Effect of Corneal Thickness on the Penetration of Topical Vancomycin.

PURPOSE: To study the influence of corneal thickness on intraocular penetration of topical ophthalmic drops, using vancomycin 50 mg/mL drops as a model. METHODS: The study included 58 eyes of 58 patients undergoing phacoemulsification cataract extraction. The central corneal thickness was measured by ultrasonic pachymetry on the day of surgery. Thirty minutes before the surgery, one drop of topical vancomycin 50 mg/mL was instilled three times with 10-minute intervals: 30 minutes, 20 minutes, and 10 minutes before the surgery. At the beginning of surgery, a small specimen of aqueous humor was aspirated and sent to the laboratory for measurement of drug concentration to determine the effect of corneal thickness on vancomycin concentration in the anterior chamber. RESULTS: There was insufficient amount of aqueous humor for analysis in 9 samples, leaving a total of 49 samples. The mean central corneal thickness was 539.7 (±39.5) µm (range, 458 to 635 µm). The mean vancomycin concentration in the anterior chamber was 0.220 (±0.209) µg/mL. There was no significant association between vancomycin concentration and corneal thickness (r = -0.07, p = 0.62, Pearson correlation). When patients were divided into three groups based on the mean (±1 SD) central corneal thickness, no significant differences in vancomycin concentrations (in micrograms per milliliter) were encountered: 0.267 (±0.247) (for corneal thickness <500.2 µm), 0.209 (±0.212) (for corneal thickness of 500.2 to 579.2 µm), and 0.200 (±0.160) (for corneal thickness >579.2 µm) (p = 0.73, analysis of variance). CONCLUSIONS: Corneal thickness does not influence the penetration of topically applied vancomycin into the anterior chamber.

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

Effect of brimonidine tartrate on basophil activation in glaucoma patients.

AIM: To evaluate the mechanism of which brimonidine tartrate 0.15% causes clinical hypersensitivity. METHODS: A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to a control group consisting 13 healthy volunteers. Blood samples were stimulated with brimonidine 0.15%, timolol 0.5% or brimonidine tartrate/timolol maleate 0.2%/0.5%. Premixed antibodies (CD63/FITC and aIgE/PE) were added for direct staining and whole-blood samples were lysed, fixed and analyzed by a flow cytometer. The basophil population was defined by high IgE cell expression. Degranulation was identified by the expression of the activation molecule CD63. RESULTS: Basophil activation was not significant when comparing percent of activated basophils of patients and healthy controls after exposure to brimonidine (2.58%, 2.45%, respectively, P=0.72). There was a significant suppression of basophil activation when a combination of brimonidine-timolol (0.87%) was compared to timolol (2.27%; P=0.012) and to brimonidine alone (2.58%; P=0.017). CONCLUSION: The results of our study do not support the hypothesis that brimonidine induces an immediate allergic reaction. Basophil activation was suppressed by the presence of ß-blockers in patients hypersensitive to brimonidine and in healthy individuals. This finding indicates that timolol suppress brimonidine drug reaction by a different mechanism.

Pressure phosphene tonometry versus Goldmann applanation tonometry for measuring intraocular pressure before and after LASIK.

PURPOSE: To compare pressure phosphene tonometry with Goldmann applanation tonometry for measuring intraocular pressure (IOP) before and after LASIK. METHODS: Forty-three (18 men and 25 women) consecutive healthy patients underwent complete pre- and postoperative LASIK ophthalmologic assessments including manifest and cycloplegic refraction, keratometry, and central corneal thickness. Three repetitive sets of pressure phosphene tonometry and Goldmann applanation tonometry measurements were performed the day before and 3 months following uneventful LASIK. RESULTS: Mean preoperative spherical equivalent refraction was -4.70 +/- 2.50 diopters (D) (range: -1.50 to -12.90 D) and mean preoperative keratometry was 43.95 +/- 1.08 D. After LASIK, spherical equivalent refraction was +0.23 +/- 0.11 D and mean keratometry was 39.46 +/- 2.28 D. Preoperative pressure phosphene tonometry (12.16 +/- 1.58 mmHg) and Goldmann applanation tonometry (12.01 +/- 1.55 mmHg) IOP measurements were similar. Postoperative IOP was 10.30 +/- 1.16 mmHg with Goldmann applanation tonometry and 12.20 +/- 1.62 mmHg with pressure phosphene tonometry. The postoperative IOP difference between Goldmann applanation tonometry and pressure phosphene tonometry was 0.15 +/- 1.12 mmHg (P = .41). The mean change in pachymetry after LASIK was 68.73 +/- 73 microm. The change in Goldmann applanation between preoperative and postoperative LASIK values was 1.71 +/- 1.43 mmHg (P < .0001), a change that was strongly correlated with changes in corneal thickness (R = 0.75, P < .0001) and keratometry (R = 0.72, P < .0001). No such correlations were found with pressure phosphene tonometry. CONCLUSIONS: Goldmann applanation tonometry-measured IOP decrease after LASIK is strongly correlated with a decrease in central corneal thickness and changes in keratometry, whereas pressure phosphene tonometry-measured IOP is independent of corneal thickness. Pressure phosphene tonometry appears to be a more reliable method for recording tonometry in these patients.

