Purpose

To evaluate the risk of and risk factors for a second episode (relapse) among patients with remitted primary anterior uveitis.

Design

Retrospective cohort study.

Participants

Patients with primary anterior uveitis presenting to one of 4 academic ocular inflammation subspecialty practices achieving remission of the primary episode within 90 days of initial uveitis diagnosis.

Methods

Data were obtained by standardized chart review.

Main outcome measures

Time-to-relapse of anterior uveitis and risk factors for relapse.

Results

102 patients with a first episode of anterior uveitis were seen within 90 days of first-ever uveitis onset and followed for 165 person-years after achieving remission of the initial episode. Most patients were female (60%) and white (78%). Forty patients had a recurrence of anterior uveitis. The incidence of relapse was 24% per person-year (95% Confidence Interval [CI]: 17–33%). At 1.5 years after remission, 61% (95% CI: 48–71%) were still in remission. Younger adults had significantly higher relapse risk than middle-aged adults (hazard ratio [18–35 year-old persons vs. 35–55 year-old persons]=2.7, 95% CI: 1.3–6.0).

Conclusions

Our results suggest that many patients with remitted primary anterior uveitis presenting for tertiary uveitis care will relapse. Age in the young adult range was associated with higher risk of relapse. Given the high relapse risk, management of patients with primary anterior uveitis should include an explicit plan for detecting and managing relapses.

This study reveals that Suppressor of cytokine signaling-1 mitigates uveitis by inhibiting the infiltration of inflammatory cells into the retina and conferring protection to retinal cells by inhibiting activities of proapoptotic cytokines.

Purpose.

Suppressors of cytokine signaling (SOCS) proteins regulate the intensity and duration of cytokine signals and defective expression of SOCS1 and SOCS3 has been reported in a number of human diseases. The purpose of this study was to investigate the role of SOCS1 in intraocular inflammatory diseases (uveitis) and whether SOCS1 expression is defective in patients with ocular inflammatory diseases.

Methods.

Blood from patients with scleritis or healthy human volunteers was analyzed for SOCS expression by RNase protection assay and RT-PCR. The authors generated SOCS1 transgenic rats and mice (SOCS1-Tg), induced experimental autoimmune uveoretinitis (EAU) by active immunization with interphotoreceptor retinal binding protein or adoptive transfer of uveitogenic T cells, and investigated effects of SOCS1 overexpression on EAU. SOCS1-mediated protection of retinal cells from apoptosis was assessed by annexin V staining.

Results.

Induction of cytokine-induced SH2 protein was comparable between patients and volunteers, whereas 80% of lymphocytes from patients with scleritis failed to induce SOCS1 in response to IL-2. Compared with wild-type littermates, SOCS1-Tg rats/mice developed less severe EAU. Constitutive overexpression of SOCS1 in retina inhibited expression of chemokines (CCL17, CCL20, CXCL9, CXCL10), reduced Th17/Th1 expansion, and inhibited recruitment of inflammatory cells into the retina. The authors also show that SOCS1 protected retinal cells from staurosporine as well as H2O2-induced apoptosis.

Conclusions.

Defective expression of SOCS1 in patients with scleritis, taken together with SOCS1-mediated protection of neuroretinal cells from apoptosis, suggest that SOCS1 has neuroprotective function in the retina, implying that administration of SOCS1 mimetic peptides may be useful in treating uveitis or scleritis.

Background

To evaluate how smoking affects the time to disease quiescence and time to disease recurrence in patients with ocular inflammation.

Methods

A retrospective cohort study of patients with ocular inflammation who were followed longitudinally and had smoking information available in the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study database.

