Time filter

Source Type

Yang P.,Massachusetts Eye Research and Surgery Institution | Yang P.,Ocular Immunology and Uveitis Foundation | Foster C.S.,Massachusetts Eye Research and Surgery Institution | Foster C.S.,Ocular Immunology and Uveitis Foundation | Foster C.S.,Harvard University
American Journal of Ophthalmology | Year: 2013

Purpose: To determine the peripheral levels of 20 immune mediators in serum samples from patients with birdshot retinochoroidopathy (BSRC). Design: Single-center prospective case-control study. Methods: The serum of 17 BSRC patients during different phases of disease activity and therapy were analyzed with a quantitative multiplex sandwich enzyme-linked immunosorbent assay-based microarray to determine the levels of 20 immune mediators (T cell and proinflammatory). The serum of 12 healthy volunteers was used as controls. Results: Serum levels of interleukin (IL)-21 (P =.0005), IL-23 (P =.0005), and transforming growth factor (TGF)-β1 (P =.0011) were elevated in BSRC patients with active disease naïve to systemic therapy compared with that of controls. There was no significant difference in the serum levels of immune mediators between controls and BSRC patients who had a current or past history of IMT or who were in remission. The levels of IL-21, IL-23, and TGF-β1 were positively correlated (IL-23/IL-21, r = 0.91; TGF-β1/IL-21, r = 0.97; TGF-β1/IL-23, r = 0.87; for all, P <.0001). Conclusions: BSRC patients with active disease naïve to systemic therapy have elevated serum levels of 3 key immune mediators known to promote T helper 17 (Th17) cells in autoimmune disease. Our results suggest that IL-21, IL-23, and TGF-β1 may play an important role in the development of site-specific Th17 cell-mediated inflammation in BSRC, which underscore the importance of systemic therapy and offer new insights into the potential of targeted treatments. © 2013 Elsevier Inc. All rights reserved.


Foster C.S.,Massachusetts Eye Research and Surgery Institution | Chang P.Y.,Massachusetts Eye Research and Surgery Institution | Ahmed A.R.,Center for Blistering Diseases
Ophthalmology | Year: 2010

Purpose: To compare the effectiveness and safety of the combination therapy of rituximab (RTX) and intravenous immunoglobulin (IVIg) to other immunosuppressive regimens in the treatment of ocular cicatricial pemphigoid (OCP). Design: Retrospective, comparative, interventional case series. Participants: Twelve patients with OCP. Methods: We reviewed medical records of 12 patients with OCP. Ten of the 12 patients were blind in 1 eye after initial systemic immunosuppressive therapies (phase 1 treatment). The patients were then divided into 2 groups based on treatments received during phase 2. The study group consisted of 6 patients who received the combination of RTX and IVIg during phase 2 of their treatment. For comparison purposes, the control group consisted of 6 patients who during phase 2 of their treatment received more aggressive immunosuppressive therapies, but not RTX and IVIg, because the insurance carriers refused to pay for the combination therapy. Main Outcome Measures: Blindness (best-corrected visual acuity [BCVA] ≤20/200) and OCP staging (Foster). Results: The median total follow-up periods were 57.5 and 55.5 months in the control group and the study group, respectively. After phase 1 treatment, all 6 patients in the control group were blind in 1 eye. Similarly, 4 of the patients in the study group were blind in 1 eye, whereas 2 had good BCVA bilaterally but experienced persistent conjunctival inflammation despite phase 1 treatment. After phase 2 treatment, all 6 patients in the control group had OCP progression and became blind in both eyes. In contrast, BCVA was stable and no further progression of OCP staging was observed in all 6 patients in the study group. In the study group, the median follow-up from completion of the RTX and IVIg treatment protocol was 11 months. No adverse events, immediate or delayed, were reported in any of the patients who received the combination therapy of RTX and IVIg. Conclusions: In this preliminary study, the combination therapy of RTX and IVIg arrested disease progression and prevented total blindness in patients with recalcitrant OCP. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. © 2010 American Academy of Ophthalmology.


