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Purpose: Topical corticosteroids used to treat ocular inflammation are associated with a high risk of clinically significant toxicities. Therefore, corticosteroid-sparing medications to treat ocular inflammation are needed. Noninfectious anterior uveitis (NAU) is a sight-threatening ocular inflammatory condition typically treated with topical corticosteroids. This corticosteroid-controlled comparator trial examines the safety and efficacy of reproxalap, a novel inhibitor of reactive aldehyde species (RASP), for the treatment of ocular inflammation, by using NAU as a model. Methods: Forty-five patients with mild-to-moderate acute NAU were randomly assigned 1:1:1 to receive reproxalap 0.5% ophthalmic solution (4 times daily for 6 weeks), prednisolone 1% ophthalmic solution (Pred Forte®, 4 times daily taper for 6 weeks), or a combination of reproxalap 0.5% ophthalmic solution (4 times daily for 6 weeks) and prednisolone 1% ophthalmic solution (twice daily taper for 6 weeks). Results: All treatments improved anterior cell count and grade, and no differences were observed in change from baseline between groups. Reproxalap monotherapy and combination therapy were statistically noninferior to prednisolone. The proportion of patients requiring rescue therapy was comparable across treatment groups. No safety issues were identified for reproxalap-treated patients, whereas treatment with prednisolone resulted in an average increase of intraocular pressure of ∼2 mm Hg. Conclusions: Reproxalap may be a safe and effective alternative to topical corticosteroids for patients with NAU and other forms of ocular inflammation. These results represent initial clinical evidence of the importance of RASP in ocular inflammation and the applicability of RASP inhibition to immune modulation in ocular disease. Clinical trial (NCT02406209).

Purpose: To report the clinical outcome of a patient with ocular cicatricial pemphigoid, treated with adrenocorticotropic hormone gel. Observations: A 75-year-old female with a biopsy proven ocular cicatricial pemphigoid (OCP) presented with bilateral conjunctival inflammation, fornix shortening, subepithelial fibrosis and corneal scarring. The patient was previously treated with topical steroids, topical cyclosporine and lubricating drops, and had undergone several amniotic membrane transplants due to recurrent corneal erosions. Once OCP diagnosis was established, the patient was started on oral corticosteroids (60 mg daily). In order to wean the patient off from systemic steroids, other immunomodulatory agents had been tried, including mycophenolate mofetil (1000 mg twice daily) and methotrexate (up to 25 mg weekly). However, none of these agents adequately controlled the ocular surface inflammation, and the patient experienced bilateral progressive cicatrization and corneal decompensation, as well as the development of side effects from the systemic corticosteroids, methotrexate and mycophenolate mofetil therapies. Treatment with twice weekly subcutaneous adrenocorticotropic hormone (ACTH) gel was initiated, along with tapering of systemic corticosteroids. During the 19 months treatment period, the patient demonstrated significant improvement in the ocular surface inflammation, visual acuity was stable and no significant adverse effects were observed. Systemic corticosteroids dosage was successfully reduced from 10 mg/day to none at last follow up. Conclusions and importance: ACTH gel has shown to be an effective and safe treatment option for chronic, refractory and progressive ocular inflammatory disease. To the best of our knowledge, this is the first case report of a patient with OCP, treated successfully with ACTH gel. This case report may encourage ophthalmologists to employ ACTH gel in the management of OCP. Keywords: Adrenocorticotropic hormone, Ocular cicatricial pemphigoid, Clinical outcome

Background Herpes Zoster Ophthalmicus (HZO) affects 10-20% of adults with herpes zoster; ≥ 50% of these cases manifest as serious ocular diseases. This 1-year prospective observational cohort study aims to determine patient-reported HZO symptoms as well as economic and quality of life burden among 300 HZO patients from 6 major US ophthalmology practices. Here, we report baseline data from 13 initial enrollees. Methods Inclusion criteria were: participants ≥ 18 years, diagnosis of clinically active HZO, English or Spanish speaking, be willing and able to respond to study assessments, not be enrolled in a concurrent interventional HZO trial. Information are collected via 1) a clinical assessment form completed by the practice (baseline) and 2) patient questionnaires (baseline, 3, 6, and 12 months) on symptoms, medications, healthcare use, vision function, depression, and work productivity impact. Baseline results are presented for patients recruited during the first 6 months of enrollment from the first 4 sites to go live: diagnoses, and patient-reported symptoms and outcomes (eight-item Patient Health Questionnaire [PHQ-8] for depressive symptoms, National Eye Institute 25-item Visual Function Questionnaire [NEI-VFQ-25] for vision-related quality of life, and Zoster Brief Pain Inventory [ZBPI] for pain). Results The mean age of participants is 71 years; 11 are female and 9 are retired. Seven participants are college graduates or hold other degrees. All have health insurance coverage, with most (10) having primary insurance through Medicare. HZO diagnoses (Table 1) were: keratitis (4), iridocyclitis (4), conjunctivitis (1), other HZO diagnosis (3), other ocular diagnosis (6). Patient-reported symptoms (Table 2) were: pain above the eye, sensitivity to light, redness, feeling of sand/grit in the eye (9 each). The mean overall PHQ-8 and NEI-VFQ-25 scores were 5.9 (Standard Deviation [SD]:4.5) and 74.6 (SD:13.9), respectively; the mean ZBPI score for worst pain severity was 3.3 (SD:3.8) (Table 3). Table 1. HZO Diagnosis at Baseline based on Clinical Assessment Form (N=13) Table 2. Patient-reported Symptoms in the HZO-Affected Eye at Baseline (N=13) Table 3. Patient-reported Outcomes: Depressive Symptoms, Vision-Related Quality of Life, and Herpes Zoster Pain at Baseline (N=13) Conclusion This study represents the first large scale effort to quantify HZO burden. Findings will inform development of a formal patient-reported symptom scale for use in research and clinical practice. Funding GlaxoSmithKline Biologicals SA (GSK study identifiers: 209235/HO-17-17967) Disclosures Laura T. Pizzi, PharmD, MPH, ORCID: 0000-0002-7366-7661, GlaxoSmithKline (Research Grant or Support) Soham Shukla, PharmD, ORCID: 0000-0002-4139-0856, GSK (Employee)Rutgers University (Employee) Brandon J. Patterson, PharmD, PhD, GSK (Employee, Shareholder) Debora A. Rausch, MD, ORCID: 0000-0001-9759-2687, GSK (Employee) Philip O. Buck, PhD, MPH, ORCID: 0000-0002-3898-3669, GSK (Employee, Shareholder) Ann P. Murchison, MD, MPH, GSK (Grant/Research Support)

