Penetrating keratoplasty in infancy and early childhood.

Penetrating keratoplasty in infants and young children is performed on an infrequent basis. The most common indication is visually significant congenital corneal opacity. Surgery must be performed early to avoid amblyopia. Surgical techniques differ from those used in adult penetrating keratoplasty because of the reduced ocular rigidity encountered in infants and young children. Use of a multispecialty team approach is important to improve visual outcome. Poor prognostic indicators include bilateral disease, concomitant infantile glaucoma, lensectomy and vitrectomy at the time of surgery, previous graft failure, extensive goniosynechiae, and extensive corneal vascularization. Prompt postoperative optical rehabilitation, combined with occlusion therapy when appropriate, is an important determinant of success.

Recurrent erosions of the cornea: epidemiology and treatment.

PURPOSE: To evaluate the epidemiologic characteristics of a large clinical population of patients with recurrent erosions of the cornea. The efficacy of different modalities of treatment was also evaluated. METHODS: A retrospective chart review of all patients with the diagnosis of recurrent corneal erosion treated between January 1990 and December 1998 was performed. RESULTS: Clinically confirmed recurrent erosions were identified in 104 patients. There were 36 males and 68 females. A history of trauma was present in 47 patients (45%), 30 patients (29%) had epithelial basement membrane dystrophy (EBMD), and 18 patients (17%) had both a history of trauma and evidence of EBMD. More than 87% of all erosions occurred on the inferior third of the cornea. Conservative therapy was used as the primary treatment in 52 patients with a recurrence rate of 6%. Corneal stromal micropuncture was performed on 38 patients with a recurrence rate of 40%. Eleven patients had epithelial debridement with a recurrence rate of 18%. Four patients had a superficial keratectomy with a diamond bur with a recurrence rate of 25%. Only one patient had an excimer phototherapeutic keratectomy, and she had a minor recurrence posttreatment. CONCLUSIONS: In our series, the distribution of trauma and EBMD in patients with recurrent erosions of the cornea is roughly equivalent. Conservative therapy was effective in approximately one half of the patients. All surgical treatment modalities were associated with recurrences. Those patients with both EBMD and trauma were more likely to have a recurrence after treatment. More effective treatment modalities for recurrent erosions of the cornea need to be investigated.

Clinical features of bleb disorder of the cornea.

BACKGROUND: Bleb disorder of the cornea is a rare corneal epithelial disorder that has previously been described in asymptomatic patients or those with recurrent nontraumatic corneal erosions. METHODS: We report two cases of bleb disorder, each presenting with blurred vision from irregular astigmatism secondary to the bleb changes. We also report on the detection of bleb disorder in siblings. RESULTS: Both patients underwent surgical debridement of the epithelium with resolution of symptoms on epithelial resurfacing. CONCLUSION: The diagnostic clues, inheritance pattern, differential diagnosis, and treatment options of bleb disorder of the cornea are discussed.

Infection of the conjunctiva by Rhinosporidium seeberi.

Rhinosporidiosis is an unusual fungal disease that rarely affects the eye. It was first described as a pathogen in humans at the turn of the century. The etiologic agent, Rhinosporidium seeberi, commonly produces granulomatous inflammation of the upper respiratory mucosa. Most reported ocular infections have occurred in hot, dry climatic regions. We present a case of conjunctival rhinosporidiosis in an 11-year-old boy from western New York state, the first such report from the temperate zones of North America. The clinical characteristics, histopathologic features, and recommended therapeutic measures are discussed.

Comparison of corneal epithelial wound healing after photorefractive and lamellar keratectomy.

