ASSOCIATION OF ORAL MONTELUKAST WITH REDUCED ODDS OF DEVELOPING EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development. METHODS: This case-control study was conducted using institutional cohort finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Subanalysis among 1913 exAMD and 324 nonexudative AMD was also conducted. RESULTS: A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use before exAMD diagnosis, compared with 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted odds ratio [OR]: 0.50, 95% confidence interval: 0.31-0.80) and nonsteroidal anti-inflammatory drug usage (adjusted OR: 0.69). Caucasian race, history of smoking, and nonexudative macular degeneration in either eye were also found to have a significant relationship with increased odds of exAMD. In the subanalysis, montelukast usage showed significant association with reduced odds of developing exAMD from nonexudative AMD (adjusted OR: 0.53, 95% confidence interval: 0.29-0.97) and the presence of atopic disease (adjusted OR: 0.60). CONCLUSION: The study results suggested that oral montelukast is linked to reduced odds of exAMD development.

Birdshot Chorioretinopathy in Early Adulthood: Review of Current Literature and Case Report.

Purpose: We describe the course of a patient diagnosed with birdshot chorioretinopathy (BSCR) in early adulthood and summarize clinical findings from similar BSCR patients reported in the literature. Observations: A 37-year-old male presented to our tertiary uveitis facility with bilateral ocular discomfort, hazy vision, and floaters. Ocular examination was notable for vitritis, optic disc edema, and ovoid hypopigmented chorioretinal lesions, visible on indocyanine green chorioangiography as multiple hypocyanescent spots in the intermediate phase. Full-field electroretinography and visual evoked potential showed global retinal dysfunction and optic nerve dysfunction. Laboratory evaluations were notable only for human leukocyte antigen (HLA)-A29 positivity. The patient was diagnosed with BSCR and started on oral prednisone and eventually managed with infliximab. Conclusions and Importance: BSCR can affect patients in early adulthood. Proper diagnostic work-up, including assessing HLA-A29 positivity, is needed to manage atypical cases.

Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further?

INTRODUCTION: Diabetic retinopathy (DR) is one of the most frequent microvascular complications of diabetes that can lead to blindness. Laser treatment has been the gold standard treatment for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) for many years. Recently, the role of vascular endothelial growth factor (VEGF) has been established in the pathogenesis of DR, and the use of intravitreal anti-VEGF therapy has gained popularity for the management of DR. AREAS COVERED: This review includes a brief overview of the efficacy and safety of currently available (bevacizumab, ranibizumab, and aflibercept) and potential future (brolucizumab, faricimab, and KSI-301) anti-VEGF agents in patients with DR based mainly on publicly available data from phase 1, 2 and 3 clinical trials. EXPERT OPINION: Clinical trials investigating the efficacy of intravitreal bevacizumab, ranibizumab, and aflibercept injections demonstrated favorable functional and anatomical outcomes in patients with DME. Moreover, the use of these anti-VEGF agents showed a significant improvement in the severity of DR. Recent clinical research for future anti-VEGF molecules aims to provide higher target-protein binding affinity and prolonged therapeutic effect. Brolucizumab, faricimab, and KSI-301 are three novel anti-VEGF agents that demonstrate promising data for the management of DME and potentially DR.

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.

Efficacy and Safety of Tocilizumab in the Management of Non-Infectious Uveitis Failed with Conventional Immunomodulatory and Anti-TNFα Therapies.

PURPOSE: To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies. METHODS: Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4-10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score. RESULTS: Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7-24) years. Median duration of TCZ therapy was 15 (range, 5-32) months. Mean CST reduced from 373 ± 101.0 µm to 298.2 ± 40.3 µm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases. CONCLUSION: IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.

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.

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.