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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 To report occurrence of cicatrizing conjunctivitis as an extraglandular ocular manifestation of primary Sjogren's syndrome (SS). Methods Medical charts of all patients with SS evaluated at two tertiary ophthalmological referral centers were reviewed. Patients who demonstrated clinical findings of cicatrizing conjunctivitis were included in this review. Patient and disease-related data including ocular complications, therapies and outcomes were collected. Results Eight patients with a diagnosisis of SS were noted to have cicatrizing conjunctivitis findings over a period of 11 years (between 2009 and 2020). Mean age of patients was 79. All patients had a negative immunoreactant deposition in conjunctival biopsy. Mean follow-up time was 6 years (range, 18–197 months). Three patients had progression of conjunctival scarring. Worsening of vision occurred in 4 patients due to corneal complications, including ulceration, perforation and scarring. Conclusions SS is an under-recognized etiology of severe progressive cicatrizing conjunctivitis that can lead to ocular morbidity and loss of vision without appropriate management.

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).

The ability of the adrenocorticotropic hormone (ACTH) to induce steroidogenesis and upregulate anti-inflammatory processes has long been known. More recently, however, extrasteroidal mechanisms, through which ACTH exerts anti-inflammatory processes, have been described. This has renewed hope that ACTH can combat inflammatory conditions even when resistant to steroids. This review article summarizes the literature on the use of ACTH in ocular disease. Unfortunately, much of the data regarding the clinical utility of ACTH are outdated, with many studies published in the 1950s and 1960s. Many of these older studies are inconsistent or incomplete with their reporting, making it difficult to ascertain the meaning of the outcomes. Despite the limitations, 2 important trends are evident. First, when used to treat an inflammatory disease, ACTH can be effective at decreasing or eliminating ocular inflammation, even in a refractory disease resistant to multiple treatment modalities. Second, adverse effects of ACTH are rare and are most likely to be reported with relatively high doses of ACTH therapy. Taken as a whole, these studies offer initial promising data that ACTH may be a safe and effective alternative in refractory ocular inflammatory disease. However, they highlight an important lack of prospective data to more rigorously understand the true safety and efficacy of this therapy.

Purpose The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI). Methods Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications. Results Included were 15 patients (10 women and 5 men; 36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient. Conclusions RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated.

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)

Purpose To report the primary endpoint analyses of the safety and efficacy of 2 different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Design Randomized, controlled, multicenter clinical trial. Methods STOP-Uveitis is a randomized, open-label safety, efficacy, and bioactivity clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with noninfectious uveitis (NIU). Thirty-seven patients with NIU were randomized into one of 2 treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Primary outcome measure was incidence and severity of systemic and ocular adverse events through month 6. Secondary outcome measures included mean change in visual acuity (VA), vitreous haze (VH), and central macular thickness (CMT) at month 6. Results A total of 37 patients were randomized in the study. At month 6, 43.5% of patients who had the potential for a 2-step decrease in VH demonstrated a 2-step decrease (40% in Group 1 and 46.1% in Group 2). Mean change in CMT was −83.88 ± 136.1 μm at month 6 (−131.5 ± 41.56 μm in Group 1 and −38.92 ± 13.7 μm in Group 2). Mean change in VA was +8.22 ± 11.83 ETDRS letters at month 6 (10.9 ± 14.6 in Group 1 and 5.5 ± 7.8 in Group 2). Repeated infusions of TCZ were well tolerated. Conclusions Repeated IV administrations of TCZ are well tolerated. TCZ (both 4 and 8 mg/kg) is effective in improving VA and reducing VH and CMT in eyes with noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

Objective To describe clinical characteristics and outcomes of adults with uveitis associated with juvenile idiopathic arthritis (JIA). Methods Retrospective chart review from 2001 to 2014 of adult patients with JIA and follow-up ≥2 months. Outcome measures included visual acuity, intraocular pressure (IOP), inflammation grade, ocular findings/complications, immunosuppressive therapies, and surgeries. Results Nineteen patients were included (95% female, 84% bilateral uveitis, 47% anterior uveitis). Mean (SD) ages at presentation and JIA diagnosis were 25.6 (7.8) years and 8.9 (5.6) years, respectively. Visual acuity and IOP did not significantly change throughout the study. Mean (SD) presenting inflammation grade was significantly decreased at 6 and 12 months. Fifteen (79%) patients were on topical medications, and 17 (89%) were on systemic immunosuppression. Two (12%) patients developed side effects requiring medication cessation. Conclusion Uveitis associated with JIA may extend into adulthood despite the use of topical medications and/or systemic immunosuppression and result in significant ocular morbidity, including the need for surgical intervention.

