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ABSTRACT: PURPOSE:: Ocular hypertension is a potentially serious complication after penetrating keratoplasty (PKP). Our objective is to determine the risk factors, incidence, patient characteristics, response to pressure-lowering medical therapy, and graft outcome associated with elevation of intraocular pressure after PKP. METHODS:: One hundred forty-six consecutive eyes that had PKP between June 2001 and June 2003 were operated and managed at Hadassah-Hebrew University Medical Center. Chart review was performed seeking preoperative and postoperative data on risk factors for ocular hypertension after PKP. Univariate and logistic regression analysis were performed to identify significant risk factors. RESULTS:: After surgery, 70 eyes (47.9%) had at least 1 period of ocular hypertension, with a mean intraocular pressure (IOP) of 27.15±5.66 mm Hg. Ocular hypertension appeared after a mean postoperative period of 70.3±15.8 days, and continued for an average period of 15.6±2.0 days. In 35 eyes (23.9%), a second episode of IOP elevation was noted 212.2±46.8 days after the surgery. Logistic regression analysis revealed that preexisting glaucoma (P=0.009) and an additional surgical procedure combined with PKP (P=0.007) were the main factors predicting ocular hypertension after PKP. In 11 eyes (7.53%) the topical pressure-lowering therapy failed, and they required glaucoma filtering surgery. CONCLUSIONS:: The incidence of ocular hypertension after PKP is high, and at least 1 episode of high IOP was noted in almost half of our patients. A history of preexisting glaucoma and an additional surgical procedure combined with PKP were found to be significant factors predicting the occurrence of ocular hypertension.
Journal of glaucoma 02/2013; · 1.74 Impact Factor
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ABSTRACT: to evaluate the effects of laser refractive surgery in adult patients with mild to moderate amblyopia due to anisometropic myopia.
a retrospective review of 30 patients (60 eyes) with unilateral amblyopia (corrected distance visual acuity [CDVA] 0.6 or worse) who underwent simultaneous bilateral laser vision correction using the Technolas 217z excimer laser (Bausch & Lomb) was performed. Mean patient age was 31.03 ± 10.05 years (range: 18 to 53 years). Visual outcomes in the amblyopic eye were compared with those in the fellow nonamblyopic control eye of the same patient.
mean preoperative CDVA improved in amblyopic eyes from 0.50 ± 0.13 to 0.57 ± 0.20 postoperatively (average gain of 0.075 ± 0.14; P=.007) and improved from 0.92 ± 0.12 preoperatively to 0.93±0.15 after surgery (mean gain of 0.013 ± 0.14; P=.603) in the fellow nonamblyopic eyes. The safety index was significantly greater in the amblyopic eyes compared with the nonamblyopic fellow eyes (1.15 ± 0.30 vs 1.02 ± 0.15, P=.035), therefore, no difference was noted in efficacy (P=.913). Five of 30 eyes with mild to moderate amblyopia gained 2 to 4 lines of CDVA.
laser refractive surgery for myopic correction was found to be safe and effective in eyes with mild to moderate amblyopia.
Journal of refractive surgery (Thorofare, N.J.: 1995) 04/2010; 27(1):18-22. · 2.54 Impact Factor
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ABSTRACT: To describe the incidence, characteristics, risk factors, and clinical outcome of limbal stem cell deficiency (LSCD) resulting from topical treatment with mitomycin C (MMC) for primary acquired melanosis (PAM) with atypia.
Retrospective, observational case series.
Patients with LSCD who had been managed with topical MMC for PAM with atypia at the Ocular Oncology Service at the Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, between 2000 and 2007.
Retrospective chart review of all patients with PAM with atypia was performed. Impression cytologic analysis of the corneal and conjunctival epithelium was performed in patients suspected of having LSCD.
Evaluation of risk factors for LSCD, including demographic characteristics, MMC dosage, and length of treatment; and clinical and visual outcome of patients diagnosed with LSCD.
Limbal stem cell deficiency was identified in 5 (23.8%) of 21 patients. The mean age+/-standard deviation of the 5 patients was 61.8+/-12.7 years compared with 43.7+/-16.1 years in patients in whom this complication did not develop (P = 0.025). Longer treatment periods of MMC were noted in eyes in which LSCD developed (78.4+/-24.8 days) compared with eyes without LSCD (37.7+/-3.1 days; P = 0.07). In 3 patients, spontaneous partial resolution of the LSCD was noted.