Background Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. Methods This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. Results The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P

Purpose. To report the use of Descemet stripping endothelial keratoplasty (DSEK) in a patient with keratoglobus and chronic hydrops.Case Report. We describe a case of a 28-year-old man with bilateral keratoglobus and chronic hydrops in the right eye secondary to spontaneous Descemet membrane tear. The patient presented with finger counting (CF) vision, itching, foreign body sensation, and severe photophobia in the right eye. Peripheral corneal thinning with central corneal protrusion and Descemet membrane tear spanning from 4 to 7 o'clock was noted on slit lamp examination. The right eye cornea was 15 mm in the horizontal diameter. After a 5.5-month loss to follow-up, the patient presented with discomfort, photophobia, decreasing vision, and tearing in the right eye. Vision was 20/60 with pinhole. 360-degree peripheral corneal ectasia with mild neovascularization and hydrops was present. Over the next few months, the patient complained of photophobia and intermittent eye pain. His vision deteriorated to CF, he developed corneal scarring with bullae, and a DSEK was performed. Eight months postoperatively, best-corrected vision improved to 20/30, cornea was clear, and the DSEK graft was stable.Conclusions. Nonresolving hydrops secondary to Descemet membrane tear in a patient with keratoglobus may result in permanent endothelial cell damage and scar formation. This may be successfully treated with DSEK.

Purpose. To describe the use of intravitreal ranibizumab for choroidal neovascular membrane (CNVM) secondary to Vogt-Koyanagi-Harada (VKH) syndrome.Methods. Interventional case report.Results. A 50-year-old woman presented with conjunctival injection and bilateral eye pain. Vision was 20/400 and 20/80 in the right and left eyes, respectively. Bilateral iritis, vitritis, and choroidal thickening were evident. Exudative retinal detachment was present in the left eye. Corticosteroid treatment improved vision to 20/40 bilaterally. Methotrexate (MTX) was initiated and vision remained stable for 3 months. After a 5-month loss to follow-up, vision in the left eye decreased to finger counting (CF) and a parafoveal CNVM was identified. After 3 intravitreal ranibizumab injections, vision improved to 20/40. Twelve months later, despite inflammation control, vision decrease to CF due to recurrent CNVM. A fourth ranibizumab injection was given. Twenty months later, best-corrected vision was 20/400, and an inactive CNVM was present in the left eye.Conclusion. After initial CNVM regression and visual acuity improvement due to ranibizumab, the CNVM recurred and became refractory to treatment. Despite control of inflammation and neovascularization, VKH chronicity lead to permanent vision loss in our patient. A combinational treatment approach may be required in such patients.

Background The purpose of this study was to describe comorbidities, healthcare costs, and resource utilization among patients with chronic non-infectious uveitis initiating corticosteroid, immunosuppressants, or biologics. In this retrospective cohort study, patients with a non-infectious uveitis diagnosis and continuous insurance coverage during a 6-month baseline were selected from a privately insured claims database with 80.7 million enrollees. Index dates were defined as the first prescription/administration of a corticosteroid, immunosuppressant, or biologic between 2003 and 2009. Comorbidities, healthcare costs, and utilization were analyzed in a per-member-per-month (PMPM) framework to account for varying between-patient treatment periods, defined as continuous medication use within the same class. Wilcoxon rank-sum and chi-square tests were used for comparisons of costs and categorical outcomes. Results Patients on corticosteroids (N = 4,568), immunosuppressants (N = 5,466), and biologics (N = 1,694) formed the study population. Baseline PMPM inpatient admission rates were 0.029 for patients on corticosteroids, 0.044 for patients on immunosuppressants, and 0.045 for patients on biologics (p