Effect of OTX-101 in Patients with Dry Eye Disease at Day 14 of Treatment: Ocular Surface Endpoint Results from the Phase 2b/3 Clinical Trial.

Dry eye disease (DED) is a multifactorial disorder characterized by loss of tear film homeostasis, which initiates a cycle of ocular surface inflammation and damage. As ocular discomfort symptoms associated with DED can decrease quality of life, affected patients prefer treatments that rapidly improve the underlying disease process. OTX-101 0.09% (CEQUA®) is indicated to increase tear production in patients with DED. The current analysis assessed early efficacy of OTX-101 0.09% in adult patients with bilateral DED by evaluating ocular surface endpoints after 14 days of treatment in the phase 2b/3 trial. In this randomized, double-masked, vehicle-controlled, dose-ranging study, patients received one drop of OTX-101 0.05%, OTX-101 0.09%, or vehicle per eye twice daily for 84 days. Corneal staining, conjunctival staining, tear breakup time (TBUT), and modified Symptom Assessment iN Dry Eye (SANDE) total global symptom score were assessed at baseline and Days 14, 28, 42, 56, and 84/early discontinuation. Overall, 455 patients were randomized (OTX-101 0.05%, n=151; OTX-101 0.09%, n=152; vehicle, n=152); only baseline and Day 14 results for the approved OTX-101 0.09% formulation and vehicle are presented. Least squares (LS) mean (standard error [SE]) change from baseline in conjunctival staining score was -1.3 (0.1) for OTX-101 and -1.0 (0.1) for vehicle. LS mean (SE) change from baseline in corneal staining score was -1.1 (0.17) for OTX-101 and -0.7 (0.17) for vehicle. LS mean (SE) change from baseline in TBUT was 0.52 (0.15) for OTX-101 and 0.36 (0.15) for vehicle. LS mean (SE) change from baseline in modified SANDE total global symptom score was -4.93 (1.54) for OTX-101 and -9.1 (1.54) for vehicle. OTX-101 0.09% demonstrated a numerically greater treatment effect compared with vehicle in conjunctival staining, corneal staining, and TBUT after 14 days.

Phase 3 Efficacy (Worse-Eye Analysis) and Long-Term Safety Evaluation of OTX-101 in Patients with Keratoconjunctivitis Sicca.

BACKGROUND: OTX-101 is approved for treatment of keratoconjunctivitis sicca (KCS). We present results of a phase 3 worse-eye efficacy analysis and 1-year safety extension. METHODS: During the double-masked treatment phase, patients with bilateral KCS were randomized 1:1 to 12 weeks OTX-101 or vehicle 1 drop per eye twice daily. Efficacy assessments included Schirmer's test and corneal and conjunctival staining. All patients who completed the treatment phase were eligible for enrollment in the open-label extension and received 1 drop OTX-101 twice daily for up to 52 weeks. Safety endpoints included adverse event (AE) monitoring, Snellen visual acuity (VA), intraocular pressure (IOP), slit-lamp examination (SLE), and dilated fundoscopy. RESULTS: Overall, 745 and 258 patients enrolled in the treatment and safety extension phases, respectively. At 12 weeks, number (%) of patients with Schirmer's score increase of ≥10 mm from baseline was 76 (20.5%) vs. 42 (11.3%) for OTX-101 vs. vehicle (P=0.0005). OTX-101 significantly improved total conjunctival staining vs. vehicle at week 12 (least squares mean change from baseline -1.65 [0.12] vs. -1.12 [0.12], P=0.0013), and number (%) of patients with clear central corneas vs. vehicle at week 12 (222 [64.0%] vs. 199 [55.3%], P=0.0179). In the 1-year safety extension, AEs were mostly mild; instillation site pain was most common in 59 (22.9%) patients (17 [13.2%] vs. 42 [32.6%] patients receiving prior OTX-101 and vehicle). No safety concerns were raised by VA, IOP, SLE, and fundoscopy. CONCLUSION: OTX-101 efficacy was confirmed in the eye with lower baseline Schirmer's score. OTX-101 was well tolerated long term. CLINICAL TRIAL: Registered at ClinicalTrials.gov on July 27, 2016. NCT02845674 https://clinicaltrials.gov/ct2/show/NCT02845674?term=OTX-101&draw=2&rank=1.