Silpa-archa S.,Massachusetts Eye Research and Surgery Institution
Retina | Year: 2016

PURPOSE:: To identify prognostic factors for poor visual outcome in patients with birdshot retinochoroidopathy. METHODS:: A case–control study of 98 patients with birdshot retinochoroidopathy (196 eyes) was evaluated with a follow-up period of at least 12 months. After exclusion of glaucoma, optic atrophy, and macular scar, the remaining eligible patients were categorized into two groups: poor visual outcomes and good visual outcomes. Poor visual outcome was defined as less than −6 mean deviation score on Swedish interactive threshold algorithm (SITA) short-wavelength automated perimetry (SWAP) test and abnormality (amplitude or implicit time) of 30 Hz flicker electroretinogram at 4-year follow-up and at the most recent visit for separate analysis. Potential factors between both groups were statistically analyzed by Chi-square test and logistic regression model. RESULTS:: After the aforementioned exclusion, the remaining 77 patients with an average follow-up period of 52 ± 29 months (335 person-years, 36% with follow-up of more than 5 years) were divided into two groups. Sixteen patients were categorized as having poor visual outcome. Univariate analysis identified significant association of abnormal 30 Hz flicker electroretinogram amplitude (P = 0.004), implicit time (P = 0.002), and SITA SWAP mean deviation at the initial visit (P < 0.001) in the poor visual outcome group. Multivariate logistic regression analysis identified only SITA SWAP mean deviation to be associated with poor visual outcome (adjusted odds ratio, 32.50; 95% confidence interval [3.84–275.32]; P = 0.001) at the initial visit. To verify the model validity, an analysis of 42 patients at 4-year follow-up was performed and the outcome was confirmed (adjusted odds ratio, 8.80; 95% confidence interval [1.58–49.16]; P = 0.013). CONCLUSION:: Worse SITA SWAP mean deviation at the initial visit is a predictor of poor visual outcome in patients with birdshot retinochoroidopathy, and may serve as a proxy marker for delayed effective steroid sparing therapy in patients with birdshot retinochoroidopathy. © 2016 by Ophthalmic Communications Society, Inc.


Maleki A.,Massachusetts Eye Research and Surgery Institution
Retina | Year: 2016

PURPOSE:: To describe the clinical course, visual outcome, and prognosis of isolated, idiopathic retinal vasculitis. METHODS:: Eighty patients (150 eyes) with isolated, idiopathic retinal vasculitis were included. Demographic data, clinical data, complications at the initial visit and during follow-up, fluorescein angiography, and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution (MERSI) database from September 2005 to February 2015. RESULTS:: Seventy-five (93.7%) patients required treatment with immunomodulatory therapy. Of those 75 patients, 60 (75%) patients were able to achieve durable remission. Factors which were independently significant predictive of poor visual outcome were lower initial visual acuity (OR: 3.78; 95% CI: 1.75–8.16; P = 0.001), cystoid macular edema (OR: 5.54; 95% CI: 1.81–16.99; P = 0.003), and macular ischemia (OR: 5.12; 95% CI: 1.12–23.04; P = 0.036). CONCLUSION:: The majority (67.25%) of our patients enjoyed a good visual outcome (most recent visit best-corrected visual acuity equal to or better than 20/40 and within one line or better from the baseline) with immunomodulatory therapy. We found that cystoid macular edema, macular ischemia, and lower best-corrected visual acuity during the first consultation visit were significant independent risk factors for poor visual outcome. © 2016 by Ophthalmic Communications Society, Inc.


Silpa-archa S.,Massachusetts Eye Research and Surgery Institution
Retina | Year: 2016

