Bilateral retinal vasculitis associated with cold agglutinin disease treated with obinutuzumab and infliximab.

Purpose: To describe the clinical course and management of a patient with bilateral retinal vasculitis associated with cold agglutinin disease (CAD) treated with obinutuzumab and infliximab. Observations: A 69-year-old Hispanic woman was referred to a tertiary Uveitis Clinic with progressively worsening blurry vision, right eye (OD) worse than left eye (OS). Past ocular history was significant for epiretinal membranes in both eyes (OU). Past medical history was notable for non-specific joint disease, primarily affecting her knees bilaterally, and pulmonary symptoms (e.g., dyspnea, productive cough) of unclear etiologies one year before presentation. She had been evaluated by rheumatologists and pulmonologists and was placed on low doses of prednisone and methotrexate. Upon examination, her visual acuity was 20/40 in OD and 20/25 in OS. Anterior segment exam was unremarkable with no cell or flare in OU. Dilated fundus examination was notable for 0.5+ vitreous haze in OU and mild vessel attenuation in OU. Wide-angle fluorescein angiography (FA) revealed mild bilateral periphery peri-vasculature leakage in OU. Initial blood evaluations revealed decreased hematocrit, and positive anti-nuclear antibody. Her peripheral smear disclosed 3+ agglutination. She was initially treated with mycophenolate mofetil 1000 mg twice daily and prednisone 20 mg then referred to hematology. Further work up revealed high-titer cold agglutinin and positive thermal amplitude screen at 30 °C. Bone marrow examination demonstrated a chronic lymphocytic leukemia (CLL)-like monoclonal B-cell lymphocytosis. Anti-CD20 monoclonal antibody therapy with obinutuzumab was started in an effort to treat the underlying CLL clone and address the associated ocular vasculitis related to CAD. Three months later, after eight cycles of obinutuzumab, the patient's best- corrected visual acuity (BCVA) continued to be stable at 20/30 in OD and 20/20 in OS. However, FA showed persistent diffuse perivascular leakage. Intravenous infliximab with concurrent intravenous methylprednisolone infusions were started. After two cycles of treatment, FA showed significantly improved perivascular leakage. Visual acuity remained stable at 20/25 in OU. Conclusions and importance: Ocular involvement in CAD is rare. The index case is the first report of retinal vasculitis in a patient with CAD. Our report not only describes the unique course of CAD-related retinal vasculitis, but also introduces and underscores a successful therapeutic plan.

Reperfusion of retinal ischemia in retinal occlusive vasculitis with nicotinic acid and infliximab in Adamantiades-Behçet's disease.

To describe a case of ischemic retinal vasculitis in Adamantiades-Behçet disease (ABD) that demonstrated significant resolution of retinal ischemia following treatment with nicotinic acid and infliximab.Observations: A 12-year-old male with a history of recurrent oral ulcers, fevers, and failure to thrive was admitted to the hospital with fever, oral and perirectal mucositis, and poor oral intake one month before presentation to uveitis clinic. He was suspected to have ABD and was treated with three doses of intravenous (IV) methylprednisolone (30 mg/kg/day) which led to improvement in his systemic symptoms. One week after admission, he complained of decreased vision in both eyes (OU), during which he was found to have anterior uveitis in OU and was referred to the Uveitis Clinic. Upon examination, his visual acuity was 20/80 in OU. Intraocular pressures were within normal limits. Anterior chamber evaluation revealed 0.5+ cells and 1.5+ flare in OU. Posterior examination revealed pale optic nerve, sclerosis and vascular sheathing of retinal arteries, and collateral vessels in OU. Fluorescein angiography (FA) showed optic disc leakage and widespread retinal ischemia in OU. The patient was diagnosed with retinal occlusive vasculitis associated with ABD. He was initially treated with infliximab (5 mg/kg), systemic methylprednisolone, and mycophenolate mofetil. Three months later, his BCVA improved to 20/70 OU with slight improvement of retinal ischemia on FA. Nicotinic acid was added to his treatment regimen. Due to logistic challenges, he did not receive infliximab treatment during the subsequent three months. However, three months after beginning nicotinic acid therapy, FA revealed significant improvement of his retinal ischemia OU. Conclusion: To our knowledge, the index report is the first to show that nicotinic acid may improve retinal ischemia in vaso-occlusive retinal vasculitis and be an integral part of the treatment regimen of this sight-threatening condition.

Impending central retinal vein occlusion in patient with idiopathic cutaneous leukocytoclastic vasculitis.

