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Purpose To evaluate the safety and efficacy of dexamethasone phosphate ophthalmic solution (EGP-437) delivered by a transscleral iontophoresis delivery system (EyeGate II) compared to that of topical prednisolone acetate 1% (PA 1%) in subjects with noninfectious anterior uveitis. Design Prospective, randomized, double-masked, parallel group, noninferiority clinical trial. Methods A total of 193 subjects with active noninfectious anterior uveitis (anterior chamber [AC] cell count ≥11 cells) were randomized to EGP-437 delivered by iontophoresis (days 0 and 7) or self-administered PA 1% daily (tapered schedule, days 0-28). Masking was maintained with placebo iontophoresis or eye drops. The primary efficacy endpoint was the proportion of subjects with an AC cell count of zero on day 14. Noninferiority of EGP-437 was defined if the lower limit of the confidence interval (CI) for the difference (EGP-437 minus PA 1%) was less than −10%. Results At day 14, 32 of 96 EGP-437 subjects (33.3%) and 32 of 97 PA 1% subjects (33.0%) had an AC cell count of zero (difference, 0.34; 95% CI, −12.94 to 13.63; P = 0.064). Efficacy trended better with EGP-437 among patients with more severe baseline uveitis (AC cell count >25). Safety and tolerability were good with both treatments. EGP-437 subjects experienced fewer IOP elevations ≥6 mm Hg versus PA 1% subjects (13 vs 24 incidents, respectively, through day 28). Conclusions Despite clinically similar response rates, statistical noninferiority of EGP-437 versus a tapered regimen of PA 1% was not achieved. Numerical trends suggesting fewer IOP elevations with EGP-437, similar efficacy overall, and possibly better efficacy in more severe disease warrant further study.

Background: Iontophoresis is a noninvasive delivery system designed to overcome barriers to ocular penetration of topical ophthalmic medications by employing a low-amplitude electrical current to promote the migration of a charged drug substance across biological membranes. Trans-scleral iontophoresis of dexamethasone phosphate has demonstrated dramatically increased intraocular concentrations of dexamethasone in rabbit ocular tissues compared with topical instillation, including 50- to 100-fold greater aqueous humor concentrations. Methods: This article reviews available data on recent clinical applications of iontophoretic ophthalmic drug delivery. Results: The EyeGate II delivery system (EGDS) is a trans-scleral iontophoresis system that has been used in conjunction with EGP-437, a proprietary-charged formulation of dexamethasone phosphate for iontophoretic delivery. In patients with noninfectious anterior uveitis, EGP-437, delivered through 2 iontophoretic treatments using the EGDS, demonstrated similar efficacy to topical prednisolone acetate 1% eye drops instilled 8 times daily over 28 days, suggesting the potential to decrease or eliminate the need for daily dosing of topical steroids in this patient population. Other applications for EGP-437 delivered through the EGDS that have been explored in clinical trials include treatment of dry eye, postsurgical inflammation and pain, and scleritis. In addition, transcorneal iontophoresis has been used outside of the United States to enhance riboflavin penetration in patients undergoing corneal cross-linking as therapy for progressive keratoconus. Conclusions: The reviewed studies demonstrate the feasibility of using iontophoresis to enhance drug delivery to ocular tissues and support the potential of this noninvasive technique across a range of ophthalmic indications.

Purpose To evaluate netarsudil 0.02% ophthalmic solution in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Design Double-masked, randomized, multicenter, parallel-group, noninferiority clinical study. Methods After a washout of all prestudy ocular hypotensive medications, 756 eligible patients with elevated IOP were randomized to receive netarsudil 0.02% once a day (q.d.) (251); netarsudil 0.02% twice a day (b.i.d.) (254); or timolol 0.5% b.i.d. (251) for 12 months, as well as a noninterventional Corneal Observation Study (COS) for patients manifesting cornea verticillata. Results On treatment, mean IOP at 8:00 AM decreased from a baseline IOP of 22.5-22.6 mm Hg to 17.9-18.8 mm Hg, 17.2-18.0 mm Hg, and 17.5-17.9 mm Hg for netarsudil q.d., netarsudil b.i.d., and timolol, respectively, over 12 months. The most frequently reported adverse events (AEs) were ocular, with the most frequent ocular AE being conjunctival hyperemia, with an incidence of 61%, 66%, and 14%, respectively. The next most frequent AEs were corneal deposits (corneal verticillata), with an incidence of 26%, 25%, and 1%, respectively, and conjunctival hemorrhage (typically petechial), with an incidence of 20%, 19%, and 1%, respectively. All 3 AEs were generally scored as mild, with conjunctival hyperemia and/or hemorrhage appearing sporadically during the study. In the observational follow-up component of this study, there was no clinically meaningful impact of corneal verticillata on visual function in affected patients. Conclusions In this randomized, double-masked trial, once-daily dosing of netarsudil 0.02% was effective, consistently lowering IOP through 12 months, and was tolerated by the majority of patients.

Cataracts are a leading cause of preventable blindness globally. Although care varies between developing and industrialized countries, surgery is the single effective approach to treating cataracts. From the earliest documented primitive cataract removals to today's advanced techniques, cataract surgery has evolved dramatically. As surgical techniques have developed, so have approaches to surgical pain management. With current cataract surgical procedures and advanced technology, anesthesia and intraoperative pain management have shifted to topical/intracameral anesthetics, with or without low-dose systemic analgesia and anxiolysis. Despite this, pain and discomfort persist in some patients and are underappreciated in modern cataract surgery. Although pain management has progressed, opioids remain a mainstay intraoperatively and, to a lesser extent, postoperatively. This paper will discuss the evolution of pain management in cataract surgery, particularly the use of opioids and the associated risks as well as how ophthalmology can have a positive impact on the opioid crisis.

