Ümit Übeyt Inan

Prevention of posterior capsule opacification by intraoperative single-dose pharmacologic agents

Purpose: To determine whether an intraoperative single dose of dexamethasone, diclofenac, ethylenediaminetetraacetic acid (EDTA), a combination of EDTA and RGD peptide (arginine‐glycin‐aspartic acid sequence), or mitomycin‐C (MMC) is a pharmacological means of preventing or reducing the development of posterior capsule opacification (PCO). Setting: Department of Ophthalmology, Celal Bayar University, School of Medicine, Manisa, and Department of Pathology, Dokur Eylül University, School of Medicine, Izmir, Turkey. Methods: Fifty‐four rabbits were randomly divided into 6 groups. Dexamethasone (4 mg/cc), diclofenac (2.5 mg/cc), EDTA (8 mg/cc), a combination of EDTA and RGD peptide (2.5 mg/cc), or MMC (0.04 mg/cc) was given, 0.1 cc by hydrodissection and 0.9 cc into the capsular bag after phacoemulsification. The sixth group served as a control group. After 3 months, the PCO was graded clinically and the proliferation of lens epithelial cells (LECs) was evaluated histologically. Results: The drugs were significantly effective in preventing PCO compared with the control (P < .005). Dexamethasone had a weaker effect than the other drugs. In histological analysis, although monolayer LECs in the dexamethasone and diclofenac groups were observed, there was no proliferative activity on the posterior capsules in the EDTA, EDTA+RGD, and MMC groups in contrast to the multilayer cells in the control. Conclusions: Intraoperative single‐dose application of EDTA, EDTA+RGD peptide combination, and MMC significantly prevented the development of PCO in rabbit eyes. Diclofenac was less effective but also reduced PCO. Although dexamethasone did not prevent the proliferation of LECs, it decreased PCO clinically.

Evaluation of cystoid macular edema using optical coherence tomography and fundus fluorescein angiography after uncomplicated phacoemulsification surgery.

Purpose: To evaluate the central macular thickness (CMT) and the cystoid macular edema (CME) after uncomplicated phacoemulsification surgery. Material and methods: Ninety-one eyes of 88 patients who underwent uncomplicated phacoemulsification surgery between December 2008 and May 2009 were included in the study. Detailed ophthalmologic examinations and spectral domain optical coherence tomography (OCT) measurements were done preoperatively and at postoperative 1st, 4th, 12th, and 24th weeks. Best corrected visual acuity (BCVA) was measured as logMAR units at preoperative and all postoperative visits. Mean CMT, and perifoveal macular thickness in superior, inferior, nasal and temporal quadrants were recorded. CME was defined as three standard deviations (SD) above the preoperative mean CMT in OCT measurements. Fundus fluorescein angiography (FFA) was performed at postoperative 12th weeks. Data was analyzed statistically by using ANOVA test, and paired samples t test with Bonferroni correction. Results: The mean preoperative CMT was 255.68 ± 23.04 µm. The increase in CMT was statistically significant at postoperative 1st, 4th, 12th, and 24th weeks (p = 0.043). The most significant increase in CMT was seen at 12th weeks (p = 0.028). The change in perifoveal macular thickness measurements in the temporal, nasal, superior and inferior quadrant was statistically significant at postoperative 12th weeks (p < 0.001, for all measurements). The increase in macular thickness did not correlate with BCVA at postoperative 1st and 4th weeks but there was a significant correlation at postoperative 12th and 24th weeks. The incidence of angiographic CME at postoperative 12th weeks was 3.2%. The appearance of CME in OCT was observed in 5.5% of eyes at postoperative 12th weeks. Conclusion: Macular thickness changes after uncomplicated phacoemulsification surgery and Spectral domain OCT is helpful in detecting cystoid abnormalities and any increase in macular thickness at postoperative early periods. Changes seen on OCT do not completely correlate with FFA findings.

