0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial.

We determined the efficacy and safety of 0.1% RGN-259 ophthalmic solution (containing the regenerative protein thymosin ß4) in promoting the healing of persistent epithelial defects in patients with Stages 2 and 3 neurotrophic keratopathy. Complete healing occurred after 4 weeks in 6 of the 10 RGN-259-treated subjects and in 1 of the 8 placebo-treated subjects (p = 0.0656), indicating a strong efficacy trend. Additional efficacy was seen in the significant healing (p = 0.0359) with no recurrent defects observed at day 43, two weeks after cessation of treatment, while the one healed placebo-treated subject at day 28 suffered a recurrence at day 43. The Mackie classification disease stage improved in the RGN-259-treated group at Days 29, 36, and 43 (p = 0.0818, 0.0625, and 0.0467, respectively). Time to complete healing also showed a trend towards efficacy (p = 0.0829, Kaplan-Meier) with 0.1% RGN-259. RGN-259-treated subjects had significant improvements at multiple time points in ocular discomfort, foreign body sensation, and dryness which were not seen in the placebo group. No significant adverse effects were observed. In summary, the use of 0.1% RGN-259 promotes rapid healing of epithelial defects in neurotrophic keratopathy, improves ocular comfort, and is safe for treating this challenging population of patients.

Canonical Grading Scales of Corneal and Conjunctival Staining Based on Psychophysical and Physical Attributes.

Purpose: In this study, we apply psychophysical scaling principles based on physical (photometric) attributes of images to better understand the factors involved in clinician judgement of ocular surface staining and, using that knowledge, to develop photographic scales for the assessment of staining for dry eye (DE) and related conditions. Methods: Subjects with noninfectious ocular surface staining were enrolled at five clinical sites. Following instillation of fluorescein, photographs of corneal staining were taken every 30 seconds for at least 5 minutes. The same procedure was followed for conjunctival staining after instillation of 2 µl of 1% lissamine green. A subset of the best corneal and bulbar conjunctival staining images were anonymized and a spectroradiometer measured photometric attributes (luminance and chromaticity). The images were scaled psychophysically by study investigators, who participated in constructing grading scales based on physical and psychophysical analyses. The final grading scales were refined following consultation with outside DE experts. Results: Photographs were collected from 142 subjects (81% women), with an average age of 58 ± 17 years; 89% were diagnosed with DE. There was a monotonic relationship between between physical measurements and psychophysically scaled staining of both corneal (fluorescein) and bulbar (lissamine green) staining. Michelson contrast and u' (chromaticity) accounted for 66% and 64% of the variability in the psychophysically scaled images of fluorescein corneal and lissamine green conjunctival staining, respectively. Translational Relevance: This paper provides examples of the first ever clinically usable ocular surface staining scales validated using psychophysical scaling and the physical attributes (luminance and chromaticity) of the staining itself. In addition, it provides a generalizable method for the development of other clinical scales of ocular appearance.

Ocular surface disease in patients with glaucoma or ocular hypertension treated with either BAK-preserved latanoprost or BAK-free travoprost.

PURPOSE: The preservative benzalkonium chloride (BAK) may adversely affect ocular surface health. This study evaluated symptoms of ocular surface disease (OSD) in patients previously treated with a BAK-preserved therapy to lower their intraocular pressure, who either continued that therapy or switched to a BAK-free therapy. METHODS: Eligible adult patients with ocular hypertension or open-angle glaucoma that had been controlled with BAK-preserved latanoprost 0.005% monotherapy (Xalatan ®) for at least one month and had a score of ≥ 13 (0 = none, 100 = most severe) on the Ocular Surface Disease Index (OSDI) questionnaire were entered into this prospective, double-masked, randomized, active-controlled, multicenter trial. By random assignment, patients either continued with BAK-preserved latanoprost 0.005% or transitioned to BAK-free travoprost 0.004% (Travatan Z ® ophthalmic solution). OSDI scores were assessed again after six and 12 weeks. RESULTS: For the 678 evaluable patients, mean change in OSDI score from baseline to week 12 favored the travoprost 0.004% BAK-free group, but was not statistically different between groups (P = 0.10). When patients with mild OSD at baseline were assessed after 12 weeks, the mean OSDI score was significantly lower (P = 0.04) in the BAK-free travoprost 0.004% group (score = 11.6 ± 10.8 units) than in the BAK-preserved latanoprost 0.005% group (score = 14.4 ± 11.9 units), and a significantly larger percentage (P < 0.01) improved to normal OSDI scores in the BAK-free travoprost 0.004% group (62.9% of group) than in the BAK-preserved latanoprost 0.005% group (47.0% of group). Patients pretreated with BAK-preserved latanoprost 0.005% for >24 months were significantly more likely (P = 0.03) to improve to a normal OSDI score after 12 weeks if they were switched to BAK-free travoprost 0.004% (47.9% of group) than if they remained on BAK-preserved latanoprost 0.005% (33.9% of group). CONCLUSIONS: Switching from BAK-preserved latanoprost 0.005% to BAK-free travoprost 0.004% yielded significant improvements in symptoms of OSD in patients with glaucoma or ocular hypertension.

Novel hydroxypropyl-guar gellable lubricant eye drops for treatment of dry eye.