Excised redundant, forniceal "conjunctival" tissue from a 67-year-old man who experienced a chemical injury to his OS 25 years earlier was evaluated histopathologically with the hematoxylin-eosin, periodic acid Schiff (PAS) with and without diastase, mucicarmine, and Alcian blue methods. Additional immunoperoxidase testing for gross cystic disease fluid protein-15 (GCDFP-15) was undertaken. Non-keratinizing squamous epithelium composed of 8 to 10 layers of swollen keratinocytes without goblet cells surmounted a variably dense and well-vascularized collagenized lamina propria deep to which, in submucosal fibroadipose tissue, was embedded an accessory gland. The acini of the gland were composed of both GCDFP-15-positive serous cells and mucicarmine-positive goblet cells, indicating they were seromucinous rather than entirely serous, as is characteristic of normal lacrimal glandular tissue. Different features of the surface epithelium, the lamina propria, and the submucosa can separate the conjunctival and oral mucous membranes. A close analysis of the cytologic composition of associated accessory glands can reinforce the correct diagnosis of an oral mucous membrane graft when the past surgical history is unclear, because only serous cells but not mucocytes comprise the lacrimal glandular units.

Drugs across many pharmacologic classes induce corneal epithelial changes. Many of these drugs have cationic amphiphilic structures, with a hydrophobic ring and hydrophilic cationic amine side chain that allow them to cross cell membranes. These drugs lead to intracellular phospholipid accumulation, often manifested in the cornea by vortex keratopathy, with no effect on visual acuity and few ocular symptoms. Other drugs, notably antineoplastic agents, produce a fine diffuse corneal haze, sometimes accompanied by decreased vision that can be dose limiting. Still other medications cause crystalline epithelial precipitation that might require debridement for resolution. An understanding of the variety of drugs involved, the multiple mechanisms responsible, and the systemic diseases that produce similar changes can lead to improved management strategies for patients with corneal epithelial deposits. In most cases, drug therapy need not be modified or discontinued, but if visual acuity is affected, close collaboration with the prescribing physician can result in determining an optimized dose that treats systemic disease and minimizes these deposits. Additionally, close monitoring might be required if the drug is also associated with other ocular findings, such as optic neuropathy or retinopathy.

To evaluate the efficacy and safety of a topical ophthalmic suspension combination of povidone-iodine 0.6% (PVP-I) and dexamethasone 0.1% (DEX) for infectious and inflammatory components of bacterial conjunctivitis.Randomized, double-masked, multicenter, phase 3 clinical trial.Subjects of all ages (those3 months had to be full-term) with a diagnosis of bacterial conjunctivitis were randomized 3:1:3 to either PVP-I/DEX, PVP-I alone, or placebo. The primary endpoint was clinical resolution in the study eye, and the key secondary efficacy endpoint was bacterial eradication, both at the day 5 visit. Adverse events (AEs) were documented at all visits.Overall, 753 subjects were randomized (intent-to-treat [ITT] population; PVP-I/DEX [n = 324]; PVP-I [n = 108]; placebo [n = 321]); mean and standard deviation (SD) age was 44.3 (22.9) years, and most were female (61.2%) and white (78.1%). In all treatment groups, mean treatment compliance was98%. The modified ITT population for the efficacy analysis comprised 526 subjects. In the study eye at the day 5 visit, clinical resolution was achieved by 50.5% (111/220) subjects in the PVP-I/DEX group vs 42.8% (95/222) in the placebo group (P = .127), and bacterial eradication was achieved by 43.3% (94/217) and 46.8% (102/218), respectively (P = .500). Treatment-emergent AEs were experienced by 32.8% (106/323), 39.8% (43/108), and 19.0% (61/321) of subjects in the safety population treated with PVP-I/DEX, PVP-I, and placebo, respectively (most mild in severity).In this study, PVP-I/DEX did not demonstrate additional benefit in clinical efficacy compared with placebo in subjects with bacterial conjunctivitis.

Purpose: Corneal collagen crosslinking (CXL) through an intact epithelium (epi-on) at high irradiance could potentially improve patient comfort, visual recovery, and clinical workflow compared to conventional epi-off CXL. However, intact epithelium limits stromal delivery of the oxygen, photosensitizer, and ultraviolet-A (UV-A) radiation needed to drive CXL. This ex vivo study evaluated three different epi-on CXL protocols compared to positive and negative controls, specifically focusing on the impact of supplemental oxygen. Endpoints included stromal oxygen levels, stiffness of crosslinked tissue, and acute flattening of whole eyes.Materials & Methods: Ex vivo porcine eyes were held in a custom environmental chamber. Intrastromal oxygen levels were continuously measured before, during, and after UV illumination by a fiberoptic probe inserted into a laser-cut flap. Accelerated, high irradiance, epi-on CXL protocols using riboflavin formulated with benzalkonium chloride (BAC) were studied, with and without supplemental oxygen. These were compared to an alternate, low irradiance, epi-on protocol using riboflavin formulated with sodium iodide. Both negative (no CXL) and positive (epi-off modified Dresden protocol) controls were performed. Post-CXL elastic modulus was measured using extensiometry and anterior tangential curvature was measured using a Scheimpflug tomographer.Results: Protocols including supplemental oxygen resulted in an approximately 5-fold increase in stromal oxygen levels prior to CXL. During epi-on, high-irradiance UV-A delivery under hyperoxic conditions, an aerobic state was maintained. Conversely, under normoxic conditions, stromal oxygen rapidly depleted to 0-5% for all other protocols. The combination of supplemental oxygen, BAC formulation, and high-irradiance UV-A resulted in the largest biomechanical changes and most pronounced flattening effects of the three epi-on protocols.Conclusions: Ex vivo analysis of stromal oxygen levels, corneal stiffness, and acute anterior curvature change indicates that simultaneous optimization of the oxygen environment, riboflavin formulation, and UV-A protocol can significantly increase the effects of corneal collagen crosslinking.

