Ebenezer Daniel

University of Pennsylvania, Philadelphia, PA, USA

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Publications (27)71.19 Total impact

  • Article: Risk Factors for Loss of Visual Acuity among Patients with Uveitis Associated with Juvenile Idiopathic Arthritis: The Systemic Immunosuppressive Therapy for Eye Diseases Study.
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    ABSTRACT: PURPOSE: To describe the incidence of and risk factors for visual acuity (VA) loss and ocular complications in patients with juvenile idiopathic arthritis (JIA)-associated uveitis. DESIGN: Multicenter retrospective cohort study. PARTICIPANTS: A total of 327 patients (596 affected eyes) with JIA-associated uveitis managed at 5 tertiary uveitis clinics in the United States. METHODS: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) cohort study. Demographic and clinical characteristics were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. MAIN OUTCOME MEASURES: Loss of VA to 20/50 or to 20/200 or worse thresholds and the development of ocular complications. RESULTS: At presentation, 240 eyes (40.3%) had a VA of ≤20/50, 144 eyes (24.2%) had a VA of ≤20/200, and 359 eyes (60.2%) had at least 1 ocular complication. The incidences of VA loss to the ≤20/50 and ≤20/200 thresholds were 0.18 and 0.09 per eye-year (EY), respectively; the incidence of developing at least 1 new ocular complication over follow-up was 0.15/EY (95% confidence interval [CI], 0.13-0.17). However, among eyes with uveitis that had no complications at presentation, the rate of developing at least 1 ocular complication during follow-up was lower (0.04/EY; 95% CI, 0.02-0.06). Posterior synechiae, active uveitis, and prior intraocular surgery were statistically significantly associated with VA to the ≤20/50 and ≤20/200 thresholds both at presentation and during follow-up. Increasing (time-updated) anterior chamber cell grade was associated with increased rates of visual loss in a dose-dependent fashion. Use of immunosuppressive drugs was associated with a reduced risk of visual loss, particularly for the ≤20/50 outcome (hazard ratio, 0.40; 95% CI, 0.21-0.75; P<0.01). CONCLUSIONS: Ocular complications and vision loss were common in our cohort. Increasing uveitis activity was associated with increased risk of vision loss, and use of immunosuppressive drugs was associated with reduced risk of vision loss, suggesting that control of inflammation and use of immunosuppression may be critical aspects in improving the outcomes of patients with JIA-related uveitis. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
    Ophthalmology 10/2012; · 5.45 Impact Factor
  • Article: Risk of Hypotony in Noninfectious Uveitis.
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    ABSTRACT: OBJECTIVE: We sought to describe the risk and risk factors for hypotony in a noninfectious uveitis cohort. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with noninfectious uveitis seen between 1979 and 2007 at 4 academic ocular inflammation specialty clinics. METHODS: Data were collected from medical records by trained, certified, expert reviewers. MAIN OUTCOME MEASURES: Hypotony (<5 mmHg) and low intraocular pressure (<8 mmHg), each sustained for ≥2 visits spanning ≥30 days. RESULTS: During follow-up, 126 of 6785 patients (1.86%) developed hypotony at the rate of 0.61% (95% confidence interval [CI], 0.50-0.75%) per eye-year. Cataract surgery was associated with a 7.5-fold risk (adjusted hazard ratio [aHR], 7.51; 95% CI, 3.97-14.23) of incident hypotony. Phacoemulsification, the type of cataract surgery associated with the least hypotony risk still was associated with nearly 5-fold higher hypotony incidence (aHR, 4.87; 95% CI, 2.25-10.55). Increased risk was observed in children (aHR, 2.92; 95% CI, 1.20-7.10) with respect to young adults, and duration of uveitis of >5 years (aHR, 3.08; 95% CI, 1.30-7.31) with respect to uveitis of <6 month duration. Band keratopathy, ≥3+ vitreous cells, exudative retinal detachment, posterior synechia, and a history of pars plana vitrectomy also were associated with greater hypotony incidence. With respect to anterior uveitis, intermediate uveitis (aHR, 0.17; 95% CI, 0.05-0.56) and posterior uveitis (aHR, 0.11; 95% CI, 0.03-0.45) were associated with lower hypotony risk, whereas panuveitis (aHR, 1.25; 95% CI, 0.67-2.35) was similar. Approximately five-sixths (84.1%) of eyes presenting with hypotony had a visual acuity of ≤20/200 (aOR for visual acuity ≤20/200, 13.85; 95% CI, 7.23-26.53). Risk factors for prevalent hypotony were similar. CONCLUSIONS: The risk of hypotony is low among eyes with noninfectious uveitis, but is more frequently observed in cases with anterior segment inflammation. Signs of present or past inflammation were associated with greater risk, suggesting excellent inflammatory control may reduce the risk of hypotony. Prior ocular surgery also was associated with higher risk; cataract surgery in particular was associated with much higher risk of hypotony. Lower risk of hypotony with phacoemulsification than with alternative cataract surgery approaches suggests the phacoemulsification approach is preferable. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
    Ophthalmology 07/2012; · 5.45 Impact Factor
  • Article: Risk of corticosteroid-induced hyperglycemia requiring medical therapy among patients with inflammatory eye diseases.