Pterygium Surgery Utilizing Limbal Conjunctival Autograft and Subconjunctival Amniotic Membrane Graft in High-Risk Populations.

OBJECTIVE: To measure the outcomes of primary pterygium excision with a limbal conjunctival autograft when combined with the adjunctive use of a prophylactic subconjunctival graft of amniotic membrane to decrease the recurrence rate after surgery in an ethnically diverse population with a statistically higher risk for recurrence (African American, Asian, Caribbean, Asian, Latin). DESIGN: This is a retrospective, non-comparative study of post-operative outcomes. PARTICIPANTS: A total of 355 patients, totaling 493 eyes, with clinically significant, primary pterygia. PATIENTS AND METHODS: Patients were enrolled into the study based on the need for pterygium surgery and if they underwent primary pterygium excision with conjunctival autograft with subconjunctival amniotic membrane placement. Patients with recurrent pterygium or those with pseudopterygium were excluded from this study. All surgeries took place at the Florida Eye Microsurgical Institute (Boynton Beach, FL) between June 2006 and October 2013 by a single surgeon (BAS). Patients were seen on post-operative day 1, 7, 30, 90, 180 and 365 to evaluate for pterygium recurrence. Pterygium recurrence is defined in this study as growth greater than 1 mm past the corneal limbus at or after 6 months. RESULTS: There were six cases of recurrent pterygium for a recurrence rate of 1.22% ± 0.97% (n=493, p=0.05). Follow-up ranged from 6 months to 6 years (mean 28 months). CONCLUSION: Primary pterygium excision with a limbal conjunctival autograft and placement of a subconjunctival amniotic membrane graft has a low recurrence rate consistent with previously published data.

An Evaluation of Staphylococci from Ocular Surface Infections Treated Empirically with Topical Besifloxacin: Antibiotic Resistance, Molecular Characteristics, and Clinical Outcomes.

INTRODUCTION: Understanding antibiotic resistance and toxin profiles among staphylococcal isolates in ocular infections can aid in therapeutic management and infection prevention strategies. We evaluated in vitro antibiotic resistance patterns and molecular traits of staphylococci isolated from patients with ocular surface infections. We also report on clinical outcomes for these patients following empirical treatment with topical besifloxacin ophthalmic suspension 0.6%. METHODS: This was a small observational study. Participating investigators from three clinical sites collected an initial ocular culture from the affected eye of patients presenting with ocular surface infections with presumed staphylococcal etiology. Clinical outcome data for patients with confirmed staphylococcal infections were collated later through retrospective review of patient medical records. Staphylococcal species identification in ocular cultures, in vitro antibiotic susceptibility testing, and PCR-based determination of methicillin resistance cassettes and toxin genotypes were conducted at a central laboratory. Isolates were categorized as susceptible or resistant based on systemic breakpoints, where available. RESULTS: Cultures were collected from 43 patients, and staphylococcal infections were confirmed in 25 patients. Two isolates of Staphylococcus aureus and 27 isolates of Staphylococcus epidermidis were identified. Both S. aureus isolates were methicillin-susceptible, lacked the gene encoding Panton-Valentine leukocidin, and carried few enterotoxin genes. Eight (30%) S. epidermidis were methicillin-resistant (MRSE), and 10 (37%) were ciprofloxacin-resistant. All but two MRSE isolates demonstrated multidrug resistance (MDR), and the staphylococcal cassette chromosome mec (SCCmec) type IVa was detected in five of the eight MRSE isolates. Clinical resolution of the ocular surface infection was reported in all 25 patients following treatment with besifloxacin. CONCLUSIONS: In this study, S. aureus contained few toxins, while SCCmec IVa and MDR was predominant among MRSE from ocular surface infections. Despite significant in vitro fluoroquinolone resistance, there were no cases of treatment failure with topical besifloxacin ophthalmic suspension 0.6%. FUNDING: Bausch Health US, LLC.

Use of topical bromfenac for treating ocular pain and inflammation beyond cataract surgery: a review of published studies.

Topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat postoperative inflammation and pain following cataract surgery and for treatment and prophylaxis of pseudophakic cystoid macular edema (CME). Bromfenac is a brominated NSAID with strong in vitro anti-inflammatory potency. Like other ophthalmic NSAIDs, bromfenac is often used outside of the cataract surgery setting. This paper provides an overview of bromfenac's preclinical ocular pharmacology and pharmacokinetics, followed by a review of 23 published clinical studies in which various marketed bromfenac formulations were used for conditions other than cataract surgery or pseudophakic CME. These include: post-refractive eye surgery; macular edema associated with diabetes, uveitis, or retinal vein occlusion; inflammation associated with age-related macular degeneration; pain related to intravitreal injections; and other ocular anterior segment and surface disorders with an inflammatory component. The published evidence reviewed supports the safety and effectiveness of bromfenac in these additional ophthalmic indications. Bromfenac was well tolerated when given alone or in combination with intravitreal anti-vascular endothelial growth factor agents, topical corticosteroids, or topical mast-cell stabilizers. The most common adverse event reported was ocular irritation. No serious adverse events (ie, corneal epithelial disorders) were reported, although the majority of studies did not systematically evaluate potential side effects. Corneal complications, such as melts reported with diclofenac and ketorolac, were not observed with bromfenac in the studies. In summary, published study data support the clinical utility of bromfenac in various ocular disorders beyond post-cataract surgery. Additional studies are warranted to further define the potential role of bromfenac ophthalmic solution in clinical practice.

Effect of OTX-101, a Novel Nanomicellar Formulation of Cyclosporine A, on Conjunctival Staining in Patients with Keratoconjunctivitis Sicca: A Pooled Analysis of Phase 2b/3 and 3 Clinical Trials.

Purpose: Keratoconjunctivitis sicca (KCS), a multifactorial disease, is the most common ocular condition for patients seeking medical treatment and is characterized by ocular burning, stinging, and dryness. This pooled analysis examined the effect of OTX-101 0.09% versus vehicle on the total and individual conjunctival staining in patients with KCS from phase 2b/3 and phase 3 studies. Methods: In these randomized, multicenter, double-masked, and vehicle-controlled studies, patients received 1 drop of OTX-101 0.09% or vehicle in both eyes twice daily. The time points for the pooled analysis were baseline (day 0) and study days 28, 56, and 84/early discontinuation. Conjunctival staining was graded on a 0- to 3-point scale per zone and averaged over both eyes at each assessment. Pooled safety assessments included adverse event (AE) reporting. Results: The total mean (standard deviation) conjunctival staining scores at baseline were 5.4 (1.7) for OTX-101 (n = 523) and 5.5 (1.7) for vehicle (n = 525). OTX-101 versus vehicle significantly reduced the total conjunctival staining scores (P = 0.0316, <0.0001, and 0.0002) for days 28, 56, and 84, respectively. The most common treatment-related AE was instillation site pain (21.8% OTX-101 vs. 4.0% vehicle); most AEs were mild in nature. Conclusions: Treatment with OTX-101 versus vehicle significantly improved the conjunctival staining in KCS as early as 4 weeks, and the improvement was maintained through 12 weeks. OTX-101 was effective and well tolerated for use in KCS.

Effect of OTX-101, a Novel Nanomicellar Formulation of Cyclosporine A, on Corneal Staining in Patients With Keratoconjunctivitis Sicca: A Pooled Analysis of Phase 2b/3 and Phase 3 Studies.

BACKGROUND: Keratoconjunctivitis sicca affects 5% to 33% of the population and is often accompanied by symptoms such as burning and dryness. This pooled analysis evaluated total and central corneal fluorescein staining (CFS) in patients receiving OTX-101 0.09% or vehicle in phase 2b/3 and 3 studies and whether improvements in corneal staining correlated with improved visual acuity. METHODS: In these randomized, vehicle-controlled studies, patients received 1 drop of OTX-101 or vehicle in both eyes twice daily. Corneal staining was performed at baseline and days 28, 56, and 84. CFS was evaluated in each zone (0-to-4 scale); total corneal staining (0-to-20 scale per eye) was averaged over both eyes. Pooled safety assessments included adverse event monitoring. RESULTS: Mean baseline CFS total scores (SD) were 4.2 (2.5) and 4.3 (2.6) for the OTX-101 (n = 523) and vehicle (n = 525) groups, respectively. For total corneal staining, least squares mean changes from baseline (standard error) were -0.9 (0.08) versus -0.5 (0.08) for OTX-101 and vehicle, respectively (P = 0.0008), on day 28 and -1.4 (0.09) versus -0.9 (0.09) on day 84 (P = 0.0002). There was a significantly high correlation (P = 0.0117) between reduced central corneal staining and improved visual acuity on day 84. Treatment-related adverse events were mostly mild, with instillation site pain reported by 21.8% and 4.0% of patients receiving OTX-101 and vehicle, respectively. CONCLUSIONS: Treatment with OTX-101 led to greater improvements versus vehicle in corneal surface staining as early as 4 weeks, and further improvements were seen up to 12 weeks. OTX-101 was well tolerated in patients with keratoconjunctivitis sicca.

