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Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells.We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study.Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed.Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions.Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.

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 Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases. Methods The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). Results The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent. Conclusions Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.

Purpose of review Autoimmune and immune-mediated diseases are considered contraindications for laser refractive surgeries according to the US Food and Drug Administration's guideline. This guideline, however, is based on limited case reports or complications reported during other intraocular procedures. There have been only a handful of new clinical studies that evaluate the efficacy and safety of refractive surgery in this specific patient population. The aim of this article is to review currently available research and offer updated recommendations for the evaluation and management of laser refractive surgery (LRS) in patients with autoimmune diseases. Recent findings More recent retrospective studies have reported good refractive outcomes in patients with well controlled autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, seronegative spondyloarthropathy, among others. No severe sight-threatening complications have been reported in these reports. Although postoperative complications occur, the risk of refractive surgery is comparable with those without autoimmune diseases. Summary With the exception of primary Sjogren's syndrome, patients with autoimmune diseases may be good candidates for LRS if diseases are well controlled and have minimal ophthalmic manifestation. Patients should be made aware of the potential surgical complications and be informed of the currently available data. More multicenter and larger prospective studies are needed to compare the refractive outcomes and surgical complications in patients with and without autoimmune diseases. This will help patients make better informed medical decisions.

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)

We present the case of successful repair of an exposed glaucoma drainage tube by cornea graft fixation with tissue adhesive, and without subsequent coverage by adjacent conjunctiva or donor tissues. Patient with history of keratoglobus with thin cornea and sclera, and phthisical contralateral eye, underwent three unsuccessful corneal grafts followed by Boston type 1 keratoprosthesis in the right eye. Ahmed drainage device with sclera patch graft was implanted to control the intraocular pressure. Two years later the tube eroded through sclera graft and conjunctiva. Repair was performed by covering the tube with a corneal patch graft secured by tissue adhesive after the conjunctiva in this area was dissected away. The cornea graft was left uncovered due to fragility of adjacent conjunctiva. The healing of ocular and graft surfaces was complete prior to the 1 month follow-up. Conjunctival epithelium covered the corneal patch graft. At 12 months follow-up, the graft and the tube remained stable. Our report suggests that corneal patch graft fixation to the sclera by means of tissue adhesive, without closing the conjunctiva, can be considered as an effective alternative surgical approach for managing exposed glaucoma drainage tube, accompanied by adjacent conjunctiva tissue deficiency. How to cite this article: Berezina TL, Fechtner RD, Cohen A, Kim EE, Chu DS. New Technique of Exposed Glaucoma Drainage Tube Repair: Report of a Case. J Curr Glaucoma Pract 2015;9(2):62-64.

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 The purpose of this study is to report a case of Providencia stuartii conjunctivitis. Methods This study is a retrospective chart review of a patient with persistent conjunctivitis. Results We report the first case of P. stuartii conjunctivitis. Our patient was an elderly man living in a nursing home who was likely immunocompromised from longstanding diabetes mellitus. A conjunctival swab culture was able to identify the infecting bacteria and its antibiotic susceptibility. The conjunctivitis was successfully treated with vancomycin drops and oral sulfamethoxazole and trimethoprim. Discussion P. stuartii is an increasingly common bacterium found in the urine of immunocompromised nursing home residents with indwelling Foley catheters. While it has rarely been found to cause ocular infections, P. stuartii may be suspected in elderly, immunocompromised nursing home residents.

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.

Aim: To describe the complications related to cataract surgery performed by phacoemulsification technique by third-year ophthalmology residents at New Jersey Medical School, who are trained to perform phacoemulsification without any prior experience with extracapsular extraction. Design: Retrospective, observational case series. Methods: A retrospective chart review of 755 patients who underwent cataract surgery by third-year residents between July 2000 and June 2005 at the Institute of Ophthalmology and Visual Science was performed. Details of intraoperative complications (posterior capsular rupture, vitreous loss, subluxation of lens fragments into the vitreous, extracapsular cases converted to phacoemulsification, retinal detachment, vitreous haemorrhage and haemorrhagic choroidals) of the cases done by phacoemulsification technique were recorded. Results were analysed and compared with complication rates reported from other residency programmes and from experienced ophthalmologists. Results: Of 755 cataract surgeries, 719 were performed using phacoemulsification technique. Posterior capsule disruption occurred in 48 (6.7%), vitreous loss in 39 (5.4%) and dislocated lenticular fragments in 7 (1.0%) of 719 cases that underwent phacoemulsification technique. Subsequent pars plana lensectomy was required in 5 (0.7%) cases; 1 case (0.1%) experienced retinal detachment and haemorrhagic choroidal detachment. Conclusion: The residents can perform phacoemulsification well with a very low complication rate, without prior training with extracapsular cataract extraction technique.