BACKGROUND: The rate of corneal epithelial wound healing may be determined, in part, by the characteristics of the stromal surface. The excimer laser has the ability to produce a highly uniform ablated surface, which may facilitate reepithelialization after photorefractive keratectomy (PRK). METHODS: The rate of corneal epithelial wound healing after excimer laser PRK was compared with the rate of reepithelialization after manual lamellar keratectomy. Ten rabbits received a 4-mm diameter ablation in one eye (fluence = 160 mJ/cm2) and a shallow, 5-mm diameter, manual lamellar keratectomy in the contralateral eye. At 0, 4, 8, 12, 24, 36, 48, 60, and 72 hours after wounding, sodium fluorescein was instilled, and photographs were taken, converted to video images, and digitized. Wound area was calculated for each time point and converted to wound radius; the slopes of the wound radius, plotted over time, were compared to determine rates of healing. Scanning electron microscopy was performed immediately after wounding to examine surface regularity. RESULTS: By 24 hours after wounding, corneas that had undergone PRK demonstrated a significantly faster rate of epithelial wound healing compared with eyes that underwent lamellar keratectomy (33.4 +/- 1.9 microns/hr vs 27.8 +/- 1.4 microns/hr, respectively, for 12 to 72 hours) (p < 0.0001). Scanning electron microscopy showed greater stromal surface irregularity in the corneas that had undergone lamellar keratectomy, compared with the laser-ablated corneas. CONCLUSIONS: This study demonstrates that the rate of epithelial wound healing is significantly faster after excimer laser PRK than after lamellar keratectomy in the rabbit. Variations in surface regularity and wound edge profile may contribute to differences in wound healing.

Effectiveness of specific antibiotic/steroid combinations for therapy of experimental Pseudomonas aeruginosa keratitis.

Ciprofloxacin and prednisolone, but not an aminoglycoside and dexamethasone, were previously found to be effective in killing bacteria and reducing inflammation for the treatment of Pseudomonas keratitis. We investigated the therapeutic effectiveness of tobramycin/prednisolone and ciprofloxacin/dexamethasone in a rabbit model of experimental keratitis to increase our understanding of the effectiveness of antibiotic/steroid combinations. To our knowledge, this is the first analysis of the effectiveness of a combination of ciprofloxacin and dexamethasone for experimental keratitis. Two experiments were conducted. In the first experiment, 36 rabbits were divided into six groups: 1) untreated; 2) prednisolone acetate, 1.0%; 3) prednisolone phosphate, 1.0%; 4) tobramycin, 1.36%; 5) tobramycin plus prednisolone acetate; 6) tobramycin plus prednisolone phosphate. In the second experiment, 23 rabbits were divided into four groups: 1) untreated; 2) ciprofloxacin, 0.3%, plus dexamethasone alcohol, 0.1%; 3) ciprofloxacin; 4) dexamethasone alcohol. Topical antibiotic and/or steroid was given for 10 h, from 16 to 26 h postinfection, one drop every 15 min for the first hour and then every 30 min for the remaining 9 h. At 27 h postinfection, eyes were evaluated by slit lamp examination (SLE) and assayed for the presence of bacteria in terms of colony forming units (CFU) per cornea. Both prednisolone acetate and prednisolone phosphate reduced ocular inflammation (as determined by SLE), compared with no treatment (P < or = 0.036); the phosphate was more effective (P = 0.005). Tobramycin alone and in combination with prednisolone also significantly reduced SLE, compared with no treatment (P < or = 0.006). The bactericidal activity of tobramycin was not affected by either steroid formulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of topical beta blockers on corneal epithelial wound healing in the rabbit.

Topical beta adrenergic receptor blocking agents (beta blockers) are among the most frequently prescribed ophthalmic drugs. It has been suggested that some of these agents have a toxic effect on the corneal epithelium. In the present study, four beta blockers in common therapeutic concentrations, as well as their vehicles, were applied to rabbit corneas that had undergone mechanical removal of epithelium from a 6 mm diameter corneal wound. The tested drugs (0.25% timolol, 0.25% levobunolol, 0.25% betaxolol, and 0.3% metipranolol) were found significantly to accelerate wound closure, compared with saline treatment in controls. Eyes treated with two of the vehicles (betaxolol vehicle and metipranolol vehicle) also demonstrated more rapid healing than controls, but the magnitude of the effect was not as great as that seen with the drugs. Only the beta blockers were responsible for wound closure before 60 hours, whereas the saline treated controls and vehicle treated eyes required longer times for wound closure. In this model of wound healing, beta blockers appear to have no deleterious effect on corneal epithelial wound healing.