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    ABSTRACT: To identify the incidence and risk factors for corticosteroid-induced hyperglycemia requiring medical therapy among patients with inflammatory eye diseases. Retrospective cohort study. Patients with ocular inflammation followed at 5 United States tertiary centers that initially were neither diabetic nor taking hypoglycemic medications. Eligible patients who used oral corticosteroids during follow-up were identified and followed longitudinally for initiation of hypoglycemic medication over 1 year after beginning corticosteroids. The remaining eligible patients were followed for 1 year after their initial visit. Survival analysis was used to calculate the risk of hyperglycemia requiring medical therapy and to identify potential risk factors. Initiation of hypoglycemic medications. Among 2073 non-diabetic patients treated with oral corticosteroids, 25 (1.21%) initiated hypoglycemic therapy compared with 5 of 2666 patients (0.19%) not treated with oral corticosteroids (relative risk [RR], 4.39; 95% confidence interval [CI], 1.68-11.5). The RR tended to be higher in association with higher initial doses (for initial doses <40 mg of prednisone per day: RR, 3.23; 95% CI, 1.08-9.64; for initial prednisone dose ≥40 mg/d: RR, 5.51; 95% CI, 2.01-15.1). Other risk factors for the initiation of hypoglycemic therapy included older age (RR [per each additional 10 years], 1.46; 95% CI, 1.15-1.85; P = 0.002) and African-American race (RR, 2.94; 95% CI, 1.34-6.43; P = 0.007). These results suggest that the absolute risk of corticosteroid-induced hyperglycemia that is detected and treated with hypoglycemic therapy in the tertiary ocular inflammation setting is low (an excess cumulative risk on the order of 1% within 1 year), although on a relative scale it is approximately 4.4-fold higher than in patients not treated with oral corticosteroids. Older age and African-American race also were risk factors. Physicians who use systemic corticosteroids for ocular inflammatory diseases should be aware of this risk, and should consider surveillance for hyperglycemia among high-risk patients. However, given the low absolute risk, routine laboratory monitoring or referral for monitoring may not be necessary for low-risk patients.
    Ophthalmology 04/2012; 119(8):1569-74. · 5.45 Impact Factor
  • Article: Risk of relapse in primary acute anterior uveitis.
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    ABSTRACT: To evaluate the risk of and risk factors for a second episode (relapse) among patients with remitted primary anterior uveitis. Retrospective cohort study. Patients with primary anterior uveitis presenting to 1 of 4 academic ocular inflammation subspecialty practices achieving remission of the primary episode within 90 days of initial uveitis diagnosis. Data were obtained by standardized chart review. Time to relapse of anterior uveitis and risk factors for relapse. We included 102 patients with a first episode of anterior uveitis who 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- to 35-year-old persons vs. 35- to 55-year-old persons], 2.7; 95% CI, 1.3-6.0). 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. Proprietary or commercial disclosure may be found after the references.
    Ophthalmology 06/2011; 118(10):1911-5. · 5.45 Impact Factor
  • Article: Cyclosporine for ocular inflammatory diseases.
