Long-term outcome in corneal endotheliitis with molecular detection of herpes simplex virus 1 and human herpes virus 6: a case report.

BACKGROUND: Human herpesvirus 6B (HHV-6B) is known to cause exanthema subitem and has been detected in various ocular diseases, including keratitis, uveitis, optic neuritis, and endophthalmitis; however, the long-term outcome after the reactivation of HHV-6B has not been well-addressed. Sugita et al. previously reported the concomitant presence of HHV-6B with herpes simplex virus-1 (HSV-1) in the aqueous fluid at the onset of corneal endotheliitis. We focused on the same patient with corneal endotheliitis, in whom both HSV-1 and HHV-6B sequences were observed, and reported the clinical course and long-term outcomes. CASE PRESENTATION: A 64-year-old woman was referred to our center for visual disturbances in the left eye. Her best-corrected visual acuity in the left eye was 0.5 and the left intraocular pressure was elevated to 33 mmHg. Mid-sized keratic precipitates and 2+ cells were observed in the anterior chamber with corneal endothelial edema and reduction of the corneal endothelial cell density to 1828 cells/mm2. The patient was diagnosed with corneal endotheliitis with increased intraocular pressure. Polymerase chain reaction analysis revealed the concomitant presence of both HSV-1 and HHV-6B sequences in the left aqueous fluid. After treatment with oral valacyclovir and topical betamethasone, her intraocular inflammation gradually improved and has not recurred at 12 years after corneal endotheliitis onset although corneal opacity remained. CONCLUSIONS: Reactivation of HHV-6B infection might be associated with HSV-1 corneal endotheliitis; however, no serious late sequelae occurred after appropriate treatment for HSV-1 infection in this immunocompetent host.

Multiplex Solid-Phase Real-Time Polymerase Chain Reaction without DNA Extraction: A Rapid Intraoperative Diagnosis Using Microvolumes.

PURPOSE: Current polymerase chain reaction (PCR) methods for the diagnosis of infections are time consuming and require large sample volume and skilled technicians. We developed a novel, easy-to-use, and rapid (processing time, 1 minute; total time, 33 minutes) multiplex real-time PCR test (Direct Strip PCR) that did not require DNA extraction to detect 9 pathogens that could cause uveitis in 20-µl samples. DESIGN: Multicenter prospective evaluation of a diagnostic PCR test. PARTICIPANTS: A total of 511 participants (patients with infectious uveitis and controls) were examined at 18 institutes worldwide. METHODS: After validation, intraocular fluid samples were subjected to etiologic or exclusive diagnosis, including intraoperative rapid diagnosis. MAIN OUTCOME MEASURES: The concordance and correlations between Direct Strip PCR and quantitative PCR (qPCR) results. RESULTS: Direct Strip PCR exhibited rapid detection, good repeatability and specificity, long storage stability, and detection ability equal to that of qPCR. It also showed low interinstitutional variability compared with qPCR, even when PCR beginners used various real-time PCR machines. The Direct Strip PCR for 9 pathogens exhibited high concordance against the qPCR (positive concordance rate, 98.8%-100%; negative concordance rate, 99.8%-100%; κ coefficient, 0.969-1.000; P < 0.001-0.031). Additionally, results obtained using Direct Strip PCR and qPCR were highly correlated (ρ = 0.748; P < 0.001). This assay was used for rapid intraoperative diagnosis. CONCLUSIONS: The Direct Strip PCR test may improve the prognosis of various infectious diseases because it facilitates rapid etiologic evaluation at the first hospital visit and can be used for intraoperative diagnosis.

Gene expression profiling of primary vitreoretinal lymphoma.