Purpose To describe 7 patients with paraproteinemic keratopathy and to highlight the clinical and pathologic diversity of this rare entity and the importance of timely, systemic evaluation. Design Retrospective, multicenter collaborative case series. Participants Seven patients with paraproteinemic keratopathy. Methods Clinical and pathologic records were reviewed to identify patients with well-documented corneal immunoglobulin deposits. Detailed ophthalmologic and medical histories were assembled. In 6 patients, corneal tissue was evaluated histochemically and immunohistochemically; in selected cases, corneal tissue was evaluated by in situ hybridization and ultrastructurally. Main Outcome Measures Visual acuity and anterior segment examination at presentation and follow-up; local therapy; systemic diagnosis and management; and histopathologic, immunohistochemical, in situ hybridization, and ultrastructural findings. Results Seven patients were identified with corneal immunoglobulin deposition. In addition to previously reported crystalline, nummular, patch-like, and lattice-like corneal opacities, prominent corneal vascularization was present in 2 patients mimicking interstitial keratitis and limbal stem cell deficiency. All patients had evidence of paraproteinemia in a setting of monoclonal gammopathy of undetermined significance, smoldering plasma cell myeloma, or Waldenstrom macroglobulinemia. Corneal findings were the first manifestation of systemic disease in 4 patients, and the diagnosis was not suspected in 3 of these patients. Pathologic evaluation of biopsied corneal and conjunctival tissues demonstrated immunoglobulin deposits. Previously unreported ultrastructural patterns in the cornea were noted: large scroll-like immunotactoid deposits, immune complex-like deposits, and randomly arranged fibrils morphologically intermediate between amyloid and immunotactoid deposits. Surgical intervention to improve vision was performed in 4 patients, with recurrence of deposits in 3 patients. Three patients underwent systemic therapy with diminution of the deposits and improvement in vision in 1 patient. Conclusions The clinical and pathologic expressions of corneal immunoglobulin deposits are protean and present a diagnostic challenge. Early recognition of this rare entity is important to address the potentially serious associated systemic disease.

To report a novel plasminogen gene mutation and detection of anti-plasminogen antibodies in a patient with ligneous conjunctivitis successfully treated with 60% fresh frozen plasma (FFP).Retrospective data collected on a 45-year-old Caucasian female presenting with unilateral chronic membranous lesions.Laboratory investigation demonstrated decreased plasminogen antigen level, plasminogen activity, and rate of plasminogen activation by u-PA or t-PA, and elevated plasminogen activator inhibitor-1. Anti-plasminogen IgG and IgA antibodies were detected. DNA analysis revealed a novel Asp432Asn heterozygous missense mutation in the plasminogen gene (exon 11). The patient was treated with topical 60% FFP, achieved complete remission after four months, and remained membrane-free for over five years of follow-up.A novel plasminogen gene mutation, deficiency of plasminogen antigen and activity, and anti-plasminogen IgG and IgA antibodies were identified in a patient with adult-onset ligneous conjunctivitis. Sixty percent FFP maintained this patient disease-free for over five years.

