Hiroki Imai

Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation

PURPOSE To report cases of Blau syndrome with a CARD15/Nod2 mutation. DESIGN Observational and interventional case report. PARTICIPANTS A 10-year-old Japanese boy (proband) was seen with secondary angle-closure glaucoma (iris bombe), uveitis, skin rashes, and camptodactyly. His sister had posterior synechia and camptodactyly. She had iritis in both eyes during the follow-up period. Both eyes of the father were phthisical because of granulomatous uveitis and secondary glaucoma. The father also had camptodactyly. METHODS Surgery was performed to release the iris bombe. Ocular inflammation was treated by topical and systemic steroids. Biopsy specimens from the skin rash and from the iris (from iridectomy) were obtained from the proband. Genetic analyses were performed on the proband, his sister, and their mother for a CARD15/Nod2 mutation. MAIN OUTCOME MEASURES Clinical features, pathologic findings of the skin and iris specimens, and genetic analysis of the CARD15/Nod2 gene. RESULTS Phacoemulsification, intraocular lens implantation, and peripheral iridectomy released the iris bombe. The biopsy specimen from the skin rash showed noncaseating, granulomatous infiltration with epithelioid cells and lymphocytes. The iridectomy specimen showed nonspecific inflammation. Systemic and topical steroid therapy partly reduced the ocular inflammation. Genetic analyses showed that the proband and his sister had an R334W mutation in the CARD15/Nod2 gene, but their mother was of the wild type. CONCLUSIONS Blau syndrome should be considered in the differential diagnosis of childhood uveitis. Genetic analysis of the CARD15/Nod2 gene is helpful in the diagnosis.

Microperimetric determination of retinal sensitivity in areas of dissociated optic nerve fiber layer following internal limiting membrane peeling

PurposeTo investigate the effects of a dissociated optic nerve fiber layer (DONFL) on retinal sensitivity.MethodsThe medical records of 17 eyes with an idiopathic macular hole that underwent vitrectomy and internal limiting membrane (ILM) peeling were examined. All patients underwent a complete ophthalmic examination, color fundus photography, and argon blue-filter photography to determine whether a DONFL was present. The retinal function was assessed by comparing the mean retinal sensitivities in the DONFL area to those in the surrounding normal retina by static microperimetry >3 months after the surgery. The retinal sensitivities of eight regions nearest the fovea and all at the same distance from it were determined in all patients. We divided the retinal sensitivities in the two areas, that is, inside and outside the area of the DONFL, and compared each mean value.ResultsFollowing the initial vitrectomy, the macular holes of all eyes were closed. The mean retinal sensitivities in the area of the DONFL did not differ significantly from those in the surrounding areas (P = 0.60).ConclusionsDONFL associated with ILM peeling does not alter retinal function in the area of the DONFL as it does with a nerve fiber layer defect.

Performance evaluation of a robust method for mathematical expression recognition

We proposed two methods for mathematical expression recognition. One is based on projection profile cutting and the other uses top-down and bottom-up strategies to analyze the two-dimensional structure of expressions. The paper describes the improvement of the latter method in terms of structural analysis robustness and application to matrix recognition. To evaluate the performance of our method, intensive experiments were carried out on a large variety of mathematical expression images which were collected from many mathematical journals.

Cytokine and Molecular Analyses of Intraocular Lymphoma

Purpose: The authors investigate the efficacy of using the cytokine levels and clonal heavy-chain immunoglobulin (IgH) gene rearrangements in the vitreous as adjunctive tools to diagnose intraocular lymphoma (IOL). Methods: The IL-10 and IL-6 levels and IgH gene rearrangements were analyzed in vitreous samples from 8 cases of IOL and in 14 uveitis patients. Results: The level of IL-10 with an IL-10/IL-6 ratio > 1 was significantly higher in all eyes with IOL. B-cell monoclonality was detected in only 5 of 8 eyes with IOL. Conclusions: The measurements of the levels of cytokines are valuable as a reliable biomarker.

