Kazuomi Mizuuchi

Choroidal thickening prior to anterior recurrence in patients with Vogt–Koyanagi–Harada disease

Aim To assess choroidal thickness changes associated with anterior segment recurrences in patients with Vogt–Koyanagi–Harada (VKH) disease using enhanced depth imaging optical coherence tomography (EDI-OCT). Methods EDI-OCT images were obtained periodically from 11 patients with VKH disease (22 eyes) who were followed-up due to anterior segment recurrences. Subfoveal choroidal thickness (SCT) values at the following stages were evaluated: (1) during the remission phase, (2) 1 month before detecting the anterior recurrence, (3) during the anterior recurrence and (4) after systemic prednisolone (PSL) treatment leading to remission. In comparison with SCT values in remission as baseline, the changing ratios of SCT were statistically analysed at subsequent three stages. Results The average of the SCT changing ratios compared with the remission phase significantly increased to 1.45±0.11 during anterior segment recurrences (p=0.00044) lacking any funduscopic signs of posterior involvement. Interestingly, the average SCT ratio 1 month before detecting the recurrence had already increased to 1.30±0.08 (p=0.002). After the PSL treatment, the ratio of SCT recovered to 0.95±0.03, which was equivalent to the remission level. However, in patients with their remission SCT values less than 240 µm, the SCT ratio did not increase significantly at any time points evaluated. Conclusions The choroid in eyes with VKH disease thickened in association with the anterior segment recurrence, and this thickening was observed prior to the recurrence. EDI-OCT may be useful for detecting latent choroidal inflammation in VKH disease, whereas it may not for patients with the relatively thin choroid. Trial registration number The trial registration number of the internal review board of Hokkaido University Hospital is 014-0384.

Development and validation of new diagnostic criteria for acute retinal necrosis

PurposeThe purposes of this study are to develop and validate new diagnostic criteria for acute retinal necrosis (ARN) based on the ocular findings, clinical course, and virologic testing of intraocular fluids.Subjects and methodsThe Japanese ARN Study Group, comprising 8 uveitis specialists and 1 statistician, was formed to develop new diagnostic criteria for ARN. The criteria used a combination of clinical features consistent with ARN including 6 early-stage ocular findings ([1a] anterior chamber cells or mutton-fat keratic precipitates; [1b] yellow-white lesion(s) in the peripheral retina [granular or patchy in the early stage, then gradually merging]; [1c] retinal arteritis; [1d] hyperemia of the optic disc; [1e] inflammatory vitreous opacities; and [1f] elevated intraocular pressure), 5 clinical courses ([2a] rapid expansion of the retinal lesion(s) circumferentially, [2b] development of retinal breaks or retinal detachment, [2c] retinal vascular occlusion, [2d] optic atrophy, and [2e] response to antiviral agents), and the results of virologic testing of intraocular fluids by means of either polymerase chain reaction or the Goldmann-Witmer coefficient for herpes simplex virus or varicella zoster virus. Various combinations of findings were analyzed to maximize the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The criteria were then used to retrospectively analyze patients who had been diagnosed as having ARN or control uveitis. Patients were followed at 1 of 7 tertiary uveitis clinics between 2009 and 2011.ResultsAnalysis of the data allowed delineation of 2 levels of diagnosis: “virus-confirmed ARN” (defined as the presence of both early-stage ocular findings 1a and 1b, the presence of any 1 of the 5 clinical courses, and a positive virologic test result) and “virus-unconfirmed ARN” (defined as the presence of 4 of 6 early-stage ocular findings including 1a and 1b, presence of any 2 of the 5 clinical courses, and a negative virologic test result, or when virologic testing had not been performed). The new diagnostic criteria were applied to 45 patients with ARN and 409 patients with control uveitis, resulting in a sensitivity of 0.89, a specificity of 1.00, a PPV of 1.00, and an NPV of 0.99.ConclusionsNew diagnostic criteria for ARN were developed and found to achieve high statistical values.