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    ABSTRACT: To evaluate the clinical outcomes of cyclosporine treatment for noninfectious ocular inflammation. Retrospective cohort study. A total of 373 patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to use cyclosporine as a single noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007 inclusive. 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. Control of inflammation, sustained control after reducing corticosteroid dosages, and discontinuation of therapy because of toxicity. Of the 373 patients (681 eyes) initiating cyclosporine monotherapy, 33.4% by 6 months and 51.9% by 1 year gained sustained, complete control of inflammation over at least 2 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 < or = 10 mg/day) was achieved by 22.1% by 6 months and 36.1% within 1 year. Toxicity led to discontinuation of therapy within 1 year by 10.7% of the population. Patients aged more than 55 years were more than 3-fold more likely to discontinue therapy because of toxicity than patients aged 18 to 39 years. Doses of 151 to 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 seem to offer a therapeutic advantage. Cyclosporine, with corticosteroid therapy as indicated, was modestly effective for controlling ocular inflammation. Our data support a preference for cyclosporine adult dosing between 151 and 250 mg/day. Although cyclosporine was tolerated by the majority of patients, toxicity was more frequent with increasing age; alternative agents may be preferred for patients aged more than 55 years.
    Ophthalmology 03/2010; 117(3):576-84. · 5.45 Impact Factor
  • Article: Mycophenolate mofetil for ocular inflammation.
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    ABSTRACT: To evaluate mycophenolate mofetil as a single noncorticosteroid immunosuppressive treatment for noninfectious ocular inflammatory diseases. Retrospective cohort study. Characteristics of patients with noninfectious ocular inflammation treated with mycophenolate mofetil at 4 subspecialty clinics from 1995 to 2007 were abstracted by expert reviewers in a standardized chart review of every eye at every visit. Main outcomes measured were control of inflammation, corticosteroid-sparing effects, and discontinuation of mycophenolate mofetil (including the reasons for discontinuation). Survival analysis was used to estimate the incidence of outcomes, and to identify risk factors for each. Among 236 patients (397 eyes) treated with mycophenolate mofetil monotherapy, 20.3%, 11.9%, and 39.8% had anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis respectively; 14% had scleritis; 7.6% had mucous membrane pemphigoid; and 6.4% had other ocular inflammatory diseases. By Kaplan-Meier estimation, complete control of inflammation--sustained over consecutive visits spanning at least 28 days--was achieved in 53% and 73% of patients within 6 months and 1 year respectively. Systemic corticosteroid dosage was reduced to 10 mg of prednisone or less, while maintaining sustained control of inflammation, in 41% and 55% of patients in 6 months and 1 year respectively. Twelve percent of patients discontinued mycophenolate mofetil within the first year because of side effects of therapy. Given sufficient time, mycophenolate mofetil was effective in managing ocular inflammation in approximately half of the treated patients. Treatment-limiting side effects were observed in 12% of patients and typically were reversible.
    American journal of ophthalmology 03/2010; 149(3):423-32.e1-2. · 3.83 Impact Factor
  • Article: Hypopyon in patients with uveitis.
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    ABSTRACT: To evaluate the risk of and risk factors for hypopyon among patients with uveitis and to evaluate the risk of visual changes and complications after hypopyon. Retrospective cohort study. Patients with uveitis at 4 academic ocular inflammation subspecialty practices. Data were ascertained by standardized chart review. Prevalence and incidence of hypopyon, risk factors for hypopyon, and incidence of visual acuity changes and ocular complications after hypopyon. Among 4911 patients with uveitis, 41 (8.3/1000) cases of hypopyon were identified at the time of cohort entry. Of these, 2885 initially free of hypopyon were followed over 9451 person-years, during which 81 patients (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), spondyloarthropathy (adjusted RR=2.86; 95% CI, 1.48-5.52), and human leukocyte antigen (HLA)-B27 positivity (adjusted RR=2.04; 95% CI, 1.17-3.56). Patients with both a spondyloarthropathy and HLA-B27 had a 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 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. Hypopyon is an uncommon occurrence in patients with uveitis. Risk factors included Behçet's disease, HLA-B27 positivity, and spondyloarthropathy. Intermediate uveitis cases (+/- anterior uveitis) had a lower risk of hypopyon. On average, post-hypopyon eyes were no more likely than other eyes with uveitis to develop structural ocular complications or lose visual acuity.