High-dose topical MMC for PAM with atypia may be associated with a relatively high incidence of LSCD. Mitomycin C concentration and treatment regimen should be reevaluated to improve the safety of this treatment protocol.
Ophthalmology 03/2010; 117(3):431-7. · 5.45 Impact Factor
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ABSTRACT: To evaluate the efficacy and tolerability of overnight bandage soft contact lenses applied immediately after LASIK.
Bandage soft contact lenses were applied immediately following bilateral simultaneous LASIK in 161 consecutive patients. Signs and symptoms associated with contact lens wear were prospectively recorded at 1 hour, 4 hours, and the following morning, using a standardized questionnaire. Contact lenses were removed at 1 hour if patients were symptomatic of intolerance. If no signs of contact lens intolerance appeared at 1 hour, the lenses were removed the following morning. No contact lenses were applied in 61 patients after LASIK.
One hour after the procedure, contact lenses were removed from 47 patients due to intolerance. In these patients, contact lens removal was associated with a significant decrease of the total score the next morning (0.31±0.55) compared to 1 hour (5.65±1.60, P<.0001). A similar decrease of the total score was noted in those patients who tolerated the contact lenses (0.20±0.52 vs 1.30±1.78) and those in whom the contact lenses were not applied (0.76±1.19 vs 3.24±1.93). Mucoid discharge at the lid margins was noted in 52.6% of patients and mild corneal edema was noted in 28.8% of patients with bandage soft contact lenses at 12 to 18 hours.
Bandage soft contact lens application after LASIK is associated with significant reduction of symptoms during the immediate postoperative period. However, removal of these lenses may be necessary shortly after the procedure.
Journal of refractive surgery (Thorofare, N.J.: 1995) 12/2009; 26(10):744-8. · 2.54 Impact Factor
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ABSTRACT: To evaluate the prevalence of clinical asymptomatic retinal detachment (ARD) in myopic population.
A retrospective study including all myopic individuals who underwent ophthalmic evaluation prior to excimer laser procedures at the Hadassah Center for Refractive Surgery between March 2002 and March 2006. Medical records were reviewed to extract demographics and refraction, and to identify patients who were diagnosed as having asymptomatic retinal detachment.
Data were collected on 6547 myopic individuals (12 815 eyes); of these, 2907 (44.4%) were males, and 3640 (55.6%) were females. The mean age was 31.5 (SD 10) years (range 18-64 years). The mean preoperative spheric equivalence was -4.42 (2.07) (range -0.75 to -16.00). The mean best spectacle-corrected visual acuity was 20/20 (range 20/32 to 20/12.5). Five eyes (0.039% or one of approximately 2563 eyes) of four patients had clinical ARD which was diagnosed during the routine preoperative examination. Three eyes underwent successful scleral buckling procedure while two patients were lost to follow-up.
Clinical asymptomatic retinal detachment is uncommon, accounting for a minority of retinal detachments in myopes, and may be diagnosed during routine ophthalmoscopy prior to a refractive procedure.
The British journal of ophthalmology 09/2008; 92(10):1374-6. · 2.92 Impact Factor
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ABSTRACT: The aim of this study was to evaluate methylprednisolone penetration into ocular structures after low-current trans-scleral hydrogel iontophoresis, as compared with the common intravenous (i.v.) treatment.
Methylprednisolone hemisuccinate (MPH) iontophoresis was studied in rabbits, using drug-loaded hydrogels mounted on a portable iontophoretic device. Cathodal iontophoresis of 2.6 mA/cm(2) was applied for 5 min at two opposite sites on the sclera or for 10 min at the same site. Ocular drug levels were determined 2 h after iontophoretic treatment, then compared to mock iontophoresis and i.v. infusion of 10 mg/kg methylprednisolone.
Significantly higher methylprednisolone levels were found in ocular tissues after iontophoresis, compared with the control groups, except for the sclera concentrations, which were similar to the concentrations achieved after mock iontophoresis. Two (2) h after the trans-scleral iontophoretic treatment, 178.59 +/- 21.63 microg/g, 6.74 +/- 2.38 microg/ml, and 2.71 +/- 0.57 microg/mL were found in the retina, aqueous humor, and vitreous, respectively. No significant differences were found between one or two site treatments of trans-scleral iontophoresis. Nondetectable concentrations were found 2 h after the i.v. infusion of 10 mg/kg of methylprednisolone in all evaluated ocular tissues and fluids.