To evaluate the use of topical cyclosporine A (CsA) 1% emulsion in the treatment of chronic ocular surface inflammation (OSI).We conducted a retrospective chart review of patients with various forms of OSI treated with topical CsA 1% from 2001 to 2012.Twenty-nine patients (52 eyes) with various forms of OSI, including epidemic keratoconjunctivitis (n=14), chronic follicular conjunctivitis (n=12), Thygeson superficial punctate keratopathy (n=2), and vernal keratoconjunctivitis (n=1), were included. Twenty-seven patients had inflammation refractory to prior therapies. Twenty-four patients received concurrent medications with CsA 1%. Twenty-three of 24 patients on concurrent corticosteroids (CS) were able to taper their use while receiving CsA 1%. Thirteen patients experienced ocular discomfort with CsA 1%; one patient discontinued therapy all together as a result of these side effects; another switched to CsA 0.5% with improvement of adverse symptoms. Inflammation was controlled in 22 (92%) of the 24 patients who received CsA 1% for at least 2 months in duration.Topical CsA 1% helps to control inflammation and spares CS use in patients with chronic OSI.

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.

To investigate whether lacrimal gland uptake on (67)Ga-gallium citrate scintigraphy correlates with histopathologic evidence of sarcoidosis.A retrospective, pilot study of 31 patients with suspected sarcoidosis who underwent gallium scintigraphy and lacrimal gland biopsy. Lacrimal gland gallium uptake was assessed by subjective visual scoring (SVS) and lacrimal uptake ratio (LUR).Eleven (36%) patients had lacrimal gland biopsies containing noncaseating granulomas. A statistically significant correlation was found between lacrimal gland gallium uptake and biopsy positivity using SVS (p = 0.03) or LUR (p = 0.01). Using SVS, biopsy positivity rate increased from 0 to 50% in patients with mild to intense uptake. Using LUR, biopsy positivity rate increased linearly as the ratio increased from 13% (LUR 4) to 100% (LUR 8).Lacrimal biopsy positivity rate significantly correlated with gallium uptake on scintigraphy. Both SVS and LUR methods appear to correlate with histologic results and may potentially aid in patient selection for biopsy.

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 describe the demographics, characteristics, management, and outcomes of eyes with endophthalmitis related to infectious keratitis. Methods Retrospective chart review of all patients treated for infectious keratitis-associated infectious endophthalmitis between 2001 and 2014 at University Hospital, Rutgers New Jersey Medical School. Results Thirty-eight cases with infectious keratitis-associated infectious endophthalmitis were identified (21 men [55%], mean age: 66.2 ± 20.7 years), with average time from the beginning of ulcer symptoms to endophthalmitis of 11.0 days. Associated systemic conditions (diabetes, HIV, immunosuppressive therapy, cirrhosis, or dementia) were present in 57.9%; 60.5% had previous intraocular surgery. Etiology showed gram-positive bacteria in 14 cases (36.9%), gram-negative bacteria in 7 (18.4%), fungi in 4 (10.5%), and no growth/unknown in 12 (31.6%). Nineteen cases (50%) presented with no light perception and were primarily enucleated. The remaining 19 eyes each received intravitreal antibiotics (mean: 1.5 injections); 8 (42.0%) underwent pars plans vitrectomy with vitreous biopsy, whereas 5 (26.3%) received emergency corneal transplantation. Final visual acuity was no light perception in 6 eyes (3 secondarily enucleated), light perception in 2, hand motion in 7, counting fingers in 2, and ≥20/50 in 2. Conclusion Our study of 38 eyes with infectious keratitis-associated infectious endophthalmitis revealed generally poor visual outcomes and a high rate of systemic conditions and previous intraocular surgery.

The authors aimed to analyze the causes and outcomes of golf-related ocular injuries in this retrospective meta-analysis, literature review, and original case series.Forty-one articles identified by PubMed search resulted in 11 included studies yielding 102 subjects. Included articles described all ocular golf injuries that presented to an institution during a determined period. Eight factors were analyzed: age, sex, location and mechanism of injury, protective eyewear use, resulting open-globe injury, resulting enucleation, and visual acuity changes.No subjects wore adequate protective eyewear. Significantly more subjects were injured by golf balls (72%) than golf clubs (27%) or foreign body (1%) (P0.0001). The ratio of golf ball to club injuries was significantly higher in adults (92%) than in children (23%) (P0.0001). Forty-seven of 93 (51%) injuries resulted in an open globe, whereas 27/82 (33%) injuries resulted in enucleation. The mean ± SD logMAR visual acuity improved by -0.641 ± 0.745 after treatment (6 lines of improvement; P = 0.0001).Reported ocular golf injuries occur less frequently than other ocular sports injuries, but may result in devastating outcomes. Supervision of children using golf equipment should be encouraged.

