Pulsed Low-dose Intravenous Methotrexate for the Treatment of Recalcitrant, Chronic Ocular Inflammation
Karina Quinones, MD, Pooja Bhat, MD, C. Stephen Foster, MD Massachusetts Eye Research & Surgery Institute, Cambridge, MA
Purpose: To report our experience with intravenous Methotrexate (IV-MTX) as an induction agent to control acute episodes of ocular inflammation.
Methods: Retrospective chart review of 8 patients (14 eyes) with active disease that received an average of 6.1 ± 3.6 infusions (25100 mg) followed by oral or subcutaneous MTX in 4 patients.
Results: Over 5.8 ± 0.88 months, disease activity improved in 78.6% of eyes. Topical corticosteroid therapy was reduced in all patients, and oral corticosteroids were discontinued in 2 patients. Mean visual acuity (log MAR) increased from 0.25 ± 6 lines at baseline to 0.4 ± 4.8 lines and 0.45 ± 6.9 lines at I and 3 months, respectively. Three eyes underwent successful cataract surgery. IV MTX was interrupted in 2 cases, due to transient leukopenia and uncontrolled inflammation, respectively.
Conclusions: IV MTX appears to be a well tolerated and useful agent.
Daclizumab in the Treatment ofRecalcitrant Ocular Inflammatory Disease
Pooja Bhat MD, Rene A. Cervantes-Castaneda MD, Priyanka Doctor MD, C. Stephen Foster, MD Massachusetts Eye Research & Surgery Institute, Cambridge, MA
Purpose: To evaluate outcomes ofpatients with recalcitrant ocular inflammation treated with intravenous daclizumab.
Design: Retrospective case-series.
Participants: Seventeen patients (33 eyes) with ocular inflammation who had failed several previous systemic immunomodulatory therapies were included in this study.
Methods: Dac1izumab was infused intravenously at a dose of Img per kilogram every 2 weeks. The dose and intervals were adjusted according to control of inflammation off systemic and/or topical corticosteroid therapy.
Outcome measures: Control ofocular inflammation without corticosteroid therapy was the primary efficacy end point.
Results: The mean patient age at the commencement ofdaclizumab therapy was 34.83(range, 8 to 64 years). Three patients were less than sixteen years of age at the initiation oftherapy. The duration ofdrug use was 23.61 ± 15.79 months (range 8-68 months) and the time to control inflammation was 9.82 ±
11.37 weeks which was achieved in 15 patients (88.23%). Flare-up rate was 44% per 100 person-years follow-up. Based on standard Snellen visual acuities measured at the time ofcommencement ofdaclizumab therapy compared with visual acuities at the time ofdata analysis, 15 of33 eyes [45%] had an improvement in the visual acuity, 13 eyes (39.3%) had stable acuities and 5 eyes [15%] had a worsening oftheir acuities. Two patients [14%] exhibited worsening ofocular inflammation and were declared as treatment failures. Side effects associated with daclizumab included nausea, fatigue and muscle aches. Adverse events included raised liver enzymes and transient leukopenia. The medication was well tolerated by eleven patients who reported no side-effects.
Conclusion: Dac1izumab is effective in controlling inflammation in patients with stubborn non infectious ocular inflammation. It has a corticosteroid sparring effect, can be used as long term therapy in children and adults and is capable ofinducing durable remission.
Choroidal granuloma as a manifestation of paradoxical reaction in a patient with pulmonary tuberculosis
Emilio Dodds. MD
Consultores Oftalmologicos, Argentina
Purpose: to report the development ofa choroidal granuloma in a patient with pulmonary tuberculosis treated with four drugs.
Methods: we reviewed the medical record ofa 53 year-old patient, HIV positive, with 333 cel/ul and no HAART therapy.
Results: the patient was diagnosed with pulmonary tuberculosis and started systemic therapy with four drugs (isoniazid, rifampicin, pyrazinamide, ethambutol). Twenty days later he complains ofdecrease vision in his right eye and four months later was seen at Hospital Fernandez in Buenos Aires with an active, elevated lesion that was diagnosed as a choroidal granuloma. This lesion developed despite an excellent response of his pulmonary and systemic disease to anti TB drugs. After nine months of therapy the choroidal lesion resolved, leaving a flat, pigmented scar.
Conclusion: the development ofa new lesion or worsening of
previous disease in patients with systemic tuberculosis is known
as paradoxical reaction and is seen in up to 30% ofHIV +
patients. These patients may need longer therapies to see a
clinical response or even therapy with corticosteroids.
Ulcerative Keratitis on Therapeutic Doses ofTumor Necrosis Factor Antagonists
Steven Swan, Chandra Altemare, Matt Giegengack, Anh-Danh Phan, Madison Slusher, Craig Greven, Shree K Kurup. Dept ofOphthalmology, Wake Forest University.