A short, low-current noninvasive iontophoretic treatment, using methylprednisolone-loaded hydrogels, has potential clinical value in treating ocular inflammatory diseases.
Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):344-50. · 1.51 Impact Factor
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ABSTRACT: To investigate in vitro and in vivo hydrogel-iontophoresis delivery of carboplatin to the eye.
Iontophoresis was applied on agar gels resembling the eye using different current intensities and durations. Transscleral iontophoresis was performed on healthy rabbits, applying 0, 1, and 3 mA current for 10 min.
Similar drug concentrations were obtained in all experimental groups, in in vitro and in vivo studies, regardless of the iontophoretic current applied. A 20-mm penetration depth was found for carboplatin at the agar model. High drug levels were found at the sclera and retina, while lower levels were found at ocular fluids.
Carboplatin-iontophoretic application at the above conditions does not have an obvious advantage over passive penetration due to high diffusion properties and insufficient molecular charge. Passive carboplatin diffusion from loaded hydrogels inserted in the lower cul-de-sac should be further investigated as a potential clinical treatment for intraocular retinoblastoma.
Current Eye Research 04/2008; 33(3):269-75. · 1.28 Impact Factor
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ABSTRACT: Ocular iontophoresis has been investigated for many years as a non-invasive technique for enhancing ionized drug penetration through ocular tissues. In this study we assessed the penetration of charged fluorescent nanoparticles into rabbit eyes using hydrogel iontophoresis. Particle distribution into ocular tissues and penetration efficiency of negative nanoparticles compared with positive nanoparticles was also evaluated. Cathodal and anodal iontophoretic administrations were performed using polyacrylic hydrogels loaded with charged nanoparticle suspension (20-45 nm), applying a current intensity of 1.5 mA for 5 min onto the cornea and sclera. At pre-set time points post treatment, eyes were dissected and tissues were evaluated for fluorescence intensity. Strong fluorescence evidence was observed at anterior and posterior ocular tissues. Negative particle distribution profile revealed fast uptake into the outer ocular tissues, within 30 min post treatment, followed by particle migration into the inner tissues up to 12 h post treatment. The positively charged particles demonstrated better penetration abilities into inner ocular tissues compared to the negatively charge particles. This work provides an opening for the development of a new ocular therapeutic pathway using iontophoresis of extended release drug-loaded charged nanoparticles.
Journal of Controlled Release 04/2008; 126(2):156-61. · 5.73 Impact Factor
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ABSTRACT: To report the clinical course of early transient reduction of uncorrected visual acuity (UCVA) after LASIK surgery resulting from steroid-induced elevation of intraocular pressure (IOP).
Twenty-nine eyes of 15 patients who received topical corticosteroids after uneventful myopic LASIK surgery and had a decrease in UCVA within the first 3 weeks were evaluated retrospectively.
Intraocular pressure increased by 4 to 30 mmHg from preoperative to postoperative days 4 to 20. Twenty-seven of 29 eyes had a decrease in UCVA and/or best spectacle-corrected visual acuity (BSCVA). All eyes, except one, had edema without evidence of inflammation in the interface or the remainder of the cornea. Discontinuation of topical corticosteroids and application of anti-glaucoma medications resulted in a decrease of IOP to normal levels, reduction or disappearance of the edema, and recovery of BSCVA.
Early onset steroid-induced elevation of IOP after LASIK may cause corneal edema and a sudden decrease in UCVA. Rapid diagnosis and treatment can control IOP and recover the visual loss.
Journal of refractive surgery (Thorofare, N.J.: 1995) 04/2007; 23(3):244-51. · 2.54 Impact Factor
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ABSTRACT: To evaluate the efficacy of iontophoresis using a hydrogel probe containing gentamicin for the treatment of Pseudomonas keratitis in the rabbit cornea.
Five groups (Groups 1-5) of 8 rabbits each were infected by injecting Pseudomonas aeruginosa into their corneas. Three dosings of corneal iontophoresis were performed, at intervals of 3.5 hours, using soft disposable gentamicin-loaded hydroxyethyl methacrylate hydrogel discs mounted on a portable iontophoretic device. Groups 1 and 2 were treated with corneal iontophoresis for 60 seconds and a current of 0.5 and 0.2 mA. Groups 3 and 4 were treated with hydrogel loaded with 0.9% NaCl solution, using a current of 0.2 mA and mock iontophoresis. Group 5 was treated with eye drops of 1.4% gentamicin every hour for 8 hours. One and a half hours after the last treatment, the animals were killed, and the corneas were excised and cultured for P. aeruginosa count after 24-hour incubation.