PURPOSE: To report a case of impending central retinal vein occlusion (CRVO) associated with idiopathic cutaneous leukocytoclastic vasculitis (LCV) that demonstrated significant resolution following treatment with intravenous (IV) methylprednisolone. OBSERVATIONS: A 27-year-old man presented to a tertiary Uveitis Clinic with a five-day history of blurry vision in the right eye (OD). He had a history of a purpuric rash and arthralgias five years ago and a biopsy-confirmed diagnosis of LCV controlled with colchicine two years ago in India. Recently, he presented with a recurrent rash and severe abdominal pain. After being evaluated by rheumatology and gastroenterology, he was placed on Helicobacter pylori treatment and high dose oral prednisone, which improved his skin and gastrointestinal symptoms. At the first ophthalmic exam, his systemic findings included lower extremity purpura. His best-corrected visual acuity (BCVA) was 20/20 in both eyes (OU). Slit-lamp examination revealed no cells or flare in OU. Dilated fundus exam showed mild enlarged, tortuous veins, optic nerve hemorrhage, and intraretinal hemorrhages temporal to the macula in OD. Spectral-domain optical coherence tomography (SD-OCT) demonstrated multiple hyper-reflective, plaque-like lesions involving the inner nuclear layer, consistent with paracentral acute middle maculopathy (PAMM). The patient was diagnosed with impending central retinal vein occlusion (CRVO) in OD. Laboratory evaluations were unremarkable. Aspirin was initially started for the patient but was later held due to the worsening of retinal hemorrhage and retinal vein tortuosity at the one-week follow-up. The patient then received three doses of intravenous methylprednisolone, followed by systemic oral prednisone and mycophenolate mofetil. One month later, retinal hemorrhages, venous stasis, and skin manifestations resolved. CONCLUSION AND IMPORTANCE: Ocular involvement in LCV is rare and may present with different manifestations. The index case is the first report of impending CRVO in a patient with idiopathic LCV and without any other known risk factors for CRVO. Our report not only describes the unique course of LCV-related ocular involvement, but also introduces and underscores a potentially effective therapeutic plan.

Anti-interleukin-6 receptor therapy with tocilizumab for refractory pseudophakic cystoid macular edema.

PURPOSE: To describe the clinical course of a patient with refractory pseudophakic cystoid macular edema treated with interleukin-6 receptor antagonist tocilizumab. OBSERVATIONS: An 80-year-old Caucasian man with past ocular history significant for glaucoma (right eye) and iritis presented with cystoid macular edema (CME) in the right eye (OD). His ocular surgery history was significant for cataract extraction with posterior chamber intraocular lenses in 1999 and YAG laser capsulotomy in 2014 in both eyes (OU). His medications at time of presentation included latanoprost and dorzolamide-timolol in OD for glaucoma, as well as prednisolone in OD for iritis. Upon examination, his visual acuity was 20/250 in OD and 20/20 in the left eye (OS). Intraocular pressure was 20 mmHg in OD and 10 mmHg in OS. Slit-lamp examination revealed no cells or flare in OU. Dilated fundus exam showed CME and a cup-to-disk ratio of 0.9 in OD and normal findings in OS. Initial spectral domain optical coherence tomography (SD-OCT) demonstrated intraretinal fluid in both outer and inner layers as well as mild subretinal fluid with an intact ellipsoid zone in OD. Fluorescein angiography revealed perifoveal leakage in OD. Laboratory evaluations, including infectious work-up, were unremarkable. While the patient's CME initially improved after initiation of therapy with topical prednisolone and oral acetazolamide, the CME later recurred after systemic acetazolamide was stopped due to intolerable side effects. Despite multiple therapeutic approaches, including topical and systemic corticosteroids (both oral and intravenous) and topical interferon α2b over the course of more than one year, the patient's visual acuity continued to worsen with increasing intra- and subretinal fluid in the macula. Due to the refractory CME, the patient was started on monthly infusions of anti-interleukin (IL)-6 receptor tocilizumab (8 mg/kg) with three days of methylprednisolone infusions (500 mg/day). After nine cycles of treatment, SD-OCT demonstrated restoration of normal foveal contour with complete resolution of CME. CONCLUSIONS AND IMPORTANCE: IL-6 inhibition with tocilizumab may be a safe and effective treatment for refractory CME. Further studies are needed to elucidate the nature and extent of therapeutic IL-6 inhibition in CME.

Yet another case of ocular sarcoidosis.

PURPOSE: To report a case of bilateral pan-uveitis resembling fungal and viral endophthalmitis in a patient who was ultimately diagnosed with sarcoidosis. OBSERVATION: A 64-year-old female presented with a four-day history of painless vision loss in the right eye. She presented with multiple concurrent systemic complaints, including a history of oral and genital sores, patches of hypopigmented skin on her forearms, and occasional shortness of breath. Upon further examination, she was noted to have bilateral pan-uveitis, which was more severe in the right than left eye. Posterior pole examination of the right eye revealed dense vitritis with multiple large whitish round balls that seemed suggestive of fungal or viral endophthalmitis. Initial therapies included intravitreal (IVT) foscarnet and intravenous (IV) acyclovir, followed by IV amphotericin B and oral voriconazole, which did not improve ocular signs and symptoms. Further evaluations ruled out infectious etiologies and lymphoma. Chest computerized tomography (CT) scan revealed findings suggestive of sarcoidosis, which was confirmed with lung biopsy. Anti-viral and -fungal treatments were discontinued, and the patient was started on IV methylprednisolone followed by oral prednisone and mycophenolate mofetil. Ocular symptoms improved, and the patient remained stable after treatment. CONCLUSION AND IMPORTANCE: The index report illustrates a case of ocular sarcoidosis that imitated the presentation of infectious endophthalmitis. Though ocular sarcoidosis is known to masquerade as a range of disorders and constitutes part of the differential diagnosis for infectious endophthalmitis, sarcoidosis has not been reported in recent literature to imitate the presentation of fungal endophthalmitis. The index case suggests that ocular sarcoidosis should be considered in the differential diagnoses of fungal endophthalmitis.