    Ophthalmology 12/2009; 117(2):366-72. · 5.45 Impact Factor
  • Article: Cyclophosphamide for ocular inflammatory diseases.
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    ABSTRACT: To evaluate the outcomes of cyclophosphamide therapy for noninfectious ocular inflammation. Retrospective cohort study. Two hundred fifteen patients with noninfectious ocular inflammation observed from initiation of cyclophosphamide. Patients initiating cyclophosphamide, without other immunosuppressive drugs (other than corticosteroids), were identified at 4 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. Control of inflammation, corticosteroid-sparing effects, and discontinuation of therapy. 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%) gained sustained control of inflammation 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 6 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 before 2 years was 63.1% (95% CI, 51.5%-74.8%). Cyclophosphamide was discontinued by 33.5% of patients within 1 year because of side effects, usually of a reversible nature. The data suggest that cyclophosphamide is effective for most patients for controlling inflammation and allowing tapering of systemic corticosteroids to 10 mg prednisone or less, although 1 year of therapy may be needed to achieve these goals. Unlike with most other immunosuppressive drugs, disease remission was induced by treatment in most patients who were able to tolerate therapy. 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 seems to be 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.
    Ophthalmology 12/2009; 117(2):356-65. · 5.45 Impact Factor
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    Article: Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study.
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    ABSTRACT: Whether immunosuppressive treatment adversely affects survival is unclear. To assess whether immunosuppressive drugs increase mortality. 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. 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. Overall mortality, cancer mortality. 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). 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.
    BMJ (Clinical research ed.). 02/2009; 339:b2480.
  • Article: Ocular inflammation in Behçet disease: incidence of ocular complications and of loss of visual acuity.
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    ABSTRACT: To estimate the risk of structural ocular complications and loss of visual acuity (VA) in cases of Behçet disease (BD) and to evaluate potential risk and protective factors for these events. Retrospective cohort study. A total of 168 consecutive patients with BD-associated ocular inflammation treated at five academic center ocular inflammation subspecialty practices were included. Clinical data for these patients were ascertained by standardized chart review. Main outcome measures included VA, structural ocular complications of inflammation, and intraocular pressure (IOP). 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 per eye-year (EY). Rates of loss of VA to 20/50 or worse and to 20/200 or worse were 0.12 per EY and 0.09 per EY, respectively. Risk factors for loss of VA 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 VA to 20/50 or worse (relative risk [RR], 2.45; 95% confidence interval [CI], 1.1 to 5.5; P = .03) and to 20/200 or worse (RR, 2.67; 95% CI, 1.2 to 5.8; P = .01). Loss of VA and occurrence of ocular complications were common in patients with ocular inflammation associated with BD, even with aggressive therapy. Ongoing inflammation during follow-up, presence or occurrence of posterior synechiae, hypotony, and elevated IOP were associated with an increased risk of loss of VA.
    American journal of ophthalmology 09/2008; 146(6):828-36. · 3.83 Impact Factor
  • Article: Recent advances in mucous membrane pemphigoid.
    Ebenezer Daniel, Jennifer E Thorne
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    ABSTRACT: The aim of this article is to review articles on mucous membrane pemphigoid published in the English literature from 2006 to 2007. The risk of ocular disease among patients with oral only mucous membrane pemphigoid is estimated at 15-20% at 5 years. Biopsy with direct immunofluorescent testing is essential to confirm the diagnosis because histopathology even with electron microscopy does not appear to be specific enough to confirm the diagnosis of mucous membrane pemphigoid with consistency. Autoantibodies to IgG and IgG4 appear to be the most common findings observed on direct immunofluorescent testing in patients with mucous membrane pemphigoid. Treatment for mucous membrane pemphigoid typically involves immunosuppressive drugs, including biologic therapy, as well as intravenous immunoglobulin, although results have been mixed and the majority of data reported still are from case series and anecdotal evidence. Mucous membrane pemphigoid continues to be a potentially life and sight threatening disease. Therapy for this disease continues to show varied results although benefits are clearly seen in some patients. The immunosuppressive drugs used for treating mucous membrane pemphigoid and certain definitive categories of mucous membrane pemphigoid continue to evolve.