To evaluate the use of selective vs. non-selective cyclo-oxygenase inhibitors (COXIs) for the treatment of chronic non-infectious, non-necrotizing scleritis and episcleritis.Sixty-nine patients with scleritis and episcleritis treated for ≥2 months with COXIs were included. Outcome measures were rates of inflammation control, corticosteroid sparing, and COXI discontinuation, as well as side effects.Initial inflammation control was achieved in 78-81% of scleritis patients and 73-80% episcleritis patients on COXIs (p.05). Rates of steroid sparing after 4-24 months of consecutive treatment were similar. Gastrointestinal side effects were observed in 1 (2.7%) patient on selective vs. 3 (9.4%) patients on non-selective COXIs (p = .33). Overall discontinuation rate was 6/37 (16%) for selective vs. 7/32 (22%) for non-selective COXIs (p = .76).Selective vs. non-selective COXIs were equally efficacious for the treatment of chronic non-infectious, non-necrotizing scleritis and episcleritis. Prospective studies to elucidate potential differences in side effect profiles may be warranted.

To evaluate surgical outcomes using a temporary intraoperative keratoprosthesis (KP) in patients undergoing combined pars plana vitrectomy (PPV) and penetrating keratoplasty (PKP).From January 2001 to August 2008, medical records of 23 patients undergoing combined KP/PPV/PKP for traumatic and nontraumatic corneal and retinal pathologies were studied. Only patients withor=6 months follow-up were included. Patient characteristics, diagnoses, visual acuity, intraocular pressure, and status of the retina and cornea at baseline, and postoperatively on day 1, months 1 and 6, and yearly until the last follow-up, were collected. Functional (best-corrected visual acuity: improved, stable, worsened) and anatomic outcomes (clear corneal graft, retinal reattachment) were defined prior to review.Twenty-four eyes underwent combined KP/PPV/PKP (mean follow-up 36 months). At final follow-up, best-corrected visual acuity improved in 8 (40%) eyes, remained stable in 8 (40%), and worsened in 4 (20%). Corneal graft was clear in 18 (79%) eyes; 5 (21%) had graft failure. Retinal reattachment occurred in 22 (92%) eyes; 2 (8%) developed a localized traction retinal detachment not warranting additional surgery. Derangement in intraocular pressure was common (13 [54%] eyes). Three eyes (13%) showed signs of phthisis preoperatively that resolved with reestablishment of normal intraocular pressure postoperatively.Temporary KP during PPV/PKP surgery allowed surgical intervention in eyes with complex anterior and posterior segment disease. Corneal graft clarity and successful retinal reattachment was possible in the majority of eyes.

Objectives To examine seven cases of contact lens-related Fusarium keratitis that resulted in therapeutic penetrating keratoplasty, to investigate which factors were associated with favorable versus poor graft outcome in this population. Methods Seven patients who underwent corneal transplant after contact lens-related, culture-proven Fusarium keratitis were identified through a retrospective chart review. The cases occurred between September 2005 and January 2006 at the University of Medicine and Dentistry of New Jersey and Wills Eye Hospital. All seven patients had used Bausch and Lomb's ReNu with MoistureLoc. The outcomes studied were graft status, infection recurrence, and 6-month postoperative visual acuity. Results The rejection rate was 57.1% and the recurrence rate was 28.6% in this study. No eyes were lost to fungal endophthalmitis. In this population, larger ulcer size and a greater total number of medical agents used before and after penetrating keratoplasty were significantly associated with poor outcomes, namely graft rejection and poor visual acuity. In addition, it was noted that the patients who suffered recurrence of infection had both a larger median graft size and a longer median duration of postoperative antifungal use although these results did not reach statistical significance. Conclusions Larger ulcer size, larger graft size, a greater number of medical agents used, and a longer duration of postoperative antifungal therapy may be useful parameters in predicting surgical outcomes in patients with fungal keratitis. Further research is needed to validate our results and to elucidate the mechanisms behind graft rejection in the setting of fungal keratitis.