Ciprofloxacin and prednisolone therapy for experimental Pseudomonas keratitis.

Rabbit corneas were injected intrastromally with Pseudomonas aeruginosa. Sixteen hours after injection, the rabbits were divided randomly into four treatment groups (3 rabbits/6 eyes per group: 1, ciprofloxacin and prednisolone; 2, ciprofloxacin only; 3, prednisolone only; 4, untreated. Ocular signs of inflammation were graded in a masked fashion by slit lamp examination before injection and 16 and 27 hours after injection. Slit lamp examination scores were significantly lower in eyes receiving ciprofloxacin and prednisolone or prednisolone alone, compared with scores in untreated eyes. Slit lamp examination scores were not significantly lower in eyes receiving ciprofloxacin alone, compared with untreated controls. The numbers of viable bacteria in the corneas treated with ciprofloxacin and in the corneas treated with ciprofloxacin and prednisolone were similar and were significantly less (P less than 0.0001) than those in untreated corneas, indicating that the presence of the steroid did not interfere with the bactericidal action of ciprofloxacin.

Effect of intracanalicular collagen implants on the absorption of topically applied sodium fluorescein.

Absorbable intracanalicular collagen implants were placed in both canaliculi of one eye of nine human volunteers. The other eye served as a control. Twenty-four hours later 2% sodium fluorescein was placed into both conjunctival sacs. Serial corneal fluorescein concentrations were measured with a scanning ocular fluorophotometer from 2 to 90 min after fluorescein administration. The mean corneal fluorescein concentration averaged over all time points was greater in 7 of 9 eyes with collagen implants compared to unimplanted controls. When the data from each subject were analyzed collectively, the mean corneal fluorescein concentration in the implanted eyes (1,218 micrograms/ml +/- SEM 83) was significantly greater (p less than 0.001) than the mean concentration in the control eyes (823 micrograms/ml +/- SEM 83). The use of absorbable intracanalicular collagen implants may increase the bioavailability of topically applied ocular solutions.

Immunogenicity of epikeratophakia tissue lenses containing living donor keratocytes.

The purpose of this study was to compare the survival of epikeratophakia tissue lenses prepared with cryolathing and lyophilization (frozen lenses) and without (fresh lenses) in donor-sensitized recipients with vascularized corneas. Fresh lenses placed in vascularized corneas of immune recipients were subjected to immune attack. Frozen lenses placed in vascularized corneas of immunized recipients did not elicit an immune reaction. Neither fresh nor frozen lenses elicited immune reactions in nonvascularized corneas of immune recipients or in nonvascularized, nonimmune recipients. These results indicate that although the fresh lenses are more antigenic than the lenses in which the cells have been killed by freezing and lyophilization, the fresh lenses prepared using the BKS-1000 technique containing living stromal keratocytes are not likely to stimulate allograft immune reactions in unsensitized patients with avascular graft sites.

The efficacy of topical ciprofloxacin and norfloxacin in the treatment of experimental Pseudomonas keratitis.

An aminoglycoside-resistant strain of Pseudomonas aeruginosa was injected intrastromally into the corneas of rabbits, and keratitis was allowed to develop over a 22-h period. Rabbits were treated with either 0.75% ciprofloxacin, 1% norfloxacin, or 1.36% tobramycin administered topically every 15 min for 1 h and then every 30 min for the following 3 h. All therapy ceased 26 h postinoculation. Rabbits were killed 1 h after the treatment, and the number of bacteria per cornea were quantified in terms of bacterial colony-forming units. Aqueous humor specimens were obtained from rabbits receiving norfloxacin and ciprofloxacin, and bioassays were performed to determine drug concentration. Ciprofloxacin caused a 5 log reduction in the number of bacterial colony-forming units, as compared with untreated controls (p less than 0.0001); it also produced a significantly greater reduction in bacterial colony-forming units than either norfloxacin or fortified tobramycin drops (p less than 0.0001). Norfloxacin produced a 2 log reduction in bacterial colony-forming units, as compared with untreated controls (p less than 0.0001). The mean aqueous concentration of norfloxacin (7.5 micrograms/ml) was substantially less than that achieved by ciprofloxacin (30.5 micrograms/ml). We conclude that ciprofloxacin may be a useful broad spectrum, topical chemotherapeutic agent in the therapy of aminoglycoside-resistant P. aeruginosa keratitis.