The Comparative Cardiovascular, Pulmonary, Ocular Blood Flow, and Ocular Hypotensive Effects of Topical Travoprost, Bimatoprost, Brimonidine, and Betaxolol

OBJECTIVE This study evaluated systemic and ocular acute safety and intraocular pressure (IOP)-lowering efficacy of travoprost 0.004% and bimatoprost 0.03%, compared to brimonidine 0.2% and betaxolol 0.25% in healthy subjects. PATIENTS AND METHOD Nineteen (19) young men, ages between 24 and 42, were enrolled in a single-center, institutional randomized, double-masked, crossover clinical trial. Baseline IOP, heart rate, blood pressure, and respiratory rate were recorded at hour 0. At minute 30, heart rate, blood pressure, respiratory rate, and spirometry were measured. At hour 1, color Doppler imaging of retrobulbar vessels was performed. At hour 2, heart rate, blood pressure, and respiratory rate were measured; spirometry and a 15-minute treadmill test were performed. The same protocol was applied after one drop of a study medication was instilled into each eye on four subsequent visits at 5-day intervals. RESULTS Travoprost and bimatoprost did not cause significant reductions in systolic blood pressure during exercise and recovery. The mean respiratory rate and forced expiratory volume in 1 second were not significantly altered by any study medication. Travoprost reduced the resistive index and increased blood velocities in the ophthalmic artery and its branches. Bimatoprost caused a significant increase in end diastolic velocity of the ophthalmic artery. At hour 6, all medications reduced IOP significantly (p < 0.05). The most frequent ocular side effect of travoprost and bimatoprost was conjunctival hyperemia. CONCLUSION Travoprost and bimatoprost were found to be systemically safe and caused an increase in blood-flow velocities of the retrobulbar vessels after a single-dose application. Their ocular hypotensive effect was comparable to that of brimonidine and greater than that of betaxolol in healthy subjects.

Penetration of topical and oral ofloxacin into the aqueous and vitreous humor of inflamed rabbit eyes.

PURPOSE This study aimed to investigate the penetration of topical and oral ofloxacin into aqueous humor and vitreous humor in post-traumatic endophthalmitis model in rabbits. METHODS A standardized intraocular infection after penetrating injury was made in the right eyes of 16 rabbits. Intraocular infection was induced by intravitreal injection of a suspension of Staphylococcus aureus. The intact left eyes were maintained as controls. The animals were divided randomly into two groups. (1) In the topical group, two drops of ofloxacin 0.3% eyedrops were instilled to both eyes every 30 min for 4 h. (2) In the topical-oral group, two doses of 25 mg/kg of ofloxacin at 12-h intervals were given orally, then the protocol of the first group was applied. Aqueous and vitreous humor samples were taken 30 min after the last drop. Ofloxacin concentrations were measured by using HPLC. RESULTS Mean aqueous levels of ofloxacin in control eyes were: 3.25 +/- 2.55 microg/ml in topical group. 4.58 +/- 5.39 microg/ml in topical-oral group. Mean aqueous levels in inflamed eyes were: 5.21 +/- 4.55 microg/ml in topical group, 10.34 +/- 8.88 microg/ml in topical-oral group. Mean vitreous levels of ofloxacin in control eyes were: 0.17 +/- 0.07 microg/ml in topical group, 1.30 +/- 1.23 microg/ml in topical-oral group. Mean vitreous levels in inflamed eyes were: 0.35 +/- 0.22 microg/ml in topical group, 3.48 +/- 2.69 microg/ml in topical-oral group. There was no significant difference among the groups (P > 0.05), however. CONCLUSIONS The result of this study suggests that oral supplementation of ofloxacin to topical instillation increased the ocular levels of ofloxacin in the post-traumatic endophthalmitis model. Mean drug concentrations in aqueous and vitreous humors were above the 90% minimum inhibitory concentrations (MIC90) for most of the common microorganisms causing endophthalmitis in all eyes, except in the vitreous humors of the intact eyes instilled topically.