Air transportation of corneal tissue: experience with local compared to transatlantic donor corneas.

PURPOSE: To compare the outcome of corneas obtained at the same hospital in which they were transplanted (group 1) to that of corneas obtained in the United States and grafted in Israel (group 2). METHODS: One hundred twenty-six patients undergoing corneal grafting in Israel during the years 1995 to 1998 were included in a retrospective, nonrandomized clinical trial. Group 1 included 31 procedures, and group 2 included 95. Data regarding preoperative condition, tissue characteristics, and postoperative outcome were collected from hospital charts. Statistically significant difference between groups was considered as P < 0.05. RESULTS: Follow-up time was 796 +/- 523 days for group 1 (mean +/- SD) and 815 +/- 510 days for group 2. Donor age and gender, recipient age and gender, graft size, and length of follow-up were similar. Time from preservation to transplantation was longer for group 2 (8.8 +/- 2.29 days) compared with in group 1 (3.13 +/- 2.38 days). Graft clarity was similar between groups 1 and 2 at 1 year (79% versus 71%) and at last follow-up visit (57% versus 62%). Visual acuity, intraocular pressure, and incidence of complications such as rejection (32% versus 38%), failure (35% versus 28%), secondary glaucoma (35% versus 43%), corneal ulcer (13% versus 6%), and regrafts (13% versus 7%) showed no difference between the groups. CONCLUSIONS: Air transport of corneal tissue, including loss of time due to travel and handling, did not compromise corneal transplantation success rate.

Retinal pathology occurring after excimer laser surgery or phakic intraocular lens implantation: evaluation of possible relationship.

The increasing number of patients undergoing refractive surgery has led to an awareness of the potential retinal complications of these procedures. The purpose of this review is to summarize the reports of retinal pathology and myopic maculopathy that have occurred after excimer refractive surgery or implantation of phakic intraocular lenses, and to evaluate theoretical pathogenetic mechanisms. We found it reasonable to conclude that retinal detachments and macular hemorrhages are not caused by laser surgery, but are rather characteristic of the natural history in the myopic eye. However, although there is no clear-cut evidence for a cause-and-effect relationship between excimer laser surgery and retinal pathology, it is very important to inform patients that refractive surgery only corrects the refractive aspect of myopia, and that the myopia itself still has the potential for serious complications.

Effect of brimonidine tartrate 0.2% ophthalmic solution on pupil size.

PURPOSE: To evaluate the effect of brimonidine tartrate 0.2% ophthalmic solution on pupil size under scotopic and photopic luminance conditions in persons considering laser refractive surgery. SETTING: Ophthalmic Health Center, Tel Aviv, Israel. METHODS: The pupil size was measured in 36 eyes of 36 participants under scotopic and photopic conditions using the Colvard pupillometer (Oasis Medical) before and after brimonidine tartrate drops were administered. The pupil size was subsequently measured after 30 minutes and 4 and 6 hours. RESULTS: No difference was found in pupil size before brimonidine tartrate instillation in eyes with light or dark irides. Before instillation, the mean photopic pupil size was 4.81 mm +/- 0.54 (SD) (range 4.0 to 6.0 mm). At 30 minutes, all pupils became miotic, with a mean size of 3.77 +/- 0.51 mm (range 3.0 to 5.0 mm) (P<.0001). After 6 hours, 27.8% of the pupils had returned to their previous size. Before brimonidine tartrate administration, the mean scotopic pupil size was 6.22 +/- 0.73 mm (range 5.0 to 8.0 mm). There was significant miosis to 4.57 +/- 0.84 mm (range 3.0 to 6.5 mm) (P<.0001) that continued for at least 6 hours. The miotic effect of brimonidine tartrate was stronger in eyes with light irides. CONCLUSIONS: Brimonidine tartrate caused significant miosis, especially under scotopic conditions, most likely from its alpha-2 adrenergic effect. Under photopic luminance conditions, the miotic effect was pronounced.