Results

Among 2676 patients with active ocular inflammation, smokers were more likely to have bilateral ocular disease and poorer visual acuity on presentation compared with non-smokers and previous smokers. In a multivariate analysis, there was no statistically significant difference in the time to disease quiescence between groups. However, the median time to recurrence of ocular inflammation was statistically significantly longer for non-smokers (9.4 months) and for previous smokers (10.7 months) than for current smokers (7.8 months) (p=0.02). The RR of ocular inflammation recurrence was higher for smokers than for non-smokers (adjusted HR=1.19, 95% CI 1.03 to 1.37) and tended towards significance in previous smokers (adjusted HR=1.11, 95% CI 0.93 to 1.35).

Conclusions

Smoking was associated with an increased likelihood of bilateral ocular inflammation and reduced vision upon presentation, and an increased risk of recurrence compared with not smoking. These results suggest that patients with ocular inflammation should be counselled to stop smoking as part of routine management.

Purpose

To evaluate the clinical outcomes of cyclosporine treatment for non-infectious ocular inflammation

Design

Retrospective cohort study

Participants

Three hundred seventy-three patients with non-infectious ocular inflammation managed at four tertiary ocular inflammation clinics in the United States observed to use cyclosporine as a single non-corticosteroid immunosuppressive agent to their treatment regimen, between 1979-2007 inclusive.

Methods

Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage of cyclosporine and main outcome measures were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Main Outcome Measures: Control of inflammation, sustained control after reducing corticosteroid dosages, and discontinuation of therapy because of toxicity.

Results

Of the 373 patients (681 eyes) initiating cyclosporine monotherapy, 33.4% by six months and 51.9% by one year gained sustained, complete control of inflammation over at least two visits spanning at least 28 days. Approximately 25% more improved to a level of slight inflammatory activity by each of these time points. Corticosteroid-sparing success (completely controlled inflammation for at least 28 days with prednisone 10 mg/day or less) was achieved by 22.1% by six months and 36.1% within one year. Toxicity led to discontinuation of therapy within one year by 10.7% of the population. Patients over 55 years of age were over 3-fold more likely to discontinue therapy because of toxicity than patients ages 18-39 years. Doses of 151-250 mg/day tended to be more successful than lower doses, and were not associated with a higher discontinuation for toxicity rate; higher doses did not appear to offer a therapeutic advantage.

Conclusion

Cyclosporine, with corticosteroid therapy as indicated, was modestly effective for controlling ocular inflammation. Our data support a preference for cyclosporine adult dosing between 151-250 mg/day. While cyclosporine was tolerated by the majority of patients, toxicity was much more frequent with increasing age; alternative agents may be preferred for patients over 55 years of age.

Purpose

To evaluate the outcomes of cyclophosphamide therapy for non-infectious ocular inflammation.

Design

Retrospective cohort study

Participants

Two hundred fifteen patients with non-infectious ocular inflammation observed from initiation of cyclophosphamide.

Methods

Patients initiating cyclophosphamide, without other immunosuppressive drugs (other than corticosteroids), were identified at four centers. Dose of cyclophosphamide, response to therapy, corticosteroid-sparing effects, frequency of discontinuation and reasons for discontinuation were obtained by medical record review of every visit.

Main Outcome Measures

Control of inflammation, corticosteroid-sparing effects, discontinuation of therapy.

Results

The 215 patients (381 involved eyes) meeting eligibility criteria carried diagnoses of uveitis (20.4%), scleritis (22.3%), ocular mucous membrane pemphigoid (45.6%) or other forms of ocular inflammation (11.6%). Overall, approximately 49.2% (95% confidence interval (CI): 41.7%-57.2%) gained sustained control of inflammation (for at least 28 days) within 6 months, and 76% (95% CI: 68.3%-83.7%) within 12 months. Corticosteroid-sparing success (sustained control of inflammation while tapering prednisone to 10 mg or less among those not meeting success criteria initially) was gained by 30.0% and 61.2% by six and 12 months respectively. Disease remission leading to discontinuation of cyclophosphamide occurred at the rate of 0.32/person-year (95% CI: 0.24 -0.41), and the estimated proportion with remission at or prior to 2 years was 63.1% (95% CI: 51.5%-74.8%). Cyclophosphamide was discontinued by 33.5% of patients within one year because of side effects-usually of a reversible nature.