Two Cases of Subfoveal Choroidal Neovascularization with Tubulointerstitial Nephritis and Uveitis Syndrome

Purpose. Tubulointerstitial nephritis and uveitis (TINU) syndrome usually shows anterior segment intraocular inflammation, but severe posterior segment intraocular inflammation is rarely observed. We report 2 children with TINU syndrome complicated by subfoveal choroidal neovascularization (CNV). Methods. Case reports. Results. Patients were a 12-year-old girl and a 12-year-old boy diagnosed with probable TINU syndrome on the basis of typical ocular findings and high value of urinary β2 microglobulin even though renal biopsy was not performed. The girl showed development of CNV with subretinal macular hemorrhage along with the exacerbation of anterior chamber inflammation in her left eye. Subretinal macular hemorrhage recurred frequently even with oral prednisolone; therefore, intravitreal injection of bevacizumab (IVB) was performed. After IVB, the subretinal proliferative tissue shrunk and subretinal hemorrhage has not recurred for 5 years. The boy showed subretinal hemorrhage from CNV with severe anterior chamber inflammation in his left eye. With oral prednisolone, anterior chamber inflammation and subretinal hemorrhage disappeared, but shrunken subretinal fibrosis in the macula remained. Final visual acuity was poor due to residual subretinal fibrosis in both cases. Conclusions. Tubulointerstitial nephritis and uveitis syndrome has a potential to develop CNV that leads to severe visual loss; therefore, prompt anti-inflammatory therapy is required, and IVB should be regarded as a potential choice of treatment.

HLA-B51 Carriers are Susceptible to Ocular Symptoms of Behçet Disease and the Association between the Two Becomes Stronger towards the East along the Silk Road: A Literature Survey

ABSTRACT Purpose: Behçet disease (BD) is predominantly found between East Asia and the Mediterranean basin along the historic Silk Road. HLA-B51 is known to be strongly associated with BD. We investigated the association between HLA-B51 and the ocular manifestations of BD among various ethnic groups. Methods: A literature survey was conducted, and 18 articles written in English were reviewed. Results: A strong correlation was found between HLA-B51 and ocular lesions in the entire cohort discussed in the reviewed articles (OR = 1.76, p = 0.000057). HLA-B51 was shown to have a strong association with ocular manifestations of BD patients in East-Eurasian (OR = 2.40, p = 0.0030) and Middle-Eurasian (OR = 1.87, p = 0.0045), but not in West-Eurasian (OR = 1.28, p = 0.35) areas. This correlation seemed to become stronger towards the east. Conclusions: A meta-analysis showed that the correlation became stronger towards the east along the Silk Road. The study results may facilitate understanding of the etiology and characteristics of BD.

Choroidal circulation impairment during the anterior recurrence of Vogt-Koyanagi-Harada disease confirmed with indocyanine green angiography and laser speckle flowgraphy.

To assess choroidal inflammation‐related circulatory changes associated with the anterior recurrence of Vogt–Koyanagi–Harada (VKH) disease, using indocyanine green angiography (ICGA) and laser speckle flowgraphy (LSFG).

Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde‐derived advanced glycation end‐product formation

AGEs are permanently modified macromolecule derivatives that form through nonenzymatic glycation of amino groups of proteins. Glycer‐AGEs are highly toxic and play an important role in the pathogenesis of chronic inflammatory diseases. However, the contribution of glycer‐AGEs to the pathogenesis of uveitis is unclear. In this study, we measured serum levels of glycer‐AGEs in 100 patients with endogenous uveitis (22 with HLA‐B27‐associated uveitis, 20 with VKH disease, 14 with Behçets disease, and 44 with sarcoidosis) and 33 healthy volunteers. We then examined the effect of the AGE inhibitor in a mouse model of human endogenous uveitis (EAU) by continuous oral administration of pyridoxamine at 200 or 400 mg/kg/day. Regardless of the etiology, serum glycer‐AGE levels were significantly higher in patients with uveitis than in healthy subjects. Treatment with 400 mg/kg pyridoxamine significantly reduced the clinical and histological severity of EAU and was accompanied by a significant decrease in serum and retinal glycer‐AGE levels and suppression of translocation of NF‐κB p65 into the nucleus of retinal cells. Serum glycer‐AGE levels may therefore serve as a biomarker of human uveitis, as well as systemic inflammation, and may contribute to the progression of uveitis, including diabetic iritis, via the activation of NF‐κB.