Winston Salem NC 27101
Purpose: To report on two rheumatoid arthritis patients who developed immune mediated UK leading to corneal perforation while on therapeutic combinations of anti tumor necrosis factors (A-TNF) along with MTX.
Design: Interventional observational cases
Participants: Two rheumatoid arthritis (RA) Caucasian female patients with unilateral immune mediated ulcerative keratitis whose RA was well controlled on parenteral infliximab or etanercept along with methotrexate (MTX) who developed immune mediated ulcerative keratitis with corneal perforation.
Intervention: Both patients were treated with a combination of pulsed cyclophosphamide, cyclosporine (CSA), parenteral MTX, intravenous and oral corticosteroids until the cornea was healed. Chimeric antibodies to A-TNF were undetectable.
Results: A combination ofCSA, MTX and corticosteroids was effective in restoring the integrity of the globe within a month in both patients. The corneas healed with residual scarring. Visual acuity improved from 20/200 to 20/40 and HM to 20/70.
Conclusions: Severe immune mediated ocular disease can occur under therapeutic doses ofanti tumor necrosis factor therapy in RA patients and the cited approach may be useful in this subset of patients. This could indicate inefficacy, resistance or sub therapeutic dosage of the drugs.
The Association of Candidemia and Ocular Candidiasis: Meta Analysis of the Literature
Leila 1. Kump MD, Eyal Margalit MD, PhD University of Nebraska
Objective: To evaluate prevalence of fungal endophthalmitis and
chorioretinitis in patients with candidemia using meta-analytical
techniques.
Methods: Medline review covering January 1966 through March 2007 with the search terms "Candida or candidemia or candidiasis" and "endophthalmitis or chorioretinitis"was conducted. Analysis ofall peer-reviewed articles of candidemia-associated fungal endophthalmitis and chorioretinitis published in the English language was performed. Inverse variance method was applied to the study.
Results: Twenty two articles met the inclusion criteria. Ten studies were prospective and 12 retrospective. Seven studies were on adults and 15 on pediatric patients.Total number of patients was 1014; there were 64 patients with ocular candidiasis. Mean and confidence interval weighted by meta-analytic I/v2 technique. A weighted mean prevalence of 1.78% was found with a 95% confidence interval of approximately 0.95% to 2.62%.
Conclusion: The linkage of candidal sepsis with candidal endophthalmitislchorioretinitis suggested the use of ocular examinations to diagnose invasive candidiasis. Our analysis reveals that ocular involvement in candidemic patients is rare. It is attributed to prompt systemic antifungal therapy. In the reviewed literature the results of eye evaluations did not alter the course of antifungal therapy. Randomized prospective multi-center trial on patients with ocular candidiasis and candidemia could potentially elucidate the incidence of ocular involvement in fungal sepsis. Development and acceptance of universal guidelines are necessary for ocular evaluation ofcandidemic patients.
Evaluation ofpatients with retinal vasculitisfor systemic disease
Michael Straiko MD. I, David Sutton B.S.2, Travis Meredith MD. l, Russell Van Gelder MD. I
I Department ofOphthalmology and Visual Sciences, Washington University Medical School, Saint Louis. MO. 2Department of Ophthalmology, University of North Carolina Medical School, Chapel HUI, NC.
Background and Rationale: Many ocular inflammatory conditions are associated with an underlying systemic etiology. The relationship of systemic disease and retinal vasculitis has not been well characterized. This study examines the incidence of systemic disease and the yield of a systemic workup in patients with retinal vasculitis.
Patients and Methods: Retrospective chart review. 55 patients diagnosed with retinal vasculitis at one institution (Barnes Retina Institute) over a 31 year period met inclusion criteria. The primary measure was the presence and nature of pre-existing or subsequent systemic disease diagnosis. Secondary measures included: retinal arteritis vs. phlebitis, retinitis, choroiditis, vitritis, visual acuity, laterality, and associated anterior chamber reaction.
Results: Fifty-five patients (age range: 13-82, median age: 41) with retinal vasculitis were included in this study. A potentially associated systemic disease was identified in 45.4% of patients. In 80% of these cases, the systemic disease was a new diagnosis discovered as a result of the vasculitis work-up. The most common systemic etiology was Behcet disease, which accounted for 28% of patients found to have an underlying diagnosis. Next most prevalent were sarcoidosis and multiple sclerosis, each accounting for 20% of patients with an underlying diagnosis.
Conclusions: Retinal vasculitis is frequently associated with previously undiagnosed, potentially serious systemic diagnoses, and thus warrants a complete systemic workup. The most commonly identified systemic diseases associated with newly diagnosed retinal vasculitis in this tertiary referral practice setting were Behcet disease, sarcoidosis, and multiple sclerosis.