Conclusions

Our data suggest that cyclophosphamide is effective for the majority of patients for controlling inflammation and allowing tapering of systemic corticosteroids to 10 mg of prednisone or less, although a year of therapy may be needed to achieve these goals. Unlike with most other immunosuppressive drugs, disease remission was induced by treatment in the majority of patients who were able to tolerate therapy. In order to titrate therapy properly and to minimize the risk of serious potential side effects, a systematic program of laboratory monitoring is required. Judicious use of cyclophosphamide appears beneficial for severe ocular inflammation cases where the potentially vision-saving benefits outweigh the substantial potential side effects of therapy, or when indicated for associated systemic inflammatory diseases.

PURPOSE

To evaluate the risk of and risk factors for hypopyon among patients with uveitis, and to evaluate the risk of visual changes and structural complications following hypopyon.

DESIGN

Retrospective cohort study.

PARTICIPANTS

Patients with uveitis at four academic ocular inflammation subspecialty practices.

METHODS

Data were ascertained by standardized chart review.

MAIN OUTCOME MEASURES

Prevalence and incidence of hypopyon, risk factors for hypopyon, and incidence of visual acuity changes and of structural ocular complications following hypopyon.

RESULTS

Among 4,911 patients with uveitis, 41 (8.3/1000) cases of hypopyon were identified at the time of cohort entry. Of these, 2,885 initially free of hypopyon were followed over 9,451 person-years, during which 81 (2.8%) developed hypopyon (8.57/1000 person-years). Risk factors for incident hypopyon included Behçet’s disease (adjusted relative risk (RR)=5.30, 95% confidence interval (CI): 2.76–10.2), diagnosis of a spondyloarthropathy (adjusted RR=2.86, 95% CI: 1.48–5.52), and HLA-B27 positivity (adjusted RR=2.04, 95% CI: 1.17–3.56). Patients with both a spondyloarthropathy and HLA-B27 tended to have higher risk than either factor alone (crude RR=4.39, 95% CI: 2.26–8.51). Diagnosis of intermediate uveitis (+/− anterior uveitis) was associated with a lower risk of hypopyon (with respect to anterior uveitis only, adjusted RR=0.35, 95% CI: 0.15–0.85). Hypopyon incidence tended to be lower among patients with sarcoidosis (crude RR=0.22, 95% CI: 0.06–0.90; adjusted RR=−0.28, 95% CI: 0.07–1.15). Post-hypopyon eyes and eyes not developing hypopyon had a similar incidence of band keratopathy, posterior synechiae, ocular hypertension, hypotony, macular edema, epiretinal membrane, cataract surgery, or glaucoma surgery. Post-hypopyon eyes were more likely than eyes which not developing hypopyon to gain 3 lines of vision (crude RR=1.54, 95% CI: 1.05–2.24) and were less likely to develop 20/200 or worse visual acuity (crude RR=0.41, 95% CI: 0.17–0.99); otherwise visual outcomes were similar in these groups.

CONCLUSIONS

Hypopyon is an uncommon occurrence in patients with uveitis. Risk factors included Behçet’s disease, HLA-B27 positivity, and diagnosis of a spondyloarthropathy. Intermediate uveitis cases (+/− anterior uveitis) had lower risk of hypopyon than other forms of uveitis. On average, post-hypopyon eyes were no more likely than other eyes with uveitis to develop structural ocular complications or lose visual acuity.

Purpose

To compare the differences in vision and health-related quality of life (HRQOL) of individuals with ocular and non-ocular sarcoidosis; and to examine the impact of specific demographic and clinical factors on the noted differences.

Methods

A cross-sectional study using non-randomized prospective cohort was conducted at the National Eye Institute (protocol number: 06-EI-0239, NCT00379275) from August 31, 2006 until November 15, 2007. Each participant completed vision and HRQOL questionnaires, the Sarcoidosis Health Questionnaire (SHQ) and the National Eye Institute Visual Function Questionnaire (NEI-VFQ), along with a demographic/environmental exposure survey. Clinical data were collected through an ophthalmic exam as part of the research protocol.