A Case of Severe Panuveitis Associated with Psoriasis Vulgaris Successfully Treated with Infliximab

Purpose: Uveitis associated with psoriasis vulgaris is usually seen as an anterior segment inflammation, and it is very rare that the inflammation extends to the posterior segment. We herein report a case of severe panuveitis associated with psoriasis vulgaris presenting as retinal neovascularization, leading to vitreous hemorrhages that were successfully treated with infliximab (IFX). Case Report: A 27-year-old male with psoriasis vulgaris was referred to our hospital due to prolonged severe uveitis OU. He showed a severe anterior chamber inflammation with fibrin formation and total posterior iris synechia OU. With topical corticosteroid treatment, these conditions were relieved for a short time; however, the intraocular inflammation was exacerbated with vitreous hemorrhages caused by retinal neovascularization OS. After the administration of IFX therapy, the intraocular inflammation and retinal neovascularization was resolved, and so far, no severe recurrences have been seen for 3 years with the therapy. Conclusion: When we see patients with severe panuveitis associated with psoriasis extending to the posterior segment, IFX treatment may be a good therapeutic option.

Immunohistochemical and Immunocytochemical Analyses in Patients with Vitreoretinal Lymphoma

ABSTRACT Purpose: The aim of this study was to analyze immunohistochemical and immunocytological findings by examining enucleated eyes and vitreous cell block (CB) in patients with vitreoretinal lymphoma (VRL). Methods: Histological specimens were obtained from two enucleated eyes with VRL associated with neovascular glaucoma. CB specimens were prepared in 18 patients from diluted waste fluids containing shredded vitreous. Histological and cytological specimens were submitted for hematoxylin-eosin staining and immunopathological analyses. Results: Both specimens demonstrated massive infiltration of large lymphoma cells. The lymphoma cells were positive for CD20 and MUM-1 in enucleated eyes. Membranous immunoreactivity for CD20 was observed in lymphoma cells in CB with VRL. Bcl-6 and MUM-1 were marked in five and eight out of nine cases examined, respectively Conclusions: Cytological findings in CB specimens indicated similar histopathological characteristics of enucleated eyes. CB specimens obtained from vitreous waste diluted fluids may serve as effective materials for cytological diagnosis of VRL.

Two cases of cytomegalovirus panuveitis in immunocompetent patients

Purpose To report two cases of panuveitis in immunocompetent patients in which cytomegalovirus was involved. Observation Case 1 was a 46-year-old man who had a history of recurrent anterior chamber inflammations in his left eye. After Nd:YAG laser posterior capsulotomy, he developed panuveitis with vitreous haze and periphlebitis. Polymerase chain reaction (PCR) examination revealed the presence of cytomegalovirus (CMV) DNA in the anterior chamber (AC). He responded well to a series of intravitreal injections of ganciclovir (GCV). Case 2 was a 63-year-old woman who had a history of recurrent anterior uveitis in her left eye. Two years after cataract surgery, AC inflammation, diffuse vitreous haze, and periphlebitis had developed. CMV DNA was detected in the AC. Intravitreal injections of GCV and oral valganciclovir were administered, and ocular inflammation finally improved. Conclusions and importance: We experienced two cases of CMV panuveitis in immunocompetent adults, both of which responded well to anti-viral therapies.

Early post-treatment choroidal thickness to alert sunset glow fundus in patients with Vogt-Koyanagi- Harada disease treated with systemic corticosteroids

Purpose To determine if early post-treatment central choroidal thickness (CCT) changes can predict sunset glow fundus (SGF) development in patients with Vogt-Koyanagi-Harada (VKH) disease treated using systemic corticosteroids. Methods This retrospective case series included 39 eyes of 21 treatment-naïve patients with acute VKH disease who could be followed up for more than 12 months after systemic corticosteroid therapy. The eyes were divided into two groups according to whether SGF was present or absent at 12 months (9 eyes of 5 patients versus 30 eyes of 16 patients, respectively). Using enhanced depth imaging optical coherence tomography, CCT values were measured before treatment, then at 1 week and 1 and 3 months after treatment in both groups and compared between the two groups. Results Development of SGF was found 4–11 months after treatment. Mean post-treatment CCT decreased significantly at all examinations compared with baseline in both groups, along with resolution of serous retinal detachment. One week after treatment, mean CCT was significantly higher in eyes with SGF than in those without (P = 0.024). SGF was present at 12 months in 9 of 22 eyes with CCT values > 410 μm at 1 week after starting treatment, in contrast with none of 17 eyes with CCT ≤ 410 μm at this time (P = 0.003). Conclusions The current study suggested the potential validity of early post-treatment CCT as a feasible index to alert future progression to SGF in patients with VKH disease treated using systemic corticosteroids.