The characteristics of tumor cells of primary vitreoretinal lymphoma (PVRL) have not been defined, although researches have shown that most cases are of diffuse large B-cell lymphoma (DLBCL). To determine the subtype and biological characteristics of tumor cells of PVRL, we performed a gene expression profiling analysis. RNA was extracted from the vitreous fluid of 7 PVRL patients and from nodal samples of 10 DLBCL patients: 6 of germinal center B-cell (GCB) type and 4 of activated B-cell (ABC) type determined by Hans' criteria. Six PVRL samples showed gene expression profiles that were similar to each other. The patterns were different from those of the ABC-type nodular DLBCL but relatively close to those of the GCB-type nodular DLBCL. Interestingly, all of the 6 examined PVRL samples had either MYD88L265P or mutation in the immunoreceptor tyrosine-based activation motif (ITAM) region of CD79B. Five PVRL patients with similar gene expression profiles were treated with a standardized regimen: intravitreal administration of methotrexate (MTX) followed by six courses of systemic high doses of MTX. As a result, 2 patients had CD79B mutations and showed early central nervous system (CNS) progression. Patients without CNS progression did not have this mutation. In conclusion, PVRL had unique genetic features: an expression pattern different from ABC-type and relatively close to GCB-type DLBCL. CD79B mutations showed potential to serve as prognostic markers for CNS progression.

Traumatic medial luxation of the triceps brachii tendon with medial subluxation of the elbow joint in a dog.

OBJECTIVE: To describe the surgical reduction of luxation of the triceps brachii tendon in a dog. ANIMAL: One 2.5-year-old 2.58 kg castrated male toy poodle. STUDY DESIGN: Clinical case report. METHODS: The dog displayed intermittent, non-weight bearing lameness of the right forelimb for approximately 18 months before presenting at the veterinary medical center. Medial subluxation of the right elbow joint was detected by palpation. The Campbell test was consistent with an increased range of motion during supination. At ultrasonographic examination, medial luxation of the triceps brachii tendon was noted, whereas collateral ligaments appeared normal. No skeletal deformities were found on radiographs of the right forelimb. The luxation of the triceps brachii tendon was surgically corrected with antirotational suture, a stopper pin, medial retinaculum release, and imbrication of the lateral retinaculum. RESULTS: The right triceps brachii tendon and elbow joint were successfully reduced. Gait returned to normal by 55 days postoperatively. No implant failure or recurrence were observed 3.5 years after surgery. CONCLUSION: Surgical reduction of a luxation of the triceps brachii tendon in a dog resolved lameness and restored the range of motion of the affected elbow, leading to good long-term outcome.

CD79B mutations in primary vitreoretinal lymphoma: Diagnostic and prognostic potential.

OBJECTIVE: Primary vitreoretinal lymphoma (PVRL) is a rare type of lymphoma wherein the lesions are limited to the eyes. PVRL is difficult to diagnose because of the challenges related to obtaining sufficient samples for biopsy. Moreover, PVRL has poor outcomes and often leads to the development of central nervous system (CNS) lesions during its course. Two studies recently reported that approximately 70%-80% of patients with vitreoretinal lymphoma have MYD88L265P , which is frequently mutated in primary CNS lymphoma (PCNSL). PCNSL is closely associated with PVRL. The mutation of CD79BY196 has been also frequently detected in PCNSL. Thus, we examined the mutation in PVRL to clarify its diagnostic and prognostic potential. METHOD: By using direct sequencing and allele-specific polymerase chain reaction, we examined the mutation of CD79BY196 and MYD88L265P in the DNA extracted from the vitreous fluid of 17 patients with PVRL upon diagnosis. We also retrospectively analyzed their prognostic potential for PVRL. RESULTS: Among the included patients, six patients (35%) were found with CD79BY196 mutations. Twelve (71%) patients were positive for MYD88L265P , and six samples from patients with benign uveitis were negative for both mutations. Interestingly, six patients with CD79BY196 mutations developed CNS diseases significantly earlier (16.5 months) than 11 patients with CD79BWT (67 months; P = 0.0135). CONCLUSION: Detecting CD79BY196 in vitreous DNA may contribute to the confirmation of the diagnosis and may have a prognostic potential for patients with PVRL.

Bilateral granulomatous panuveitis in two patients with T-cell type of chronic active Epstein-Barr virus infection.