Colchicine in tear fluid of treated patients with familial Mediterranean fever.

PURPOSE: The study aimed to determine whether detectable concentrations of colchicine are present in the tear fluid of treated patients with familial Mediterranean fever (FMF) and thus demonstrate a possible route by which colchicine reaches the corneal surface. METHODS: Tear fluid samples (50-100 microL) were collected from eight FMF patients on long-term colchicine treatment. Colchicine tear fluid concentrations were determined in all patients by radioimmunoassay using goat anticolchicine antibodies and [3H]colchicine (Dupont, Wilmington, DE). RESULTS: Detectable concentrations of colchicine, with no apparent effect on the ocular surface, were found in all tear fluid samples (median, 0.46 ng/mL; range, 0.24-1.05 ng/mL). CONCLUSIONS: This study provides evidence of the route by which colchicine, given systemically, reaches the corneal surface and thus gives credence to the possible inhibitory effect of this drug on corneal wound healing in the cases described in the literature.

Hyperhomocystinemia in pseudoexfoliation glaucoma.

PURPOSE: To determine the prevalence of hyperhomocystinemia in patients with pseudoexfoliation glaucoma. PATIENTS AND METHODS: This prospective study included 30 patients with glaucoma and 30 age-matched controls with no history of ocular disease who were undergoing routine physical checkups. Plasma homocysteine levels of all the study participants were determined using high-performance liquid chromatography, and values exceeding 15 micromol/L were considered elevated. RESULTS: The mean plasma homocysteine level was 16.80 +/- 3.20 and 12.39 +/- 1.97 micromol/L in glaucoma patients and controls, respectively (P<0.0001). Fifteen glaucoma patients (50%) had hyperhomocystinemia compared with 3 controls (10%) (P=0.0015). CONCLUSION: Hyperhomocystinemia may be associated with pseudoexfoliation glaucoma, which may partially explain the increased risk of vascular diseases among patients with pseudoexfoliation syndrome.

Interferon alpha-2a for proliferative diabetic retinopathy after complete laser panretinal photocoagulation treatment.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the effect of interferon alpha-2a, an angiogenesis inhibitor, on eyes with active neovascularization after complete laser panretinal photocoagulation treatment. PATIENTS AND METHODS: Eight patients with active neovascularization persisting for 6 months or more after completion of full panretinal photocoagulation were included in the study. All patients were treated with subcutaneous injections of 6 million international units of interferon alpha-2a, 3 times a week, for an average period of 10 months. Visual acuity, contrast sensitivity, blood tests, fundus photographs, fluorescein angiography, and physical examination were performed periodically. The main outcome measures were visual acuity and extent of neovascularization as assessed by fundus photography and fluorescein angiography. RESULTS: The 5 men and 3 women (mean age, 60 years) had a mean duration of diabetes of 19 years. The average study follow-up was 42.2 +/- 8.7 weeks. Visual acuity and extent of neovascularization improved or remained stable in 7 patients. In none of the patients was there progression of neovascularization, but in 1 patient it could not be assessed due to vitreous hemorrhage. Most patients had malaise during the first weeks of treatment, but none of the patients suffered from nonreversible side effects associated with interferon alpha-2a. CONCLUSION: This pilot study provides evidence that interferon alpha-2a might have a role in the regression of proliferative diabetic retinopathy and that further investigation is warranted.

Urrets-Zavalia syndrome (fixed and dilated pupil following penetrating keratoplasty for keratoconus) and its variants.

Urrets-Zavalia Syndrome (UZS) was described 50 years ago as the appearance of a fixed and dilated pupil following penetrating keratoplasty for keratoconus in patients receiving atropine. The mechanism of UZS has still not been fully determined, but an acute increase in intraocular pressure and ischemia of the iris most probably play a major role. Fixed and dilated pupils also occur in association with other ophthalmic surgeries, such as lamellar keratoplasties, cataract surgery, and glaucoma procedures. Some have questioned the existence of this syndrome, as well as the linkage to keratoconus and use of mydriatics. We review the pathophysiology, etiology, and clinical presentation of fixed and dilated pupils following ophthalmic procedures.

Intense exercise causing central retinal vein occlusion in a young patient: case report and review of the literature.

