Irina S. Barequet

Treatment of Dry Eye Syndrome with Orally Administered CF101: Data from a Phase 2 Clinical Trial

OBJECTIVE To explore the safety and efficacy of CF101, an A(3) adenosine receptor agonist, in patients with moderate to severe dry eye syndrome. DESIGN Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study. PARTICIPANTS Sixty-eight patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. INTERVENTION Patients were treated orally with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week posttreatment observation. MAIN OUTCOME MEASURES An improvement of more than 25% over baseline at week 12 in one of the following parameters: (1) tear break-up time (BUT); (2) superficial punctate keratitis assessed by fluorescein staining results; and (3) Schirmer tear test 1 results. Clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements, and monitoring of adverse events. RESULTS A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group. CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. CONCLUSIONS CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate to severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Refractive results with secondary piggyback implantation to correct pseudophakic refractive errors

PURPOSE: To assess the efficacy and safety of implanting a second intraocular lens (IOL) to correct pseudophakic refractive errors. SETTING: Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel. METHODS: This prospective noncomparative case series included 10 pseudophakic eyes, 5 with a myopic residual refractive error and 5 with a hyperopic residual refractive error. All eyes had secondary piggyback IOL implantation with the IOL placed in the ciliary sulcus. Five types of IOLs were used to correct the residual refractive error. RESULTS: The mean preoperative myopia was −6.6 diopters ± 3.3 (SD), and the refractive outcome was within 0.5 ± 0.7 D of the desired refraction (range –1.5 [undercorrected] and +1.0 D [overcorrected]). The mean preoperative hyperopia was +3.8 ± 0.8 D, and the refractive outcome was within 0.46 ± 0.4 D of the desired refraction (range 0 and 1.0 D overcorrected). All patients showed visual acuity improvement. Best spectacle‐corrected visual acuity improved from 20/44 to 20/30 (P<.05). CONCLUSION: An IOL type that is appropriate for implantation in the ciliary sulcus is a viable option for correcting pseudophakic refractive error using the piggyback technique.

Herpes simplex keratitis after cataract surgery.

Purpose: Herpetic keratitis is a rare complication of cataract surgery. We describe 3 cases of herpes simplex keratitis after cataract surgery in eyes with no clinical history of this disease. Methods: Three patients underwent uneventful phacoemulsification of cataract with intraocular lens implantation. All were treated postoperatively with topical steroids. On subsequent development of corneal dendritic epithelial lesions in the operated eyes, the corticosteroids were replaced by treatment with topical acyclovir. Results: The first postoperative day was uneventful. Corneal dendritic epithelial lesions were observed 1-5 weeks postoperatively and healed without sequelae after topical acyclovir treatment. Conclusions: In view of the surgical trauma along with the topical corticosteroid treatment commonly prescribed after cataract surgery, physicians should be aware of the possible development of herpetic epithelial keratitis even in patients with no clinical history of this disease.

The inhibitory effect of different concentrations of topical bevacizumab on corneal neovascularization

Acta Ophthalmol. 2010: 88: 862–867

Laser in situ keratomileusis improves visual acuity in some adult eyes with amblyopia.

PURPOSE To report the results of laser in situ keratomileusis (LASIK) in a series of adult patients with amblyopia. METHODS A retrospective noncomparative review was performed on patients with amblyopia who underwent LASIK for correction of ametropia, using the Summit Krumeich Barraquer microkeratome and the Nidek EC-5000 excimer laser. Data were collected on uncorrected visual acuity, best spectacle-corrected visual acuity, manifest refraction, anterior segment evaluation, intraocular pressure, corneal topography, and dilated fundus examination (preoperative and postoperatively on day 1, months 2 and 6). RESULTS Eight eyes of seven patients were included, with a mean patient age of 30 +/- 10 years (range 21 to 49 yr). Mean preoperative spherical equivalent refraction was -4.70 D (range -12.62 to +4.71 D) and the best spectacle-corrected visual acuity varied from 20/32 to 20/80. At 2 months after LASIK, mean spherical equivalent refraction was -0.37 +/- 0.60 D (range -1.37 to + 0.60 D), uncorrected visual acuity ranged between 20/20 to 20/30, and a mean gain of 3 Snellen lines (range 2 to 4 lines) was observed. All patients reported significant subjective improvement in their perception of vision. The visual acuity and subjective improvement were maintained throughout 6 months postoperatively. CONCLUSIONS LASIK with the Nidek EC-5000 laser for correction of ametropia in adult amblyopic eyes provided encouraging results for visual acuity improvement beyond correction of the refractive error.