    Current opinion in ophthalmology 08/2008; 19(4):292-7. · 2.49 Impact Factor
  • Article: Long-term risk of malignancy among patients treated with immunosuppressive agents for ocular inflammation: a critical assessment of the evidence.
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    ABSTRACT: To critically assess potentially carcinogenic effects of immunosuppressive therapy in the ocular inflammation setting. Focused evidence assessment. Relevant publications were identified by MEDLINE and EMBASE queries and reference list searches. 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 < or =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 six to 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 nontransplant data are limited for the latter agents. Immunosuppression in general may increase skin cancer risk in a sun exposure-dependent manner. 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.
    American journal of ophthalmology 06/2008; 146(6):802-12.e1. · 3.83 Impact Factor
  • Article: Smoking as a risk factor for cystoid macular edema complicating intermediate uveitis.
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    ABSTRACT: To describe risk factors for the presence of cystoid macular edema (CME) among patients presenting with intermediate uveitis. Cross-sectional study. Single-center, academic practice. Two hundred and eight patients with intermediate uveitis evaluated from July 1, 1984 through September 30, 2006. Clinical and demographic data were entered retrospectively into a database and analyzed. Presence of CME at presentation to our clinic; risk factors for presenting with CME. Of the 208 patients, 74% had bilateral intermediate uveitis, yielding 363 affected eyes. Eighty-nine patients (43%) had CME in at least one eye at the time of presentation to our clinic. After controlling for potentially confounding variables including demographics, duration of disease, active intraocular inflammation, history of diabetes mellitus or hypertension, and presence of epiretinal membrane, actively smoking at presentation was associated with a four-fold increased risk of CME at presentation vs never smoking (odds ratio (OR), 3.90; 95% confidence interval (CI), 1.43, 10.66; P = .008). Former smoking also appeared to increase the risk of CME at presentation in the multivariate analysis, but the result was of borderline statistical significance (OR, 1.97; 95% CI, 0.99, 3.94; P = .055). After adjusting for confounding, there was a 4% increased risk of CME at presentation for each cigarette smoked per day (OR, 1.04; 95% CI, 1.01, 1.7; P = .005). CME was a common structural ocular complication observed in our cohort. Current smoking was associated with a dose-dependent increased risk of having CME at the time of presentation to our clinic.
    American Journal of Ophthalmology 06/2008; 145(5):841-6. · 4.22 Impact Factor
  • Article: Evolution of vision reducing cataract in skin smear positive lepromatous patients: does it have an inflammatory basis?
    Ebenezer Daniel, P S S Sundar Rao
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    ABSTRACT: To describe the incidence and risk factors of vision reducing cataract in skin smear positive lepromatous patients. Prospective longitudinal cohort study: 212 newly diagnosed lepromatous patients were followed during the two years of treatment with multidrug therapy and for a further five years, with biannual ocular examinations. Incidence of vision reducing (< or =6/18) cataract was calculated as the number of patients with cataract per person year of cataract-free follow up among those who did not have cataract at baseline. Cataract was present in 27 (11%) of lepromatous patients at diagnosis. Forty nine patients (2.87%/person year (95% confidence interval (CI), 2.17% to 3.80%)) developed cataract during a total follow up period of 1704 person years; 45 of these were > or =41 years old and were followed for a total of 638 person years with an incident rate of 0.070 (95% CI, 0.0523 to 0.094). Stepwise multiple regression confirmed the association of age (per decade) (hazard ratio (HR) = 2.50 (95% CI, 1.82 to 2.78), p<0.001), clofazimine crystals on the cornea (HR = 49.92 (5.48 to 454.82), p = 0.001), grade 2 deformity in all limbs (HR = 3.17 (1.12 to 8.97), p = 0.029), and uveal inflammation (HR = 3.52 (1.42 to 8.67), p = 0.006). No significant association was found with oral steroids. Cataract develops at the rate of 7%/person year in lepromatous patients over 40 years of age. It is associated with increasing age, subclinical intraocular inflammation, and grade 2 deformity.
    British Journal of Ophthalmology 09/2007; 91(8):1011-3. · 2.90 Impact Factor
  • Article: Iris atrophy in patients with newly diagnosed multibacillary leprosy: at diagnosis, during and after completion of multidrug treatment.