BACKGROUND: To report 2 cases of bilateral granulomatous panuveitis accompanied by chronic active Epstein-Barr virus infection (CAEBV). CASE PRESENTATION: Case 1 was a 38-year-old man who had a history of bilateral mild panuveitis who was diagnosed with CAEBV. Fifteen months later, a severe bilateral granulomatous panuveitis developed. White infiltrates covered the optic disc and all the retinal vessels of the right eye, and white nodules were seen along the retinal veins and arteries of the left eye. Case 2 was a 34-year-old man with bilateral panuveitis showing mutton-fat keratic precipitates and diffuse vitreous opacity in both eyes. A snow ball-like vitreous opacity was present in the right eye. Systemic investigations revealed the presence of CAEBV. In both cases, a comprehensive polymerase chain reaction (PCR) analyses of the aqueous humor detected significant copy numbers of EBV-DNA. The intraocular inflammation did not respond to steroid, methotrexate, and other immunosuppressive therapies, but was ameliorated after hematopoietic stem cell transplantation with preceding chemotherapy and low-dose total body irradiation in both cases. CONCLUSION: Granulomatous panuveitis can develop in eyes with CAEBV as a primary symptom. Ophthalmologists should rule out CAEBV when EBV-DNA is positive in the intraocular fluids of steroid-resistant panuveitis.

Acquired myopia in Vogt-Koyanagi-Harada disease.

PURPOSE: To analyze the change in refractive error and the axial length of chronic Vogt-Koyanagi-Harada (VKH) disease. METHODS: Medical records of 106 eyes of 54 adult VKH patients were analyzed. The refractive error and the axial length were compared between the baseline (defined as the time point at least 2 weeks after acute stage of VKH) and the final visit. The rate of the eyes with significant myopia progression [defined as refraction change toward myopia > 1 diopter (D)] was examined. The correlation of the degree of sunset glow fundus/choroidal thickness with the change in refractive error was also evaluated. RESULTS: At the final visit, the mean refractive error was more myopic and the axial length was longer than at baseline. Seventeen of the 106 eyes (16.0%) showed significant myopia progression. The mean change in refractive error during a follow-up in these 17 eyes was - 2.7 D (range - 7.5 to - 1.1 D). The axial length data both at baseline and at the final visit were obtained only in 8 eyes. The mean change in axial length during a follow-up in these 8 eyes was 1.3 mm (range 0-3.7 mm). In the cases with myopia progression, sunset glow fundus was more frequent and subfoveal choroid was thinner than those without myopia progression. CONCLUSIONS: Myopia progression as well as increase in axial length occurs in VKH disease. The link between choroidal thinning and axial length elongation in VKH patients gives some insights into axial length increase of pathologic myopia.

Distinguishing Features of Ocular Sarcoidosis in an International Cohort of Uveitis Patients.

PURPOSE: To determine which clinical features distinguish ocular sarcoidosis from other forms of uveitis in an international population and to estimate the sensitivity and specificity of the International Workshop on Ocular Sarcoidosis (IWOS) clinical signs and laboratory tests. DESIGN: Multicenter, retrospective medical record review. PARTICIPANTS: Eight hundred eighty-four patients with uveitis from 19 centers in 12 countries. METHODS: Data collected included suspected cause of uveitis, clinical findings, and laboratory investigations within 6 months of presentation. The IWOS criteria were used to classify patients as having definite (biopsy-proven), presumed (evidence of bilateral hilar lymphadenopathy [BHL] on chest radiograph or CT scan), probable, or possible ocular sarcoidosis. Patients with biopsy positive results or BHL on chest radiograph or CT scan were considered sarcoidosis cases. MAIN OUTCOME MEASURES: Sensitivity and specificity of clinical signs and laboratory investigations for diagnosing ocular sarcoidosis. RESULTS: Of the 884 uveitis patients, 264 (30%) were suspected to have ocular sarcoidosis. One hundred eighty patients (20%) met the IWOS criteria; 98 were definite (biopsy-proven) disease, 69 presumed disease (BHL), 10 probable disease, and 3 possible disease. Among sarcoidosis cases, the most common clinical signs were bilaterality (86%); snowballs or string of pearls (50%); mutton-fat keratic precipitates, iris nodules, or both (46%); and multiple chorioretinal peripheral lesions (45%). Sixty-two percent of sarcoidosis cases had elevated angiotensin converting enzyme or lysozyme and 5% demonstrated abnormal liver enzyme test results. Of the patients suspected of having sarcoidosis, 97 (37%) did not meet the IWOS criteria. CONCLUSIONS: With the exception of BHL, IWOS clinical findings and investigational tests had low sensitivities for diagnosing ocular sarcoidosis. In particular, liver function tests seem to have little usefulness in diagnosing ocular sarcoidosis. Many patients suspected of having sarcoidosis did not fit into the classification system, indicating that the guidelines may need to be reconsidered. Adding novel laboratory tests and using more advanced statistical methods may lead to the development of a more generalizable classification system.

