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.

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.

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.

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.

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.

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.

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.

CTLA4-Ig suppresses development of experimental autoimmune uveitis in the induction and effector phases: Comparison with blockade of interleukin-6.

Recently, a number of biologics have been used in the treatment of autoimmune diseases. However, in the treatment of severe autoimmune uveitis, only TNF-alpha inhibitors are preferably used and the effect of other biologics such as interleukin-6 (IL-6) signaling blockade or cytotoxic T-lymphocyte antigen-4-immunoglobulin fusion protein (CTLA4-Ig) has not been well studied. Previously, we reported that IL-6 blockade effectively suppresses the development of experimental autoimmune uveitis (EAU), a mouse model for uveitis, by inhibiting Th17 cell development. In this study, we investigated the effect of CTLA4-Ig on EAU development and compared it with the effect of anti-IL-6 receptor monoclonal antibody (MR16-1). C57BL/6J mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) and treated once with CTLA4-Ig or MR16-1. Both CTLA4-Ig and MR16-1 administered in the induction phase (the same day as immunization) significantly reduced the clinical and histopathological scores of EAU. Fluorescence-activated cell sorting studies using draining lymph node (LN) cells from EAU mice 10 days after immunization showed that CTLA4-Ig can suppress early T-helper cell activation. CTLA4-Ig administered in the effector phase of the disease (one week after immunization), when IRBP-reactive T cells have been primed, also significantly reduced the clinical and histopathological scores of EAU. In contrast, MR16-1 administered in the effector phase did not ameliorate EAU. To investigate the differences between these biologics in the effector phase, in vitro restimulation analysis of LN cells obtained from EAU mice one week after immunization was performed and revealed that CTLA4-Ig, but not MR16-1, added to culture media could inhibit the proliferation of IRBP-specific CD4(+) T cells which possessed capacities of producing IFN-gamma and/or IL-17. Collectively, CTLA4-Ig ameliorated EAU through preventing initial T-cell activation in the induction phase and suppressing proliferation of IRBP-specific T cells in the effector phase. Blockade of IL-6 signaling did not have such inhibitory effects after T-cell priming. CTLA4-Ig may have therapeutic effects on human chronic uveitis.

Efficacy and Complications of Intravitreal Rituximab Injection for Treating Primary Vitreoretinal Lymphoma.

PURPOSE: To assess the long-term clinical outcomes of intravitreal injections of rituximab (IVR), an anti-CD20 monoclonal antibody, to treat CD20-positive primary vitreoretinal lymphoma (PVRL). METHODS: Twenty eyes of 13 women (mean age, 66.2 ± 9.9 years) with CD20-positive PVRL were included in this prospective, interventional case series. All patients had discontinued previous intravitreal methotrexate (IVM) treatment because of severe corneal epitheliopathy. Weekly IVR injections (1 mg/0.1 ml) for 4 weeks were administered as a one-course protocol. Additional injections were administered when the PVRL recurred. The effects and the adverse events associated with IVR injections were evaluated. RESULTS: All patients completed a 1-year follow-up (mean observation after IVR injections, 24.7 ± 6.3 months). Before treatment, diffuse keratic precipitates (KPs), anterior vitreous cells, or both were observed in 18 (90%) eyes of 11 patients, and typical subretinal infiltrates were seen in eight (40%) eyes of six patients; all improved with one treatment course. The anterior segment lesions recurred in 11 (55%) eyes of nine patients and resolved with another course of injections. Transient IOP elevations occurred in 12 (60%) eyes of 10 patients within 3.8 ± 1.9 weeks after the first treatment course; iridocyclitis with mutton-fat KPs developed in seven (35%) eyes of six patients with elevated IOP and resolved with topical treatment. No other significant ocular complications or systemic side effects developed. CONCLUSIONS: Injections of IVR were shown to be an efficacious alternative treatment for PVRL, although the disease recurred in approximately half of the eyes. Complications included transient IOP elevations and iridocyclitis with mutton-fat KPs that were managed topically. TRANSLATIONAL RELEVANCE: The results of this trial support IVR as one element of combined modality therapy for treating PVRL patients without CNS involvement, particularly for those who respond poorly and have side effects with IVM. (http://www.umin.ac.jp/ctr/ number, UMIN000005604).

Blockade of interleukin-6 signaling suppresses not only th17 but also interphotoreceptor retinoid binding protein-specific Th1 by promoting regulatory T cells in experimental autoimmune uveoretinitis.

