Bruton Tyrosine Kinase Inhibitor in 2 Patients With Vitreoretinal Lymphoma.

This case report describes the use of tirabrutinib to treat 2 individuals with vitreoretinal lymphoma.

Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: A multicenter retrospective study.

Purpose: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. Design: Retrospective longitudinal cohort study. Participants: 140 BD uveitis patients treated with IFX enrolled in our previous study. Methods: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). Main outcome measures: 10-year IFX continuation rate and change in LogMAR VA. Results: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. Conclusions: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.

A multicenter study of ocular inflammation after COVID-19 vaccination.

PURPOSE: To report the characteristics of a case series of ocular inflammatory events following COVID-19 vaccination in Japan. STUDY DESIGN: Retrospective multicenter study METHODS: In this retrospective multicenter survey, a questionnaire was sent to 16 Japanese hospitals that had uveitis specialty clinics. Information on patients who developed ocular inflammatory events within 14 days of COVID-19 vaccination between February 2021 and December 2021 was collected. RESULTS: Thirty-seven patients were diagnosed with ocular inflammatory events following COVID-19 vaccination. The mean age was 53.4 ± 16.4 years (range, 26-86 years), and the mean time to onset after vaccination was 6.3 ± 4.2 days (range, 1-14 days). Vogt-Koyanagi-Harada disease (VKH) was the most common event (n = 17 patients, 46%), followed by anterior uveitis (n = 6), infectious uveitis (n = 3), acute zonal occult outer retinopathy (AZOOR) (n = 2), sarcoidosis-associated uveitis (n = 1), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1), optic neuritis (n = 1), multiple evanescent white dot syndrome (MEWDS) (n = 1), Posner-Schlossman syndrome (n = 1), and unclassified uveitis (n = 4). Twenty-eight cases occurred after BNT162b2 vaccination (Pfizer-BioNTech) and 8 after mRNA-1273 vaccination (Moderna), whilst 1 patient had no information about vaccine type. CONCLUSIONS: COVID-19 vaccination can be related to various types of ocular inflammatory events. When we encounter patients with ocular inflammatory disease, we should consider that it may be an adverse effect of COVID-19 vaccination.

Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance.

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors. Notably, some HCMV strains carry UL40 genes that encode peptide sequences identical to the signal peptide sequences of specific HLA-A and HLA-C allotypes, which enables these CMV strains to escape HLA-E-restricted CD8+T cell responses. Variations in UL40 sequences have been studied mainly in the peripheral blood of CMV-viremia cases. In this study, we sought to investigate how ocular CMV disease develops from CMV infections. CMV gene sequences were compared between the intraocular fluids and peripheral blood of 77 clinical cases. UL40 signal peptide sequences were more diverse, and multiple sequences were typically present in CMV-viremia blood compared to intraocular fluid. Significantly stronger NK cell suppression was induced by UL40-derived peptides from intraocular HCMV compared to those identified only in peripheral blood. HCMV present in intraocular fluids were limited to those carrying a UL40 peptide sequence corresponding to the leader peptide sequence of the host's HLA class I, while UL40-derived peptides from HCMV found only in the peripheral blood were disparate from any HLA class I allotype. Overall, our analyses of CMV-retinitis inferred that specific HCMV strains with UL40 signal sequences matching the host's HLA signal peptide sequences were those that crossed the blood-ocular barrier to enter the intraocular space. UL40 peptide repertoires were the same in the intraocular fluids of all ocular CMV diseases, regardless of host immune status, implying that virus type is likely to be a common determinant in ocular CMV disease development. We thus propose a mechanism for ocular CMV disease development, in which particular HCMV types in the blood exploit peripheral and central HLA-E-mediated tolerance mechanisms and, thus, escape the antivirus responses of both innate and adaptive immunity.

Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis.