Characteristics of cases needing advanced treatment for intractable Posner-Schlossman syndrome.

BACKGROUND: In Posner-Schlossman syndrome (PSS), which is characterized by recurrent unilateral attacks of ocular hypertension. Surgical treatment is sometimes necessary because intraocular pressure (IOP) cannot be controlled with anti-glaucoma medications. To identify the clinical features of Posner-Schlossman syndrome (PSS) indicative of the need for intraocular pressure (IOP)-controlling surgery. METHODS: This study was a retrospective case-series analysis of the clinical charts of 33 patients diagnosed with PSS, who underwent surgery to control IOP or received medication only. Various clinical factors were compared between the surgical and medication groups. RESULTS: The surgical group had a higher corneal endothelial cell (CEC) density loss (p < 0.05), higher maximum IOP (p < 0.01), greater visual field loss (p < 0.01) and higher positive number for cytomegalovirus (CMV) (p < 0.001) than the non-surgical group. Eighteen of the 33 patients had a high CEC reduction ratio. Of these 18, 16 required glaucoma surgery. CONCLUSIONS: PSS patients with a higher CEC reduction ratio, higher maximum IOP, greater visual field loss and higher positive number for CMV in the aqueous humor tended to be more likely to require progressive treatment, such as glaucoma surgery.

Repair of segmental radial defects in dogs using tailor-made titanium mesh cages with plates combined with calcium phosphate granules and basic fibroblast growth factor-binding ion complex gel.

Repair of large segmental defects of long bones are a tremendous challenge that calls for a novel approach to supporting immediate weight bearing and bone regeneration. This study investigated the functional and biological characteristics of a combination of a tailor-made titanium mesh cage with a plate (tTMCP) with tetrapod-shaped alpha tricalcium phosphate granules (TB) and basic fibroblast growth factor (bFGF)-binding ion complex gel (f-IC gel) to repair 20-mm segmental radial defects in dogs. The defects were created surgically in 18 adult beagle dogs and treated by implantation of tTMCPs with TB with (TB-gel group) or without (TB group) f-IC gel. Each tTMCP fitted the defect well, and all dogs could bear weight on the affected limb immediately after surgery. Dogs were euthanized 4, 8 and 24 weeks after implantation. Histomorphometry showed greater infiltration of new vessels and higher bone union rate in the TB-gel group than in the TB group. The lamellar bone volume and mineral apposition rate did not differ significantly between the groups, indicating that neovascularization may be the primary effect of f-IC gel on bone regeneration. This combination method which is tTMCP combined with TB and f-IC gel, would be useful for the treatment of segmental long bone defects.

High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.

In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m2 ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).

Ocular Behçet's disease is less complicated with allergic disorders. A nationwide survey in Japan.

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. METHODS: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). RESULTS: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. CONCLUSIONS: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.

Co-lyophilized Aspirin with Trehalose Causes Less Injury to Human Gastric Cells and Gastric Mucosa of Rats.

BACKGROUND: Aspirin is one of the most popular NSAIDs worldwide because of its anti-inflammatory and anticoagulant effects, and however, gastrointestinal injury remains a major complication. We previously reported co-lyophilized aspirin/trehalose (Lyo A/T) decreased the aspirin-induced gastric lesions in dogs. AIM: This study investigated the mechanism of gastroprotective effects of trehalose in vitro and in vivo. METHODS: The apoptotic assays were performed in a human gastric carcinoma cell line, which was treated with aspirin, mixed aspirin/trehalose (Mix A/T) or Lyo A/T. Gastric ulcer severity was examined after oral administration of drugs in rats. In addition, the mucosal tissue apoptotic status in drug-treated rats was evaluated. Molecular dynamics simulations and laser Raman spectroscopy were performed in order to examine the molecular properties of Lyo A/T. RESULTS: DNA fragmentation was detected in AGS cells that were treated with aspirin and Mix A/T, but not in the Lyo A/T-treated cells. There were fewer apoptotic cells in the Lyo A/T-treated cells than in the other cells. Gastric injury was reduced in rats that received oral Lyo A/T compared with the others, while PGE2 synthesis was equally decreased in all groups. TUNEL assay and immunohistochemistry of cleaved caspase-3 in the mucosal tissues also revealed that Lyo A/T treatment induced less apoptosis than the others. The Lyo A/T spectrum showed clear differences in several Raman bands compared with that of Mix A/T. CONCLUSIONS: Our data showed that co-lyophilization of aspirin with trehalose reduced gastric injury, potentially through suppression of aspirin-induced mucosal cell apoptosis while retaining its anti-inflammatory effects.

