Evangelia Papavasileiou

Ipilimumab-induced Ocular and Orbital Inflammation—A Case Series and Review of the Literature

Abstract Purpose: Ipilimumab, a monoclonal antibody directed against the immune protein cytotoxic T-lymphocyte antigen-4 (CTLA-4), characteristically induces side effects called “immune-related adverse events” (IRAE). Although ophthalmic involvement is rare, we report 7 cases of eye and orbit complications related to ipilimumab therapy. Methods: We performed a retrospective review of patients with metastatic melanoma who developed ipilimumab-related ocular or orbital inflammation who were seen at our institutions. Results: Seven patients were identified: 4 patients had orbital inflammation, 2 had uveitis, and 1 had peripheral ulcerative keratitis. Four patients developed inflammation after the second ipilimumab infusion, 2 after the third infusion and 1 after the first infusion. All 4 patients with orbital inflammation were treated with systemic corticosteroids. Two patients with uveitis were treated with topical steroids, but were also treated with systemic corticosteroids for other IRAE, including colitis and hypophysitis. The patient with keratitis was treated with topical corticosteroids alone with resolution of inflammation. All 7 patients discontinued ipilimumab therapy, 5 due to systemic IRAE and 2 due to tumor progression. Five of 7 patients had tumor progression on ipilimumab therapy. Conclusions: Ocular and orbital inflammation may occur in patients with metastatic melanoma receiving ipilimumab, is frequently accompanied by other IRAEs, and resolves with corticosteroid treatment, often leaving no long-term sequelae.

Intravitreal tissue plasminogen activator, perfluoropropane (C3F8), and ranibizumab or photodynamic therapy for submacular hemorrhage secondary to wet age-related macular degeneration.

Purpose: To report a combined intravitreal treatment for submacular hemorrhage. Methods: This retrospective, noncomparative, interventional case series included 7 patients with neovascular age-related macular degeneration and 2 with idiopathic polypoidal choroidal vasculopathy, presenting with fovea-involving submacular hemorrhage ≥ 4 disk areas in size, of <10 days of duration. All patients received a single 0.05-mL intravitreal injection of 50 &mgr;g alteplase, 0.3 mL of 100% C3F8, and facedown positioning for 1 week. Patients with newly diagnosed age-related macular degeneration received 3 consecutive monthly intravitreal injections of 0.5 mg ranibizumab, followed by monthly retreatment as needed. Those with idiopathic polypoidal choroidal vasculopathy were treated with photodynamic therapy. Results: Mean (±SD) logarithm of the minimum angle of resolution visual acuity improved from 0.75 ± 0.35 at presentation to 0.35 ± 0.30 at a mean final follow-up of 15.1 months (P = 0.0078). Median Snellen acuity improved from 20/200 to 20/32. Visual acuity was stable in one case and improved in eight. The average size of submacular hemorrhage was 6.8 disk areas at presentation, reducing to 2.6 within 1 month (P = 0.0039). Subfoveal hemorrhage was displaced in all cases within 9 weeks. The mean pretreatment central retinal thickness of 669 &mgr;m reduced to 528 &mgr;m (P = 0.0039). One case developed transiently elevated intraocular pressure. Two developed breakthrough vitreous hemorrhage. No adverse events were attributed to tissue plasminogen activator. Conclusion: Tissue plasminogen activator and C3F8, combined with intravitreal ranibizumab or photodynamic therapy, may result in anatomical clearance of submacular hemorrhage and improved visual acuity, in a condition with an otherwise poor visual prognosis.

Risk Factors for Proliferative Diabetic Retinopathy in African Americans with Type 2 Diabetes

ABSTRACT Purpose: To assess personal and demographic risk factors for proliferative diabetic retinopathy in African Americans with type 2 diabetes. Methods: In this prospective, non-interventional, cross-sectional case-control study, 380 African Americans with type 2 diabetes were enrolled. Participants were recruited prospectively and had to have either: (1) absence of diabetic retinopathy after ≥10 years of type 2 diabetes, or (2) presence of proliferative diabetic retinopathy when enrolled. Dilated, 7-field fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study scale. Covariates including hemoglobin A1C (HbA1C), blood pressure, height, weight and waist circumference were collected prospectively. Multivariate regression models adjusted for age, sex and site were constructed to assess associations between risk factors and proliferative diabetic retinopathy. Results: Proliferative diabetic retinopathy was associated with longer duration of diabetes (odds ratio, OR, 1.62, p < 0.001), higher systolic blood pressure (OR 1.65, p < 0.001) and insulin use (OR 6.65, p < 0.001) in the multivariate regression analysis. HbA1C was associated with proliferative diabetic retinopathy in the univariate analysis (OR 1.31, p = 0.002) but was no longer significant in the multivariate analysis. Conclusions: In this case-control study of African Americans with type 2 diabetes, duration of diabetes, systolic hypertension and insulin use were strong risk factors for the development of proliferative diabetic retinopathy. Interestingly, HbA1C did not confer additional risk in this cohort.

OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS OF MACULAR EDEMA AND HARD EXUDATES AND THEIR ASSOCIATION WITH LIPID SERUM LEVELS IN TYPE 2 DIABETES.

