 74.6 +/- 31.4:19.2 +/- 5.3 (p < 0.01) in group III. M1:M2 in humans was respectively 0:0 ng/ml in group A, 50.6 +/- 22.3:3.2 +/- 1.3 (p < 0.05) in group B, 125.0 +/- 23.1:12.2 +/- 3.4 (p < 0.001) in group C, 144.9 +/- 33.8:24.5 +/- 6.2 (p < 0.01) in group D, and 56.7 +/- 21.5:18.7 +/- 5.3 (p < 0.05) in group E. CONCLUSIONS: A free acid of isopropyl unoprostone is the major intraocular metabolite of isopropyl unoprostone that is expected to act on target tissues in the eyes of both monkeys and humans.

Purpose: To report the recent incidence of endogenous uveitis at the University of Tokyo Hospital. Cases and Method: This retrospective study involved 311 patients who were diagnosed with intraocular inflammation during 3 years through 2003. The clinical records were statistically analysed. Results: The 311 patients comprised 2.7% of new outpatients in the same period. There were 136 males (43.7%) and 175 females (56.3%). Their ages averaged 49.5±17.7 years. The series comprised anterior uveitis 153 cases (49.2%), panuveitis 118 cases (37.9%), posterior uveitis 35 cases (11.3%), and intermediate uveitis 5 cases (1.6%). Classification was possible in 154 cases (49.5%). The most frequent entity was Behçet disease 9.3%, and was followed by sarcoidosis 8.0%, Vogt-Koyanagi-Harada disease 6.1%, and glaucomatocyclitis crisis 5.1%. Conclusion: Behçet disease is reportedly decreasing in Japan. Our present survey shows that it is still the most frequent entity among ocular inflammations.

We evaluated 41 eyes of 27 patients of Behçet disease regarding acute attacks after cataract surgery. The series comprised 32 eyes of 22 males and 9 eyes of 5 females. Their ages ranged from 15 to 95 years, average 46.0±13.7 years. Simultaneous insertion of intraocular lens was performed in 39 eyes. All the cases were followed up longer than 6 months before and 12 months after surgery. Best visual acuity during 6 months after surgery was better than that before surgery in 30 eyes (79%), unchanged in 6 eyes (16%), and worse in 2 eyes (5%). The frequency of acute attacks in the anterior chamber or the fundus was statistically independent of attacks during 6 or 3 postoperative months, use of colchicine, corticosteroid, or immunosuppressive agents. These findings may serve as a guideline in the timing of cataract surgery in patients of Behçet disease.

AIMS: To characterise a novel strain of adenovirus (Ad) type Ad8 (genome type Ad8I) involved in an epidemic keratoconjunctivitis (EKC) outbreak in Hiroshima city using serological testing and sequence analysis of the fibre and hexon gene. METHODS: A neutralisation test (NT) was performed in microtitre plates containing a confluent monolayer of A549 cells using 100 tissue culture infectious doses of virus and type specific antisera. The haemagglutination inhibition test was also carried out in microtitre plates with rat erythrocytes using four haemagglutination units of virus and twofold dilutions of serum. The fibre gene was sequenced by generating overlapping polymerase chain reaction products or by direct sequencing of genomic DNA. Primer selection was based on alignment of the fibre genes of human adenovirus serotypes Ad8, Ad19, Ad37, Ad9, and Ad15 available from Gene Bank. RESULTS: The virus strain was specifically neutralised by anti-Ad8 antibodies, although there was a major crossreaction with anti-Ad9 antibodies. Haemagglutination was equally inhibited by anti-Ad8 and anti-Ad9 antibodies. The predicted amino acid sequences of the hypervariable regions (HVRs) of the Ad8I hexon gene showed higher homology with Ad9 (83.3%) than with Ad8 (62.0%). However, the Ad8I fibre knob was more homologous to Ad8 (94.4%) than to Ad9 (91.6%). CONCLUSIONS: Ad8I is a unique strain of adenovirus because of its lower genomic homology with Ad8, major crossreactivity with Ad9 in NT, and mixed genetic organisation of HVRs of the hexon gene. These factors may have enabled the virus to circumvent acquired immunity, resulting in the outbreak.