Comparison between Outcomes of Vitrectomy in Granulomatous and Nongranulomatous Uveitis.

PURPOSE: The aim of this study was to compare the outcomes of vitrectomy in granulomatous uveitis and nongranulomatous uveitis insufficiently managed by immunosuppressive therapy. METHODS: Thirty-eight eyes with granulomatous uveitis and 17 eyes with nongranulomatous uveitis that underwent vitrectomy for ocular complications between July 2006 and August 2012 were reviewed retrospectively. Visual acuity and ocular inflammation scores before and 6 months after surgery were compared. Patients treated with vitrectomy alone and those in whom vitrectomy was combined with phacoemulsification were analyzed separately. RESULTS: The mean visual acuity improved significantly both in granulomatous and nongranulomatous uveitis. In granulomatous uveitis, the mean inflammation scores decreased significantly both in the anterior segment and in the posterior segment. In nongranulomatous uveitis, the mean inflammation score in the posterior segment decreased significantly, although it did not change in the anterior segment. CONCLUSION: Vitrectomy was effective for treating ocular complications both in granulomatous uveitis and nongranulomatous uveitis, with favorable outcomes of improved visual acuity and decreased uveitis activity.

Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia.

Severe myopia (defined as spherical equivalent < -6.0 D) is a predominant problem in Asian countries, resulting in substantial morbidity. We performed a meta-analysis of four genome-wide association studies (GWAS), all of East Asian descent totaling 1603 cases and 3427 controls. Two single nucleotide polymorphisms (SNPs) (rs13382811 from ZFHX1B [encoding for ZEB2] and rs6469937 from SNTB1) showed highly suggestive evidence of association with disease (P < 1 × 10(-7)) and were brought forward for replication analysis in a further 1241 severe myopia cases and 3559 controls from a further three independent sample collections. Significant evidence of replication was observed, and both SNP markers surpassed the formal threshold for genome-wide significance upon meta-analysis of both discovery and replication stages (P = 5.79 × 10(-10), per-allele odds ratio (OR) = 1.26 for rs13382811 and P = 2.01 × 10(-9), per-allele OR = 0.79 for rs6469937). The observation at SNTB1 is confirmatory of a very recent GWAS on severe myopia. Both genes were expressed in the human retina, sclera, as well as the retinal pigmented epithelium. In an experimental mouse model for myopia, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for Zfhx1b and Sntb1. These new data advance our understanding of the molecular pathogenesis of severe myopia.

Standardization of Quantitative PCR for Human T-Cell Leukemia Virus Type 1 in Japan: a Collaborative Study.

Quantitative PCR (qPCR) analysis of human T-cell leukemia virus type 1 (HTLV-1) was used to assess the amount of HTLV-1 provirus DNA integrated into the genomic DNA of host blood cells. Accumulating evidence indicates that a high proviral load is one of the risk factors for the development of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, interlaboratory variability in qPCR results makes it difficult to assess the differences in reported proviral loads between laboratories. To remedy this situation, we attempted to minimize discrepancies between laboratories through standardization of HTLV-1 qPCR in a collaborative study. TL-Om1 cells that harbor the HTLV-1 provirus were serially diluted with peripheral blood mononuclear cells to prepare a candidate standard. By statistically evaluating the proviral loads of the standard and those determined using in-house qPCR methods at each laboratory, we determined the relative ratios of the measured values in the laboratories to the theoretical values of the TL-Om1 standard. The relative ratios of the laboratories ranged from 0.84 to 4.45. Next, we corrected the proviral loads of the clinical samples from HTLV-1 carriers using the relative ratio. As expected, the overall differences between the laboratories were reduced by half, from 7.4-fold to 3.8-fold on average, after applying the correction. HTLV-1 qPCR can be standardized using TL-Om1 cells as a standard and by determining the relative ratio of the measured to the theoretical standard values in each laboratory.