We report a 19-year-old patient who developed a central retinal vein occlusion (CRVO) with significant macular edema and visual impairment following intense exercise and dehydration. The patient was treated with 3 intravitreal bevacizumab injections with complete resolution. A review of the literature on the cause and treatment for CRVO in young patients was performed, focusing on the role of intense exercise and dehydration as a rare pathogenesis mechanism of CRVO.

Intraocular pressure reduction using a fixed combination of timolol maleate 0.5% and brimonidine tartrate 0.2% administered three times daily.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of a fixed combination of timolol maleate 0.5% + brimonidine tartrate 0.2% (Combigan®) for reduction for intraocular pressure (IOP) in patients with glaucoma when the dose frequency is increased from twice to three times daily. METHODS: The patients included had either primary open angle glaucoma or ocular hypertension. Those who were previously on treatment completed a drug washout period prior to inclusion. IOP was measured at baseline, after 4 weeks of treatment with Combigan twice daily, and again after a further 4 weeks of Combigan three times daily. Blood pressure, heart rate, and oxygen saturation were also recorded at each assessment. RESULTS: Thirty-one eyes from 31 patients were included. Increasing the Combigan dose frequency resulted in a statistically significant (P < 0.001) additional reduction in IOP of 2.25 ± 1.18 mmHg, corresponding to a further 10.3% reduction in IOP from baseline. No local or systemic adverse effects were documented. CONCLUSION: Treatment with Combigan three times daily was more effective in reducing IOP than the twice-daily regimen, with no increase in adverse effects.

Pterygium excision with conjunctival autograft: true survival rate statistics.

PURPOSE: To evaluate the factors influencing long-term survival rate (ie, probability of recurrence-free eye over time) after pterygium excision with conjunctival autograft. METHODS: A retrospective cohort study was performed. All patients who underwent excision of pterygium and conjunctival autograft at a single institution by the same surgeon during the years from 1997 to 2008 were included. Preoperative and postoperative patient data were collected. The patients were invited for follow-up examinations performed by the surgeon, and the recurrence was analyzed using survival rate statistics. RESULTS: There were 20 recurrences (20/176, 11.4%) during an average follow-up time of 34.4 ± 36.2 months (range, 0.03-129.7 months), with no apparent leveling of the graph. Using survival rate statistics, the estimated mean time to recurrence was 104.5 ± 4.9 months (95% confidence interval, 94.9-114.0 months). Patients younger than 30 years (P = 0.031) and grafts attached with thicker sutures (6/0-8/0, P = 0.005) were more prone to have recurrences. Thin (9/0 or 10/0) nylon and polyglactin sutures had similar results (P = 0.819). Interestingly, pterygia invading less into the cornea probably had more recurrences (P = 0.054). There was an average improvement of logarithm of the minimum angle of resolution from 0.26 (preoperative) to 0.19 (postoperative) (P < 0.014). There were no major complications. CONCLUSIONS: Use of survival rate statistics is indicated because the potential for pterygium recurrence is continuous. Worse prognosis is expected for younger patients, use of thicker sutures and possibly in less invading pterygia.

Double use of corneal graft for Descemet stripping automated endothelial keratoplasty and coverage of glaucoma drainage device tube.

PURPOSE: To describe the efficacy and safety of using a single corneal graft for 2 different ocular surgeries, Descemet stripping automated endothelial keratoplasty in one patient and coverage of a glaucoma drainage device tube in another patient. MATERIALS AND METHODS: The records of 12 consecutive patients who underwent Ahmed glaucoma valve implantation using the anterior lamella of a donor cornea that had been previously used for Descemet stripping automated endothelial keratoplasty were reviewed. RESULTS: Nine eyes (75%) had superotemporal Ahmed valve implantation and 3 eyes (25%) had inferotemporal implantation. No intraoperative complications were encountered in any of these cases. During postoperative follow-up there were no graft rejections, wound dehiscences, tube exposures, or any glaucoma drainage device-related complications. In 1 patient, graft thinning was noticed 12 months after surgery, but without erosion of the conjunctiva or exposure of the tube. Mean intraocular pressure (IOP) before surgery was 32.8±9.3 mm Hg. The mean postoperative IOPs were 13.2±6.8 mm Hg (P<0.001) at day 1, 10.5±2.7 (P<0.001) at week 1, 12.2±3.5 (P<0.001) at month 1, 12.9±3.0 (P<0.001) at month 3, 14.2±7.0 (P<0.001) at month 6, and 13.0±6.4 (P<0.001) at the final visit. The mean reduction in IOP was 59%. Mean follow-up time after surgery was 21.7±7.5 months. CONCLUSIONS: The use of the anterior corneal graft cap for patching a tube is safe and effective. The double use of a corneal graft is economically worthwhile and especially useful in countries where there is shortage of donor corneal tissues.