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    ABSTRACT: To describe the prevalence and incidence of iris atrophy in patients with multibacillary (MB) leprosy. Methods and patients: Prospective longitudinal cohort study. 301 newly diagnosed patients with MB leprosy were followed up during the 2 years of treatment with multidrug therapy (MDT) and for a further 5 years with biannual ocular examinations. Incidence of iris atrophy was calculated as the number of patients with iris atrophy per person-year (PY) of follow-up among those who did not have iris atrophy at baseline. Stepwise multiple regression confirmed the presence of specific associations of demographic and clinical characteristics (p<0.05) with iris atrophy, detected by univariate analysis. Iris atrophy was present in 6 (2%) patients at enrolment. During MDT, with 445 PYs of follow-up, 9 patients developed iris atrophy (IR 0.02, 95% CI 0.01 to 0.04) that was associated with cataract (HR 15.13, 95% CI 3.71 to 61.79, p<0.001) and corneal opacities (HR 6.83, 95% CI 1.62 to 28.8, p = 0.009). After MDT, with 2005 PYs of follow-up, 60 patients developed iris atrophy (IR 0.03, 95% CI 0.023 to 0.039) that was associated with age (per decade; HR 1.40, 95% CI 1.10 to 1.78, p = 0.006), skin smear positivity (HR 3.50, 95% CI 1.33 to 9.24, p = 0.011), cataract (HR 3.66, 95% CI 1.85 to 7.25, p<0.001), keratic precipitates (HR 2.76, 95% CI 1.02 to 7.47, p = 0.046) and corneal opacity (HR 3.95, 95% CI 1.86 to 8.38, p<0.001). Iris atrophy continues to develop in 3% of patients with MB leprosy every year after they complete a 2-year course of MDT, and is associated with age, increasing loads of mycobacteria, subclinical inflammation, cataract and corneal opacity.
    British Journal of Ophthalmology 08/2007; 91(8):1019-22. · 2.90 Impact Factor
  • Article: Recurrent nodular scleritis preceding an adult TINU syndrome.
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    ABSTRACT: To describe the occurrence of nodular scleritis in a patient developing tubulointerstitial nephritis and uveitis (TINU) syndrome. Observational case report. The case notes of a 57-year-old female presenting with recurrent nodular scleritis, who later developed interstitial nephritis with bilateral uveitis, were reviewed. Common and established causes of scleritis were not present in an adult who developed the TINU syndrome a decade later. Although scleritis has not been reported as a tubulointerstitial nephritis-associated ocular inflammation, it may be part of the possible spectrum of ocular inflammation occurring as part of the TINU syndrome.
    Ocular Immunology and Inflammation 09/2006; 14(4):239-40. · 1.25 Impact Factor
  • Article: Impaired contrast sensitivity among leprosy patients with normal visual acuity.
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    ABSTRACT: Contrast sensitivity is a person's ability to identify an object from its background. Patients with normal visual acuity can have reduced contrast sensitivity and may experience trouble in identifying objects at night or moving around in dimly lit places. Contrast sensitivity has never been studied in leprosy patients having normal visual acuity. This study aimed to determine if contrast sensitivity is impaired in leprosy patients who have normal visual acuity and to identify possible associations with demographic, leprosy and ocular characteristics. A hospital based study measuring and comparing contrast sensitivity using the VCT 6500 chart in 127 consecutive leprosy patients without clinically apparent ocular complications and 123 non-leprosy controls was done. Contrast sensitivity was impaired in leprosy patients in all five spatial frequencies (1.5, 3.0, 6.0, 12 and 18 cycles/degree) investigated. Among leprosy patients, contrast sensitivity falling outside the normative range was associated with increasing age (adjusted OR 1.28, 95% CI: 1.14-1.42), being female (adjusted OR 11.05, 95% CI: 2.93-41.69) and having a grade 2 deformity (adjusted OR 6.43, 95% CI:1.68-24.61). Contrast sensitivity is impaired in leprosy patients having normal visual acuity. Elderly, deformed, female patients are particularly burdened with this vision loss.