Pseudomonas aeruginosa LasA Protease in Treatment of Experimental Staphylococcal Keratitis

ABSTRACT LasA protease is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. We have examined the effectiveness of LasA protease in the treatment of staphylococcal keratitis caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates in a rabbit model. Keratitis was induced by intrastromal injection of the bacteria. The eyes were treated topically, and the efficacy of LasA protease was compared to those of lysostaphin (a staphylolytic protease secreted by Staphylococcus simulans) and vancomycin. When treatment was initiated early (4 h) after infection, practically all of the MSSA- and MRSA-infected corneas were sterilized by LasA protease, and its efficacy in eradicating the bacteria was comparable to those of lysostaphin and vancomycin. By contrast, most of the control corneas were heavily infected, with median values of 4.5 × 106 (MSSA) and 5 × 105 (MRSA) CFU/cornea (P < 0.001). When treatment was initiated late (10 h) after infection, LasA protease reduced the numbers of CFU in both MSSA- and MRSA-infected corneas by 3 to 4 orders of magnitude compared to the numbers of CFU for the controls (median values, 1,380 and 30 CFU/cornea, respectively, for the treated animals compared to 1.2 × 106 and 5 × 105 CFU/cornea for the respective controls [P = 0.001]), and it was more effective than vancomycin in eradicating MRSA cells (P = 0.02). In both the early- and the late-treatment protocols, the clinical scores for eyes treated with LasA protease were significantly lower than those for the eyes of the corresponding controls and comparable to those for the lysostaphin- and vancomycin-treated eyes. We conclude that LasA protease is effective in the treatment of experimental S. aureus keratitis in rabbits and may have potential for the treatment of disease in humans.

Central corneal thickness in congenital glaucoma.

Purpose: The aim of this study was to compare central corneal thickness between eyes with congenital glaucoma and normal fellow eyes in unilateral glaucoma or less affected fellow eyes in bilateral glaucoma. Methods: Eyes of consecutive phakic children with congenital glaucoma and previous glaucoma surgery were examined under chloral hydrate. Complete ophthalmologic examination, central corneal thickness (CCT), axial length, and corneal diameter measurements were performed. Patients were included in the study if presented with intraocular pressure (IOP) less than 21 mm Hg and no biomicroscopic signs of corneal edema. Results: Nine patients were included in the study. The mean CCT in the more affected eye/glaucomatous eye was 522.3 ± 65.2 μm and in the less affected eye/healthy eye was 579.7 ± 44.5 μm. This difference was statistically significant (P = 0.0013). Conclusion: CCT was significantly thinner in glaucomatous eyes than in normal fellow eyes in phakic children with congenital glaucoma. This finding may be another confounding factor when measuring IOP in these patients.

Effect of Amniotic Membrane Transplantation on the Healing of Bacterial Keratitis