Purpose To evaluate the effectiveness of a hydrogel sealant versus a suture in preventing fluid egress after wound leakage in cataract surgery. Setting Twenty-four ophthalmic clinical practices in the United States. Design Prospective randomized parallel-arm controlled multicenter subject-masked study. Methods Healthy patients having uneventful clear corneal incision (CCI) cataract surgery were eligible for the study. Spontaneous and provoked fluid egress from wounds was evaluated at the time of surgery using a calibrated force gauge. Eyes with leakage were randomized to receive a hydrogel sealant (Resure) or a nylon suture at the main incision site. Incision leakage was reevaluated 1, 3, 7, and 28 days postoperatively. Results Of 500 eyes, 488 had leakage at the time of cataract surgery. The leak was spontaneous in 244 cases (48.8%), and 488 (97.6%) of all incisions leaked with 1.0 ounce or less of applied force. After randomization, 12 (4.1%) of 295 eyes in the sealant group and 60 (34.1%) of 176 eyes in the suture group had wound leakage with provocation ( P P Conclusions In this study, 97.6% of CCIs leaked after cataract surgery. The hydrogel sealant was safe and effective and better than a suture for the intraoperative management of CCIs with leakage as seen on Seidel testing and for the prevention of postoperative fluid egress. Financial Disclosure Proprietary or commercial disclosures are listed after the references.

Importance Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (−103 [−196 to −9] cells/mm 2 ), lower screening ECD (−234 [−331 to −137] per 500 cells/mm 2 ), recipient diagnosis of PACE (−257 [−483 to −31] in cells/mm 2 ), and operative complications (−324 [−516 to −133] in cells/mm 2 ). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

Purpose To develop and evaluate a calibrated force gauge designed to simulate the effect of patient-induced manipulation of the eye with resultant elevation of intraocular pressure (IOP) and use the device to determine the stability of cataract incisions. Setting Three private practice study sites. Design Clinical trials. Methods A calibrated force gauge was developed to apply controlled and quantifiable amounts of force to the eye. In study 1, the calibrated force gauge was used to evaluate the change in IOP during application of 1 oz of external force in a group of healthy volunteers. In studies 2 and 3, the calibrated force gauge was used to assess wound leakage of clear corneal incisions that were subjected to stromal hydration or sutures, respectively. Results In study 1, with the application of 1.00 oz of external force, the mean IOP rose from a baseline of 17.49 mm Hg to 43.44 mm Hg. In study 2 (stromal hydration) using up to 1.00 oz of force, the leak rate was 67% for the main incision. The overall leak rate for study 3 (sutures) using up to 1.00 oz of force was 23.8%. No adverse events or serious adverse events occurred during these studies. Conclusions Study 1 confirmed that 1.00 oz of force is a realistic approximation of the amount of force a patient's eye may experience during rubbing. After clear corneal cataract surgery, the application of 1.00 oz of force to the ocular surface for approximately 2 to 3 seconds may simulate the propensity for postoperative wound leak resulting from patient manipulation. Financial Disclosure Drs. Masket, Hovanesian, and Raizman are consultants to Ocular Therapeutix. Dr. Masket is also a medical monitor for Ocular Therapeutix. Drs. Hovanesian and Masket are shareholders in Ocular Therapeutix. Drs. Wee and Fram have no financial disclosures.

Vernal conjunctivitis is a bilateral, seasonal, external ocular inflammatory disease of unknown cause. Afflicted patients experience intense itching, tearing, photophobia, and mucous discharge, and usually demonstrate large cobblestone papillae on their superior tarsal conjunctiva and limbal conjunctiva. It primarily affects children, may be related to atopy, and has environmental and racial predilections. Although usually self-limited, vernal conjunctivitis can result in potentially blinding corneal complications. Treatment of chronic forms of ocular allergies may necessitate collaborative efforts between the ophthalmologist and the allergist or immunologist.

Purpose To describe the clinical and histopathologic finding of very limited ophthalmic Wegener granulomatosis (WG). Methods Thirteen patients with scleritis, orbitopathy, episcleritis, and panuveitis were studied. They presented without evidence of lung or kidney disease, though eight had sinus involvement. We reviewed the biopsies for histopathologic findings consistent with WG, and tested for antineutrophil cytoplasmic antibodies antineutrophil cytoplasmic antibody (ANCA). Results WG was suggested by granulomatous foci, collagen necrosis, neutrophils/nuclear dust, plasma cells and infiltrating eosinophils. Granular degeneration of the interstitial collagen; mummification of the collagen with disappearance of fibroblastic nuclei; and a polymorphous infiltrate exhibiting plasma cells, lymphocytes, neutrophils, and eosinophils within the epithelioid granulomas should suggest the diagnosis. ANCA test results supported the diagnosis of WG in all cases. Conclusion The described histologic characteristics are highly suggestive of WG. These findings along with clinical or laboratory findings, allow the diagnosis of very limited ophthalmic WG in the absence of systemic involvement.

Age-related macular degeneration is the leading cause of blindness in the USA. For the 1.8 million patients in the most advanced stages, there are currently no available treatments to improve vision. A visual prosthetic device that provides one eye with an enlarged retinal image of the central visual field has been developed with the goal of improving central vision in patients with bilateral end-stage macular degeneration. The other eye is left unimplanted to provide peripheral vision. This device is designed for implantation in the posterior chamber of the eye during an outpatient surgical procedure. In US Food and Drug Administration clinical trials, 72% of patients experienced an improvement in their level of visual impairment (profound or severe, to severe or moderate). This was accompanied by a clinically significant improvement in quality of life.

To evaluate the safety and analgesic efficacy of ketorolac tromethamine 0.4% ophthalmic solution in postoperative photorefractive keratectomy (PRK) patients.Fifteen clinical sites in the eastern and southern United States.This pooled analysis of 2 multicenter, randomized, double-masked, vehicle-controlled, parallel-group studies comprised 313 patients having unilateral PRK. After surgery, patients were treated with 1 drop of ketorolac tromethamine 0.4% ophthalmic solution (Acular(R) LS) (n = 156) or vehicle (n = 157) 4 times daily for up to 4 days. Pain intensity, pain relief, use of escape medication, and severity of ocular symptoms were assessed. Adverse events, epithelial healing, and visual acuity were recorded.There was significantly less pain intensity experienced by patients in the ketorolac group (P.001). During the first 12 hours post PRK, 50% fewer patients in the ketorolac group than in the vehicle group had severe to intolerable pain (41.6% [64/154] and 84.5% [131/155], respectively). The median time to no pain was 30 hours in the ketorolac group and 54 hours in the vehicle group (P.001, survival analysis). Ketorolac patients reported significantly greater pain relief than vehicle patients throughout the study (P.001). Ketorolac patients used significantly less escape medication than vehicle patients for 48 hours post PRK (Por =.008). Treatment-related adverse events occurred in 2.6% (4/156) of ketorolac patients and 6.4% (10/157) of vehicle patients.Ketorolac 0.4% ophthalmic solution is safe and effective in reducing ocular pain when used 4 times daily for up to 4 days post PRK.