OBJECTIVE|: The objective of this review is to evaluate the safety and efficacy of polyethylene glycol 400/propylene glycol/hydroxypropyl-guar (Systane® Ultra [PEG/PG with HP-guar], Alcon Laboratories, Inc., Fort Worth, TX, USA) lubricant eye drops in reducing the signs and symptoms of dry-eye disease. METHODS|: A systematic literature search utilizing MEDLINE was conducted to identify peer-reviewed articles related to dry-eye disease and PEG/PG with HP-guar lubricant eye drops. The search covered the period prior to October 2009. Additionally, a manual search based on citations in the published literature was conducted. RESULTS|: The PEG/PG with HP-guar artificial tears shows in-vitro viscoelastic properties with pH optimization. The pH of the solution adjusts to the pH of the ocular surface upon instillation, which results in tear film elasticity and viscosity similar to that of subjects without dry-eye disease. The reviewed literature demonstrated that this delivery system showed a reduction in corneal and conjunctival staining in dryeye disease, an improvement in tear film stability, a low coefficient of friction in an in-vitro model, and improved maintenance of best-corrected visual acuity over time. CONCLUSION|: A few small-sized studies with short-term follow-up demonstrated that PEG/PG with HP-guar is a safe and effective lubricant eye drops for the treatment of dry-eye disease. Larger studies with longer duration are warranted to assess the long-term safety and efficacy of this formulation in patients with dry.eye disease.

Novel ocular lubricant containing an intelligent delivery system: details of its mechanism of action.

OBJECTIVE: The purpose of this review is to outline the mechanism of action of a novel ocular lubricant incorporating hydroxypropyl-guar (HPG) and the demulcents polyethylene glycol 400 and propylene glycol. METHODS: The literature relating to the mechanism of action of Systane Ultra is presented. The literature search covered the period prior to June 2008. A manual search was also conducted based on citations in the published literature. Additional original reports were referenced if relevant to the subject matter of the review. RESULTS AND CONCLUSION: The published literature supports the efficacy of an ocular lubricant containing HPG at reducing the signs and symptoms of dry eye through its multiphasic behavior and duration of action. This new formulation presents an additional benefit of a delivery system to further reduce the assimilation time of the product on-eye. Beneficial outcomes have been documented for tear film interaction, blur profile, viscoelasticity and tensile strength.

Tectonic lamellar keratoplasty utilizing a microkeratome and an artificial anterior chamber system.

PURPOSE: To describe a technique and report results of tectonic lamellar keratoplasty using tissue harvested with a microkeratome from a corneoscleral rim mounted in an artificial anterior chamber system. METHODS: A donor lenticule was prepared from a corneoscleral rim utilizing the Moria LSK-1 (Moria/Microtek Inc., Doylestown, PA, U.S.A.) microkeratome and artificial anterior chamber. This tissue was used in the procedures of 6 eyes of 6 patients requiring tectonic lamellar keratoplasty. Three eyes were in danger of imminent perforation due to corneal ulceration. Other indications for lamellar engraftment include persistent wound leak following cataract extraction, persistent epithelial defect following a Grade 4 chemical burn, and limbal dermoid. RESULTS: A successful outcome, defined as restoration or preservation of globe integrity, vision, and intact epithelium, was achieved in all patients. Follow-up ranged from 2-8 months with a mean of 4.5 months. CONCLUSIONS: Donor lenticules prepared with the ALTK (Moria/Microtek Inc.) system can be used in the successful management of eyes requiring tectonic lamellar keratoplasty.

Predictability of donor lamellar graft diameter and thickness in an artificial anterior chamber system.

PURPOSE: To identify factors affecting the predictability and report results of donor lamellar graft diameter and thickness in an artificial anterior chamber obtained with a microkeratome. METHODS: Lamellar lenticules were obtained from 25 human corneoscleral rims mounted in an artificial anterior chamber. Lenticules measuring 9 mm were attempted at two thicknesses (250 microm and 350 microm heads). Intrachamber pressure of 65 mm Hg was confirmed with Barraquer tonometry. Keratometry, pachymetry, limbal white-to-white, and qualitative mires with the diameter applanation lens were evaluated as possible factors predictive of lenticule diameter and thickness. Diameters and thicknesses were measured with calipers and pachymetry, respectively. RESULTS Ninety-two percent (23/25 lenticules; 14/15 in 250 microm, 9/10 in 350 microm) were +/- 0.25 mm of the intended diameter and 76% (19/25 lenticules; 12/15 in 250 microm, 7/10 in 350 microm) were within +/- 100 microm of the intended thickness. Ovoid applanation mires with the diameter applanation lens represented tissue herniation within the artificial anterior chamber and led to ovoid lenticules (2/25). CONCLUSIONS: Lenticules of 9 mm +/-0.25mm in diameter were highly reproducible with proper corneoscleral rim seating. Intrachamber pressure confirmed with Barraquer tonometry is important in obtaining lenticules of consistent diameter and adequate thickness. Ovoid applanation mires may herald improper corneoscleral rim seating and result in a similarly shaped lenticule. A 2 mm or greater corneoscleral rim is recommended to prevent tissue herniation within the artificial anterior chamber used in this study.