Ciprofloxacin microprecipitates and macroprecipitates in the human corneal epithelium.

In 4 corneal transplantation patients treated preoperatively with ciprofloxacin ophthalmic drops, microprecipitates associated with damaged corneal epithelium were noted in 2 patients. Another patient developed a large macroprecipitate in a corneal ulcer. All specimens were examined by electron microscopy and high-pressure liquid chromatography. The crystalline precipitates were pure ciprofloxacin. The macroprecipitate demonstrated a large zone of inhibition on agar plates seeded with a susceptible organism at 24 and 48 hours. It was bioactive and bioavailable in vitro.

Histological comparison of corneal ablation with Er:YAG laser, Nd:YAG optical parametric oscillator, and excimer laser.

PURPOSE: To use histological techniques to assess and compare the ablation depth, local damage, and surface quality of corneal ablations by a Q-switched Er:YAG laser, an optical parametric oscillator laser at 2.94 microm, a long pulse Er:YAG laser, and a 193-nm excimer laser. METHODS: Human cadaver eyes and in vivo cat eyes were treated with a 6.0-mm diameter, 30-microm-deep phototherapeutic keratectomy ablation and a 6.0-mm diameter, -5.00-D photorefractive keratectomy ablation. Human cadaver eyes were also treated with a 5.0-mm diameter, -5.00-D laser in situ keratomileusis (LASIK) ablation. Fluences and pulse widths used were 200 mJ/cm2 and 70 ns for the Q-switched Er:YAG, 150 mJ/cm2 and 7 ns for the optical parametric oscillator laser (OPO), 500 mJ/cm2 and 50 microseconds for the long pulse Er:YAG, and 160 mj/cm2 and 20 ns for the excimer laser. In the ablation rate study, 12 porcine eyes were ablated by the OPO laser with a range of layers and at different fluences ranging from 60 to 150 mJ/cm2, all using a 1.5-mm spot on the eye. The ablation depth of these acute ablations was evaluated by light microscopy examination. RESULTS: In the acute damage study, light microscopy showed a thin surface layer in all samples with minimal thermal damage except on the long pulse Er:YAG corneas. Transmission electron microscopy revealed less than 0.3-microm surface damage for all specimens of both the optical parametric oscillator and the excimer laser samples with no evidence of collagen shrinkage. Transmission electron microscopy showed damage layers of 0.5 to 3 microm for Q-switched Er:YAG and 3 to 10 microm for long pulse Er:YAG. Scanning electron microscopy showed smooth surfaces in all eyes, although the excimer was the roughest. In the porcine eye study, ablations were produced in both PTK and PRK modes with the ablation rate per layer increasing with the fluence. At 120 mJ/cm2, the average ablation rate was 1.9 microm per layer. CONCLUSIONS: The histology from the short pulse mid-infrared optical parametric oscillator laser at 2.94 microm was comparable to the 193-nm excimer with a smooth, damage-free, ablation zone when performing PRK and LASIK.

Healing after photorefractive keratectomy in cat eyes with a scanning mid-infrared Nd:YAG pumped optical parametric oscillator laser.

PURPOSE: To evaluate the healing characteristics of cat corneas treated with a new scanning mid-infrared laser system. METHODS: Six adult cats were treated with 6-mm diameter photorefractive keratectomy (PRK) corrections. One eye in each animal was untreated as a control and the other was treated with either a -3.00 or -6.00 diopter ablation. The laser was a new Nd:YAG pumped optical parametric oscillator laser at 2.94 microm with a new scanning delivery system. The pulse width was 7 nanoseconds, the repetition rate was 10 Hz, the size of the laser spot on the eye was 1.0 mm, and the fluence was 150 mJ/cm2. Healing of the cat corneas was followed for 4 months. Slit-lamp and corneal topography evaluations were done at each follow-up examination. Histology was performed at the end of the study. RESULTS: The corneal epithelium healed within 1 week. There was no stromal haze in any eye after the epithelium healed. After the first 2 weeks, slit-lamp examination could not identify which eye was treated. Corneal topography showed corneal flattening. Light microscopy at 4 months revealed normal epithelium and increased keratocyte density in the anterior third of the cornea. Electron microscopy showed discontinuities in the basement membrane and hemidesmosomes. The deep stroma and endothelium were normal. CONCLUSIONS: Cat corneas treated with the new optical parametric oscillator laser healed normally with no adverse effects. Increased keratocyte activity in the anterior stroma was the only noticeable response besides the flattening shown by topography.

Comparison of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers. Ciprofloxacin Bacterial Keratitis Study Group.