PURPOSE: To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan. STUDY DESIGN: A retrospective, observational study. METHODS: Patients newly registered at the Japan Medical Data Center health insurance claims database with a diagnosis of NIU who received systemic corticosteroids were identified, and their systemic corticosteroid dose (prednisolone equivalent) was assessed over 12 months of treatment (data extraction period: January 2008 to May 2017). RESULTS: The mean cumulative systemic corticosteroid dose in 12 months in 1641 new patients with NIU who received systemic corticosteroids was 593.7 mg. The mean systemic corticosteroid dose was highest at month 1 (10.7, 218.1, 16.7, and 23.0 mg/day in Behçet's disease [BD]-associated NIU [n = 19], Vogt-Koyanagi-Harada [VKH] disease-associated NIU [n = 49], sarcoidosis-associated NIU [n = 27], and "undifferentiated NIU" [NIU without specific primary disease information, n = 1545], respectively) and decreased over time. Systemic corticosteroids were prescribed at month 12 to 68.4%, 22.4%, 44.4%, and 5.6% of patients with BD-associated NIU, VKH disease-associated NIU, sarcoidosis-associated NIU, and undifferentiated NIU, respectively (mean dose, 6.0-14.3 mg/day). Multivariate regression analysis identified female sex, middle age (30 to < 40 years), VKH disease, and immunosuppressive agent use as background factors associated with higher systemic corticosteroid dose. CONCLUSIONS: The systemic corticosteroid dose was highest at month 1 and decreased over time in all disease categories. This database research revealed that some patients with NIU continued being prescribed systemic corticosteroids for at least 1 year.

Relationship between vitreoretinal lymphoma and the site of lymphoma development in the central nervous system.

PURPOSE: To investigate diffuse large B-cell lymphoma lesions with central nervous system (CNS) involvement in patients with vitreoretinal lymphoma (VRL) during long-term clinical courses. STUDY DESIGN: Multicenter, retrospective, and observational research. METHODS: Seventy-one patients participated in this study, 45 were newly diagnosed VRL patients with CNS involvement initially or during follow-up of at least 12 months. We identified the CNS lesions in the patients that had VRL and investigated whether the onset sites of the CNS lesions were associated with the VRL lesions or optic pathways. RESULTS: There were 42 patients with bilateral ocular lesions; 29 had unilateral lesions; 26 had incidental CNS lymphomas. Twenty patients developed recurrent CNS lymphoma 1-73 months after VRL diagnosis; 25 patients had no CNS lesions during the follow-up period. Most CNS lesions were in forebrain-originating tissues (95 lesions/total 124 CNS lesions total), followed by hindbrain-originating tissues, especially the cerebellum. Sixty-seven lesions were found in the non-optic pathway or non-visual cortex. CONCLUSION: Over 60% of the VRL patients had CNS lesions. CNS involvement was not associated with the optic pathway or visual cortex, suggesting that clinicians should carefully examine CNS lesions occurring in both forebrain- and hindbrain-originating tissues during a patient's clinical course. Moreover, the CNS lymphomas that manifest as VRL show multifocal tumor development.

Corrigendum: Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance.

[This corrects the article DOI: 10.3389/fimmu.2022.1008220.].

Comparison of combination therapy of prednisolone and cyclosporine with corticosteroid pulse therapy in Vogt-Koyanagi-Harada disease.

PURPOSE: To compare the efficacy and safety of a combination therapy of prednisolone and cyclosporine and corticosteroid pulse therapy in Vogt-Koyanagi-Harada (VKH) disease. STUDY DESIGN: A prospective, multicenter, randomized, non-inferiority trial. METHODS: Patients of new-onset acute VKH disease at 11 centers in Japan between 2014 and 2018 were randomized to a combination (oral prednisolone 60 mg daily with gradual taper-off to 35 mg/day and cyclosporine 3 mg/kg/day) and corticosteroid (methylprednisolone 1000 mg for 3 days followed by oral prednisolone) groups, and were followed for 1 year. RESULTS: Thirty-four were assigned to the combination and thirty-six patients to the corticosteroid group. Recurrence/worsening risk was 0.15 (95% confidence-interval [CI] 0.03-0.27) in the combination group and 0.25 (95% CI 0.11-0.39) in the corticosteroid group, with a risk difference of - 0.10 (90% CI - 0.27 to 0.06), demonstrating non-inferiority of the combination group with a non-inferiority margin of 0.20 (P = 0.0013). Serious adverse events occurred in three patients (two with hyponatremia and one with severe headaches) in the combination group and none in the corticosteroid group. Sunset glow fundus grades and cataract rates at 1 year were 0.57 (95% CI 0.42-71) and 4.3% in the combination group and 0.91 (95% CI 0.78-1.04) and 34.0% in the corticosteroid group, respectively. CONCLUSIONS: Combination therapy was noninferior to corticosteroid therapy with respect to recurrence/worsening risk. Notably, the recurrence/worsening risk, sunset glow fundus grade, and cataract rate were lower in the combination group than in the corticosteroid group.