PURPOSE:: To describe changes in three-dimensional choroidal volume and thickness with full raster scans of enhanced depth imaging optical coherence tomography in patients with birdshot retinochoroidopathy. METHODS:: This prospective case series collected spectral domain optical coherence tomography images with the enhanced depth imaging technique from eight eyes of eight patients with birdshot retinochoroidopathy including four active patients (four eyes) and four quiet patients (four eyes). Fifty scans of each patient were manually segmented before automated built-in calibration software was used. RESULTS:: Of all active patients, there were no statistically significant differences in the total choroidal volume and mean central choroidal thickness between the active and inactive phase over 6 months of follow-up. Alterations in choroidal parameters were evident and consistent after amelioration of inflammation, whereas the retinal volume and thickness remained stable. Regarding the eight inactive eyes at 6 months, the mean total choroidal volume and mean central choroidal thickness were significantly less than historical controls (P = 0.03 and P < 0.001, respectively). Persistent suprachoroidal hyporeflective space in two patients was noted despite the fact that clinical inflammation completely subsided at 6 months. CONCLUSION:: Choroidal volume and thickness changes were consistent with inflammation in patients with birdshot retinochoroidopathy. Patients with inactive birdshot retinochoroidopathy have significant reduction in choroidal volume and thickness than do normal patients. © 2016 by Ophthalmic Communications Society, Inc.


Kruh J.,Massachusetts Eye Research and Surgery Institution | Foster C.S.,Massachusetts Eye Research and Surgery Institution
Developments in Ophthalmology | Year: 2012

The introduction of corticosteroids in the mid-20th century to control inflammatory eye disease revolutionized treatment practices. As long-term use of corticosteroids became the backbone of immunosuppressive therapy, it soon became evident that it was associated with significant morbidity to the patient. For this reason, other immunosuppressant agents were sought. Thereafter, the first generation of immunosuppressive agents were born. The main action of all such agents involves the inhibition of lymphoid proliferation. The agents can be further subdivided into the following categories based on their specific mechanism of action: alkylating (cyclophosphamide and chlorambucil), antimetabolite (methotrexate, mycophenolate mofetil and azathioprine), and antibiotic/calcineurin inhibitor (cyclosporine, tacrolimus and sirolimus). These immunomodulating agents serve as the foundation to modern corticosteroid- sparing immunosuppressive therapy. Many times, these agents are now even indicated as first-line therapy for the treatment of systemic inflammatory diseases with destructive ocular sequela, e.g. Behet's disease and granulomatosis with polyangiitis (Wegener's). Choosing the most appropriate immunomodulatory agent to initiate therapy can often be difficult; a multifactorial approach in the decision-making process is essential. Special attention must be given to the patient's medical history, type and severity of inflammatory disease, social history, compliance, age, and sex. Oftentimes, it takes a joint effort between the ophthalmologist and multiple sub-specialists (rheumatology, oncology, and hematology) to administer and monitor these therapies. Even though each of these systemic immunosuppressive agents has its own array of potential side effects, with careful monitoring and titration of dosages, such potential side effects can be minimized or avoided altogether. Ultimately, these patients are afforded a much more favorable long-term outcome, free of the devastating effects of chronic corticosteroid use. Copyright © 2012 S. Karger AG, Basel.


Ebrahimiadib N.,Massachusetts Eye Research and Surgery Institution
Cornea | Year: 2016

PURPOSE:: Management of granulomatosis with polyangiitis (GPA)–associated peripheral ulcerative keratitis (PUK) is challenging and lacks definite guidelines. We aimed to summarize our treatment and outcome experience with patients with GPA-PUK. METHODS:: The Massachusetts Eye Research and Surgery Institution patient database was searched from 2005 to 2015 to identify patients with diagnosis of PUK who suffered from GPA. Individual patient histories were examined, and treatment strategies and outcomes were summarized. RESULTS:: There were 16 patients who started treatment with a mean duration follow-up of 64 months (range: 12–110 mo). Rituximab and cyclophosphamide, either alone or in combination with other agents, were the most successful agents in controlling inflammation. Rituximab was administered in 11 patients with remission being achieved in all. Cyclophosphamide successfully controlled inflammation in 50% (5/10). Two of the patients (2/5, 40%) who had achieved initial control on cyclophosphamide had flares of their PUK. Two of 11 (18%) patients on rituximab had flares of scleritis and orbital inflammation but not PUK. Two patients, one in each treatment group, stopped treatment after achieving remission after 6 months of therapy but suffered disease recurrence within 2 months of treatment cessation. CONCLUSIONS:: Rituximab achieved a high rate of disease control in PUK patients with GPA and is the preferred agent in halting disease progression. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Lee F.F.,Massachusetts Eye Research and Surgery Institution | Foster C.S.,Massachusetts Eye Research and Surgery Institution
Expert Opinion on Pharmacotherapy | Year: 2010