OBJECTIVE: To compare clinical findings in patients with Behçet's disease (BD) seen in 2 different decades (1980s and 1990s) to determine if there has been a shift toward the appearance of less severe disease. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Two hundred forty patients with uveitis caused by BD who had their first visit and at least a 4-month follow-up at the uveitis clinic of University of Tokyo Hospital between January 1980 and December 1999 were enrolled. METHODS: Patients were divided into 2 groups according to the date of the first visit. The clinical profiles were then compared between the 1980s group (133 patients, observed for 33.5+/-26.4 months) and the 1990s group (107 patients, observed for 46.9+/-32.6 months). MAIN OUTCOME MEASURES: Number of ocular attacks per year, visual outcomes, and the percentage of patients who had cyclosporine or cyclophosphamide therapy. RESULTS: Age of onset, type of inflammation, incidence of secondary glaucoma, and surgical history of glaucoma and cataract did not differ between the 1980s and the 1990s. Conversely, in patients in the 1990s, the number of ocular attacks per year and the percentage of patients with cyclosporine or cyclophosphamide therapy decreased significantly. Furthermore, the percentage of eyes with good visual acuity (VA) (?20/30) increased, and the percentage of eyes with poor VA (<20/200) decreased significantly at both the first and the last examinations. There was a trend for less bilateral disease and fewer genital ulcers in the 1990s as well. CONCLUSIONS: Through a study of Japanese patients, we confirmed that the clinical outcomes of BD, especially judging by the number of ocular attacks per year and VA, indeed improved during the 1990s.

BACKGROUND: To investigate the effects of a new biodegradable dexamethasone drug delivery system, Surodex, in two experimental intraocular inflammation models; endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU). METHODS: Surodex was inserted into the right anterior chambers (ACs) of rats. In the EIU experiment, protein concentration, cell infiltration, and myeloperoxidase (MPO) activity in the aqueous humor were measured 24 h after injection. Eyes were evaluated histopathologically. In the EAU experiment, firstly, Surodex was administered at various days after immunization. Then, Surodex was administered on day 9 and eyes were evaluated histopathologically. Intraocular cytokine levels (IFN-gamma and IL-4) were investigated. RESULTS: In the EIU experiments, eyes with Surodex exhibited significantly reduced inflammation compared with contralateral controls. Protein concentrations, cell infiltrations, as well as MPO activity were reduced. In the EAU experiments, all rats with Surodex given on days 0 or 7 showed no or significantly reduced inflammation in both eyes. Rats treated on day 12 developed reduced inflammation only in the treated eyes. IFN-gamma levels were significantly lower in the eyes with Surodex, whereas IL-4 was not detectable. CONCLUSIONS: This new, biodegradable corticosteroid drug-delivery system is highly effective in suppressing intraocular inflammation, and should be a useful tool to manage uveitis in humans.

BACKGROUND: Chemokines are a family of chemoattractants of leukocytes that play a critical role for leukocyte recruitment in various inflammatory diseases. The purpose of this study is to investigate the involvement of chemokines, interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in the peripheral blood, with a special reference to disease activities of the patients with Behçet's disease (BD). METHODS: The study population consisted of totally 55 patients with BD who had panuveitis (20 patients with active BD, 35 patients with inactive BD) as well as 19 healthy volunteers as control. Disease activity was defined according to the existence of ocular inflammation. IL-8 and MCP-1 concentration levels in the plasma and whole-blood samples were measured by enzyme-linked immunosorbent assay. Whole-blood samples were obtained by lysing cell membranes of peripheral blood cells. RESULTS: Most of the plasma IL-8 samples were below the detectable limit. Whole-blood IL-8 levels were readily measured. The levels in the patients with active BD were significantly higher than the other two groups. The patients with active and inactive BD showed higher plasma and whole-blood levels of MCP-1 than controls. The plasma and whole-blood MCP-1 levels of the samples collected at the same time showed a linear correlation. CONCLUSION: A close relationship was found to exist between the cell-associated IL-8 and the disease activity, while a persistent role of MCP-1 was observed in BD. Measuring the whole-blood levels of chemokines is useful for monitoring the disease activity.