Aim: To compare the efficacy and safety of levofloxacin 0.5% ophthalmic solution (Quixin) with placebo for treatment of bacterial conjunctivitis. Methods: In this prospective, randomised, placebo controlled, double masked, multicentre study, 249 patients with bacterial conjunctivitis received either 0.5% levofloxacin (n = 126) or placebo (n = 123) for 5 days, administered every 2 hours on days 1–2, then every 4 hours on days 3–5. Cultures were obtained and signs/symptoms evaluated at baseline, interim, and final visits. The end point was the last evaluable observation. Primary microbial outcomes were based on culture results; clinical outcomes were based on resolution of cardinal signs. Results: 117 patients (60 levofloxacin, 57 placebo) were evaluated. Microbial eradication rates were significantly greater with levofloxacin at all time points, reaching 90% at end point. In a subgroup analysis, differences in eradication rates at end point were most pronounced in children but were also statistically significant for levofloxacin in adults. Clinical cure rates were significantly greater with levofloxacin at final visit and end point. Statistically significant differences favouring levofloxacin were measured at end point for resolution of conjunctival discharge, bulbar conjunctival injection, palpebral conjunctival injection, burning/stinging, itching, and photophobia. Adverse events were similar between groups. Safety composite scores analysed by age indicated significantly fewer children on levofloxacin experienced worsening symptoms. Conclusions: Levofloxacin 0.5% ophthalmic solution is safe and effective for treatment of bacterial conjunctivitis.

Background: Several fluorinated carboxyquinolones are used to treat ocular infectious disease. Levofloxacin, in particular, has demonstrated activity against both gram-negative and gram-positive bacteria. Objectives: An open-label study was undertaken to assess the pharmacokinetics and ocular bioavailability of levofloxacin in human tears, and to determine the tear concentration of levofloxacin in healthy volunteers, following topical administration of a single-dose of 0.5% levofloxacin ophthalmic solution. Methods: Volunteers received 1 drop of 0.5% levofloxacin in each eye and were assigned sequentially to 1 of 5 groups for tear sampling. Tear samples were collected on Schirmer test strips at 9 predetermined time points ranging from 5 minutes to 24 hours after administration. Six tear samples were collected at each time point (1 eye each from 6 volunteers), except the 24-hour time point, at which 12 samples were collected (both eyes of 6 volunteers). No eye had >1 tear sample taken during the study. Levofloxacin concentrations were measured using reverse-phase high-performance liquid chromatography. Results: Thirty volunteers were enrolled, with 6 assigned to each of the 5 sampling groups. At 5 minutes after administration of a single topical dose of levofloxacin, the mean tear concentration was 49.19 ± 26.73 μg/mL. The mean peak concentration of levofloxacin in the tear film, 221.06 ± 256.68 μg/mL, was reached at 15 minutes after administration. At 4 hours after administration, the mean tear concentration of levofloxacin was 17.04 ± 15.13 μg/mL. At 6 hours after administration, the mean concentration of levofloxacin was 6.57 ± 5.26 μg/mL. At 24 hours after administration, levofloxacin concentrations >2 μg/mL were measured in 2 of 6 (33%) subjects. Conclusions: Levofloxacin concentrations in the tear fluid after a single topical dose (1 drop) reached high levels quickly and remained above the minimuminhibitory concentration for most suspected ophthalmic pathogens (≤2 μg/mL) for at least 6 hours in most healthy volunteers, and for up to 24 hours in some volunteers.

Objective To evaluate the effect of eye rubbing on signs and symptoms of allergic conjunctivitis in cat-sensitive individuals. Design Two prospective, nonrandomized comparative studies. Participants Thirteen patients in the first study and 20 patients in the second study with a documented history of acute allergic conjunctivitis induced by exposure to cats were enrolled. Intervention In the first trial, all patients had one eye rubbed 15 times by the investigator without exposure to airborne allergens. Both eyes were evaluated after 5, 15, 30, and 60 minutes using subject questionnaires and slit-lamp examination. At least 1 week later, each patient was exposed to cat dander for 75 minutes; 15 minutes after entering the cat room, each patient had one eye rubbed 15 times by the examiner. Subjects' eyes were then evaluated using questionnaires and slit-lamp examination. In the second trial, the visits were identical to the first trial, except that the rubbed eye in each visit was rubbed 20 times and with more force, and that patients wore masks during exposure to cat dander. Main outcome measures In both studies, the difference between patients' rubbed and nonrubbed eyes with respect to ocular itching, chemosis, and hyperemia was noted 5, 15, 30, and 60 minutes after controlled eye rubbing. Results Without exposure to the cat room, rubbed eyes exhibited increased itching at 5 minutes in both studies and at 15 minutes in the second study ( P P P P P Conclusions Firm eye rubbing causes a mild and transient increase in ocular itching, chemosis, and hyperemia. However, after exposure to cat allergens in cat-sensitive individuals, the effects of eye rubbing are longer and more dramatic. Eye rubbing may play a role in ocular signs and symptoms of allergic conjunctivitis in cat-sensitive individuals, especially after exposure to cat dander.