Quinolones in collagen shields to treat aminoglycoside-resistant pseudomonal keratitis.

Rabbit corneas were infected with a tobramycin-resistant (minimum inhibitory concentration, 31.25 micrograms/ml) strain of Pseudomonas aeruginosa 27853 (10(3) colony-forming units) and were treated 22 hours later with collagen corneal shields hydrated in either 25 mg/ml ciprofloxacin, 40 mg/ml norfloxacin, 40 mg/ml tobramycin, or deionized water. Shields were removed at 26 hours postinfection, and 1 hour later, corneas were harvested for bacterial enumeration. Application of shields hydrated in ciprofloxacin reduced the number of viable bacteria per cornea approximately 4 log units compared with the application of shields containing tobramycin or deionized water (P less than 0.0001). Use of shields hydrated in norfloxacin reduced the number of P. aeruginosa organisms by greater than 2 log units compared with shields containing tobramycin or deionized water (P less than 0.0001). Ciprofloxacin was significantly more effective than norfloxacin in reducing the number of bacteria per cornea (P less than 0.0001). There was no significant difference in the number of bacteria recovered from corneas treated with tobramycin or deionized water (P less than 0.56).

Ciprofloxacin iontophoresis for aminoglycoside-resistant pseudomonal keratitis.

Studies using ciprofloxacin for the therapy of experimental aminoglycoside-resistant keratitis caused by Pseudomonas aeruginosa were conducted using transcorneal iontophoresis as the drug-delivery system. Corneas infected with P. aeruginosa ATCC 27853/pMG6 were treated 22 hours postinfection with ciprofloxacin delivered by iontophoresis (0.8 mA X 10 min), mock iontophoresis (eyecup with no current), or frequently applied topical drops. Iontophoresis of 10 mg/ml or 25 mg/ml of ciprofloxacin significantly reduced the number of viable bacteria per cornea by more than 5 log units compared with untreated controls (P less than 0.0001). Five hours after the initiation of treatment, mock iontophoresis (10 mg/ml or 25 mg/ml) or 11 applications of topical ciproflaxicin drops (7.5 mg/ml) decreased the viable bacteria relative to the untreated controls by 5 log units (P less than 0.0001). One treatment with an eyecup was as effective as 11 treatments with topical drops (P greater than 0.75). One hour after treatment with iontophoresis or mock iontophoresis of 10 mg/ml of ciprofloxacin, aqueous humor concentrations were 83.75 +/- 8.85 micrograms/ml and 24.87 +/- 4.0 micrograms/ml (mean +/- standard error of the mean), respectively. One hour after the last of five applications of 7.5 mg/ml of ciprofloxacin (every 15 min for 1 hr) the aqueous humor concentration was 4.2 +/- 1.14 micrograms/ml. These results show the value of ciprofloxacin in treating aminoglycoside-resistant infections caused by P. aeruginosa and suggest that ciprofloxacin can be efficiently delivered by iontophoresis.

Delivery of fluorescein to the anterior chamber using the corneal collagen shield.