Purpose To suggest that sub-Tenon triamcinolone acetonide (TA) injections may be a helpful supplement in patients with scleritis. Design Retrospective, interventional case series. Methods A retrospective chart review was conducted of all patients at our institution receiving sub-Tenon TA injections for scleritis between August 2001 and August 2007. Outcome measures included subjective improvement, presence of inflammation, and adverse events. Results Eleven patients (12 eyes) were included in this study. The mean age was 50 years; 2 patients were male and 9 female. Six patients had systemic autoimmune disease. All patients were receiving systemic medications for scleritis at the time of injection. Mean initial follow-up time was 3 weeks. Ten of 11 patients reported subjective improvement, and 10 patients had improvement in objective inflammation. Three patients had adverse side effects, including ocular hypertension, worsening of cataract, and subconjunctival hemorrhage with periorbital ecchymosis. Conclusions Sub-Tenon TA injections may be a useful adjunct to achieving transient, partial improvement of subjective pain and objective inflammation in patients with scleritis while awaiting systemic medications to take effect. Adverse events were manageable in this small series.

Purpose To report an outbreak of Fusarium keratitis in contact lens (CL) wearers in the northeastern United States. Methods Over a 41-month period, all cases with culture-proven corneal ulceration secondary to Fusarium at 2 tertiary care eye centers were identified through the microbiology departments of each institution, and a retrospective review of charts was performed. Statistical analyses were performed to evaluate a possible association of Fusarium keratitis with specific CL and CL solution brands. Results Fifteen cases of Fusarium keratitis were reported at the 2 tertiary centers between July 2005 and May 2006 (16.4 cases/yr) compared with 6 cases over the previous 30 months from January 2003 to June 2005 (2.4 cases/yr). All 15 of the more recent cases were CL users, and none had a history of trauma. All 15 patients claimed use of ReNu brand contact lens solution when they developed keratitis. Twelve (80.0%) of 15 patients were Acuvue soft contact lens users. Ten (66.7%) of 15 patients used tap water to rinse their contact lens cases. Six (40.0%) of 15 cases have thus far required corneal transplantation. Conclusions The incidence of corneal ulceration secondary to Fusarium has increased sevenfold over the reported 11-month period at 2 tertiary eye care centers in the northeastern United States compared with the previous 30 months. There seems to be an association between the recent outbreak of Fusarium keratitis among CL users and the use of ReNu contact lens solution. Medical treatment of Fusarium keratitis may be ineffective, and emergent penetrating keratoplasty (PKP) may be required in some patients. CL users and their physicians should reconsider the risks of CL use and discuss proper lens care techniques.

Ocular inflammatory disease is a leading cause of vision loss worldwide. Uveitis encompasses a wide spectrum of pathology, both with respect to its etiology and the anatomic location within the eye. Inflammation can be confined to the eye and may also be seen systemically. The cornerstone of management of ocular inflammatory disease historically has been corticosteroids, which are invaluable in the immediate control of inflammation; however, corticosteroids are inappropriate for long-term use as they are associated with a wide array of toxic side effects. As we continue to learn more about the various etiologies and elucidate the basic science pathways and mechanisms of action that cause intraocular inflammation, new therapeutic approaches have evolved. They include employment of immunomodulatory agents (corticosteroid-sparing therapies) that have expanded our treatment options for these vision-threatening diseases. These pharmacologics provide therapy for ocular and systemic inflammation in an individualized, patient-tailored, stepladder approach with the ultimate goal of durable, corticosteroid-free remission. We review the preferred practice patterns of a tertiary care center specializing in ocular inflammatory disease.

PURPOSE OF REVIEW To outline immunomodulatory therapy for ocular inflammatory diseases of the anterior segment and to review the current literature regarding their efficacy and safety. RECENT FINDINGS Most current studies concern immunomodulatory treatment of patients who have chronic, debilitating disease resistant to corticosteroids. The authors evaluated the efficacy of treatment, the side effect profiles and the potential for long-term remission. SUMMARY Immunomodulatory drugs are increasingly being used in ocular inflammatory disease to avoid the effects of chronic steroid therapy and to induce remission in patients with chronic disease. These therapies have shown efficacy in treating otherwise resistant disease with relative safety insofar as side effects are generally reversible and medications can be substituted if intolerable side effects arise. Future trends in treatment will emphasize more specific target molecules, less immunosuppressive drugs and modification of the immune environment to increase the rates of long-term remission.