Importance of the field: The term 'uveitis' covers a broad spectrum of ocular inflammation affecting the iris, ciliary body, and/or the choroid, all of which comprise the uveal tract. Severe cases of uveitis need be treated aggressively to prevent damage caused by chronic inflammation. Untreated or poorly managed cases can lead to ciliary body dysfunction, inadequate aqueous production, chorioretinal damage, and possibly blindness. Areas covered in this review: There are many medications that can be used to treat uveitis. Corticosteroids are available in several formulations: topical drops, regional injections, oral and intravenous. Immunomodulatory agents that can be used for uveitis are antimetabolites, T-cell inhibitors, alkylating agents, and biologic response modifiers. These medications, their appropriate uses, and side effect monitoring will be detailed. What the reader will gain: There is a stepladder approach to treatment of ocular inflammation. Corticosteroids are the treatment of choice for treating acute flares. Steroid free remission is the goal of therapy and can be achieved with the use of chemotherapeutic agents. Which medications are appropriate and how to escalate therapy will be reviewed. Take home message: Chronic systemic corticosteroid therapy is not an acceptable long treatment plan for uveitis, unless all other medications have failed. Steroid sparing immunosuppressive therapy should be pursued as soon as acute flares of uveitis have been controlled. © 2010 Informa UK Ltd.


Arcinue C.A.,Massachusetts Eye Research and Surgery Institution
Ocular immunology and inflammation | Year: 2013

To compare the efficacy and safety of cyclosporine/mycophenolate mofetil (CSA/MMF) and cyclosporine/azathioprine (CSA/AZT) in Vogt-Koyonagi-Harada (VKH) patients. Retrospective comparative case series with follow-up period of at least 1 year. Outcomes include remission rate and corticosteroid-sparing effect. A total of 10 patients were included (5 patients in CSA/MMF, 5 patients in CSA/AZT). The remission rates for CSA/MMF and CSA/AZT were 5.3 and 5.6, respectively (p = .96). The median time to remission was 15 months for CSA/MMF group and 7 months for CSA/AZT group (p = .6419). The rates of corticosteroid-sparing effect were 7.9 and 5.0 for the CSA/MMF and CSA/AZT groups, respectively (p = .65). The median time to corticosteroid-sparing effect was faster in the CSA/AZT group (2 months) compared to the CSA/MMF group (13 months) (p = .9625). Approximately 50% of patients failed with the presented IMT combination regimens. No statistically significant difference was found in the two regimens from the study as presented, although the median time to remission and to corticosteroid-sparing effect was shorter for the CSA/AZT combination.


Kruh J.,Massachusetts Eye Research and Surgery Institution | Foster C.S.,Massachusetts Eye Research and Surgery Institution
Developments in Ophthalmology | Year: 2012

Treatment of inflammatory diseases of the eye is especially challenging. Although physicians in antiquity had recognized the existence of ocular inflammatory disease, their lack of understanding of the immune system made successful treatment almost impossible. Throughout the 20th century, great advances in the diagnosis and treatment of uveitis led to unique treatment options. The development of corticosteroids in 1949 and its application to the eye in 1950 revolutionized therapeutic strategies. As the use of corticosteroids became more prevalent in treating ocular inflammatory diseases, so did its side effects. Due to the high morbidity in conjunction with long-term corticosteroid use, physicians pursued other agents, specifically through the employment of chemotherapeutic agents. The shift from exclusive corticosteroid monotherapy to steroid-sparing immunomodulatory therapy reshaped the landscape of treating ocular inflammatory disease. Over time, with increased efforts, new therapies were studied, trialed, and brought to the market. Today, in comparison to any other time in history, physicians have available to them the largest array of effective agents for achieving the ultimate goal: corticosteroid-free, durable remission. Copyright © 2012 S. Karger AG, Basel.

Loading Massachusetts Eye Research and Surgery Institution collaborators
Loading Massachusetts Eye Research and Surgery Institution collaborators