Intraocular pressure reduction of fixed combination timolol maleate 0.5% and dorzolamide 2% (Cosopt) administered three times a day.

PURPOSE: To evaluate the safety and efficacy in intraocular pressure (IOP) reduction of increasing Cosopt dosage from twice to three times a day. METHODS: The study included patients with primary open-angle glaucoma or ocular hypertension. After a washout period, IOP was measured at baseline, after 4 weeks of treatment with Cosopt twice a day, and after another 4 weeks of treatment with Cosopt three times a day. Blood pressure, heart rate, and oxygen saturation levels were also recorded. RESULTS: Twenty-nine eyes of 29 patients were included. Increasing Cosopt dosage resulted in a statistically significant (P < 0.001) additional reduction in IOP of 2.2 ± 1.58 mmHg (10.69% ± 7.49% of the baseline IOP values). There were no local or systemic adverse effects. CONCLUSION: Treatment with Cosopt three times a day was more effective in reducing IOP than twice a day, with no effect on safety.

Effect of brimonidine tartrate 0.10% ophthalmic solution on pupil diameter.

PURPOSE: To evaluate the effect of brimonidine tartrate 0.10% ophthalmic solution on pupil diameter under light and dark luminance conditions. SETTING: Ophthalmology Department, Tel Aviv Medical Center, Tel Aviv, Israel. DESIGN: Case series. METHODS: The pupil diameter was measured with a Colvard pupillometer in eyes of healthy volunteers under light (5.0 candelas [cd]/m(2)) and dark (0.0 cd/m(2)) luminance conditions before brimonidine 0.10% instillation and after 30 minutes, 3 hours, and 6 hours. RESULTS: The mean age of the 26 volunteers (52 eyes) was 34.73 years (range 19 to 60 years). Under light conditions, the mean pupil diameter was 4.98 mm ± 0.83 (SD) before instillation of brimonidine 0.10% and 4.64 ± 0.82 mm after instillation. The difference was not statistically significant, with 13.4% of eyes having a clinically significant reduction (>1.0 mm) in pupil diameter after 6 hours. Under dark conditions, the mean pupil diameter was 6.76 ± 1.08 mm before instillation of brimonidine 0.10% and 5.30 ± 0.85 mm after instillation; the difference was statistically significant (P<.001). There was a clinically significant reduction in pupil diameter after 6 hours in 90.4% of eyes. The antimydriatic effect under dark luminance conditions was more pronounced in eyes with light irides. CONCLUSIONS: Brimonidine 0.10% ophthalmic solution had an antimydriatic effect under dark luminance conditions and had a negligible effect on pupil diameter under light luminance conditions. The effect was similar to that reported in studies using higher concentrations of brimonidine.

Comparison of the transpalpebral tonometer TGDc-01 with Goldmann applanation tonometry.

PURPOSE: This study aimed to compare intraocular pressure (IOP) measurements obtained by the transpalpebral tonometer TGDc-01 and by the Goldmann applanation tonometer (GAT). METHODS: IOP was measured by the conventional GAT and the TGDc-01 tonometer. Central corneal thickness (CCT) was measured for all eyes. RESULTS: Sixty-seven consecutive patients (123 eyes) participated. The mean difference between the 2 techniques (TGDc-01-GAT) was -0.93 mmHg, SD=2.74 (p=0.0002, paired t-test), and 70% of the measurements were within +/-2 mmHg. The correlation coefficient was 0.67 (p<0.0001). A subgroup analysis according to CCT was conducted. For CCT <520 microm, the mean IOP difference was 0.67 mmHg (p=0.13); r=0.75 (p<0.001). For CCT 520 microm-580 microm, the mean IOP difference was -1.08 mmHg (p=0.001); r=0.69 (p<0.0001). For CCT>580 microm, the mean IOP difference was -2.29 mmHg (p=0.0003); r=0.57 (p=0.003). CONCLUSIONS: TGDc-01 may estimate IOP with a fair agreement to the Goldmann tonometer, although caution should be used for patients who require precise IOP measurements. TGDc-01 measured higher IOPs than Goldman tonometry for thinner corneas, a trend that was reversed for thicker corneas. This tonometer is a portable device, easy to use, does not require anesthetic drops, and may be suitable for IOP screening.