Role of IL-22- and TNF-α-producing Th22 cells in uveitis patients with Behcet's disease.

Behçet's disease is a systemic inflammatory disorder with recurrent episodes of oral ulceration, skin lesions, genital ulceration, and intraocular inflammation (uveitis). The intraocular inflammation is strictly associated with Th effector cells. IL-22 is a member of the IL-10 cytokine family that is involved in inflammatory processes. Recently, Th22 cells were identified as a Th cell population that produces IL-22 and TNF-α and are distinct from Th1, Th2, and Th17 cells. In this study, we established Th22-type T cell clones from ocular samples taken from Behçet's disease patients with active uveitis. These clones produced large amounts of IL-22 and TNF-α but not the Th1 cytokine IFN-γ and the Th17 cytokine IL-17. CD4(+) T cells from the peripheral blood of Behçet's disease patients differentiated into Th22 cells in the presence of IL-6 and TNF-α in vitro. The polarized Th22 cell lines produced large amounts of IL-22, and the polarized Th1 and Th17 cells also produced IL-22. In the presence of anti-TNF-α- and anti-IL-6-blocking Abs, Behçet's disease Th22-type T cells failed to produce IL-22. In addition, infliximab-pretreated Th22 cells and Th22-type ocular T cells produced less IL-22 and TNF-α. Moreover, IL-22-producing T cells were isolated from mice with experimental autoimmune uveitis, an animal model of Behçet's disease, and the intraocular T cells from uveitis models produced large amounts of IL-22 in the presence of retinal Ags. Our results suggest that inflammatory cytokines IL-22 and TNF-α may play a key role in the ocular immune response in Behçet's disease.

First case of primary intraocular natural killer t-cell lymphoma.

BACKGROUND: Natural killer cell tumors can be broadly divided by origin into mature-cell and progenitor-cell types. The invasion of nasal-origin natural killer cells into the ophthalmologic field is sometimes observed in patients, but primary ocular natural killer cell tumors are a rare occurrence. CASE PRESENTATION: A 66 year-old woman without any systemic disease presented with blurred vision due to a severe vitreous opacity in the right eye. Flow cytometric analysis of the vitreous fluid suggested a natural killer cell tumor. Moreover, cytologic examination of vitreal and retinal specimens revealed the infiltration of a natural killer cell tumor, while PCR and immunocytochemistry revealed Epstein-Barr virus infection. The results of a gene rearrangement analysis were positive for IGH, while TCR beta chains were all negative. We examined the patient with whole-body magnetic resonance imaging and positron emission tomography, and performed a bone marrow examination. These examinations returned no abnormal results. CONCLUSION: Thorough analysis of vitreal samples is essential when performing vitrectomies for vitreous opacities of unknown cause. Flow cytometric, cytologic, and PCR analysis of vitreal and retinal samples may reveal the presence and cause of severe illness.

[Clinical Survey of Uveitis in Tokyo Medical and Dental University--Comparison between the Periods of 1998-2001 and 2007-2011].

PURPOSE: To investigate a clinical survey of uveitis in Tokyo Medical and Dental University Hospital. SUBJECTS AND METHODS: The clinical records of patients with uveitis who were treated from October 1998 to December 2001 and from January 2007 to December 2011 were reviewed. The clinical results of both periods were compared. RESULTS: A total number of 455 patients (707 eyes) and 1091 patients (1716 eyes) were analyzed in this survey. The mean age of the first period was 45.4, and of the second 50.3 years old. The incidences of sarcoidosis (11.0%, 13.7%) and Vogt-Koyanagi-Harada disease (5.7%, 5.9%) were virtually unchanged in the two series. However, the incidence of Behçet's disease was higher in the first period (10.6%) than in the second (5.8%). The frequency of herpetic iritis (1.8%, 4.7%) and intraocular lymphoma (0.4%, 2.6%)showed apparent increase. Unclassified uveitis decreased from 55.6% to 47.5%. CONCLUSIONS: The etiologies of uveitis have changed with the progress of diagnostic techniques and the establishment of new disease concepts.