This multicenter, double-masked, randomized, parallel-group study compared the efficacy and safety of ketorolac tromethamine 0.5% ophthalmic solution with levocabastine 0.05% and ketorolac tromethamine vehicle in patients with seasonal allergic conjunctivitis. One drop of ketorolac, levocabastine, or vehicle was instilled in each eye four times daily for 6 weeks. In the majority of efficacy variables, ketorolac produced the greatest improvements, followed by levocabastine and vehicle. Ketorolac was significantly more effective (P

PURPOSE: To compare the safety and efficacy of loteprednol etabonate 0.5% ophthalmic suspension with prednisolone acetate 1.0% ophthalmic suspension in reducing the ocular signs and symptoms associated with acute anterior uveitis. METHODS: Two prospective studies were conducted in sequence. Both were parallel, randomized, double-masked, active-controlled comparisons conducted at academic or private practice clinics in the United States. Efficacy was evaluated by the proportion of patients with a score of 0 for key signs and symptoms of uveitis. Intraocular pressure was increased regularly. The first study involved up to 42 days of treatment, starting with a dose of eight times per day. The second study involved up to 28 days of treatment, starting with a dose of 16 times per day. RESULTS: In the first study (N = 70), the proportion of patients achieving resolution by the final visit was anterior chamber cell (74% loteprednol etabonate, 88% prednisolone acetate, P = .194) and flare (71% loteprednol etabonate, 81% prednisolone acetate, P = .330). In the second study (N = 175), the proportion of patients achieving resolution by the final visit was anterior chamber cell (72% loteprednol etabonate, 87% prednisolone acetate, P = .015) and flare (66% loteprednol etabonate, 82% prednisolone acetate, P = .017). In both studies, intraocular pressure increase of more than 10 mm Hg was observed more frequently in patients receiving prednisolone acetate (seven patients) than those receiving loteprednol etabonate (one patient). CONCLUSIONS: Although a clinically meaningful reduction of signs and symptoms was noted in both treatment groups, loteprednol etabonate was less effective than prednisolone acetate in both of these controlled studies. However, the more favorable profile of loteprednol etabonate with respect to intraocular pressure increase may make it useful in many patients.

Only one of several available ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) is currently FDA approved for use in acute seasonal allergic conjunctivitis (SAC). Sixty patients with SAC and moderate itching and bulbar conjunctival injection were enrolled in a multicenter, randomized, double-masked, parallel-group trial comparing diclofenac sodium (DS) with ketorolac tromethamine (KT). Patients instilled 1 drop four times daily while awake for 14 days. Ocular signs and symptoms were evaluated at one and two weeks. The primary efficacy variables were itching and bulbar conjunctival injection. For both treatments, the ocular allergy sign and symptom scores were comparable at baseline. Both treatments evaluated in this study were well tolerated. Significant clinical and statistical reductions from baseline were observed in the primary efficacy variables. Treatment group differences were observed for the pain/soreness score with an advantage observed for the DS group at 30 minutes and at day 7. Our conclusion is that diclofenac sodium and ketorolac tromethamine acted similarly to reduce the ocular signs and symptoms associated with acute seasonal allergic conjunctivitis. There was a statistically significant advantage for the DS group to be free of symptoms at the day 7 visit as compared to the KT group (20.7% vs. 3.2%).

Presentation of Case A 32-year-old man was admitted to the hospital because of unilateral vitreous hemorrhage and mediastinal lymphadenopathy. The patient had been well until 7 1/2 weeks earlier, when he experienced the gradual onset of blurred vision in the left eye, accompanied by numerous floaters, but without flashes, quadratic visual-field loss, or pain. An evaluation elsewhere showed vitreous hemorrhage with proliferative disease. A fluorescein angiographic examination showed vitreous hemorrhage, an elevated, intensely hyperfluorescent fibrovascular frond, and smaller areas of neovascularization that did not involve the optic disk. Panretinal photocoagulation was administered twice during a six-day period, and the patient's . . .

Ofloxacin is a broad spectrum fluoroquinolone antibiotic with good ocular penetration. We investigated the potential for retinal toxicity associated with increased intraocular penetration following intensive topical, oral, and combined topical and oral administration. We confirmed ofloxacin concentrations in aqueous and vitreous following these forms of administration. Rabbits received either topical, oral, or a combination of oral and topical ofloxacin. Topical administration consisted of one drop of ofloxacin 0.3% drops given every thirty minutes for a total of eight doses. Oral ofloxacin was administered at a dose of 10 mg (4 mg/kg for average weight 2.5 kg rabbit) every 12 hours for a total of three doses. Six rabbits were followed longitudinally for 4 weeks for evidence of retinal toxicity by indirect ophthalmoscopy and serial ERGs. Electron and light microscopic histopathologic examination of the retina were performed 4 weeks following drug administration. To verify intraocular penetration, ten rabbits received identical dosing schedules followed by HPLC measurement of aqueous and vitreous drug concentrations at 1, 4, 8, 12, and 24 hours following dose completion. No evidence of retinal toxicity was detected by indirect ophthalmoscopy, electroretinography, or histopathological examination. Vitreous ofloxacin levels were highest after combined oral and topical administration, peaking at 0.892 microgram/ml 8 hours following dosage completion. The peak vitreous level following oral administration was 0.230 microgram/ml and 0.026 microgram/ml following topical administration. Peak aqueous humor levels were achieved one hour following drug administration and were 11.400 micrograms/ml after topical, 0.206 microgram/ml after oral, and 8.180 micrograms/ml after combined administration. Our study suggests that intensive topical and oral ofloxacin administration does not cause retinal toxicity in rabbits, despite achieving effective aqueous and vitreous humor antimicrobial concentrations.