After iontophoretic treatment of gentamicin with a current of 0.5 mA (Group 1), the logarithmic value of Pseudomonas colony-forming units (CFUs) was 2.96 +/- 0.45. After lower current iontophoretic treatment (Group 2), the logarithmic Pseudomonas count was 5.25 +/- 0.54 CFUs. At the control groups (Groups 3-5), the Pseudomonas counts were found to be much higher, 7.62 +/- 0.28, 7.22 +/- 0.29, and 6.29 +/- 0.45 CFUs, respectively.
A short iontophoretic treatment using gentamicin-loaded hydrogels has potential clinical value in treating corneal infections.
Cornea 01/2007; 25(10):1182-6. · 1.73 Impact Factor
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ABSTRACT: To compare the clinical outcome of pterygium surgery combining intraoperative mitomycin C (MMC) with a free conjunctival autograft, with three other methods of pterygium surgery, including intraoperative MMC alone, conjunctival autograft alone, and bare sclera without adjunctive treatment.
Interventional, randomized and in part nonrandomized, prospective, comparative study.
setting: A university medical center department of ophthalmology.
One hundred and twenty patients underwent pterygium excision surgery. These patients were divided into four treatment groups.
In group 1 (30 patients), MMC, 0.2 mg/ml, was applied for three minutes. In group 2 (30 patients), conjunctival autografting was performed. Group 3 (30 patients) received sodium chloride 0.9% only, and group 4 (30 patients) underwent conjunctival autografting combined with one minute application of MMC, 0.2 mg/ml.
Recurrence rates and complications.
Pterygium recurred in two patients (6.6%) in group 1, in four patients (13.3%) in group 2, in 14 patients (46.6%) in group 3, and in none of the patients in group 4. chi(2) analysis revealed a significantly lower recurrence rate in group 4 compared with group 2 (P = .038) and with group 3 (P < .0001). Epithelialization of the wounds was complete within 14 days of surgery. No complications were demonstrated in any of the study groups except for one case of minor melting of the flap in group 4.
This study indicates that pterygium excision with a free conjunctival autograft combined with intraoperative low-dose MMC is a safe and effective technique in pterygium surgery.
American Journal of Ophthalmology 06/2006; 141(6):1044-1050. · 4.22 Impact Factor
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ABSTRACT: To evaluate dexamethasone penetration to the eye after a short transcorneal and transscleral iontophoresis using a drug loaded hydrogel assembled on a portable iontophoretic device.
Iontophoresis of dexamethasone phosphate was studied in healthy rabbits using drug loaded disposable HEMA hydrogel sponges and portable iontophoretic device. Corneal iontophoretic administration was performed with a current intensity of 1 mA for 1 and 4 min. Transconjunctival and transscleral iontophoresis were performed twice for 2 min at two near places in the pars-plana area, on the conjunctival membrane or directly on the sclera. Dexamethasone concentrations were assayed using HPLC.
Dexamethasone levels in the rabbit cornea after a single transcorneal iontophoresis for 1 min were up to 30 fold higher compared to those obtained after frequent eye drop instillation. Also, high drug concentrations were obtained in the retina and sclera 4 h after transscleral iontophoresis.
A short low current non-invasive iontophoretic treatment using dexamethasone-loaded hydrogels has potential clinical value in increasing drug penetration to the anterior and posterior segments of the eye.
Journal of Controlled Release 10/2005; 106(3):386-90. · 5.73 Impact Factor
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ABSTRACT: To evaluate the expression of inflammatory cytokines and matrix metalloproteinases in the corneal epithelium in pseudophakic corneal edema (PCE).
Tissue sections were prepared from formalin-fixed, paraffin-embedded blocks of corneal buttons removed from 20 patients with PCE during penetrating keratoplasty (PKP) and from 11 age-matched control eyes enucleated because of uveal melanoma. Expression of interleukin (IL)-1beta, -6, and -8; vascular endothelial growth factor (VEGF); and matrix metalloproteinase (MMP)-1, -3, and -9 proteins in the corneal epithelium was evaluated by immunohistochemistry. Digital image analysis was performed to quantify the expression of the various cytokines and MMPs. A mean intensity stain index (ISI), based on the staining density and the area stained, was calculated from digital images captured from sequential areas of the corneal epithelium.