AIMS: To investigate the genetic differences among the strains of adenovirus type 8 (Ad8) circulating in Hiroshima city, Japan, and to study their circulation pattern. METHODS: One hundred and twenty nine strains of adenovirus type 8 (Ad8) were isolated in Hiroshima City over a 15 year period (1983-97) from patients with keratoconjunctivitis, and analysed with six restriction enzymes-BamHI, HindIII, PstI, SacI, SalI, and SmaI-to investigate possible relations among the isolates and their genetic variability. Seven hypervariable regions of the hexon gene that carry the type specific epitope were also sequenced to investigate the variation among the genome types. RESULTS: Restriction endonuclease analyses yielded three known genome types (Ad8A, 13 samples; Ad8B, seven samples; and Ad8E, 35 samples) and a novel genome type (Ad8I, 74 samples). Ad8A, Ad8B, and Ad8E were closely related, with 96% homology, whereas Ad8I had only 71% homology. Ad8A, Ad8B, and Ad8E shared 91.8% and 96.4% homology with regard to their amino acid and nucleotide sequences, respectively, with the isolate 1127 (accession no X74663). However, when compared with Ad8A, Ad8B, Ad8E, and isolate 1127, Ad8I shared only 62.7% and 69.9% homology with regard to amino acid and nucleotide sequences, respectively. Ad8A, Ad8B, and Ad8E had a unique 31 amino acid deletion in the hypervariable region 1 of the hexon gene, whereas Ad8I had a 33 residue deletion. The Ad8E strain that circulated from 1984 to 1995 was stable among the study population. Ad8I was isolated from an outbreak of epidemic keratoconjunctivitis in 1995 and was also isolated from sporadic cases until 1997. CONCLUSIONS: These results confirmed that genetic variability occurs in Ad8 in the microenvironment and revealed the emergence of a new genome type (Ad8I).

We examined the effect of a monoclonal antibody (mAb) against interferon (IFN)-inducible protein 10 (IP-10)/CXCL10 on the development of experimental autoimmune encephalomyelitis (EAE) in rats induced by injecting xenogeneic brain homogenates into footpads. Treatment with neutralizing mAb against CXCL10 exacerbated EAE with increased infiltrating CD4+ cells in the central nervous system. Furthermore, the exacerbation by the mAb treatment was accompanied by less enlarged draining popliteal lymph nodes (LN) in parallel with cell number compared with those of EAE rats treated with control mAb, whereas other lymphoid organs such as the spleen and thymus were not significantly different between rats treated with anti-CXCL10 and the control mAb. Induction of gene expression of CXCL9/Mig and CXCL10 and their receptor CXCR3 was confirmed in the draining LN in EAE rats. Induction of the third CXCR3 ligand, CXCL11/I-TAC was not seen in the draining LN, whereas all three CXCR3 ligands and CXCR3 itself were markedly detected in the spinal cords following the development of EAE. These findings suggest that CXCL10 produced in the LN plays a specific inhibitory role in the development of Th1-mediated diseases such as EAE by holding sensitized and activated Th1s expressing CXCR3 in the draining LN.

Background: Frosted branch angiitis usually occurs in children, and has a good prognosis. We report two cases of unilateral frosted branch angiitis in adults. Both had poor visual outcomes because of associated central retinal vein occlusion and neovascular glaucoma. Cases: Case 1 was a 36-year-old woman. Almost all retinal veins and some retinal arteries showed vasculitis in her right eye, and veins were slightly dilated and sheathed. Case 2 was a 23-year-old woman. Angle hypopyon was observed in her left eye. Retinal veins were dilated, meandering, and sheathed. Retinal hemorrhages were also observed. In both cases, after systemic steroid therapy the retinal vasculitis gradually decreased, but central retinal vein occlusions gradually developed. Despite systemic administration of urokinase and panretinal photocoagulation, neovascular glaucoma developed, and visual acuity diminished in both cases. Conclusions: Two cases of frosted branch angiitis complicated by retinal vein occlusion are reported. Careful observation of retinal blood flow is necessary in frosted branch angiitis in adults. (C) 2001 Japanese Ophthalmological Society.