Objective: The purpose of the study is to define qualitative patterns of corneal topography after excimer laser photorefractive keratectomy (PRK) using a 6-mm beam diameter, investigate changes in patterns over time, and identify associations of topography patterns with clinical outcomes. Design: Multicenter, prospective cohort study. Participants: Ninety-eight eyes of 90 patients with myopia who had undergone PRK using the Summit Technology, Inc., excimer laser with a 6-mm beam diameter. Intervention: Computer-assisted videokeratography data were analyzed for eyes having undergone PRK. Topography patterns at 3, 6, and 12 months after surgery were classified and associations with clinical outcomes assessed. Main Outcomes Measured: Topography patterns after PRK were determined at 3, 6, and 12 months after surgery. Associations with preoperative characteristics of age and attempted correction, and postoperative outcomes of uncorrected and spectacle-corrected visual acuity, predictability, astigmatism, corneal haze, glare, halo, and patient satisfaction were analyzed. Results: At 1 year, 21.4% of corneas showed a homogeneous topography, 27.6% showed a toric-with-axis configuration, 10.2% showed a toric-against-axis configuration, 7.1% showed an irregularly irregular topography, 24.5% showed a keyhole/semicircular pattern, and 9.2% showed focal topographic variants. From 3 to 6 months, 40.1 % of maps changed; from 6 to 12 months, 53.1 % of maps changed, generally to optically smoother, regular patterns. Older age and higher attempted correction were associated with the development of more irregular patterns. The irregular groups showed worse predictability than did the regular groups and a tendency for slight overcorrection. The average reported glare/halo of 1.33 (scale = 0 to 5) in this study was less than in a previous study of the 4.5- to 5-mm treatment zone. However, of six patients expressing dissatisfaction with the results of surgery, three ranked their glare or halo at the maximum level. Conclusions: Topography patterns using a 6-mm beam diameter are identifiable, improve with time, and may affect clinical outcomes after photorefractive keratectomy (PRK). The keyhole/semicircular pattern is more prevalent with a 6 mm treatment zone than with smaller treatment zones. Although optical side effects of glare and halo appear to be reduced with the 6-mm treatment, a small number of patients still report substantial glare or halo after the procedure.

Purpose: To identify preoperative and intraoperative characteristics associated with outcomes of photorefractive keratectomy (PRK). Methods: In the phase III multicenter clinical trials of the Summit Technology excimer laser for corrections of 1.5 to 6.0 diopters (D) of myopia, three principal outcomes of PRK on 612 patients were examined: (1) uncorrected visual acuity of 20/40 or better, (2) predictability of refractive outcome within 1.0 D of attempted correction, and (3) stability of refractive result between 12 and 24 months. Multiple logistic regression was used to test for independent associations of multiple preoperative and intraoperative characteristics with each of these outcomes. Results: Older age was independently associated with lesser likelihood of achieving 20/40 or better uncorrected visual acuity (odds ratio=1.08 per incremental year of age, 95% confidence interval [Cl] = 1.04–1.12) and with decreased predictability, specifically with overcorrection (odds ratio=1.09, 95% Cl=1.06–1.12), but age was not associated with stability of refraction. Greater attempted correction was associated independently with a decreased likelihood of 20/40 or better uncorrected visual acuity (odds ratio=2.78 for corrections of 3.5–5.5 D, 95% Cl=1.18–6.75; odds ratio=4.19 for corrections of ≥5.5 D, 95% Cl=1.66–10.58), with decreased predictability (odds ratio=1.72 for corrections of 3.5–5.5 D, 95% Cl=1.05–2.85; odds ratio=2.95 for corrections of ≥5.5 D, 95% Cl=1.65–5.26), and with a reduced likelihood of stability of refraction (odds ratio=3.46 for corrections of ≥5.0 D, 95% Cl=1.32–9.11). No intraoperative characteristics were associated with any of the outcomes assessed. Conclusions: Using this specific excimer laser system with an optical zone of 4.5 or 5.0 mm, patient age and attempted correction are important preoperative characteristics associated with postoperative uncorrected visual acuity and predictability of PRK. Stability of refraction is strongly associated with attempted correction. Such information may help guide patient selection, determine timing of fellow eye treatment, and suggest changes in the laser treatment algorithm for individual patients. Although these findings may be representative of PRK in general, similar analyses should be performed before modifying patient treatments using either a 6.0-mm treatment zone or other laser systems.

Purpose TWO multicenter studies compared the efficacy and safety of rimexolone 1% ophthalmic suspension (Vexol 1%, Alcon) and 1% prednisolone acetate (Pred Forte, Allergan). Methods Patients with acute uveitis, recurrent iridocyclitis, or chronic uveitis treatable by topical corticosteroid were enrolled. Treatment regimen was one or two drops every hour during Week 1, every two hours during Week 2, four times a day during Week 3, and once a day for the last three days. Efficacy and safety were determined on Days 3, 4, 7 to 10, 14, 21, and 28. A poststudy evaluation was conducted 36 to 72 hours after treatment was stopped. Results When anterior chamber cell and flare were measured, rimexolone 1% was found to be as effective as 1% prednisolone. The largest differenee observed between treatments was 0.5 score unit, not clinically significant. There were no statistically significant differences in cell scores in either study (P > .05). No statistically significant differences in flare scores were found except at Day 28 in Study One (P = .04). Also, prednisolone was found to be more likely than rimexolone to cause a clinically significant increase (10 mm Hg or more) in intraocular pressure (1.7 times more likely in Study One, eight times more likely in Study Two). Conclusions Rimexolone 1% ophthalmic suspension is safe and effective for the treatment of uveitis.

Clinical isolates of Pseudomonas aeruginosa were examined for binding interactions with phospholipids of corneal epithelium. Thin-layer chromatography (TLC) of lipids extracted from corneal epithelia followed by staining with an ammonium molybdate spray reagent revealed three phospholipid components, PL1, PL2, and PL3. The chromatographic mobility of PL1 was similar to that of the phospholipid standards phosphatidylinositol (PI) and phosphatidylserine (PS), which were not well resolved from one other; PL2 and PL3 comigrated with the standards phosphatidylcholine and phosphatidylethanolamine, respectively. By use of a TLC-bacterial overlay procedure, 35S-labeled P. aeruginosa organisms were shown to bind to PL1 but not to PL2 or PL3. P. aeruginosa binding to PL1 was concentration dependent. Alkaline methanolysis abolished the binding. PL1 was separated into two components, PL1-I and PL1-S, by chromatography on borate-treated TLC plates. Both PL1-I and PL1-S contained binding sites for P. aeruginosa. Mass spectral analysis identified PL1-I and PL1-S as PI and PS, respectively. Radiolabeled P. aeruginosa organisms were subsequently shown to bind to commercially available bovine PI and PS and synthetic dipalmitoyl-PS but not to other phospholipid standards, including bovine SM and PC or synthetic dioleoyl- and distearoyl-PC. A control Escherichia coli strain did not bind to either PS or PI. Tetramethylurea, a disrupter of hydrophobic associations, did not influence the binding of P. aeruginosa to PS or PI. P. aeruginosa bound to the monolayers of corneal epithelial cells. P. aeruginosa binding to the monolayer cultures as well as to rabbit corneas pretreated with exogenous PS and PI was significantly higher than that to those preincubated with PC or medium alone. The data suggest that phospholipids PS and PI present in mucus or on the cell surface may function as P. aeruginosa receptors and contribute to selective bacterium-host interactions responsible for initial colonization.