The expression of most of the inflammatory cytokines and MMPs was significantly higher in the corneal epithelium of PCE corneal buttons than in the control specimens. MMP-9 had the highest expression when compared with the control (ISI = 55.08 +/- 23.71 in PCE compared with 0.169 +/- 0.156 in the control; P < 0.0001). Significantly higher ISIs were also recorded for MMP-1 (16.14 +/- 8.49 vs. 1.13 +/- 1.79; P < 0.0001), IL-1beta (62.62 +/- 27.23.97 vs. 1.61 +/- 1.27; P < 0.0001), IL-8 (37.91 +/- 21.18 vs. 4.24 +/- 3.60; P < 0.0001), and VEGF (81.67 +/- 26.22 vs. 19.40 +/- 16.85; P = 0.0001). The expression of MMP-3, IL-6, and TNF-alpha in PCE was not different from control expression. Significant positive correlations were found between the expression of IL-1beta and MMP-9 (r(2) = 0.37; P = 0.015), between VEGF and IL-8 (r(2) = 0.22; P = 0.042), and a significant correlation was found between the expression of MMP-3 and TNF-alpha (r(2) = 0.5197; P = 0.0007). The expression of TNF-alpha correlated significantly with the patient's age (r(2) = 0.28; P = 0.0195).
The corneal epithelium in PCE expresses high levels of cytokines and matrix-degrading enzymes, which are associated with inflammation, wound healing, angiogenesis, and tissue degradation. The expression of these mediators may partially explain the pathologic features associated with this disease, such as bulla formation, recurrent epithelial desquamation, and corneal neovascularization.
Investigative Ophthalmology & Visual Science 07/2005; 46(6):1940-7. · 3.60 Impact Factor
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ABSTRACT: To examine the leading indications for keratoplasty and identify the changing trends in the past 40 years in Israel.
Pathology reports of all penetrating keratoplasties (PKPs) performed at Hadassah-Hebrew University Hospital from 1961 to 2000 were reviewed. We evaluated the indications for keratoplasty in each decade between the years 1961 and 2000.
During the 40-year period, a total of 1681 PKPs were performed. Keratoconus (n = 478, 28.4%) was the most common indication, followed by graft failure (n = 226, 13.4%), pseudophakic corneal edema (PCE) (n = 142, 8.4%), herpetic infections (n = 125, 7.4%), nonherpetic infections (n = 114, 6.8%), scarring (n = 113, 6.7%), and trauma (n = 110, 6.5%). The 7 groups account for approximately 77.5% of all keratoplasties performed. Ocular infections were the most common indications before 1970 and have been declining ever since. Keratoconus became the leading indication in the past 30 years. In the past decade, of 663 keratoplasties, keratoconus was the most common indication (56, 38.6%) followed by graft failures/rejections and PCE (the second most common indication between the years 1981 and 1990).
Keratoconus was the leading indication for keratoplasty in our series. There was a decreasing trend in PK for ocular herpetic infections during the decades. The rate of PCE decreased while failed graft became the second most common indication for PKP during the past decade.
Cornea 05/2005; 24(3):256-8. · 1.73 Impact Factor
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ABSTRACT: To report our results of 12 consecutive patients with conjunctival primary acquired melanosis (PAM) with atypia who were treated by topical Mitomycin C (MMC).
Retrospective interventional consecutive case series.
Twelve patients with PAM with atypia in one of their eyes who were treated by topical chemotherapy with MMC were included in this case study. Eyes with histologically proven PAM with atypia were treated by two to five courses of 0.04% (0.4 mg/ml) MMC four times a day. Each course lasted 2 continuous weeks. Follow-up was conducted on patients for control of local disease, side effects, and visual acuity in the treated eye.
In all patients, there was complete or partial response to treatment. In four patients, the pigmentation disappeared, whereas in eight patients, some remnants of the pigmentation remained. In seven of these eight patients, the remnants of the pigmentation were stable during the follow-up period of 4 months to 9 years, whereas one in whom re-growth of the PAM was noticed was successfully treated again by topical MMC. No patients lost visual acuity at the end of the follow-up. All side effects of the local chemotherapy were resolved after cessation of the treatment.