Results

The study enrolled 75 biopsy-proven and 20 clinically presumed sarcoidosis participants which were divided into two cohorts, ocular (N = 60) and non-ocular groups (N = 35). The ocular group had significantly lower (P < 0.01) total NEI-VFQ scores compared to the non-ocular group. Multiple linear regression analysis showed that participants with ocular sarcoidosis who had an annual household income of < $50,000 (P < 0.01) had significantly lower total SHQ scores while participants with ocular sarcoidosis whose visual acuity was 20/100 or worse had significantly lower total NEI-VFQ scores (P = 0.03).

Conclusions

Ocular involvement impacts both overall and vision-related quality of life among sarcoidosis patients. Lower economic status appears to have a significant impact on the quality of life of sarcoidosis patients. Assessment of visual function and general health status provide pertinent information for individuals with sarcoidosis and should be included in their care to assess burden of their disease on their quality of life.

PURPOSE

To provide preliminary data regarding the safety and efficacy of high-dose intravenous daclizumab (Zenapax; Roche Inc, Nutley, New Jersey, USA) therapy for the treatment of juvenile idiopathic arthritis (JIA)-associated active anterior uveitis.

DESIGN

Interventional case series; open-label prospective, phase II pilot study.

METHODS

Six patients were recruited into the study and received daclizumab therapy at doses of 8 mg/kg at baseline, 4 mg/kg at week 2, and 2 mg/kg every 4 weeks thereafter, for a total of 52 weeks. The study was done at the National Eye Institute between June 29, 2005 and July 9, 2008. The primary outcome was a two-step decrease in inflammation grade assessed at week 12. Primary safety outcome was assessed at weeks 2 and 4. The ocular inflammation was assessed according to the Standardization of Uveitis Nomenclature criteria.

RESULTS

Four of the 6 participants achieved two-step reduction in anterior chamber cells according to Standardization of Uveitis Nomenclature Working Group grading scheme for anterior chamber cells 12 weeks into the study and met the primary efficacy endpoint. One additional patient responded to reinduction whereas 1 patient failed reinduction and was considered an ocular treatment failure. Visual acuity improved from a mean of 68 Early Treatment Diabetic Retinopathy Study letters in the worse eye to a mean of 79.6 letters (2 Snellen lines). Three participants were terminated before 52 weeks: First, because of a rash possibly induced by daclizumab; Second, because of ocular treatment failure; and Last, because of uncontrolled systemic manifestations of JIA.

CONCLUSION

High-dose intravenous daclizumab can help reduce active inflammation in active JIA-associated anterior uveitis; however, patients need to be monitored for potential side effects. Larger randomized trials are needed to better assess treatment effect and safety.

Purpose

To evaluate the therapeutic effect of intravitreal bevacizumab in patients with uveitis-associated choroidal/retinal neovascularization.

Methods

Two female patients (40 years, 15 years) with posterior uveitis, (one presumed ocular sarcoidosis, one lupus) were evaluated for neovascularization of the posterior segment. Both patients were given a single dose of 1.25 mg intravitreal bevacizumab.

Results

Significant anatomical and functional recovery was evident in both patients within a few weeks.

Conclusion

In selected uveitic patients, bevacizumab may be an option for managing neovascularization.

Anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis—the term recently applied to Wegener's granulomatosis—is a rare multi-system inflammation characterized by necrotizing granulomas and vasculitis. We investigated the ocular manifestations of this disease in a group of patients drawn from five inflammatory eye disease clinics across the United States. Of 8,562 persons with ocular inflammation, 59 individuals were diagnosed with ANCA-positive vasculitis; 35 males and 21 females, aged 16 to 96 years, were included in this study. Ocular diagnoses were scleritis (75.0%), uveitis (17.9%), and other ocular inflammatory conditions (33.9%) including peripheral ulcerative keratitis and orbital pseudotumor. Mean duration of ocular disease was 4.6 years. Oral corticosteroids and other systemic immunosuppressive agents were used by 85.7% and 78.5% of patients, respectively. Over time, patients with ANCA-positive vasculitis experienced 2.75-fold higher mortality than other patients with inflammatory eye disease.

Anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis—the term recently applied to Wegener's granulomatosis—is a rare multi-system inflammation characterized by necrotizing granulomas and vasculitis. We investigated the ocular manifestations of this disease in a group of patients drawn from five inflammatory eye disease clinics across the United States. Of 8,562 persons with ocular inflammation, 59 individuals were diagnosed with ANCA-positive vasculitis; 35 males and 21 females, aged 16 to 96 years, were included in this study. Ocular diagnoses were scleritis (75.0%), uveitis (17.9%), and other ocular inflammatory conditions (33.9%) including peripheral ulcerative keratitis and orbital pseudotumor. Mean duration of ocular disease was 4.6 years. Oral corticosteroids and other systemic immunosuppressive agents were used by 85.7% and 78.5% of patients, respectively. Over time, patients with ANCA-positive vasculitis experienced 2.75-fold higher mortality than other patients with inflammatory eye disease.

Purpose

To estimate the risk of structural ocular complications and loss of visual acuity in cases of Behçet’s Disease (BD); to evaluate potential risk and protective factors for these events

Design

Retrospective cohort study

Methods

Setting

Five academic center ocular inflammation subspecialty practices

Study Population

A total of 168 consecutive patients with BD-associated ocular inflammation

Procedures

Clinical data on these patients were ascertained by standardized chart review

Outcome Measures

Visual acuity, structural ocular complications of inflammation, intraocular pressure (IOP)

Results

Over a median follow-up of 1.05 years, the incidence of specific structural complications and IOP disturbances were common: the incidence rate of any ocular complication was 0.45/eye-year (EY). Rates of loss of visual acuity to 20/50 or worse and to 20/200 or worse were 0.12/EY and 0.09/EY respectively. Risk factors for loss of visual acuity during follow-up were persistent inflammatory activity, presence of posterior synechiae, presence of hypotony, and presence of elevated IOP. In a time-dependent analysis, current activity of ocular inflammation was associated with an increased risk of loss of visual acuity to 20/50 or worse (RR = 2.45, 95% CI: 1.1–5.5, p = 0.03) and to 20/200 or worse (RR = 2.67, 95% CI: 1.2–5.8, p = 0.01).

Conclusions

Loss of visual acuity and occurrence of ocular complications were common in patients with ocular inflammation associated with Behçet’s Disease, even with aggressive therapy. Ongoing inflammation during follow-up, presence/occurrence of posterior synechiae, hypotony, and elevated IOP were associated with an increased risk of loss of visual acuity.

Purpose

To critically assess potentially carcinogenic effects of immunosuppressive therapy in the ocular inflammation setting

Design

Focused evidence assessment.

Methods

Relevant publications were identified by MEDLINE and EMBASE queries and reference list searches.

Results

Extrapolation from transplant, rheumatology, skin disease and inflammatory bowel disease cohorts to the ocular inflammation setting suggest that: 1) alkylating agents increase hematologic malignancy risk and cyclophosphamide increases bladder cancer risk, but less so with ≤18 months’ duration of therapy and hydration respectively; 2) calcineurin inhibitors and azathioprine probably do not increase total cancer risk to a detectable degree, except perhaps some other risk factors (uncommon in ocular inflammation patients) might interact with the former to raise risk; 3) Tumor Necrosis Factor (TNF) inhibitors may accelerate diagnosis of cancer in the first 6–12 months, but probably do not increase long-term cancer risk; and 4) changes in risk with methotrexate, mycophenolate mofetil, and daclizumab appear negligible although non-transplant data are limited for the latter agents. Immunosuppression in general may increase skin cancer risk in a sun-exposure dependent manner.