Purpose: To assess the influence of corneal surface microirregularities on objective and subjective visual performance after photorefractive keratectomy (PRK). Setting: Multicenter clinical trial. Methods: The alpha version of the Potential Corneal Acuity (PCA) computer program, currently under development, was used to qualitatively and quantitatively analyze the corneal surface of 176 eyes of 176 patients 1 year after PRK. Color maps of corneal surface irregularities were reviewed and quantitative values (PCA) predicting best spectacle-corrected visual acuity (BSCVA) as limited by the cornea were evaluated for associations with qualitative topography patterns, optical zone decentration, and clinical outcomes of BSCVA, uncorrected visual acuity (UCVA), subjective patient satisfaction, and a subjective glare/halo index. Results: Qualitatively, corneas after PRK were generally characterized by a ring of optical irregularity at the juncture of the ablation zone and untreated cornea. Standard corneal topography maps graded as irregular after PRK had a significantly higher PCA value than those graded as regular. There was a trend toward higher PCA values with greater optical zone decentration that was not statistically significant. Actual BSCVA was identical to that which the PCA value predicted in 32% of patients and was within one Snellen line in 71 %, within two lines in 89%, and within three lines in 94%. The correlation between the PCA and the glare/halo index and with subjective patient satisfaction was statistically significant. The relationship between PCA and UCVA was not significant. Conclusions: A ring of optical microirregularity of the corneal surface can appear at the juncture of the treated and untreated cornea after PRK, indicating that the optical zone edge might affect objective and subjective postoperative visual outcomes. Further understanding of corneal surface topography and refinement of the PCA program should help explain visual outcome after PRK.

* BACKGROUND AND OBJECTIVE: A prospective study was performed to assess the effect of trephination on corneal curvature. * MATERIALS AND METHODS: Thirty-seven fresh porcine globes with intact corneal epithelium were used. Radius of curvature, central dioptric power, and powers and axes of the steepest and flattest meridians were obtained using a vertically mounted computerized videokeratography unit. Following 8-mm vacuum trephination of the central donor corneas, the said parameters were reassessed on the resultant buttons. No globes with epithelial defects were included in the study. * RESULTS: The mean corneal radius of curvature (mm) increased from 8.68 ± 0.79 to 10.46 ± 3.24 (P = .005), the central dioptric power (D) decreased from 39.36 ± 3.84 to 36.31 ± 10.15 (P = .08), and the total corneal asphericity (D) increased from 5.03 ± 2.99 to 7.47 ± 3.42 (P = .0001). No significant changes in the axes of the steepest and the flattest meridians were noted following trephination. * CONCLUSION: Trephination leads to significant corneal flattening and increased asphericity. Cornea! topography can be used successfully as a research tool for whole globes and trephined buttons. [Ophthalmic Surg Lasers 1995;26:560-567.]

A case of ocular leprosy as the manifestation of persistent or relapsed Mycobacterium leprae infection approximately 20 years following treatment is reported. The clinical and pathological features of this case are described, and the molecular methods needed to arrive at the definitive diagnosis are examined. If blindness is to be averted, clinicians must have a high index of suspicion for the diagnosis of ocular leprosy when anterior segment changes are noted during ophthalmologic examination of a patient from an area in which M. leprae is endemic. The indolent nature of ocular leprosy may require lifelong surveillance and therapy to insure sight preservation.

Presentation of Case A 69-year-old woman was admitted to the hospital because of a right orbital mass with chronic conjunctivitis. One month before admission she had noticed that her right eye was bloodshot. An ophthalmologist found a mass beneath the lateral aspect of the right lower lid with overlying conjunctival injection. Dexamethasone eye drops were prescribed. A computed tomographic (CT) scan of the orbits (Figure 1 and Figure 2) showed a slightly ill-defined, enhanced mass in the inferior and lateral anterior right orbit, without calcification or cavitation; there was no bone destruction, paranasal sinus disease, or evidence of an intraocular malignant tumor. . . .

Although mouse interleukin-3-dependent, bone marrow culture-derived progenitor mast cells (BMMC) and a Kirsten sarcoma virus (KiSV)-immortalized mouse mast cell line (MC4w) both express on their surfaces receptors for the Fc portion of IgG (Fc gamma R), only MC4w degranulate upon Fc gamma R perturbation. As shown by surface iodination and SDS-polyacrylamide gel electrophoresis analysis of deglycosylated proteins immunoprecipitated with the Fc gamma R-specific monoclonal antibody 2.4G2, a 26-kDa protein, identified as Fc gamma RIII by immunoblotting with antibody to Fc gamma RIII, was predominantly expressed on the surface of MC4w but minimally on BMMC. However, both BMMC and MC4w expressed mRNA for Fc gamma RIII as determined by RNA blot analysis, and both translated Fc gamma RIII as assessed by intrinsic radiolabeling and SDS-polyacrylamide gel electrophoresis analysis of deglycosylated monoclonal antibody 2.4G2 immunoprecipitates. Pulse-chase analysis showed that intrinsically radiolabeled Fc gamma RIII was stable in MC4w cells but was degraded rapidly in BMMC and that newly synthesized Fc gamma RIII remained sensitive to digestion by endoglycosidase H in BMMC but rapidly became resistant in MC4w. These data suggest that the deficiency in surface Fc gamma RIII expression on BMMC is due to the degradation of Fc gamma RIII in the endoplasmic reticulum. Immunoprecipitation of surface Fc gamma R and Fc receptors for IgE (Fc epsilon RI) from digitonin-extracted cells followed by immunoblotting with antibody to Fc epsilon RI gamma-chain showed that gamma-chain is associated with surface Fc epsilon RI and Fc gamma R in MC4w, but only with Fc epsilon RI in BMMC, which lack surface Fc gamma RIII. Inasmuch as BMMC are progenitors of serosal mast cells, which, like MC4w, express surface Fc gamma RIII and undergo Fc gamma R-mediated activation, the data suggest that maturation of BMMC enables Fc gamma RIII to bypass degradation in the endoplasmic reticulum, resulting in the acquisition of functional Fc gamma RIII/gamma-chain complexes on the cell surface.