PURPOSE: The purpose of the study is to compare the clinical efficacy and safety of ciprofloxacin ophthalmic solution 0.3% (Ciloxan) with a standard therapy regimen (fortified tobramycin, 1.3%-cefazolin, 5.0%) for treating bacterial corneal ulcers. METHODS: This randomized, parallel group, double-masked, multicenter study was conducted in 324 patients at 28 centers in the United States, Europe, and India. Patients were randomized into 2 treatment groups: 160 to ciprofloxacin and 164 to fortified tobramycin-cefazolin. Positive microbiologic cultures were obtained in 188 (58%) of 324 patients. Of these, 176 patients met protocol criteria and were evaluated for treatment efficacy: 82 in the ciprofloxacin group and 94 in the standard therapy group. The dosing schedule for both treatment groups was 1 to 2 drops of the first study medication (ciprofloxacin or fortified tobramycin) every 30 minutes for 6 hours, then hourly for the remainder of day 1; 1 to 2 drops every hour on days 2 and 3; 1 to 2 drops every 2 hours on days 4 and 5, followed by 1 to 2 drops every 4 hours on days 6 to 14. The second medication (ciprofloxacin or cefazolin) was instilled 5 to 15 minutes after the first drug, following the same dosing frequency. Physician's judgment of clinical success, cure rate, changes in ocular sings, and symptoms and the rate of treatment failures were the primary efficacy criteria. RESULTS: Topical ciprofloxacin monotherapy is equivalent clinically and statistically to the standard therapy regimen of fortified antibiotics. No statistically significant treatment differences were found between ciprofloxacin (91.5%) and standard therapy (86.2%) in terms of overall clinical efficacy (P = 0.34). Similarly, no differences were noted in resolution of the clinical signs and symptoms (P > 0.08) or the time to cure (P = 0.55). The incidence of treatment failures was less in the ciprofloxacin group (8.5%) compared with the standard therapy group (13.8%). Significantly fewer patients treated with ciprofloxacin reported discomfort than did patients treated with the standard therapy regimen (P = 0.01). CONCLUSION: Ciprofloxacin ophthalmic solution 0.3% monotherapy is equivalent clinically and statistically to standard therapy (fortified tobramycin-cefazolin) for the treatment of bacterial corneal ulcers and produces significantly less discomfort.

Rapidly polymerized collagen gel as a smoothing agent in excimer laser photoablation.

BACKGROUND: Excimer laser photoablation effectively and precisely removes corneal tissue but may not smooth irregularities on the anterior corneal surface. An even surface might be obtained by applying a smoothing substance that fills in irregularities and ablates at the same rate as corneal tissue. Evaluation of collagen gel as a smoothing agent is reported. METHODS: Pure, type I collagen solutions were prepared to remain soluble at physiological pH and to spontaneously gel when exposed to cationic buffers. Collagen gels were formed on the surface of enucleated porcine corneas and on human donor corneas and exposed to varying pulses of 193-nanometer excimer laser energy. Effects of collagen gel on ablation depth, corneal surface smoothness, and smoothing of roughened cornea were evaluated by examining scanning electron micrographs of control and treated specimens. RESULTS: Collagen gels formed from 5 mg/ml collagen solutions dramatically altered the depth of photoablation. Photoablation of roughened cornea with collagen gels produced smooth corneal surfaces, whereas control eyes remained roughened and irregular. The smoothness of photoablated cornea surfaces improved when collagen gels were applied prior to photoablation. CONCLUSIONS: The rapidly gelling collagen solution appears to exhibit the functional properties required for an effective smoothing agent for excimer laser photoablation. The substance has low viscosity when applied to the corneal surface and forms a rigid gel when exposed to cationic buffer solution. In addition, the concentration of the collagen gel can be adjusted to provide different ablation rates.

193-nm excimer photorefractive keratectomy in high myopia.

PURPOSE: To evaluate the refractive results of 193-nm excimer laser photorefractive keratectomy (PRK) performed on 48 highly myopic eyes in a multicenter study. METHODS: A Visx 2015 or 2000 argon-fluoride excimer laser and a single-zone ablation technique were used. Postoperatively, eyes were treated with topical fluoromethalone for up to 5 months. Most eyes were treated with a 6.0- to 6.2-mm beam diameter after undercorrections and increased regression were noted with a 5.5-mm beam in earlier studies. Forty-eight eyes were treated for myopia, which was between -8.0 and -15.25 diopters (D) (spherical equivalent). The mean preoperative refraction was -11.2 D. Retreatment was performed after 6 to 16 months on 11 eyes for undercorrection. All eyes not retreated were followed for at least 12 months. RESULTS: At 6 months, follow-up was available on 47 eyes. Of these eyes, 40% and 64% achieved corrections within 1 and 2 D of attempted correction, respectively. At 1 year, 60% of eyes attained 20/40 visual acuity or better uncorrected. Eleven patients (23%) were retreated between 6 to 16 months for undercorrection and/or regression. After retreatment, 47% and 81% of eyes achieved corrections within 1 and 2 D of attempted correction, respectively. At 1 year, 15% of eyes lost two lines of best-corrected visual acuity, and no eyes lost more than two lines. There was slightly more corneal haze seen in this group compared with the haze seen in patients undergoing PRK for low and moderate myopia. CONCLUSIONS: These data show that excimer PRK can correct high amounts of myopia with reasonable stability after 6 months. Excimer PRK is an effective surgical treatment of severe myopia, but long-term follow-up is still needed to assess the stability of its effect.