PURPOSE. Both Th17 and Th1 cells contribute to experimental autoimmune uveoretinitis (EAU). Interleukin-6 (IL-6) blockade inhibits Th17 differentiation in EAU and potently suppresses ocular inflammation, although its effect on Th1 cells is unknown. To clarify the mechanism of IL-6 blockade, the authors investigated T helper cells with particular focus on Th1 and regulatory T cells (Treg) in EAU of IL-6 gene knockout (KO) mice. METHODS. EAU was induced in wild-type (WT) mice and in mice lacking IL-6 (IL-6KO), IL-17 (IL-17KO), and IFN-γ (GKO) on a C57BL/6 background. Clinical scores of EAU, cytokine levels in supernatants from ocular tissue homogenates, and T helper cell differentiation in lymph nodes in each mouse were examined. To study the roles of Treg cells, EAU was induced in IL-6KO mice treated with anti-CD25 monoclonal antibody (mAb) to deplete Treg cells in vivo. RESULTS. Inflammation was comparable between WT, IL-17KO, and GKO mice but was absent in IL-6KO mice. Th17 and interphotoreceptor retinoid binding protein (IRBP)-specific Th1 cells were increased in GKO and IL-17KO mice, respectively, whereas both populations were reduced in IL-6KO mice. Th1-dominant EAU in IL-17KO mice was suppressed by anti-IL-6R mAb treatment. Treg cell depletion in vivo induced EAU in IL-6KO mice. CONCLUSIONS. After the induction of EAU, IL-6 deficiency resulted in the inhibition of the IRBP-specific Th1 response and enhanced the generation of IRBP-specific Treg cells. Furthermore, Treg was needed to inhibit Th1 responses and ocular inflammation in IL-6KO mice. Protective effects of IL-6 signaling blockade in EAU involve not only Th17 cell inhibition but also IRBP-specific Treg cell promotion.

Anterior segment optical coherence tomography findings of presumed intraocular tuberculosis.

PURPOSE: To report a case of anterior segment findings of presumed ocular tuberculosis using anterior-segment optical coherence tomography (AS-OCT; Visante, Carl Zeiss Meditec, Inc., Dublin, CA, USA). METHODS: A 78-year-old woman with persistent right ocular injection and pain of 2 weeks' duration was referred to our clinic. Unilateral stromal keratitis affecting the corneal periphery and angle granuloma with synechiae, scleritis, and anterior uveitis were noticed. Because of the patient's intensely positive tuberculin skin test, she was diagnosed with presumed intraocular tuberculosis. The anatomic structures of the anterior segment were monitored by AS-OCT before and after the treatment. RESULTS: AS-OCT imaging showed a poorly demarcated amorphous lesion in the iridocorneal angle, corneal edema, narrowing and synechiae of the iridocorneal angle, and anterior chamber exudates and cells. Improvement of the corneal edema and a decrease of corneal thickness and exudates were observed after implementation of a daily regimen of antituberculous treatment. AS-OCT was useful for investigating the extent of the anterior synechiae and angle lesions. CONCLUSIONS: AS-OCT allows noninvasive and noncontact analysis of the treatment response and is also useful to evaluate disease activity.

Blockade of interleukin-6 signaling suppresses experimental autoimmune uveoretinitis by the inhibition of inflammatory Th17 responses.

The aim of this study was to investigate the effect of anti-mouse IL-6 receptor monoclonal antibody (MR16-1) treatment on CD4 T cell differentiation and compared it to the effect of anti-TNF mAb treatment with using a murine model of experimental autoimmune uveoretinitis (EAU). C57BL/6 mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) to induce ocular inflammation treatment with control IgG or MR16-1 or anti-TNF mAb. Helper T cells differentiation was analyzed during the development of EAU. Immunization with IRBP increased the frequency of Th17 cells rather than Th1 cells in the early stage of EAU. Treatment with MR16-1 on the same day as immunization (day 0) or one day after (day 1) suppressed ocular inflammation in EAU mice. Treatment with MR16-1 on day 0 inhibited the induction of Th17 cells in vivo, and inhibited not only IRBP-responsive Th17 cells but also their Th1 counterparts and induced IRBP-responsive regulatory T (Treg) cells in vitro. The administration of anti-TNF mAb had no significant protective effect in EAU mice. The protective effect of anti-IL-6R mAb treatment, but not anti-TNF mAb treatment on EAU correlated with the inhibition of Th17 differentiation. This finding suggests that IL-6 blockade may have a therapeutic effect on human ocular inflammation which is mediated via mechanisms distinct from those of TNF blockade. IL-6 blockade may thus represent an alternative therapy for patients with ocular inflammation who are refractory to anti-TNF mAb therapy.

iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases.

OBJECTIVE: To identify a novel serum biomarker of disease activity in inflammatory autoimmune disorders. METHODS: Sera obtained from rheumatoid arthritis (RA) patients before and after anti-TNF therapy were analysed by iTRAQ (isobaric tags for relative and absolute quantitation) quantitative proteomic analysis and further validated by ELISA. RESULTS: Of 326 proteins identified by proteomic analysis, increased serum levels of leucine-rich alpha-2 glycoprotein (LRG) was identified in RA patients before therapy. Serum LRG concentrations were significantly elevated in RA patients compared with healthy controls and decreased after anti-TNF therapy. Furthermore, serum LRG concentrations correlated with disease activity in RA and Crohn's disease (CD). Interestingly, in a subpopulation of patients with active CD and normal C-reactive protein levels, serum LRG concentrations were elevated. CONCLUSIONS: LRG represents a novel serum biomarker for monitoring disease activity during therapy in autoimmune patients, particularly useful in patients with active disease but normal CRP levels.

Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis.

OBJECTIVES: Human endogenous uveitis is one of the sight-threatening diseases associated with variety of systemic disorders, such as Behcet's disease and sarcoidosis. Recently, biosynthesized antibodies against inflammatory cytokines have been recognized to be useful to control the regional inflammation. In this study, we focused on the possibility of IL-6-based biological therapies for endogenous uveitis. We initially confirmed the significant increase of several inflammatory soluble factors including IL-6 in the vitreous fluids from refractory/chronic engogenous uveitis patients. METHODS: To investigate the role of IL-6 in the formation of refractory ocular inflammation, we used the mouse experimental autoimmune uveitis (EAU) model. Both IL-6 and IL-23 are required for the development of IL-17-producing helper T subset (Th17) from naïve CD4(+) T cells. Results. In the EAU model, neither IL-6-deficient mice nor IL-23-deficient mice could induce Th17 cells and the EAU score was decreased in these mice in the entire time course. We also confirmed that systemic administration of anti-il-6 receptor antibody ameliorates EAU By suppressing both systemic and regional TH17 responses. CONCLUSIONS: IL-6 is responsible for causing ocular inflammation, and it is, at least partially, due to IL-6-dependent Th17 differentiation. IL-6 may be a target for therapy of refractory endogenous uveitis in humans.

[Survey of silicone oil for ocular diseases in Japan].

PURPOSE: To survey the use of silicone oil in clinical ophthalmology in Japan. SUBJECTS AND METHODS: Questionnaires were sent to 1,240 hospitals registered as being ophthalmology residency training institutions with the Japanese Ophthalmological Society as of September 2007. Responses were collected via the Internet and results totaled. The use of silicone oil at each institution for the 2006 one-year period was assessed, included queries regarding type of silicone oil, indication for use, results and complications. Hospitals were divided into non-specialty institutions, intermediate-specialty institutions and specialty institutions based on number of vitrectomy procedures performed in the one-year period, and trends were analyzed based on these divisions. RESULTS: Responses were received from 272 institutions (21.9% response rate). Of a total of 36,104 vitrectomy procedures, silicone oil was used in 2,170 cases (6.0%). The diagnosis was proliferative vitreoretinopathy in the majority of cases, followed by proliferative diabetic retinopathy and rhegmatogenous retinal detachment. The majority of institutions replied that the indication for use was complicated case. The type of silicone oil used was ophthalmic formulation in 120 institutions (54.1%) and industrial formulation in 73 institutions (32.9%). Specialty institutions had a higher rate of use of the industrial formulation. The average volume used at one time was 6.4 ml. The majority of institutions responded that silicone oil removal was performed at 3 months after the initial vitrectomy. Silicone oil was not removed in 530 cases in which continued tamponade was judged to be appropriate; this comprised 53.3% of cases at non-specialty institutions. The overall evaluation for silicone oil use was good; silicone oil was rated as being indispensable in 72 cases (31.2%) and effective in 130 cases (56.3%). Responses stating a high need for silicone oil were most frequent for proliferative vitreoretinopathy and proliferative diabetic retinopathy. Complications related to silicone oil use were glaucoma in 125 cases (5.6%), intraocular pressure elevation in 411 cases (18.4%), hypotony in 28 cases (1.3%), endophthalmitis in 5 cases (0.22%), retinal detachment in 13 cases (0.58%), corneal opacification in 105 cases (4.7%), inadvertant subretinal infusion in 31 cases (1.4%) and silicone oil emulsification in 82 cases (3.7%). It was the opinion of many institutions that, in cases where silicone oil could not be used, the number of necessary surgical procedures increased, with lower rates of cure and greater burden on the patient. CONCLUSIONS: Silicone oil was utilized in approximately 1 in every 17 vitrectomy procedures performed in 2006 by the Japanese institutions surveyed. Complications were observed, however overall the indications were appropriate and the use of silicone oil was judged to be necessary by nearly 90% of institutions surveyed.

Treatment of primary intraocular lymphoma with intravitreal methotrexate.

PURPOSE: To report the efficacy of intravitreal chemotherapy for primary intraocular lymphoma (PIOL). METHODS: Retrospective, noncomparative interventional case reports are presented for six patients (ten eyes; mean age, 58.8 years) with pathologically confirmed PIOL who participated in this study and were treated at our hospital with intravitreal injections of methotrexate (MTX) between January 2004 and February 2007. Intravitreal injections of MTX (400 microg MTX/50 microl Opeguard-MA) were administered once or twice weekly for 1 month followed by ten monthly injections. Interleukin-10 (IL-10) and IL-6 were measured in the vitreous before and after injections to determine tumor activity. RESULTS: All eyes were clinically cleared of malignant cells. One eye lost vision. After intravitreal chemotherapy, the vitreous IL-10 concentration reached barely detectable levels. CONCLUSIONS: Intravitreal chemotherapy achieves clinical remission and preserves vision in patients with PIOL.