PURPOSE: To provide detailed description and illustration of the lens changes found in hereditary hyperferritinemia-cataract syndrome, a newly reported autosomal dominant condition. METHODS: Observational case reports. A 19-year-old man was referred for evaluation of possible hereditary hyperferritinemia-cataract syndrome. His serum ferritin level was increased at 1291 μg/L during a routine screening examination. Genetic analysis revealed mutation G51C on chromosome 19, predicting an altered iron response element in L-ferritin mRNA. Subsequent evaluation of his 46-year-old father revealed similar findings. RESULTS: Multiple breadcrumb-like nuclear and cortical lens opacities were seen in this father-son pair. These cases represent the first detailed description and illustration of hereditary hyperferritinemia-cataract syndrome cataracts in the ophthalmic literature. CONCLUSION: Hereditary hyperferritinemia-cataract syndrome can be associated with distinct breadcrumb-like lens opacities. Recognition of these characteristic cataracts may aid identification and study of patients with this unusual disorder and provide insight into mechanisms of cataract formation.

To evaluate the efficacy and safety of twice-daily, preservative-free ketorolac 0.45% (Acuvail; Allergan, Inc, Irvine, California, USA) administration for treatment of inflammation and pain after cataract surgery.Prospective, randomized trial.Two multicenter, double-masked studies randomized 511 cataract surgery patients (2:1) to receive twice-daily ketorolac 0.45% or vehicle in the operative eye for 16 days, beginning 1 day before surgery. The primary efficacy end point was the percentage of patients with a summed ocular inflammation score of 0 for anterior chamber cell and flare on postoperative day 14. The main secondary efficacy end point was the percentage of patients with no pain on postoperative day 1.On day 14, 52.5% of ketorolac patients and 26.5% of vehicle patients had an summed ocular inflammation score of 0 (P.001). On day 1, 72.4% of ketorolac patients and 39.7% of vehicle patients had a pain score of 0 (P.001). Median time to pain resolution was 1 day in the ketorolac group and 2 days in the vehicle group (P.001). The percentage of ketorolac and vehicle patients who had a +3-line or more improvement in best-corrected visual acuity from baseline was 60.5% versus 44.0% on day 14 (P = .002). Overall, adverse events were more prevalent in the vehicle group than in the ketorolac group (48.5% vs 35.2%; P = .004). Burning or stinging (per a composite Medical Dictionary for Regulatory Activities) was reported by 1.5% of ketorolac patients and 0.6% of vehicle patients.Twice-daily ketorolac 0.45% was well tolerated and effectively treated inflammation and pain following cataract surgery.

To compare the safety and efficacy of a hydrogel bandage and a collagen corneal shield in providing wound protection and relief of pain/discomfort in the acute period after uneventful unilateral clear corneal phacoemulsification cataract surgery with foldable intraocular lens (IOL) implantation.Seventeen investigational sites in the United States.Prospective randomized single-masked parallel study.The study comprised patients scheduled to have unilateral clear corneal cataract surgery with posterior chamber intraocular lens implantation. The patients were examined preoperatively and frequently for 30 days postoperatively. The design was a noninferiority study of the 2 primary endpoints, device performance and maximum reported postoperative pain.The device performance success was 78.6% (228/290) for the hydrogel bandage and 26.5% (26/98) for the corneal shield (P.0001 for noninferiority). Analyses indicated that the hydrogel bandage was superior to the corneal shield in device performance (P.001; difference = 52.1%; 95% confidence interval, 41.6%-61.4%). The maximum postoperative pain/discomfort score of the hydrogel bandage (mean 1.3 ± 1.8 [SD]; scale 0 to 10) was noninferior to that of the corneal shield (1.1 ± 1.6) in the first 4 hours after surgery (P.001). Adverse events in the cataract surgeries were reported in 22.2% (70/316) and 36.5% (38/104) of hydrogel bandage patients and corneal shield patients, respectively (P = .0045).The hydrogel bandage was safe and effective for ocular surface protection and relief of pain/discomfort when applied topically to clear corneal incisions used in cataract or IOL implantation surgery.No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.

Isolated scleritis (without keratitis) associated with infections is uncommon, and correct diagnosis and appropriate therapy for it are often delayed. Six patients with infection-associated scleritis were seen at our institution between May 1983 and May 1990 (these patients represented 4.6% of all patients with scleritis [six of 130 patients] in that period). Three of these cases were associated with systemic infections. One was associated with syphilis, one was associated with tuberculosis, and one was associated with toxocariasis. Three cases resulted from local infections. One was associated with infection with Proteus mirabilis, one was associated with infection with herpes zoster virus, and one was associated with infection with Aspergillus. The Aspergillus infection developed after trauma and the P. mirabilis-induced infection developed after strabismus surgical procedures. Four of the six cases were initially misdiagnosed and inappropriately managed. Correct diagnosis was made seven days to four years after onset of symptoms. Review of systems, scleral biopsy, culture, and laboratory investigation were used to make the diagnosis. Differential diagnosis of scleritis must include infective agents.