Clinical Characteristics, Management, and Factors Associated with Poor Visual Prognosis of Acute Retinal Necrosis.

Purpose: To identify the clinical characteristics of acute retinal necrosis (ARN) and clarify factors associated with poor visual prognosis.Methods: a nationwide multi-center retrospective chart review study was performed in Japan using data from the medical records of 149 consecutive ARN patients. Demographics, ocular signs, virologic testing of intraocular fluids, and treatment were examined. Factors associated with poor visual prognosis were investigated by regression analysis.Results: At initial presentation, anterior chamber cells or mutton-fat keratic precipitates (97%), unilaterality (93%), and yellow-white retinal lesions (86%) were recognized. In the clinical course, rapid circumferential expansion of retinal lesions (39%), development of retinal break or retinal detachment (55%), and optic atrophy (43%) were recorded. Four variables were identified as associated with poor visual prognosis.Conclusions: The present study identified clinical characteristics and factors associated with poor visual prognosis of ARN.

Acute endophthalmitis and hyphema mimicking pink hypopyon associated with ocular toxocariasis: A case report.

PURPOSE: To report a case of acute endophthalmitis and hyphema mimicking pink hypopyon associated with ocular toxocariasis. OBSERVATIONS: An immunocompetent 56-year-old woman presented to our hospital with a sudden onset and a three-day history of decreased visual acuity in her left eye. There were no known inciting factors for her symptoms; however, she had a history of eating undercooked beef five days prior. On examination, the best-corrected visual acuity of her left eye was light perception and the intraocular pressure was 24 mmHg. Hyphema mimicking pink hypopyon and vitreous opacity suggestive of acute endophthalmitis were observed in her left eye. The patient underwent an emergency pars plana vitrectomy. The intraoperative findings included iridodialysis, severe vitritis, multiple whitish spots on the retina, white sheathed retinal vessels, and whitish peripheral granuloma. The aqueous humor tap and vitreous tap cultures were negative. Blood tests showed elevated eosinophil and total immunoglobulin (Ig) E levels. Enzyme-linked immunosorbent assay of her intraocular fluid showed positive anti-Toxocara canis IgG reactions; the patient was therefore diagnosed with ocular toxocariasis. Subsequent treatment with oral albendazole and prednisone resulted in significant improvement and recovery of visual acuity to 20/12.5. CONCLUSIONS AND IMPORTANCE: Acute endophthalmitis with hyphema mimicking pink hypopyon is a rare clinical presentation of ocular toxocariasis. The findings from this case highlight the importance of suspecting ocular toxocariasis if a patient presents with acute endophthalmitis and hyphema accompanied with peripheral granuloma. Early vitrectomy and subsequent treatment with oral albendazole and prednisone can be effective in visual recovery.

Prevalence and incidence rates and treatment patterns of non-infectious uveitis in Japan: real-world data using a claims database.

PURPOSE: To estimate the nationwide, longitudinal prevalence and incidence rates and assess treatment patterns of non-infectious uveitis (NIU) in Japan. STUDY DESIGN: A retrospective study. METHODS: Health insurance claims' data of patients with NIU were extracted from the Japan Medical Data Center (JMDC) database and analyzed descriptively (data extraction period, January 2011 to May 2017). Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, and sarcoidosis were selected as the primary diseases of NIU. RESULTS: From 2011 to 2016, the mean and median age of patients increased. Most (> 90%) patients were categorized as "undifferentiated NIU" (NIU without specific primary disease information after excluding BD-, VKH disease-, and sarcoidosis-associated NIU). Over 60% of patients with NIU were treated at non-hospital clinics, while the rest were treated at university, public, or other hospitals. The estimated prevalence rate of NIU was 386.5 per 100,000 persons (95% confidence interval [CI], 374.5-398.6) in 2011 and 439.3 per 100,000 persons (95% CI, 432.3-446.3) in 2016; the estimated incidence rate was 189.7 per 100,000 persons (95% CI, 181.2-198.5) in 2012 and 207.8 per 100,000 persons (95% CI, 202.2-213.5) in 2016. Most patients' prescribed uveitis drugs were ophthalmic drops over the first 6 months after patient presentation and entry into the JMDC database, followed by systemic corticosteroids. CONCLUSION: The estimated prevalence of NIU in Japan in recent years was approximately 400 with incidence of 200 per 100,000 persons.

Epidemiology of uveitis in Japan: a 2016 retrospective nationwide survey.