PURPOSE To report the complication of infectious ulcerative keratitis after laser photocoagulation and pars plana vitrectomy (PPV) for retinopathy of prematurity (ROP). METHODS A retrospective chart review of infants treated for ROP with plus disease between 2004 and 2013 at University Hospital, Newark, New Jersey. RESULTS Of the 110 eyes (55 patients) that underwent treatment for ROP, 8 (7.27%) eyes were noted to develop infectious ulcerative keratitis in 4 neonates (4 eyes after laser photocoagulation and 4 eyes after PPV). All 8 eyes that developed ulcerative keratitis had a preceding corneal epithelial defect followed by corneal stromal haze. Seven of 8 eyes developed epithelial defect within 8 days of the procedure. All epithelial defects progressed to ulcerative keratitis within 7 days. A total of 10 (9.1%) eyes developed postoperative epithelial defects, and 8 (80%) of these eyes were ultimately diagnosed as having ulcerative keratitis. Four (4.08%) of 98 eyes treated with laser photocoagulation alone developed infective ulcerative keratitis, compared to 4 (33.33%) of 12 eyes treated with PPV. Because keratitis healed, corneal opacification ensued and covered 10% to 90% of the corneal surface area. Five of the 8 eyes had positive culture of corneal scrapings: 2 grew coagulase-negative Staphylococcus and Stenotrophamonas; 1 grew coagulase-negative Staphylococcus; 1 grew Streptococcus viridans, and 1 grew Staphylococcus hominis, Streptococcus mitis, and Streptococcus viridans. All 8 eyes were treated with antibiotic eye drops. CONCLUSIONS Infectious ulcerative keratitis developed in a small, but significant, percentage of patients undergoing treatment for ROP. Postoperative corneal epithelial defects with subsequent corneal haze appear to be involved in the progression to ulcerative keratitis.

Purpose: To evaluate the use of TNF-alpha inhibitors for non-infectious, non-necrotizing scleritis.Methods: We conducted a retrospective chart review of patients with non-infectious, non-necrotizing scleritis treated at our institutions from 2002 to 2012.Results: Seventeen patients (26 eyes) were included. Ten patients were started on infliximab and seven on adalimumab; five patients were treated with both TNF-alpha inhibitors on separate occasions. All patients had an associated autoimmune disease. Control of active inflammation for at least 2 months was achieved in 15 (88%) of 17 patients. Seven out of eight patients successfully tapered concurrent corticosteroid use. Only one patient discontinued TNF-alpha inhibitor use due to an allergic reaction.Conclusions: TNF-alpha inhibitors appear to have a role in managing non-infectious, non-necrotizing scleritis refractory to initial therapy, mainly by reducing inflammation and decreasing concurrent CS use.

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 report the clinical use of ProKera (Bio-Tissue, Inc., Miami, FL) under topical anesthesia in an outpatient for the management of ocular manifestations of acute Stevens-Johnson syndrome (SJS). Methods Interventional case report. Results A 19-year-old woman developed acute SJS with ocular involvement after ingestion of oral antibiotics. Slit-lamp examination performed 2 weeks later showed severe inflammation and areas of ulceration along all 4 lids and complete, bilateral sloughing of bulbar and palpebral conjunctivae, including the limbus. ProKera was placed under topical anesthesia without sedation in both eyes instead of an amniotic membrane due to excess risk of general anesthesia. Three weeks after placement, slit-lamp examination showed complete re-epithelialization of both corneas and conjunctivae, with only trace conjunctival injection and minor limbal epithelial irregularities. Three months postprocedure, there were no signs of clinically significant scarring, and the visual acuity (VA) was 20/20 bilaterally. Fourteen months postprocedure, VA remained stable, and the patient did not have dry eye, photophobia, clinically significant scarring, or symblepharon. Conclusions ProKera placement performed under topical anesthesia may be appropriate for the treatment of ocular surface manifestations of acute SJS particularly in those patients followed in an outpatient setting with milder forms of disease and/or with contraindications to general anesthesia.