Effects of Intravitreal Moxifloxacin and Dexamethasone in Experimental Staphylococcus aureus Endophthalmitis

Purpose: To evaluate the effects of intravitreal moxifloxacin and moxifloxacin and dexamethasone combination in an experimental rabbit model of Staphylococcus aureus endophthalmitis. Methods: The right eyes of 24 rabbits weighing 2 to 3 kg were used. Ten thousand colony-forming units (CFU) of S. aureus in 0.1 ml saline solution were inoculated into the vitreous cavity. The eyes were randomly assigned to one of the four groups equally. Twenty-four hours after the inoculation of S. aureus, group 1 received 50 μ g moxifloxacin, group 2 received 50 μ g moxifloxacin plus 400 μ g dexamethasone, and group 3 received 1mg vancomycin intravitreally. No treatment was given to group 4. Clinical examination scores were recorded. Vitreous aspirates were obtained for microbiological analysis just before sacrifice, and the eyes were enucleated for histopathologic examination. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests. Results: In all treatment groups, mean number of CFU and histopathologic score were significantly lower compared with control group (p < 0.05), and the difference between treatment groups was not statistically significant (p > 0.05). The clinical score was not significantly different between groups (p > 0.05). Conclusions: Intravitreal injection of 50 μg moxifloxacin was effective in the treatment of S. aureus endophthalmitis. Bacteriological, histopathologic, and clinical outcomes after treatment using moxifloxacin, moxifloxacin and dexamethasone combination, and vancomycin were comparable. Intravitreal moxifloxacin may be an option in the treatment of S. aureus endophthalmitis.

Efficacy of topical caspofungin in experimental fusarium keratitis.

Purpose: To evaluate the efficacy of caspofungin in an experimental rabbit model of Fusarium keratitis and to compare it with amphotericin B. Methods: Eighteen New Zealand white rabbits were randomly divided into 2 treatment groups and 1 control group. One cornea of each rabbit was inoculated with Fusarium solani spores. The first group received topical amphotericin B 0.15%, the second group received topical caspofungin 1%, and the control group received topical balanced salt solution hourly for 2 days and then 4 times daily for 3 additional days. Treatment effects were evaluated by clinical assessment at days 3 and 5 and by fungal culture after 5 days of treatment. Results: In the treatment groups, progression of keratitis was inhibited, and cultures were sterile at the end of the study. In the control group, keratitis progressed, and cultures were positive for F. solani. Conclusions: Topical caspofungin is effective in Fusarium keratitis, and clinical efficacy studies seem justified.

The effects of prolonged acute use and inflammation on the ocular penetration of topical ciprofloxacin

PURPOSE To study the aqueous and vitreous penetration of ciprofloxacin after prolonged acute topical administration and to investigate the effects of inflammation on drug penetration. METHODS A standardized model of intraocular infection after penetrating injury was made in the right eyes of eight rabbits. The intact left eyes were maintained as the control. Two drops of ciprofloxacin 0.3% eyedrops were instilled topically every 1 h for 7 h to all eyes of the rabbits. Aqueous and vitreous samples (100 microl) were obtained half an hour after the last drop. Instillation was continued for 7 h more and samples were obtained as before. Drug concentrations were measured using HPLC. RESULTS The mean aqueous humor levels of ciprofloxacin were: in control eyes 1.31 +/- 0.78 microg/ml after 7 h and 1.85 +/- 1.69 microg/ml after 14 h of instillation: in inflamed eyes 2.18 +/- 1.02 microg/ml after 7 h and 2.91 +/- 2.12 microg/ml after 14 h. The mean vitreous humor levels were: in control eyes 0.65 +/- 0.44 microg/ml after 7 h and 0.72 +/- 0.8 microg/ml after 14 h of instillation; in inflamed eyes 0.67 +/- 0.77 microg/ml after 7 h and 1.01 +/- 0.43 microg/ml after 14 h. However, the differences among the groups were not significant (P > 0.05). CONCLUSIONS Ciprofloxacin penetration into aqueous humor was higher in 14-h topical application than that for 7 h. Inflammation increased the penetration of topical ciprofloxacin into aqueous while administered for 7 h and into both aqueous and vitreous humor while administered for 14 h. c

The effects of caspofungin and voriconazole in experimental Candida endophthalmitis.