A Phase 3, Randomized, Double-Masked Study of OTX-101 Ophthalmic Solution 0.09% in the Treatment of Dry Eye Disease.

PURPOSE: To evaluate the safety and efficacy of OTX-101, a novel aqueous nanomicellar formulation of cyclosporine (0.09%), in the treatment of patients with dry eye disease (DED). DESIGN: A randomized, multicenter, vehicle-controlled, double-masked, phase 3 clinical trial. PARTICIPANTS: Adults (18-90 years of age) with a history and clinical diagnosis of DED, a global symptom score of 40 or more (range, 0-100), and a lissamine green conjunctival staining score of 3 or more and 9 or less (range, 0-12) in at least 1 eye. METHODS: Eligible patients entered a run-in period of 14 to 20 days in which all patients administered vehicle twice daily. Patients who remained eligible at the baseline (day 0) visit were randomized in a 1:1 ratio to twice-daily treatment with OTX-101 0.09% or vehicle for 84 days. MAIN OUTCOME MEASURES: Efficacy assessments included signs (unanesthetized Schirmer tear test, corneal and conjunctival staining) and symptoms (global symptom score) of DED. The primary end point was the proportion of eyes with a clinically meaningful improvement (increase of ≥10 mm) in Schirmer test score at day 84. Safety evaluations included adverse events (AEs), visual acuity, and intraocular pressure monitoring, slit-lamp, dilated ophthalmoscopy, and fundus examinations. RESULTS: A total of 744 patients were randomized and received study medication (371 to OTX-101 0.09% and 373 to vehicle). The primary end point was achieved; a significantly greater percentage of eyes in the OTX-101 0.09% treatment group achieved an increase of 10 mm or more in the Schirmer test score at day 84 (OTX-101 0.09%, 16.6%; vehicle, 9.2%; P < 0.001). Significant improvements relative to vehicle also were observed for corneal (days 28, 56, and 84) and conjunctival (days 56 and 84) staining. The global symptom score was reduced from baseline in both treatment groups by approximately 30%; however, no significant separation between groups was observed. The OTX-101 0.09% formulation was well tolerated. Treatment-emergent AEs were primarily mild in intensity. CONCLUSIONS: Clinically and statistically significant improvements in tear production and ocular surface integrity were observed in patients treated with OTX-101 0.09% for DED.

A Phase II/III, randomized, double-masked, vehicle-controlled, dose-ranging study of the safety and efficacy of OTX-101 in the treatment of dry eye disease.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of OTX-101, a clear nanomicellar aqueous solution of cyclosporine, in the treatment of dry eye disease (DED). PATIENTS AND METHODS: This was a 12-week multicenter, randomized, prospective, double-masked, vehicle-controlled, dose-ranging clinical trial. Subjects were adults aged ≥18 years, with a total conjunctival staining score of ≥3 and ≤9, and global DED symptom score ≥40 (0-100 visual analogue scale). Following a 14-day vehicle run-in, subjects were randomized in a 1:1:1 ratio to twice daily treatment with OTX-101 0.09%, OTX-101 0.05%, or vehicle for 84 days. Co-primary efficacy end points were changes, from baseline to Day 84, in the total lissamine green conjunctival staining score in the designated study eye and in the global symptom score (both eyes). Secondary end points included total corneal fluorescein staining score, tear breakup time, and Schirmer's test score. RESULTS: In total, 455 subjects were randomized. Subjects treated with active drug experienced greater improvement in conjunctival staining than vehicle-treated patients (P<0.01 for both concentrations). All groups demonstrated improvements in global symptom score, but there were no differences among groups. Nominally significant differences were found between the active drug arms and vehicle for corneal staining scores and Schirmer's test scores. Most treatment-emergent adverse events were mild in severity; no serious ocular adverse events were reported. CONCLUSIONS: Both concentrations of OTX-101 met the co-primary sign end point (conjunctival staining) but not the co-primary symptom end point. OTX-101 0.09% demonstrated a notable impact on multiple signs of DED relative to vehicle and was well-tolerated.

Besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial keratitis: a retrospective safety surveillance study.

PURPOSE: The objective of this study was to collect and evaluate retrospective safety information about the use of besifloxacin ophthalmic suspension 0.6% for the treatment of bacterial keratitis. METHODS: This was a retrospective, postmarketing surveillance study conducted at 10 clinical centers in the United States. The study population included 142 patients treated with besifloxacin ophthalmic suspension 0.6% for bacterial keratitis in one or both eyes. For perspective, data on 85 patients treated at these centers with moxifloxacin ophthalmic solution 0.5% for bacterial keratitis were also included. The analysis was designed to measure the types and rates of adverse events (AEs) reported during the treatment of bacterial keratitis with besifloxacin ophthalmic suspension 0.6%. Other treatment outcomes of interest included the development of corneal scarring and corneal neovascularization, measured or presumed bacterial eradication, ending visual acuity, and duration of pain before and after treatment. RESULTS: There was one reported AE of mild superficial punctate keratitis in a patient using besifloxacin ophthalmic suspension 0.6%. The difference in AE frequencies between groups was not significant (P>0.999). Additional treatment outcomes were similar for both groups. Limitations of this report include the retrospective nature of the study. CONCLUSIONS: These retrospective data suggest that besifloxacin ophthalmic suspension 0.6% was well tolerated when included in the treatment of bacterial keratitis; no serious AEs were reported. A prospective clinical trial is needed to better isolate the contribution of besifloxacin to the therapeutic outcome and to confirm these observations.

Endothelial survival after Descemet-stripping automated endothelial keratoplasty in eyes with retained anterior chamber intraocular lenses: two-year follow-up.

PURPOSE: To evaluate endothelial cell survival 2 years after Descemet-stripping automated endothelial keratoplasty (DSAEK) for the treatment of endothelial dysfunction in the presence of an anterior chamber intraocular lens (AC IOL). SETTING: LSU Eye Center, New Orleans, Louisiana, and Florida Eye Microsurgical Institute, Boynton Beach, Florida, USA. DESIGN: Case series. METHODS: This study comprised eyes with endothelial failure that had DSAEK in the presence of an AC IOL. Donor central endothelial cell density (ECD) was recorded 6 months, 1 year, and 2 years postoperatively and compared with preoperative ECD eye-bank values. RESULTS: The study evaluated 25 eyes; data from 20 eyes were available up to 2 years postoperatively. The mean preoperative ECD was 2606 cells/mm(2). At 1 year, the mean ECD was 1943 cells/mm(2) ± 266 (SD), representing a mean cell loss from preoperative measurements of 24% ± 12%. At 2 years, the mean ECD was 1831 ± 291 cells/mm(2), representing a 28% ± 13% cell loss from preoperative values. The additional cell loss between the first and second postoperative years was not statistically significant (P=.265). CONCLUSIONS: Descemet-stripping automated endothelial keratoplasty grafts in the presence of a well-centered AC IOL with an AC IOL-to-endothelial depth greater than 3.0 mm had a mean postoperative donor endothelial cell loss of 24% at 1 year and 28% at 2 years. There was no significant difference in cell loss in this series compared with ECD loss in DSAEK surgeries in the presence of a posterior chamber IOL. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Efficacy and safety of bromfenac for the treatment of corneal ulcer pain.