    Leprosy review 04/2005; 76(1):55-64. · 1.04 Impact Factor
  • Article: Anesthesia of face uncovered by histopathology.
    Ebenezer Daniel, Gigi Ebenezer
    International Journal of Leprosy and Other Mycobacterial Diseases 04/2005; 73(1):22-4. · 0.22 Impact Factor
  • Article: Mycobacterium leprae infection and serum lactoferrin levels.
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    ABSTRACT: Serum lactoferrin level, using competitive enzyme linked immunosorbent assay (ELISA) method, was estimated in 298 leprosy patients admitted into the hospital and attending the out-patient department of the Schieffelin Leprosy Research and Training Center. Serum from an equal number of non-leprosy individuals served as control. Mean (SD) of serum lactoferrin in non-leprosy individuals was 0.277 (0-092) microg/ml while in leprosy patients it was 0.494 (0.394) microg/ml, the difference being significant (P=0.0001). Serum lactoferrin levels were not significantly associated with type 2 reactions (P=0.613). Serum lactoferrin was significantly associated with age (P = 0.006), duration of the disease (P=0.0001), DDS monotherapy (P =0.007), deformity (P= 0.005), average bacterial index (BI) (P=0.01) and smear positivity (P=0.0001), orbicularis oculi weakness (P= 0.001), lagophthalmos (P = 0.002), corneal opacity (P = 0.001) and cataract (P=0.004) in simple regression analysis. All these variables, with the exception of smear positivity (P=0.019), lost their significance (P>0.05) when analysed using multiple regression. Serum lactoferrin showed poor association with type 1 (P = 0.286) and type II reactions (P = 0.613) and iridocyclitis (P = 0.207). We conclude that serum lactoferrin is strongly and inversely associated with increasing BI but does not show significant association with type 2 reactions.
    Leprosy review 10/2004; 75(3):282-8. · 1.04 Impact Factor
  • Article: Elevated free tear lactoferrin levels in leprosy are associated with Type 2 reactions.
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    ABSTRACT: To determine the association of demographics, leprosy and ocular characteristics with altered levels of lactoferrin in the tears of normal subjects and leprosy patients, and to detect the presence of antibodies to lactoferrin in these tear samples. We collected light-stimulated tears from 298 leprosy patients and an equal number of normal subjects using the glass capillary method. Free lactoferrin levels were estimated using ELISA and the presence of antibodies to lactoferrin was detected using the immuno-blotting method. Significant associations were looked for between tear lactoferrin levels and demographic characteristics, leprosy characteristics such as type of disease, duration of disease, reactions, deformity and bacterial load, and ocular complications, using chi-square and regression analysis. Tear lactoferrin levels with a mean (SD) of 2.55 (2.83)mg/ml in the control group were significantly different (P<0.000) from leprosy patients with a smean (SD) of 5.66 (7.21)mg/ml. Age showed an inverse correlation with tear lactoferrin levels in controls. Increased bacterial load, grade 2 leg deformity and Type 2 reactions were significantly associated (P<0.05) with increased tear lactoferrin levels. Type 2 reactions remained significantly associated (P=0.01) on multiple regression analysis. Tear lactoferrin levels were not associated with gender, serum lactoferrin levels, Type 1 reactions, face patches, treatment status, orbicularis oculi weakness, lagophthalmos, ectropion, entropion, corneal opacity, cataract and iridocyclitis. Age is inversely related to tear lactoferrin levels in normal subjects. Free lactoferrin levels in tears are significantly higher in leprosy patients compared with normal controls. Type 2 reactions in leprosy are significantly associated with elevated tear lactoferrin levels.
    Indian Journal of Ophthalmology 04/2004; 52(1):51-6. · 1.02 Impact Factor

Institutions

  • 2009–2012
    • University of Pennsylvania
      • Department of Ophthalmology
      Philadelphia, PA, USA
    • Massachusetts Eye and Ear Infirmary
      Boston, MA, USA
  • 2006–2012
    • Johns Hopkins University
      Baltimore, MD, USA
  • 2010
    • Hospital of the University of Pennsylvania
      Philadelphia, PA, USA
    • Mount Sinai School of Medicine
      • Department of Ophthalmology
      Manhattan, NY, USA