Topical MMC chemotherapy is a good alternative to surgical excision and cryotherapy in treating conjunctival PAM with atypia.
American Journal of Ophthalmology 03/2005; 139(2):229-34. · 4.22 Impact Factor
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ABSTRACT: To evaluate the long-term effects of intraoperative application of mitomycin C on the scleral thickness and the conjunctival epithelium at the surgical site of pterygium excision.
Prospective observational case series.
Twenty-four patients who underwent excision of primary pterygium with intraoperative mitomycin C in our department during the year 1996.
Patients were evaluated by slit-lamp biomicroscopy, impression cytology, and high-frequency ultrasonography. Impression cytology was performed by applying a small nitrocellulose filter paper for a few seconds at the excision area and for a few seconds at the opposite perilimbal area, and subjecting the specimens to the periodic acid-Schiff-Gill modified Papanicolaou staining protocol. The morphology of the conjunctival epithelium and goblet cell density (GCD) were recorded. High-frequency ultrasound was performed at the same sites, and the scleral thickness was measured at a distance of 1 mm from the limbus.
Goblet cell density, conjunctival epithelial morphology, and the scleral thickness at the operated and nonoperated sites.
All patients had successful pterygium removal with no corneal recurrence after a mean follow-up of 77.2+/-3.9 months (range, 72-84). Impression cytology revealed normal nongoblet conjunctival epithelial cells at the excision area, with a 4-fold decrease in the GCD at the excision area when compared with the contralateral nonoperated site (296+/-120 cells/mm(2) and 1183+/-310 cells/mm(2), respectively; P = 0.0036). No differences were noted between the scleral thicknesses at the operated site (750+/-70 microm) and the opposite site (740+/-80 microm) (P = 0.84).
A single application of mitomycin C after pterygium excision is not associated with reduction in scleral thickness more than 6 years postoperatively. The conjunctival epithelium retains its normal phenotype, with a marked reduction of the GCD.
Ophthalmology 09/2004; 111(8):1522-7. · 5.45 Impact Factor
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ABSTRACT: To describe the surgical management and histopathologic and immunohistochemical findings in corneal plaques of shield ulcers in vernal keratoconjunctivitis.
Three children (ages 4, 7.5, and 9) presented with corneal plaques unresponsive to conservative systemic and topical medical treatment. Plaques were scraped under general anesthesia, and soft bandage contact lenses were placed. The excised tissue was evaluated by histopathology and immunohistochemistry.
During surgery, plaques were found to extend beyond the ulcer margins. Histopathology revealed granular, deeply-eosinophilic, laminar material, firmly attached to the Bowman layer in all cases. Immunohistochemistry confirmed this to be eosinophil-derived major basic protein (MBP). After surgical removal, complete epithelization was evident within 1-4 weeks in all cases.
Corneal plaque is a rare complication of vernal keratoconjunctivitis. These plaques usually do not resolve with standard conservative measures. Failure to epithelialize may be a result of the plaque material extending below the edges of adjacent epithelium. We suggest that MBP plaques precipitate on the denuded stromal bed, thereby playing a pathogenic role in nonhealing shield ulcers.
Cornea 09/2004; 23(6):608-12. · 1.73 Impact Factor
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ABSTRACT: To assess the corneal iontophoretic delivery of gentamicin by drug-loaded hydrogel probe, and to determine the resultant ocular disposition and elimination of the drug from the cornea and anterior chamber.
Corneal iontophoresis of gentamicin sulfate was studied in healthy white rabbits by using drug-loaded disposable hydroxyethyl methacrylate (HEMA) hydrogel disk probes and a portable mini-ion device designed in the authors' laboratory. The iontophoretic treatment was performed with a current intensity of 1 mA for 60 seconds only. Three control groups were used: mock iontophoresis (no current) for 60 seconds, topical eye drops of fortified gentamicin (1.4%) every 5 minutes for 1 hour, and subconjunctival injection of 0.25 mL of 40 mg/mL gentamicin solution. The animals in the iontophoretic experimental groups were killed at predetermined time points. The gentamicin concentrations in the cornea and aqueous humor were assayed with a fluorescence polarization immunoassay. Analysis of the gentamicin eye pharmacokinetics was performed with a modeling approach.