To determine the effectiveness and corticosteroid (CS) sparing capabilities of mycophenolate mofetil (MMF) in the treatment of chronic non-infectious, non-necrotizing scleritis.A retrospective chart review of patients treated for scleritis at the Institute of Ophthalmology and Visual Science at New Jersey Medical School was performed. Only those patients taking MMF for greater than or equal to six consecutive months were included. Main outcome measures were rate of inflammation control, CS, and MMF discontinuation, as well as visual acuity and side effects.Twenty-two patients (32 eyes) were included in the study. Mean ± SD age was 53.5 ± 13.3 years. Twenty (91%) patients had previously failed some form of immunomodulatory therapy. After 6, 12, 18, and 24 months of consecutive MMF treatment, 91-100% of patients achieved inflammation control. Mean time to resolution of inflammation was 2.8 months, while mean duration of inflammation control was 14.8 months. CS sparing was achieved in 100% of patients at each time point, with mean starting CS dose decreased by 91% at final visit. Vision was stable or improved in 24 (75%) eyes. Fourteen (64%) patients reported side effects including leucopenia (n = 7), gastrointestinal upset (n = 4), abnormal liver function tests (n = 3), and abnormal renal function tests (n = 2). None required hospitalization or medical treatment. Four (18%) patients discontinued MMF due to side effects (n = 3) and treatment ineffectiveness (n = 1).MMF is an effective and well-tolerated therapy that can successfully reduce inflammation and decrease CS use in the treatment of chronic non-infectious, non-necrotizing scleritis.

Objective To describe a case of Haemophilus influenza endophthalmitis after pterygium surgery. Method Retrospective case report. Results A 50-year-old Hispanic male underwent a pterygium excision with amniotic membrane graft (AMG) and 0.02% MMC. He presented 3.5 months later with severe pain, yellow-white discharge, and decreased visual acuity for several days, and conjunctival injection for 3 months. Repair of perforation with a corneal graft was performed. Intravitreal antibiotics were administered. Many β-lactamase negative H. influenza organisms were cultured from the vitreous aspirate. The vitritis significantly improved and hypopyon resolved over the next week. The patient underwent surgery for a combined tractional and rhegmatogenous RD 9 days later. The endophthalmitis resolved; however, he developed proliferative vitreoretinopathy (PVR) with redetached retina 21 days after the initial RD repair. He underwent subsequent surgery. Six months later, AMG was performed for recurrent corneal erosion with a large epithelial defect. At last follow-up, the vision remains at hand motions, the retina is flat, there is mild corneal decompensation, the eye is soft to palpation, and there are signs of early phthisis. Conclusions A prospective study to identify the optimal concentration and period of application for MMC, as well as patient characteristics resulting in the highest clinical benefit-to-risk ratio may be warranted.

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.

We describe a case of corneal chromoblastomycosis with Cladophialophora carrionii in a 69-year-old woman 4 weeks after clear corneal cataract surgery. The patient presented with right eye pain and decreased visual acuity of 20/100. Examination showed a deep posterior stromal keratitis accompanied by a dense fibrinous anterior chamber reaction. An aqueous tap was performed, and the patient was treated with topical, systemic, and intracameral antifungal and antibiotic agents. The infection was resistant to medical therapy and the course further complicated by secondary pupillary block glaucoma. After 10 days, a therapeutic penetrating keratoplasty was performed. The patient remained asymptomatic 20 months after the initial presentation, with corrected distance visual acuity restored to 20/40. To our knowledge, is the first reported case of corneal chromoblastomycosis with C carrionii. Early surgical treatment may be necessary to eradicate Cladophialophora species.

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.

We present 2 cases of spontaneous corneal perforation in patients with keratoconus. The first patient developed a corneal scleral fistula 1 year after her initial diagnosis of hydrops. We conclude that adequate eye care education, allergy prophylaxis, and fall precautions may be necessary in patients with keratoconus to prevent corneal perforations. Medical and surgical treatments are both viable first-line treatments for corneal perforations.