PURPOSE: To evaluate the efficacy and safety of bromfenac ophthalmic solution 0.09% (Xibrom™, ISTA Pharmaceuticals Inc., Irvine, CA, USA) for treating pain associated with corneal ulcers. METHODS: Twenty-five eyes of 24 patients with corneal infiltrates (bacterial or fungal) were treated with appropriate anti-infective agents along with bromfenac twice daily for up to 102 days to treat the pain caused by the infection. Follow-up visits were frequent in the first 2 weeks upon initiation of treatment, then at least weekly until infections were resolved. The best corrected visual acuity, location, size, and density of corneal infiltrates, the size and presence of a corneal epithelial defect, subjective eye pain (scale of 0-4) and time to pain resolution, the ability to conduct daily activities, and adverse events were recorded at each follow-up visit. The results of these treated patients were compared with those of 10 control eyes with corneal infiltrates (bacterial or fungal) where appropriate anti-infectives were used without adjunct medications. RESULTS: Fifty-two percent of bromfenac-treated patients reported no pain by day 3, compared with 0% of untreated controls (P=0.023). Most of the treated patients' epithelium healed by day 20 (68%) compared with only 10% of controls (P=0.040). Most bromfenac-treated patients (71%) returned to normal activities within 2 days of starting treatment with bromfenac, compared with 0% of controls (P=0.018). No adverse events were recorded. CONCLUSION: Bromfenac was effective in treating pain associated with infectious keratitis and did not delay corneal epithelialization nor cause any corneal adverse events in this group of 25 eyes.

Efficacy of topical cyclosporine for the treatment of ocular rosacea.

INTRODUCTION: This study was designed to compare the efficacy of cyclosporine ophthalmic emulsion 0.05% with an artificial tear solution for the treatment of rosacea-associated eyelid and corneal pathology. METHODS: Double-masked, randomized, 3-month clinical trial of 37 patients with rosacea-associated eyelid and corneal changes (defined as lid margin telangiectasia, meibomian gland inspissation, and/or fullness of the lid margin). All findings were standardized and compared to photographs for grading. RESULTS: There was a statistically significant increase in Schirmer (with anesthesia) scores of 2.7+/-2.2 mm after 3 months of treatment in the topical cyclosporine group (P<0.001), compared with a mean decrease of -1.4+/-4.6 mm (P=0.271) in the artificial tears group. The mean tear break-up time score significantly improved in the topical cyclosporine group (mean increase of 3.56+/-1.5 seconds, P<0.001), but worsened in the control group, although this change was not significantly significant (mean decrease of -0.04+/-1.6 seconds, P=0.929). The topical cyclosporine group exhibited a significantly greater mean reduction in corneal staining scores (-1.3+/-0.53) compared with the control group (-0.2+/-0.83; between groups P<0.001). The topical cyclosporine group had a greater improvement in Ocular Surface Disease Index scores than those using artificial tears (P=0.022). Limitations of the study included an older, predominantly Caucasian patient population and short trial length. CONCLUSIONS: Topical cyclosporine 0.05% is more effective than artificial tears for the treatment of rosacea-associated lid and corneal changes.

Ketorolac tromethamine 0.4% as a treatment for allergic conjuctivitis.

BACKGROUND: Acular LS (ketorolac tromethamine 0.4%) ophthalmic solution, a reformulation of the original Acular (ketorolac tromethamine 0.5%), is indicated for the reduction of ocular pain and burning/stinging following corneal refractive surgery. OBJECTIVE: This manuscript will review the off-label application of this topical NSAID medication as a treatment for allergic conjunctivitis. METHODS: An extensive MedLine search was undertaken to evaluate data on the use of ketorolac for allergic conjunctivitis. Data on both human and animal data were reviewed. RESULTS/CONCLUSIONS: Studies have demonstrated that ketorolac 0.4% has equivalent efficacy to ketorolac 0.5%. Several studies have demonstrated that ketorolac effectively treats allergic conjunctivitis. Ketorolac 0.4% is effective when used as either monotherapy or as adjunct therapy to steroids.

Long-term follow-up of conjunctival and corneal intraepithelial neoplasia treated with topical interferon alfa-2b.

OBJECTIVE: To evaluate the long-term recurrence rate (>1 year) of conjunctival and corneal intraepithelial neoplasia (CIN) treated with topical interferon alfa-2b. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-eight eyes of 26 patients from 2 institutions, treated between April 1997 and June 2005, with CIN lesions utilized topical interferon alfa-2b drops 4 times daily until clinical resolution was achieved. METHODS: Patients' charts and clinical photographs were reviewed, and data were analyzed. MAIN OUTCOME MEASURES: All eyes were monitored for the possibility of recurrence with a minimum of 1-year follow-up from the time of documented clinical resolution. RESULTS: Complete clinical resolution of the CIN lesions was achieved in 27 of the 28 eyes treated (96.4%). One of the 28 eyes treated (3.6%) had only a partial response to treatment. For the 27 eyes with complete response, resolution occurred after a median of 2.0 months (range, 10 days-15 months). Eyes were treated for a median of 3.2 months (range, 1-15). Median follow-up after clinical resolution (tumor-free period) was 42.4 months (range, 14-89). One eye of the 27 analyzed (3.7%) experienced a recurrence. Side effects of treatment were limited to mild conjunctival hyperemia and follicular conjunctivitis in 3 patients (12%). In all cases, there was total resolution of the side effects within 1 month after cessation of the medication. CONCLUSIONS: In this group of patients with CIN lesions observed for >1 year, topical interferon alfa-2b was effective in treating lesions with minimal self-limited side effects.