Purpose: To determine whether hyperreflective foci (HF) and macular thickness on spectral domain ocular coherence tomography are associated with lipid levels in patients with Type 2 diabetes. Methods: Two hundred and thirty-eight participants from four sites had fundus photographs and spectral domain ocular coherence tomography images graded for hard exudates and HF, respectively. Regression models were used to determine the association between serum lipid levels and 1) presence of HF and hard exudates and 2) central subfield macular thickness, central subfield macular volume, and total macular volume. Results: All patients with hard exudates on fundus photographs had corresponding HF on spectral domain ocular coherence tomography, but 57% of patients with HF on optical coherence tomography did not have hard exudates detected in their fundus photographs. Presence of HF was associated with higher total cholesterol (odds ratio = 1.13, 95% confidence interval = 1.01–1.27, P = 0.03) and higher low-density lipoprotein levels (odds ratio = 1.17, 95% confidence interval = 1.02–1.35, P = 0.02) in models adjusting for other risk factors. The total macular volume was also associated with higher total cholesterol (P = 0.009) and triglyceride (P = 0.02) levels after adjusting for other risk factors. Conclusion: Higher total and low-density lipoprotein cholesterol were associated with presence of HF on spectral domain ocular coherence tomography. Total macular volume was associated with higher total cholesterol and triglyceride levels.

Ocular ischemic syndrome presenting as retinal vasculitis in a patient with moyamoya syndrome.

PURPOSE To report a case of ocular ischemic syndrome presenting as retinal vasculitis in a patient with Moyamoya syndrome. METHODS A retrospective chart review was conducted to record clinical data including fluorescein angiography, optical coherence tomography, and serologic testing. A review of the literature from 1969 to 2014 of ocular involvement in Moyamoya syndrome was performed. RESULTS A 51-year-old woman with long history of bilateral retinal vasculitis and refractory cystoid macular edema was eventually diagnosed with Moyamoya syndrome after sustaining a perioperative cerebrovascular accident. Moyamoya syndrome has been associated in the literature with ocular ischemic syndrome, presenting with narrowed retinal arteries, dilated veins, and midperipheral retinal hemorrhages, but retinal vasculitis with cystoid macular edema has not been reported. CONCLUSION Moyamoya-related ocular ischemic syndrome can present as retinal vascular leakage and macular edema. Ophthalmologists should be cognizant that signs of the disease may be first observed in the eye before manifestations in the cerebrovascular system.

Adult Rheumatoid Arthritis

Rheumatoid arthritis is a common, chronic systemic inflammatory disease with multiple extra-articular manifestations including uveitis. Adult rheumatoid arthritis-associated uveitis is rare in the absence of concomitant scleritis or keratitis.

Ritonavir-associated Toxicity Mimicking Retinitis Pigmentosa in an Hiv-infected Patient on Highly Active Antiretroviral Therapy

Purpose: To report ritonavir-associated retinal pigment epithelium toxicity in a patient infected with the HIV on highly active antiretroviral therapy including ritonavir. Methods: Retrospective single case report. The authors describe a case of gradual onset of blurry vision in both eyes in an HIV-positive male. Visual acuity, clinical examination findings, and functional testing (electroretinogram and Goldmann perimetry) were reviewed. Diagnostic imaging, including fundus photography, spectral domain optical coherence tomography, fluorescein angiography, and fundus autofluorescence were assessed. Results: 59-year-old HIV-infected male, treated with ritonavir for eight years, presented with a history of decreased night vision and peripheral field loss. Ophthalmologic examination confirmed the diagnosis of retinal toxicity. Goldmann perimetry showed areas of central and para-central scotomas. Electroretinograms demonstrated mild to moderate photoreceptor dysfunction. Fundus examination revealed a diffuse pattern of retinal pigment epithelium mottling in both eyes. Spectral domain optical coherence tomography confirmed the presence of choroidal thinning, whereas fundus autofluorescence showed mottled hypoautofluorescence. Conclusion: Although ritonavir-associated retinal toxicity is clinically uncommon, the clinical features of our findings support this diagnosis. Consideration of highly active antiretroviral therapy–associated retinal toxicity should be given to the differential diagnosis in HIV-positive patients with retinopathy of unclear etiology. This report also highlights the need for constant monitoring of patients using the ritonavir for early detection of possible retinal toxicity.

Birdshot chorioretinopathy in a male patient with facioscapulohumeral muscular dystrophy

BackgroundWe report a case of birdshot chorioretinopathy (BSCR) in a patient with facioscapulohumeral muscular dystrophy (FSHD). A 40-year-old male with history of facioscapulohumeral muscular dystrophy with significant facial diplegia and lagophthalmos presents for an evaluation of bilateral choroiditis with vasculitis and optic disc edema. Clinical examination included fundus and autofluorescence photographs, fluorescein angiography, and optical coherence tomography. To our knowledge, this patient represents the first reported case of birdshot chorioretinopathy with facioscapulohumeral muscular dystrophy. Patients with FSHD can present with ocular findings and should be screened with dilated fundus examinations for retinal vascular changes and posterior uveitis.