PURPOSE: To investigate the epidemiology of uveitis in Japan and assess its changes over time. STUDY DESIGN: Retrospective multicenter study METHODS: Sixty-six hospitals in Japan with uveitis specialty clinics participated in this retrospective nationwide survey. A questionnaire was sent to each hospital to survey the total number of patients who made a first visit to the outpatient uveitis clinic of each hospital between 1 April 2016 and 31 March 2017. The diagnosis of uveitis was based on guidelines when available or on commonly used diagnostic criteria. RESULTS: In 2016, new patients with uveitis accounted for 3.2% of the total number of new patients with ophthalmic diseases. A total of 5378 patients were enrolled in the survey; 3408 cases could be classified with a specific uveitis entity, and 1970 cases were described as unclassified intraocular inflammation. Among the classified cases, the most frequent disease was sarcoidosis (10.6%), followed by Vogt-Koyanagi-Harada disease (8.1%), herpetic iritis (6.5%), acute anterior uveitis (5.5%), sclerouveitis (4.4%), Behçet's disease (4.2%), malignant disease (2.6%), acute retinal necrosis (1.7%), Posner-Schlossman syndrome (1.7%), and diabetic iritis (1.4%). The rates of sarcoidosis, Vogt-Koyanagi-Harada disease, and Behçet's disease were similar; however, the rate of herpes iritis increased (4.2-6.5%) when compared with the 2009 survey. CONCLUSIONS: Some changes were observed between the previous nationwide surveys (2002 and 2009) and the present survey. It must be valuable to continue such nationwide epidemiologic surveys at regular intervals.

Genetic control of CCL24, POR, and IL23R contributes to the pathogenesis of sarcoidosis.

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.

Variants in IL23R-C1orf141 and ADO-ZNF365-EGR2 are associated with susceptibility to Vogt-Koyanagi-Harada disease in Japanese population.

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.

New onset or exacerbation of uveitis with infliximab: paradoxical effects?

OBJECTIVE: To report four cases of new onset or exacerbation of uveitis following administration of infliximab. METHODS: This retrospective observational case series includes four patients who developed new onset or exacerbation of uveitis paradoxically during infliximab treatment. RESULTS: Four patients were assessed, including three women, with a mean age of 33 (14-84) years. Infliximab was introduced for the treatment of scleritis associated with rheumatoid arthritis (two cases), chronic anterior uveitis associated with juvenile idiopathic arthritis (JIA) (one case) and Crohn's disease (one case). Anterior scleritis associated with rheumatoid arthritis successfully improved following infliximab administration; however, macular oedema or dense vitritis paradoxically developed in two cases. In one case, infliximab was switched to tocilizumab. In another case, infliximab was discontinued, and additional corticosteroids and immunosuppressive medications were added. In one patient with JIA, new-onset macular oedema and exacerbation of anterior uveitis were observed during infliximab treatment, so the patient was switched to adalimumab. In the patient with Crohn's disease treated with infliximab, severe vasculitis and macular oedema occurred, requiring intravitreal triamcinolone injection. The patient was switched to adalimumab. Given that these reactions were paradoxical effects of infliximab, infliximab treatment was discontinued in all cases, and additional corticosteroids or immunosuppressive medications were added. All cases remained free of ocular inflammation at the last visit. CONCLUSION: Uveitis rarely occurs de novo or is exacerbated during infliximab treatment. Cessation of infliximab led to resolution of this paradoxical adverse effect.

Association Study of ARMC9 Gene Variants with Vogt-Koyanagi-Harada Disease in Japanese Patients.

Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population. Methods: We recruited 380 Japanese patients with VKH disease and 744 Japanese healthy controls to genotype seven single-nucleotide polymorphisms (SNPs) in ARMC9. We also performed imputation analysis of the ARMC9 region and 195 imputed SNPs were included in the statistical analysis. Results: We observed an increased frequency of the A allele of rs28690417 in patients compared with controls (P = 0.0097, odds ratio (OR) = 1.46). The A allele had a dominant effect on VKH disease risk (P = 0.011, OR = 1.51). However, these significant differences disappeared after Bonferroni correction (corrected P > 0.05). The remaining 201 SNPs did not show any significant association with disease risk. Conclusions: Our study suggests that ARMC9 variants do not play a critical role in the development of VKH disease.

The Effect of Low-dose Cyclosporine (100 mg Once Daily) for Chronic Vogt-Koyanagi-Harada Disease.

