BACKGROUND Thyroid-associated ophthalmopathy, a condition commonly associated with Graves’ disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves’ ophthalmopathy–specific quality-of-life questionnaire. Adverse events were assessed. RESULTS In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997.)

1. Objective To describe the ocular findings, visual impairment, and association of structural complications of uveitis with visual impairment in a cohort of Ebola virus disease (EVD) survivors in Monrovia, Liberia 2. Design Retrospective, uncontrolled, cross-sectional study 3. Participants EVD survivors evaluated in an ophthalmology clinic at Eternal Love Winning Africa Hospital in Monrovia, Liberia. 4. Methods A cohort of EVD survivors who underwent baseline ophthalmic evaluation at ELWA Hospital were retrospectively reviewed for demographic information, length of Ebola treatment unit (ETU) stay, visual acuity (VA), and ophthalmic examination findings. For patients with uveitis, disease activity (active vs. inactive) and grade of inflammation were recording according to Standardization of Uveitis Nomenclature (SUN) criteria. The level of VA impairment was categorized according to World Health Organization classification for visual acuity impairment as follows: Normal/Mild – VA 20/70 or better; Moderate – VA 20/70–20/200; Severe VA 20/200–20/400; Blindness – VA < 20/400. VA, length of ETU stay, and structural complications were compared between EVD survivors with and without uveitis. Structural complications associated with moderate VA impairment or poorer were also analyzed. 5. Main Outcomes Frequency of ocular complications including uveitis and optic neuropathy in EVD survivors, level of visual acuity impairment in EVD survivors with uveitis, structural complications associated with visual acuity impairment in EVD survivors. 6. Results 96 EVD survivors were examined. 21 patients developed an EVD-associated uveitis and 3 patients developed an EVD-associated optic neuropathy. VA was blind (VA>20/400) in 38.5% of eyes with uveitis. Anatomic subtypes of uveitis included anterior, posterior, and panuveitis in 2, 13 and 6 patients respectively. Exam findings associated with at least moderate visual impairment by WHO criteria (VA<20/70) included keratic precipitates (p<0.002), posterior synechiae (p<0.002), vitritis (p<0.005) and chorioretinal scars (p<0.02). 7. Conclusions EVD survivors are at risk for uveitis, which may lead to secondary structural complications, visual impairment, and blindness. Eye care resources should be mobilized for EVD survivors in West Africa owing to the frequency of this spectrum of disease complication and its potential for severe VA impairment and blindness.

BackgroundEbola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors.MethodsWe conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS).FindingsWe screened 137 EVD survivors from June 2016 – August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0 years (IQR 17–35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 – Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19 months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34 months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P < 0.001).InterpretationEBOV persistence by RT-PCR was not identified in ocular fluid or conjunctivae of fifty EVD survivors with ocular disease. Cataract surgery can be performed safely with vision restorative outcomes in patients who test negative for EBOV RNA in ocular fluid specimens. These findings impact the thousands of West African EVD survivors at-risk for ocular complications who may also require eye surgery during EVD convalescence.