Purpose: To evaluate the efficacy of newly developed antifungal agents caspofungin and voriconazole in Candida albicans endophthalmitis in rabbit eyes. Methods: Thirty New Zealand white rabbits were divided into four treatment groups and one control group. One eye of each rabbit was infected by inoculation of 1 × 104 CFU/ml of C. albicans. Seventy-two hours after the inoculation, caspofungin 100 μg/0.1 ml in group 1 (n = 6), voriconazole 50 μg/0.1 ml in group 2 (n = 6), amphotericin B 10 μg/0.1 ml in group 3 (n = 6), itraconazole 10 μg/0.1 ml in group 4 (n = 6), and 0.1 ml NaCl 0.9% in control group (n = 6) were injected into the vitreous cavity. Clinical and histopathologic examination scores and microbiological analysis of vitreous aspirates were compared. Results: There was statistically significant difference in the clinical scores, histopathologic scores, and mean CFU/ml between the treatment and control groups (p < 0.05). In caspofungin and voriconazole groups, histopathologic scores and mean CFU were lower than other treatment groups and control group. Conclusions: Intravitreal injection of caspofungin and voriconazole was effective against C. albicans endophthalmitis in this experimental rabbit model.

Effect of diclofenac on prevention of posterior capsule opacification in human eyes

BACKGROUND Diclofenac sodium has been demonstrated to be effective in preventing proliferation of lens epithelial cells both in vitro and in animal studies. The effects of diclofenac sodium given during the hydrodissection stage of phacoemulsification surgery on posterior capsule opacification (PCO) were investigated. METHODS Eleven patients undergoing phacoemulsification in both eyes were included. Patients with pseudoexfoliation, uveitis, and diabetes were excluded. Hydrodissection was done with only balanced salt solution in the first eyes. In the fellow eyes, 0.25 mg/mL diclofenac was given with hydrodissection. The same type of intraocular lens was implanted in both eyes of each patient. Follow-up was 21.8 (SD 3.5) months in the diclofenac group and 22.9 (3.7) months in the control group. PCO was evaluated clinically by dividing the posterior capsule into 24 zones. Mann-Whitney U test was used for statistical analysis. RESULTS There were no statistically significant differences of age, diameter of capsulorhexis, pupillary width, visual acuity, intraocular pressure, or length of follow-up between groups. PCO score was 0.49 (SD 0.21) in eyes receiving diclofenac and 0.73 (0.23) in the contralateral fellow eyes. The difference was not statistically significant (p=0.053). INTERPRETATION Diclofenac sodium given by hydrodissection in phacoemulsification decreased, but did not significantly prevent, the development of PCO.

Obstructive Sleep Apnea in Patients with Central Serous Chorioretinopathy

Abstract Purpose: In this study, we aimed to evaluate the relation between obstructive sleep apnea (OSA) and central serous retinopathy (CSR). Methods: Twenty-three consecutive subjects aged >18 years with the diagnosis of CSR were included in this prospective study. Overnight polysomnography was performed to all subjects. Desaturation index and apnea-hypopnea index (AHI) were recorded. Obstructive sleep apnea was classified according to AHI as mild, moderate, or severe. Statistical analysis was performed using chi-square test, Fisher’s exact test, and Mann–Whitney U test. Results: Fourteen of 23 CSR patients (60.9%) had OSA. Prevalence of OSA was significantly higher in male subjects with CSR compared to female subjects with CSR (p = 0.018). One (16.7%) female subject with CSR had OSA whereas thirteen (76.5%) male subjects were found to have OSA. Desaturation index was found to be 5.1 ± 4.2 in females and 12.9 ± 11.1 in males (p = 0.036). Conclusion: Obstructive sleep apnea is seen nearly in 2/3 of patients with the diagnosis of CSR. There are possible common pathophysiological mechanisms like oxidative stress, vasoconstriction, or blood coagulation abnormalities. Screening for OSA should be considered in subjects with the diagnosis of CSR.