μ-Crystallin, New Candidate Protein in Endotoxin-Induced Uveitis

PURPOSE. micro-Crystallin (CRYM) is a major taxon-specific lens protein. The purpose of this study was to investigate the function of CRYM in eyes of mice with endotoxin-induced uveitis (EIU). METHODS. EIU was induced by an injection of a lipopolysaccharide (LPS) into the footpad of male C57BL/6J, CRYM knockout (CRYM(-/-)), and wild-type (CRYM(+/+)) mice. The expression of CRYM in the iris-ciliary body (ICB) was investigated by Western blot analyses and real-time RT-PCR at 12 hours and 1, 3, and 5 days after the LPS injection. The number of cells that had infiltrated the anterior chamber (AC) of the CRYM(+/+) mice was compared to that in the CRYM(-/-) mice at 1, 3, 5, and 7 days. The expressions of the mRNA of interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, and granulocyte macrophage-colony stimulating factor (GM-CSF) in the ICB of the two groups of mice were compared. RESULTS. The mRNA of CRYM was upregulated at 12 hours after LPS injection, and CRYM protein increased at 3 days. The number of inflammatory cells in the AC of the CRYM(-/-) mice was not significantly different on day 1 from that in the CRYM(+/+) mice, but was significantly lower (17.9 +/- 1.6 vs. 27.1 +/- 2.4 cells/section) on day 5. Expression of the mRNA of IL-1alpha and -6 in the CRYM(-/-) mice was significantly lower than that in the CRYM(+/+) mice on day 5. CONCLUSIONS. CRYM plays an important role in the development of the second peak of murine EIU.

A case of Bardet-Biedl syndrome complicated with intracranial hypertension in a Japanese child.

Bardet-Biedl syndrome (BBS) is a rare heterogeneous autosomal recessive disorder characterized by rod-cone dystrophy, postaxial polydactyly, truncal obesity, hypogonadism, learning disability, and renal anomaly that are caused by ciliary dysfunction. 16 genes have been associated with the BBS phenotype. Although recent pathophysiological studies using animal models have shown that ciliary dysfunction may induce hydrocephalus, there have been no reports of BBS with intracranial hypertension. We here describe a 9-year-old Japanese girl who was diagnosed as having BBS and later received renal transplantation due to chronic renal failure. She also exhibited intracranial hypertension, including papilledema and increased intrathecal pressure (260-300 mmH2O), but her brain magnetic resonance imaging was normal. No genetic abnormalities were detected by DNA chip analysis or exome sequencing. Her papilledema improved following administration of acetazolamide. This is the first report of a case of BBS complicated with intracranial hypertension and its treatment.

Cancer-associated retinopathy in a patient with seminoma.

PURPOSE The purpose of this study was to report our findings on a patient with cancer-associated retinopathy who had seminoma. METHODS A 43-year-old man, who had been diagnosed with Stage 1 seminoma, complained of blurred vision. Fundus examination revealed attenuated retinal arteries, mild optic disk pallor, and a thinning of the outer nuclear layer. Ring scotomas were found in the visual fields of both eyes. The amplitudes of the electroretinograms were moderately reduced. The patients serum was analyzed for antibodies. RESULTS Antibodies against recoverin, Hu, and Ma-2 antigens were not detected. However, Western blots of the serum detected 2 bands at 41 and 64 kDa. The 41-kDa band was an anti-retina-specific antibody. Immunoreactivity was identified in the photoreceptor layer of mice retinas. From these findings, we diagnosed the patient with cancer-associated retinopathy. The visual functions remained stable after the removal of the primary lesion at an early stage, treatment with steroids, and intravenous immunoglobulin. CONCLUSION This is the first case of cancer-associated retinopathy because of seminoma. The progression of the disease was reduced by removing the seminoma at an early stage, treatment with steroids, and intravenous immunoglobulin.