Objective: To evaluate the efficacy of etanercept vs placebo in preventing relapses of uveitis in patients taking methotrexate with control of uveitis and whose methotrexate dosage was being tapered. Methods: Patients with chronic or recur-rent noninfectious uveitis with inflammation controlled by low-dose methotrexate were randomized to either the drug or placebo group in a double-masked manner, given a methotrexate taper schedule, and followed for 24 weeks. The main outcome measures were control of inflammation, visual acuity, and adverse reactions. Data were analyzed both as an attempt-to-treat analysis and an analysis only of those patients who completed the study. Results: A total of 20 patients were randomized to the drug and placebo groups. Relapse of uveitis occurred in 3 of 10 patients in the treatment group and 5 of 10 patients in the control group. Two patients in the treatment group withdrew prematurely from the study due to adverse effects. There was no significant difference between the treatment and placebo groups with regard to the rate of relapse and the final visual acuity. No patient suffered from any irreversible, long-term morbidity or mortality. Conclusion: Etanercept has no significant efficacy over placebo in preventing relapses of uveitis in patients being tapered from methotrexate. Arch Ophthalmol, 2003;121:437-440.

HEALTH CARE COSTS AND UTILIZATION FOR PRIVATELY INSURED PATIENTS TREATED FOR NON-INFECTIOUS UVEITIS IN THE UNITED STATES Johnson S1, Duh MS1, Mallya U2, Diener M3, Sorg R3, Chu D4 1Analysis Group, Inc., Boston, MA, USA, 2Novartis Pharmaceuticals Corporation, Florham Park , NJ, USA, 3Analysis Group, Inc., New York, NY, USA, 4UMDNJ, Newark, NJ, USA OBJECTIVES: Describe costs and utilization patterns of corticosteroid (CTS), immunosuppressive (IMS), and biologic (BIO) treatment use in patients with chronic non-infectious uveitis. Costs and utilization of CTS, IMS and BIO indicate economic burden but have not been studied in a large sample. METHODS: Patients with 31 NPSU diagnosis (ICD-9-CM 360.x–364.x, excluding infectious uveitis) by an ophthalmologist or 32 by a primary care physician, under age 65, with continuous insurance coverage during a six-month baseline were selected from a privately insured claims database (N 80.7 million). Sample index dates were defined as the first prescription/administration of CTS, IMS, or BIO between 2003-2009. CTS patients had 32 10-day or 31 30-day scripts. Analysis was in a per-member-per-month (PMPM) framework based on treatment episodes, 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: CTS (N 19,426), IMS (N 5,466) and BIO (N 1,694) samples were selected; average time on continuous therapy (i.e., treatment episode duration) was 1.79, 3.66, and 8.18 months (p 0.05 across groups). Baseline Charlson Comorbidity Index was highest for BIO (0.83), then IMS (0.78), then CTS (0.039) (p 0.05 across groups). Baseline PMPM inpatient admission rates were 0.021 for CTS, 0.044 for IMS, and 0.045 for BIO (p 0.05 across groups); study period values were 0.032, 0.048, and 0.024, respectively (p 0.05 CTS different vs. both). Emergency room visits had a similar ordering. Baseline average PMPM costs for CTS were $717; IMS were $1738; and BIO were $1439 (p 0.05 across groups). Study period PMPM costs excluding drug or biologic costs were $974 for CTS; were $1592 for IMS; and were $918 for BIO (p 0.05 across groups). CONCLUSIONS: BIO had the best relative change in outcomes, followed by IMS. There could be underuse of these products relative to CTS.

1. The effect of whole tetanus toxin (TeTX) and of its light chain (TeTX L-chain) on transmitter release was determined by presynaptic pressure-injection in the squid giant synapse. 2. The results indicate that whole TeTX does not modify transmission while the L-chain blocks transmission within 20-30 min. This block does not involve changes in the sodium or potassium conductances responsible for spike generation or the voltage-dependent presynaptic calcium current responsible for transmitter release. 3. Western blotting of protein fractions from the squid optic lobe demonstrated the presence of a protein which reacted with specific antibodies against mammalian synaptobrevin, a vesicular protein. In addition, this protein was enzymatically cleaved by the L-chain component of the toxin in a similar fashion to its mammalian counterpart. 4. These results demonstrate that TeTX L-chain toxin acts directly on a squid synaptobrevin and prevents synaptic release probably by interfering with the docking-fusion synaptic vesicles at the active zone.

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