PURPOSE To study, with the use of an animal model, the efficacy of amniotic membrane (AM) transplantation as adjunctive treatment in corneal healing after bacterial keratitis. METHODS Staphylococcus aureus keratitis was induced in 47 rats by injection of bacteria into the corneal stroma. Treatment was started 48 hours later with one of three randomly assigned protocols: cefazolin drops (50 mg/mL) and AM transplantation (n = 16); nonpreserved 0.9% saline drops and AM transplantation (n = 15); or cefazolin without AM transplantation (n = 16). Cefazolin and saline drops were administered every 30 minutes for 6 hours, then hourly for 6 hours. AM was transplanted 24 hours after termination of cefazolin or saline treatment. Results were clinically assessed 7 days after AM transplantation or at the corresponding time in the nontransplanted animals. The rats were then killed, and their corneas were removed for bacterial counts or histopathologic examination. RESULTS The best clinical results were observed in the group treated with cefazolin and AM transplantation, manifested by the least corneal haze and neovascularization (P = 0.007 and P = 0.014, respectively) and minimal bacterial counts (28 colony-forming units [CFU]/mL compared with 160 CFU/mL and 240 CFU/mL, respectively). Histopathologic examination showed that the central corneal vessels from rats treated with cefazolin and AM were smaller and less congested than those from the other two groups. CONCLUSIONS AM transplantation is a useful adjunctive treatment after bacterial keratitis in this rat model. The transplanted AM improved the healing process, resulting in decreased corneal haze and less neovascularization.

Wearing time as a measure of success of scleral lenses for patients with irregular astigmatism.

Objectives: To evaluate the visual correction and clinical performance with scleral contact lenses (CL) for the visual rehabilitation of irregular astigmatism and to report the effect of brief wearing breaks on the wearing time and success rate. Methods: A retrospective review was performed on consecutive patients who were fitted with scleral CL because of irregular astigmatism following failure of other optical corrections. Visual acuity (VA) and wearing times were abstracted. Results: The 97 consecutive identified patients (155 eyes) were divided according to the diagnosis: (1) keratoconus (105 eyes; 67.7%), (2) postpenetrating keratoplasty (PK) (28 eyes; 18.1%); (3) multiple diagnoses (22 eyes; 14.2%)—postradial keratotomy, keratoglobus, pellucid marginal degeneration, PK with aphakia, and iatrogenic ectasia. The mean follow-up was 34.9 ± 18.5 months (range, 2–71 months). There was a significant increase in best VA-scleral when compared with the previous best VA-prescleral (P<0.001). The best VA-scleral was similar in the 3 groups (P>0.5). Patients who took brief breaks every 4 to 5 continuous wearing hours had a significantly higher success rate (P<0.001) among all diagnosis groups. The success rate in wearing time in the keratoconus group was significantly higher than in the PK group (P<0.001). Twenty-six patients (27%) discontinued to wear scleral lenses. Conclusion: Scleral lenses can be used successfully for visual rehabilitation and management of irregular astigmatism from various causative factors. The daily wearing time was significantly improved by taking brief breaks for replenishing the CL.

Risk assessment of simple phacoemulsification in patients on combined anticoagulant and antiplatelet therapy

PURPOSE: To assess the safety of phacoemulsification cataract extraction in patients on combined anticoagulant and antiplatelet treatment. SETTING: Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel. DESIGN: Prospective interventional case series. METHODS: Consecutive patients with simple cataract on combined anticoagulant (warfarin) and antiplatelet (aspirin or clopidogrel) treatment who were unable to discontinue the treatment because of a high risk for thromboembolic events were included. Patients had cataract extraction under topical anesthesia with a clear corneal incision (CCI), phacoemulsification, and implantation of a foldable posterior chamber intraocular lens. Prothrombin time–international normalized ratio and platelet functions were evaluated immediately before surgery. Patients were also examined 1 day and 7 days postoperatively. Intraoperative and postoperative ocular bleeding and other related complications were assessed. RESULTS: Forty patients (51 eyes) with a mean age of 72 years (range 51 to 90 years) had phacoemulsification. Hemorrhagic complications were not observed at surgery or during the 1‐week follow‐up. Surgical complications included 1 rupture of the capsulorhexis and 1 implantation of a capsular tension ring due to partial zonulysis. No patient had a thromboembolic event. CONCLUSIONS: In patients with uncomplicated cataract at high risk for thromboembolic events, phacoemulsification cataract surgery using a CCI under topical needle‐free anesthesia was safely performed without discontinuing systemic anticoagulant and antiplatelet treatment. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.