PURPOSE: To develop a new detection and typing method of oculopathogenic strains of subgenus D adenoviruses directly from conjunctival scrapings by a combination of polymerase chain reaction (PCR) and restriction enzyme analysis (REA). METHODS: A new PCR method using primer pairs of AF2/AR2, which are specific for the fiber genes, were developed to amplify 1150-bp products from nine oculopathogenic prototypes of subgenus D adenoviruses. Amplicons were cleaved with three restriction enzymes: DdeI, HinfI, and RsaI. Clinical specimens of 102 conjunctival scrapings were also evaluated by this PCR method. Restriction patterns of prototypes were used for the typing of clinical samples. Detection limit was determined by the PCR amplification of a known amount of purified adenovirus serotype 8 DNA. RESULTS: A novel PCR method based on the fiber genes allowed the amplification of nine oculopathogenic serotypes of subgenus D (Ad8, Ad9, Ad15, Ad17, Ad19, Ad22, Ad28, Ad37, and Ad39). As little as 38.4 fg of adenovirus type 8 could be detected by this method. Positive results were obtained from 48 of 102 samples (47%) by both hexon- and fiber-based PCR, whereas only 29 of 102 (28.4%) yielded positive results by culture isolation/neutralization test (NT). All positive specimens (29 samples) of culture isolation and PCR-RFLP methods showed positive results by our new fiber-based PCR method, and no positive products were detected from other subgenus of adenovirus or nonadenoviral DNA. CONCLUSIONS: A newly developed fiber-based PCR-REA method for the detection and typing of adenoviruses is faster than any former PCR methods. This all-in-1-day detection and typing method will be quite useful to the rapid diagnosis of subgenus D adenovirus infection.

BACKGROUND: Frosted retinal angiitis usually occurs in children, and has a good prognosis. We report two cases of unilateral frosted retinal angiitis in adults. They resulted in visual degradation because of associated central retinal vein occlusion and neovascular glaucoma. CASES: Case 1 was a 36-year-old female. Almost all retinal veins and some retinal arteries had vasculitis in her right eye, and the veins were slightly dilated and sheathed. Case 2 was a 23-year-old female. Angle hypopyon was observed in her left eye. Retinal veins were dilated, meandered, and sheathed. Retinal hemorrhages were also observed. In both cases, systemic steroid therapy gradually improved the retinal vasculitis, but central retinal vein occlusions gradually developed, and in spite of systemic administration of urokinase and panretinal photocoagulation, neovascular glaucoma developed, and visual acuity became degraded in both cases. CONCLUSION: Two cases of frosted retinal angiitis complicated by retinal vein occlusion were reported. Careful observation of retinal blood flow is necessary in frosted retinal angiitis in adults.

Purpose: To investigate effects of anti-αβT cell receptor monoclonal antibody (antiαβTcR mAb) on corneal allograft rejection after penetrating keraloplasty (PK) in rats. Methods: We performed PK using Fischer rats (F344) as donors and Lewis rats (Lew/Crj) as recipients. Both donor and recipientcomeas were excised with a 3. 0 mm trephine and they were sutured with 11-0 nylon. The rats were divided into 2 groups: rats treated with anti-αβTcR mAb (Treated group, n=20) and those without antibody treatment (Control group, n=14). The antibody was administered intraperitoneally2 mg/kg daily from 0 to 12th day after PK in Treated group. The corneal grafts were examined by an operating microscope. The corneal grafts were defined to be rejected when they became so opaque that the pupil margins could not be discerned. The corneas were excised 14 days after PK and they were examined histologically. Results: In the Control group, all of the corneal grafts were rejected in 14 days after PK. In the Treated group, on the contrary, no allograft rejection occurred. Histological examination demonstrated marked lymphocyte infiltration, stromal edema and vessel invasion into the grafts in the Control group. In the Treated group, however, lymphocyte infiltration and vessel invasion were mild and no stromal edema was observed. Conclusion: Treatment with anti-αβTcR mAb is effective in suppression of corneal allograft rejection.