Ocular infections caused by Providencia rettgeri.

PURPOSE: To report a series of patients with ocular infections caused by the rarely described gram-negative bacterium, Providencia rettgeri. DESIGN: Retrospective case series. PARTICIPANTS: Five patients with ocular infections who grew P. rettgeri after culture (2 keratitis, 1 dacryocystitis, 1 conjunctivitis, 1 conjunctivitis/endophthalmitis). METHODS: Microbiology culture results positive for P. rettgeri were cross-referenced to identify the patients with ocular infections. Medical records of these patients were carefully reviewed. MAIN OUTCOME MEASURES: Descriptive analysis of each patient's history, potential risk factors, and clinical outcome. RESULTS: Five eyes in 2 institutions were found to be culture positive for the gram-negative bacterium P. rettgeri. The organism may cause keratitis, dacryocystitis, conjunctivitis, and endophthalmitis. Possible risk factors include a compromised ocular surface and coexisting medical morbidity, including urinary tract infections, recent hospitalizations, and an immunocompromised state. Culture and sensitivity profiles should guide treatment; resistant strains are being identified. CONCLUSIONS: Infections caused by P. rettgeri, although rare, are responsible for ocular morbidity. This report describes patient attributes, risk factors, and outcomes that will be helpful to ophthalmologists treating ocular infections. P. rettgeri should be acknowledged as a source of ocular infection.

Ketorolac during the induction phase of cyclosporin-A therapy.

PURPOSE: The aim of this study was to determine if the concomitant use of ketorolac 0.4% and cyclosporin-A improves patient comfort during the induction phase in treating chronic dry eye disease. METHODS: Patients (n = 52) with clinically diagnosed dry eye were randomized to receive either cyclosporin-A monotherapy twice-daily (BID) or a BID adjunctive regimen of ketorolac, followed by the instillation of cyclosporin-A 10 min later. Study visits were at baseline, week 2, and week 6. At each study visit, patients underwent an evaluation for corneal staining, Schirmer's scores, and tear break-up time tests. Patients were asked to rate ocular comfort on a 4-point scale and to complete the ocular surface disease index (OSDI). Changes from baseline readings were recorded at week-2 and week-6 visits, and final patient success on treatment regimen was evaluated at week 6. RESULTS: After 6 weeks, the mean ocular comfort score of adjunctive patients improved 2.55 +/- 0.95 points, versus 1.53 +/- 0.91 points for monotherapy (P = 0.309). The adjunctive regimen provided significantly greater corneal staining reductions versus monotherapy, mean reduction in staining of 1.74 +/- 0.9, versus 1.27 +/- 0.56 (P = 0.044). CONCLUSIONS: Concurrent ketorolac 0.4% use with cyclosporin-A significantly reduced corneal staining and increased comfort in the induction phase.

Corneal melt after amniotic membrane transplant.

PURPOSE: To report an eye-threatening complication associated with amniotic membrane grafting. DESIGN: Interventional case report. METHODS: Retrospective review of the clinical and surgical records of a 43-year-old man who developed melting of his corneal graft after amniotic membrane transplantation. RESULTS: Melting of a corneal graft after amniotic membrane transplantation was arrested by utilizing a tectonic, full-thickness corneal button denuded of endothelium in conjunction with a temporary tarsorraphy and systemic steroids. CONCLUSIONS: To the best of our knowledge, this is the first report of an eye-threatening complication associated with amniotic membrane grafting. Caution should be exercised in utilizing amniotic membrane in patients who have undergone multiple ophthalmologic surgical procedures, which may sensitize the ocular immune system or lead to localized ischemia.