Conclusion

Use of alkylating agents for a limited duration seems justifiable for severe, vision-threatening disease, but otherwise cancer risk may be a relevant constraint on use of this approach. Antimetabolites, daclizumab, TNF-inhibitors, and calcineurin inhibitors probably do not increase cancer risk to a degree that outweighs the expected benefits of therapy. Monitoring for skin cancer may be useful for highly sun-exposed patients. Data from ocular inflammation patients are needed to confirm the conclusions made in this analysis by extrapolation.

Objective

This study aimed to evaluate the possible safety and effectiveness of infliximab in patients with active scleritis.

Study Design

Prospective, nonrandomized, open-label pilot study (Protocol No. 04-EI-0065).

Participants

Five patients with active anterior scleritis.

Methods

This single-centre, pilot study of infliximab for the treatment of active anterior scleritis was conducted at the National Eye Institute, National Institutes of Health, between 2003 and 2007. Scleritis patients with active disease who had used at least 1 conventional immunosuppressive agent in the past were included. Primary outcome was a 2-step decrease in scleral inflammation within 14 weeks. Patients received infliximab (5 mg/kg) at baseline, at weeks 2 and 6, and every 4 weeks through week 30, after which the infusion interval was increased (week 36, 48).

Results

All patients met the primary outcome by achieving quiescence of their active scleritis by week 14 with no additional immunosuppressives. However, after 14 weeks 1 patient developed new-onset intraocular inflammation that did not respond to reinduction and was terminated from the study. Side effects attributable to infliximab included ear infection with transient decreased hearing, urinary tract infection, lower respiratory tract infection, and facial rash in 1 patient and urinary tract infection, diarrhea, upper respiratory tract infection, nasal congestion and headache, mouth sores, head tremor, and occasional numbness and tingling in extremities in another patient, all of which resolved spontaneously or with appropriate treatment.

Conclusions

Infliximab may be considered as a viable option in treating patients with active scleritis; however, patients should be monitored closely for potentially serious side effects.

Purpose

To report an unusual case of granulomatous sclerochoroiditis.

Design

Interventional case report.

Methods

A patient with ANCA-associated granulomatous vasculitis presented with nodular necrotizing scleritis, which was recalcitrant to multiple systemic immunosuppressive therapies and progressed to a blind painful eye, which was enucleated.

Results

Histopathology revealed extensive occlusive vasculitis, diffuse T- and B- cellular infiltration, and lymphoid granulomatous formation. Enhanced MHC class II antigens, adhesion molecules, and Fas (CD95) and FasL (CD95L) were detected in the lesion.

Conclusion

Granulomatous sclerochoroiditis with aggressive immune reaction can be a complication of ANCA-associated granulomatous vasculitis.

Background

The goal of the present study was to analyze differences in response to treatment of ocular Behcet’s disease (BD) in the 1960’s, 1980’s and 1990’s.

Methods

Medical records of 120 patients with uveitis due to BD followed at the National Eye Institute (NEI), National Institutes of Health, from 1962 to 2004 were reviewed.

Results

All the patients were categorized in 3 groups according to the time of follow-up: first group was followed from 1962 until 1972, second group from 1983 until 1992 and the third group from 1992 through 2004. Snellen visual acuity was converted to logMAR values. The range of values for inflammation was 0.5 (trace), 1 (mild), 2 (moderate) and 3 (severe). There were 45 patients (89 affected eyes) in the 1960’s group, 26 patients (52 eyes) in the 1980’s group and 49 patients (94 eyes) in the most recent group. Statistical analysis showed that the mean logMAR score decreased with each decade. Mean visual acuity in the 1990’s group was significantly better than in the previous decades (p<0.001 for the 1960’s group and p=0.019 for the 1980’s). The mean inflammation score was significantly higher in the 1960’s than in the subsequent decades (p<0.001 both for 1980’s and for the 1990’s).