Iridoschisis and keratoconus.

We report herein a patient with iridoschisis and keratoconus. Since the posterior layers of the cornea and the iris stroma have a common embryological deviation, the combination of these two conditions suggests an inter-related pathogenesis. This case is similar to those of patients with progressive essential iris atrophy and keratoconus described by Cavanagh.

Wound healing modulation in glaucoma filtration surgery.

In some cases, modulation of wound healing, in association with glaucoma filtration surgery, results in lower postoperative intraocular pressures than would occur without such therapy. Treatments affecting wound healing increase the likelihood of achieving long-term filtration, especially in eyes with a poor surgical prognosis. After summarizing the wound-healing process following filtration procedures, we review the mechanism of action, the effectiveness, and the complications associated with some of the most commonly used wound healing inhibitors and then discuss new alternatives currently under investigation. Although much progress has been made, the challenge remains to develop new drugs or combinations of drugs that are less toxic and can yield more predictable results.

Novel topical thiadiazoles and benzothiazoles as pharmacological probes of corneal endothelial function.

Corneal transparency is maintained by an active transport system, located at the endothelial cell membranes. This bicarbonate-dependent pump counteracts the tendency of the corneal stroma to absorb water, swell and become opaque. Carbonic anhydrase inhibitors (CAI) are capable of attenuating the bicarbonate efflux, therefore causing thickening of the cornea. Eight novel sulfonamides were evaluated as potential probes for assessing the corneal endothelial functional reserves. Five of the six thiadiazoles and both benzothiazoles have demonstrated carbonic anhydrase inhibitory properties in vitro. Of the eight compounds tested, 2-ethyladipoyl-1,3,4-thiadiazole-5-sulfonamide (compounds III), 2-epoxy-1,3,4-thiadiazole-5-sulfonamide (compound V), and 2-acetamido-1,3,4-thiadiazole-5-N-methylsulfonamide (compound VI) have induced reversible corneal thickening. Although statistically significant (p < 0.05), the magnitude of the pachymetric effect did not exceed 6-10% of the total corneal thickness, probably because carbonic anhydrase (CA) is only one component of the active pump complex. The fact that a non-CAI (compound VI) was capable of inducing a reversible corneal thickening may suggest that other mechanisms are involved. Further studies will be conducted to identify a pharmacological agent capable of reversibly inhibiting the endothelial function in normal and diseased corneas, with a higher magnitude of effect.

Excimer laser photorefractive keratectomy in high myopia. A multicenter study.

Excimer photorefractive keratectomy was performed at three centers on 16 highly myopic eyes (8 diopters [D] or more) and followed up for 6 months. Ablation depths ranged from 137 to 230 microns. The preoperative spherical equivalent of myopia ranged from -8.62 D to -14.50 D (mean +/- SD, -11.57 +/- 1.62 D). Six months after surgery, the mean refraction (spherical equivalent) was -0.90 +/- 2.13 D. Eleven of 16 eyes achieved refractions within 2 D of that attempted. All eight patients at one site were treated with a maximum-beam diameter of 6.0 mm and were corrected to within 2 D of that attempted, and all were 20/40 or better uncorrected. Three of eight eyes at the other two sites were treated with a 5.5- or 5.6-mm maximum-beam diameter, which achieved corrections within 2 D of that attempted. The epithelium healed within 3 to 4 days, and there were no erosions. Mild subepithelial reticular haze, similar to that seen with excimer photorefractive keratectomy for lower myopia, was seen in all patients, with two patients experiencing more significant corneal haze. This peaked at 3 to 6 weeks and then gradually diminished. All but two patients had a return of their best corrected preoperative visual acuity to within one Snellen line at 6 months. This preliminary study shows excimer photorefractive keratectomy to be a promising surgical treatment for patients with higher myopia.

Endothelin does not affect experimentally induced corneal neovascularization.

Endothelin, a potent vasoconstrictor, was found to be ineffective in the treatment of experimentally induced corneal neovascularization. Endothelin was administered topically, subconjunctivally, and intraluminally in serial concentrations ranging from 0.0005 to 5.0 micrograms/mL in New Zealand white rabbits without effect. Electron microscopy of the neovascular cornea revealed the vessels consisted only of endothelin and pericytes. Hence, the vessels were not responsive to endothelin because they lacked contractile smooth muscle.