Refractory Optic Nerve Head Granuloma Successfully Treated with Infliximab
LisaJ. Faia MD, Steven Yeh MD, Julie C. Lew MD, Robert B.
Nussenblatt MD, MPH, Grace Levy-Clarke MD
Laboratory of Immunology, National Eye Institute, Bethesda, MD
20892, USA.
Introduction: There are numerous etiologies for granulomatous papillitis, with sarcoidosis being a common systemic cause. One to five percent of sarcoidosis patients have optic nerve involvement. We report the successful use of infliximab for this rare condition.
Methods: Retrospective case report
Results: A 42 year-old African American male, with presumed sarcoidosis, was referred for treatment ofan optic nerve granuloma OD noted in April 2006. Ophthalmic exam 00 revealed BCVA 20/20, 1+ vitreal cells, and a 1.5 disc diameter, cauliflower-shaped optic disc head granuloma with surrounding subretinal fluid. Past medical history included hypertension and a positive PPO/negative chest x-ray in 1998 that was treated with 6 months of Isoniazid therapy. A comprehensive evaluation was negative for active TB, fungal infections, syphilis or toxoplasmosis. Chest CT scan revealed hilar adenopathy, but the biopsy via bronchoscopy was non-diagnostic. He was treated with IV Solu-Medrol, oral prednisone and mycophenolate mofetil. In December 2006, the granuloma had increased in size and was now associated with more subretinal fluid and an extensive epiretinal membrane. BCVA 00 was 20/100 in January 2007. After medical clearance, infliximab 5mg/kg infusions were initiated at week 0, week 2, week 4 and every 4 weeks subsequently. Complete resolution was seen after 6 infusions, allowing for a vitrectomy/membrane peel to remove the epiretinal membrane that continued to obscure his vision. BCVA 00 October 2007 was 20/50.
Conclusion: We report a case of an optic nerve granuloma which was
unresponsive to traditional immunosuppressive therapy, with good
response to the addition of infliximab. It appears that infliximab may
be a viable alternative for these patients.
Intravascular Lymphoma presenting as VKH masquerade
Soukiasian SH, Pahk PJ, Blaha GR, and Marx JL Lahey Clinic, Burlington, MA
56 year old male with several month history offever of unknown origin and hearing loss. Bloodwork was notable for monoclonal gammopathy. He subsequently developed decreased vision and bilateral serous detachments ofthe retina. FA revealed multiple pinpoint hyperfluorescent spots with leakage into serous detachments. "Periphlebitis" was noted bilaterally. A presumptive diagnosis of VK.H was made and the patient was treated with systemic corticosteroids. VA improved with resolution ofRDs, but patient developed a constellation ofother findings, including atrial fibrillation, mental status changes and lower extremity weakness. He had no skin abnormalities. Further workup and management will be discussed.
Pseudopapilledema vs. papilledema in NOMID
Agnieszka Nagpal, MD., Nisha Acharya, MD., M8.
F.l. Proctor Foundation University a/California, San Francisco
Purpose: To describe the optic nerve findings in a case of Neonatal Onset Multisystem Inflammatory Disease Syndrome (NOMID).
Methods: Case report.
Results: A 10-year old girl with a history ofNOMID was seen at the Francis I. Proctor Foundation. The patient had been diagnosed with NOMID at 4 months ofage based on clinical findings (rash, lymphadenopathy, fever) and laboratory values (ESR > 100 mm/hour, serum and cerebrospinal fluid leukocytosis). Since birth, she received treatment with cyclosporine, methotrexate and prednisone. At age 2, she was noted to have white fibrillar strands extending from the optic discs with extensive peripapillary blurring. At age 6, the optic nerves appeared stable but on lumbar puncture, intracranial pressure was elevated (36 cm ofH20) and there was pleocytosis. An MRI showed normal ventricles. She was treated with Diamox and the prednisone was tapered because of the concern for corticosteroid-induced intracranial hypertension. The intracranial pressure normalized, but the systemic inflammatory manifestations were not controlled, so the patient was started on Anakinra (an IL-I receptor antagonist). She has remained stable on Anakinra and off prednisone. Currently, her visual acuity measures 20/40+2 OD and 20/200 OS. The optic nerves appear unchanged from prior photographs with persistent fibrillar strands extending from the discs OU and perivascular infiltration extending into the peripheral retina.
Conclusion: NOMID is a rare pediatric inflammatory disease
characterized by a skin rash, joint involvement and chronic aseptic
meningitis. Ophthalmic manifestations that have been reported include
iritis, vitritis, vasculitis, focal chorioretinitis, and pseudopapilledema. Increased intracranial hypertension is not thought to be part ofNOMID, but may occur due to other factors including steroid treatment, as is the case with our patient. The chronic optic disc findings in our patient are most consistent with a pseudopapilledema and suggest an infiltrative process related to NOMID.