Purpose: To determine the effect of low-dose cyclosporine (CyA) treatment for patients with chronic Vogt-Koyanagi-Harada (VKH) disease resistance to systemic corticosteroid treatment. Methods: We retrospectively evaluated patients diagnosed with chronic VKH disease resistance to systemic corticosteroid treatment at Japan Community Health Care Organization (JCHO) Osaka Hospital between March 2013 and March 2016. We followed the observation with systemic low-dose CyA (100 mg once daily) treatment of these patients. The patients were divided into two groups, anterior ocular inflammation group and posterior ocular inflammation group. Demographic data were reviewed, including age, gender, the existence of inflammation at the initial visit and three months after CyA treatment, and side effect. Results: Twenty-three eyes of thirteen patients with chronic VKH disease were included in this study (11 women, 2 men; mean age, 54.6±11.9 years). Nine cases showed anterior ocular inflammation and seven cases showed posterior ocular inflammation (includes overlapping cases). Thirteen of fourteen eyes in the anterior ocular inflammation group subsided at three months after CyA treatment, and ten of thirteen eyes in the posterior ocular inflammation group subsided at three months after treatment. We had to stop the treatment in one patient because of severe increase of serum triglyceride. Conclusions: Low-dose CyA treatment was effective in patients with chronic VKH resistance to systemic corticosteroid treatment. Our results suggest that this treatment was more effective in the anterior ocular inflammation group than in the posterior ocular inflammation group; however, a larger number of patients and longer observation periods are needed to confirm these results.

Steroid Resistant Vogt-Koyanagi-Harada Disease Treated Effectively with Cyclosporine.

Purpose: To report two cases of Vogt-Koyanagi-Harada disease (VKH) resistant to systemic corticosteroid therapy, effectively treated with systemic cyclosporine. Case 1: A 52-year-old man diagnosed as VKH was administered oral corticosteroids (40 mg/day), following steroid pulse therapy. Since there was no significant improvement, he underwent a second course of steroid pulse therapy and oral corticosteroid administration (40 mg/day). However, there was still no improvement, and a combination therapy of both oral corticosteroids (40 mg/day) and cyclosporine 200 mg (3 mg/kg) was administered. As a result, the inflammation subsided and the dosage of the drugs was tapered successfully. Case 2: A 50-year-old man diagnosed as VKH underwent two courses of steroid pulse therapy, which did not improve significantly. We performed combination therapy of both corticosteroids and cyclosporine, similar to the case described above and obtained good results. Conclusion: Our experience of these two cases indicates that systemic cyclosporine treatment was effective in the management of VKH patients resistant to conventional systemic corticosteroid therapy.

Optical coherence tomography manifestations of primary vitreoretinal lymphoma.

BACKGROUND: Primary vitreoretinal lymphoma (PVRL), a subset of primary central nervous system lymphoma (PCNSL), is a high-grade malignant tumor that shows various chorioretinal findings. Optical coherence tomography (OCT) is useful for detecting these lesions, and various abnormalities on OCT images have been reported. The purpose of this report was to investigate retrospectively the OCT manifestations of various disease stages and compare the manifestations of pretreatment, recurrent, and chronic cases. METHODS: We reviewed the medical charts and OCT images of 38 consecutive cases with PVRL. When abnormalities were detected on OCT images, the patients were classified based on the treatment of the primary disease: pretreatment if not treated, recurrent if treated previously, and chronic when chronic changes. RESULTS: Twenty-six eyes (20 cases) had abnormalities in the post-pole OCT images, i.e., 16 eyes (12 cases) were in the pretreatment group, seven eyes (five cases) were in the recurrent group, and five eyes (five cases) were in the chronic group. Two eyes (two cases) had abnormalities on OCT in the pretreatment and recurrent or chronic stages. The pretreatment and recurrent groups had subretinal or retinal pigment epithelium (RPE) level abnormalities more often than intraretinal changes. Twelve of 16 pretreated eyes and all seven eyes with recurrent disease had subretinal or RPE level abnormalities. One pretreatment case and three recurrent cases had atypical OCT manifestations of intraretinal (round lesions) or epiretinal changes (villous-shaped lesions). CONCLUSIONS: Although pretreatment cases and recurrent cases showed similar OCT abnormalities and the specific changes in the various disease stages were unclarified, collecting OCT data from various disease stages will facilitate detection of typical OCT changes of PVRL and lead to early diagnosis and treatment.