Spontaneous iris stromal cyst: a case report and review of literature.

Spontaneous iris stromal cysts are rare and usually are identified early in life. They resemble implantation iris cysts after nonsurgical and surgical trauma; both have an epithelium which usually is conjunctival in nature. However, in spontaneous iris stromal cysts, no ocular trauma history is found. We present a case report and review of literature.

Growth factors and corneal endothelial cells: I. Stimulation of bovine corneal endothelial cell DNA synthesis by defined growth factors.

Peptide growth factors and other physiological growth modifiers were evaluated for their ability to stimulate DNA synthesis in early passage cultures of bovine corneal endothelial cells (BCEC). Increasing concentrations of newborn bovine serum (0.5-10%) causes a progressive increase in DNA synthesis, which approached a plateau at 10% serum. Supplementing medium with 10% serum from different lots of newborn bovine serum or fetal bovine serum stimulated significantly different levels of DNA synthesis by BCEC. Addition of epidermal growth factor (EGF) (2 nM) to medium containing 10% newborn or fetal bovine serum further increased DNA synthesis. Dose-response curves for EGF, transforming growth factor-alpha, basic fibroblast growth factor (bFGF), and insulin-like growth factor I showed that each significantly stimulated high levels of DNA synthesis (200-700% increase) compared with BCEC cultured in serum-free medium. Vaccinia growth factor, insulin, and transforming growth factor-beta each significantly stimulated lower levels of DNA synthesis (30-200% increase), whereas nerve growth factor, multiplication stimulating activity, and platelet-derived growth factor all failed to significantly stimulate DNA synthesis above the level of serum-free medium. Other physiological growth modifiers were tested for their effects on DNA synthesis of BCEC. Transferrin and low levels of 3',5'-cyclic monophosphate (cAMP) stimulated very low levels of DNA synthesis (50% increase) whereas linoleic acid, high levels of selenium, or cAMP each inhibited DNA synthesis 25-75% below the level of BCEC cultured in serum-free medium. A series of eight formulations containing various combinations of EGF, FGF, insulin, transferrin, selenium, linoleic acid, retinoic acid, cAMP, heparin, and endothelial cell growth factor were tested for their mitogenic action on BCEC cultures. A formulation containing EGF, insulin, transferrin, selenium, and linoleic acid (EGF + ITSL) stimulated the highest level of DNA synthesis of BCEC, which was approximately 25% higher than the increase stimulated by addition of 10% newborn bovine serum. The formulation consisting of EGF + ITSL was also evaluated as a supplement to corneal storage media. Addition of EGF + ITSL to three corneal storage media (McCarey-Kaufman, K-Sol, CSM) significantly stimulated increases in cell numbers of approximately 50% above the unsupplemented corneal storage media. These results demonstrate that BCEC respond selectively to different defined peptide growth factors and physiological growth modifiers, and suggest that supplementation of corneal storage media with a defined formulation (EGF + ITSL) may enhance corneal endothelial cell density.

Growth factors and corneal endothelial cells: II. Characterization of epidermal growth factor receptor from bovine corneal endothelial cells.

Epidermal growth factor (EGF) is a potent mitogen for corneal endothelial cells and may play a role in endothelial wound healing. To further characterize the interaction of EGF with endothelial cells, we measured biochemical parameters of 125I-EGF binding to cultured bovine corneal endothelial cells (BCEC), determined the pattern of EGF-induced protein phosphorylation, and investigated the influence of retinoic acid (RA) and transforming growth factor beta (TGF-beta) on EGF-induced DNA synthesis and receptor levels. Binding of 125I-EGF to BCEC was dependent on time, reaching a plateau after approximately 2 h at 37 degrees C, was specific for EGF, and had high affinity (Kd = 100 pM) with approximately 21,000 receptors per cell. Cellular substrates for the EGF receptor kinase, which may function as initial second messengers for EGF, were detected by autoradiography of sodium dodecyl sulfate polyacrylamide gels of 32P-labeled BCEC proteins. EGF stimulated phosphorylation of 170, 37, 21 and 20-kDa proteins. Addition of 1 nM, 100 nM, and 10 microM RA to BCEC cultured in serum-free medium for 24 h progressively inhibited DNA synthesis by up to 80% compared with control cultures. However, when added in combination with 5 nM EGF, 1 nM and 100 nM RA synergistically stimulated DNA synthesis by up to 80% above the level of EGF stimulation without altering EGF receptor levels or binding affinity. Thus, short-term exposure of BCEC to RA potentiated EGF-stimulated DNA synthesis, most likely by acting at a postreceptor step.(ABSTRACT TRUNCATED AT 250 WORDS)