Interpretation

BD is a severe blinding disorder. There was a definitive trend toward improvement in clinical outcome from the 1960’s to 1990’s. We attribute this trend to the introduction of newer, more potent corticosteroid-sparing agents and targeted therapy.

Context Whether immunosuppressive treatment adversely affects survival is unclear.

Objective To assess whether immunosuppressive drugs increase mortality.

Design Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases. Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage. The cohort’s mortality risk was compared with US vital statistics using standardised mortality ratios. Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis.

Setting Five tertiary ocular inflammation clinics.

Patients 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up.

Exposures Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors.

Main outcome measures Overall mortality, cancer mortality.

Results Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/100 person years), 230 (24.6%) from cancer. For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population. Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs. In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased. Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01).

Conclusions Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality. Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.

We report a case of T-cell lymphoma metastatic to the eye, with an accompanying review of the literature. A 78-year-old Caucasian male with bilateral vitritis was diagnosed with primary cutaneous peripheral T-cell lymphoma (PCPTCL) unspecified, via vitreous biopsy. The tumor was found to be clonally related to the prior cutaneous malignancy using cytology, immunophenotyping and molecular analysis. The vast majority of primary intraocular lymphomas are malignant B-cells, while intraocular T-cell lymphomas are uncommon. This case demonstrates the utility of immunophenotyping and molecular analysis with microdissection and polymerase chain reaction, as critical adjunctive studies, in patients presenting with a masquerade syndrome, and later diagnosed with T-cell intraocular lymphomas. Vitreo-retinal without uveal involvement in this case, similar to many ocular metastatic T-cell lymphomas reported in the literature, is particularly intriguing since the uvea, not retina, is the typical ocular tissue involvement in the majority of metastatic B-cell lymphomas.

Purpose

To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Behçet’s disease.

Design

Randomized, placebo-controlled, double-masked clinical trial.

Participants

Seventeen participants with Behçet’s disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Behçet’s disease.

Methods

Participants received either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for six weeks, then every four weeks while continuing their standard immunosuppressive regimens. If clinically indicated, tapering of the standard immunosuppressive medications was allowed after six months of study enrollment. Complete ocular and physical examinations and an adverse event assessment were performed at baseline and prior to each study infusion.

Main Outcome Measures

Primary safety endpoints were the development of a life-threatening complication or a severe opportunistic infection. Primary efficacy outcomes were the number of ocular attacks and an assessment of systemic immunosuppressive medications required during the study, including the ability to taper concomitant immunosuppressive therapy.

Results

Nine participants randomized to daclizumab and eight to placebo were followed monthly. Follow-up ranged from one to 34 months, with a median follow-up of 15 months. Two participants randomized to daclizumab discontinued study therapy prior to the end of the study for personal reasons. No participant experienced a safety endpoint, and visual acuity remained stable in all participants during the course of the study. Ten participants (six daclizumab, four placebo) experienced ocular attacks requiring therapy. The median ocular attack rate during the study was greater in the daclizumab arm than the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants in the placebo arm also experienced a greater reduction in the immunosuppressive medication score compared to participants receiving daclizumab (median −4.0 vs. −1.0, respectively).

Conclusions

The observed results in the placebo group demonstrate that careful follow-up and treatment with standard combination immunosuppressive therapy can be effective for the management of the ocular complications of Behçet’s disease. In our small study, there was no suggestion that daclizumab was beneficial in comparison with placebo. However, the low observed attack rate limited our ability to make a definitive treatment group comparison.

Non-Hodgkin’s lymphoma is the sixth leading cause of cancer death in the USA. Herein, a patient is presented with primary diffuse large B-cell lymphoma whose initial complaint was blurred vision and who presented with corticosteroid-responsive serous retinal detachments mimicking Vogt–Koynagi–Harada. Extensive clinical examination including imaging and blood testing was negative. Splenectomy led to a diagnosis of splenic lymphoma