Peak gentamicin concentrations in the cornea (363.1 +/- 127.3 microg/g) and in the aqueous humor (29.4 +/- 17.4 microg/mL) were reached at 0 and 2 hours after the iontophoretic treatment, respectively. The peak gentamicin concentrations after a single iontophoresis treatment were 12 to 15 times higher than those obtained after gentamicin injection or after topical eye drop instillation, and much higher than in mock iontophoresis. The concentration versus time profile of gentamicin in the cornea and the anterior chamber after iontophoresis was appropriately described by applying a two-compartment pharmacokinetic model.
A short iontophoretic treatment using gentamicin-loaded hydrogels has potential clinical value in increasing drug penetration to the anterior segments of the eye and maintaining therapeutic drug levels in the cornea for more than 8 hours.
Investigative Ophthalmology & Visual Science 09/2004; 45(8):2543-8. · 3.60 Impact Factor
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ABSTRACT: To evaluate the efficacy of penetration of gentamicin into the cornea of rabbits using iontophoresis with a hydrogel-gentamicin containing probe.
Eight of 10 groups (groups 3-10) of 6 rabbits (one eye per rabbit), underwent corneal iontophoresis using soft stable hydroxyethyl methacrylate hydrogel discs (80% water content) loaded with gentamicin sulphate which were mounted on an iontophoresis probe. The studied current intensities were 0, 0.1, 0.3 and 0.6 mAmp, and the durations of iontophoresis were 10 and 60 sec. Two control groups received 1.4% topical drops of gentamicin every 5 min for 1 hr (group 1) or sub-conjunctival injection of 10 mg gentamicin (group 2). Following sacrifice, aqueous humour was taken, corneas were excised, and gentamicin concentration was determined in aqueous humour and cornea samples.
Post-iontophoresis, the concentration of gentamicin in the corneas ranged from high (88.60 +/- 38.64 microg ml(-1)) to very low (0.10 +/- 0.89 microg ml(-1)). Both the control groups and those rabbits treated with current intensity of 0.1 mAmp or greater obtained therapeutic gentamicin levels in the corneas. Use of iontophoresis for 60 sec or current intensity greater than 0.1 mAmp obtained corneal gentamicin levels not different from sub-conjunctival injection. Application of current intensity of 0.1 mAmp or greater gave corneal gentamicin concentrations comparable to topical application of the drug, except when 0.6 mAmp were used for 60 sec (p = 0.05). Increasing current intensity or duration of iontophoresis significantly increased (p = 0.001 for both) gentamicin penetration into the cornea. Current intensity had more influence (Beta2 = 0.40) than duration (Beta2 = 0.13) on drug penetration. A significant interaction was found between the duration of iontophoresis and the current intensity. Very small or no concentrations of the drug were discovered in the anterior chambers of rabbits.
Iontophoresis using hydrogel-gentamicin probe may deliver therapeutic concentrations of gentamicin into the cornea.
Experimental Eye Research 04/2004; 78(3):745-9. · 3.26 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the use of a solid hydrogel loaded with a drug solution as a probe for ejecting drugs to the eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylene glycol dimethacrylate (EGDMA), and cross-linked arabinogalactan or dextran were prepared to form solid hydrogels. The hydrogels were examined for their mechanical suitability, absorption of drug solution and in vitro release properties when applying an iontophoretic current through the drug-loaded hydrogel into a solid-agar surface. Transconjunctival and transscleral iontophoresis of gentamicin sulfate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel disc probes. Gentamicin concentrations in different eye segments were assayed using a fluorescence polarization immunoassay. Preliminary corneal toxicity was examined in rabbits using a current intensity of 2.5 and 5.1 mA/cm2 for 60 and 120 s. The most appropriate hydrogel is composed of HEMA, 2% EGDMA and 75% water. lontophoresis onto agar gel was found indicative for the evaluation of iontophoretic activity of a hydrogel. Transscleral iontophoretic treatment resulted in high concentrations of drugs in the posterior segments of the eye. Application of iontophoresis onto the rabbit eye caused a reversible swelling of the cornea which lasted a few hours after application. Low current iontophoresis using drug-loaded hydrogel has a potential clinical value in obtaining high drug concentration at posterior segments of the eye.
Journal of Biomaterials Science Polymer Edition 02/2004; 15(4):397-413. · 1.69 Impact Factor