Collagen corneal shields show promise as an alternative method of drug delivery to the eye. The authors quantified collagen shield delivery of sodium fluorescein to the aqueous humor in human volunteers using fluorophotometry. Collagen shields that had been immersed in 0.01% sodium fluorescein were applied to eyes of human volunteers. The shields delivered significantly more fluorescein to the aqueous humor at 2 and 4 hours compared with drops of the same concentration instilled every 30 minutes for 4 hours (P less than 0.0001 and P = 0.0003, respectively) or daily wear soft contact lenses presoaked in 0.01% fluorescein (P less than 0.0001 and P less than 0.0025, respectively). Collagen shields did not induce damage to the corneal epithelium over a 2-hour wearing period. These results suggest that the collagen shield may be superior to topical drops in delivering water-soluble compounds to the cornea and aqueous humor.

The collagen shield. A new vehicle for delivery of cyclosporin A to the eye.

Collagen shields were tested as a means of delivering the immunosuppressive drug, cyclosporine A (CsA), to the cornea and aqueous humor in rabbit eyes. Gelatinous collagen was mixed with crystalline CsA and then, during drying, was formed into contact lens-shaped shields which were applied to rabbit eyes. The amount of CsA in the corneas and aqueous humor (AH) samples from shield-treated eyes was compared with samples from rabbit eyes treated with CsA in olive oil. CsA concentrations were measured by radioimmunoassay (RIA) at 2, 4, and 8 h after application of the shields or drops. Both the corneal and aqueous humor concentrations of CsA achieved with the shield delivery system were 10-fold higher than those obtained with topical CsA-olive oil drops. The CsA levels achieved in the cornea using the collagen shield are sufficient to inhibit cellular immune reactions in vivo. These results demonstrate that collagen shields may be useful as an ocular delivery system for the drug CsA.

Rigid contact lens decentration: a risk factor for corneal warpage.

Clinically significant contact lens induced corneal warpage is seen in a small proportion of soft and rigid contact lens wearers. Previous studies using the keratometer have found no correlation between the fit of the lens and the induced topographic changes. In this study, using computer-assisted topographic analysis, seven eyes (four patients) with rigid contact lens-induced corneal warpage were noted to have topographic abnormalities that correlated with the decentered resting position of the contact lens on the cornea. The warpage topography for each of these corneas was characterized by a relative flattening of the cornea underlying the resting position of the contact lens. Lenses that rode high, for example, produced flattening superiorly and resulted in a relatively steeper contour inferiorly that simulated the topography of early keratoconus patients who had not worn contact lenses. After discontinuing contact lenses the corneal topography returned to a normal pattern in five eyes. Two eyes retained asymmetry that is not characteristic of normal corneas. Up to 6 months was required for the corneas to return to a stable topography after contact lens wear was discontinued.

An adjustable single running suture technique to reduce postkeratoplasty astigmatism. A preliminary report.

The authors compared postkeratoplasty astigmatism over a 4-month period after surgery in a randomized, prospective study of two groups of patients (total N = 18) who received two different suture techniques. The test group N = 8) had a single running suture with postoperative suture adjustment; on the basis of computer-assisted topographic analysis, the suture was tightened in the flatter meridian and loosened in the steeper meridian in the first month after surgery. The control group (N = 10) had a standard double running suture procedure with no postoperative adjustment; the single running 10-0 nylon suture was removed 3 months after surgery. Four months after penetrating keratoplasty, mean (+/- standard deviation) astigmatism in the test group was 1.7 +/- 0.7 diopters (D), and all patients had less than 2.6 D of astigmatism. In the control group, mean astigmatism was significantly higher (5.4 +/- 2.4 D; range, 0.7-9.0 D; P less than 0.01). The results suggest that postkeratoplasty astigmatism can be reduced with the single running suture technique accompanied by postoperative suture adjustment.

Topographic changes in contact lens-induced corneal warpage.

Twenty-one eyes of 12 patients with contact lens-induced corneal warpage were followed prospectively using computer-assisted topographic analysis. Sixteen eyes had worn rigid contact lenses (13 eyes, polymethylmethacrylate; three eyes, gas-permeable), and five eyes had worn soft contact lenses. Initial corneal topographic patterns were characterized by the presence of central irregular astigmatism, loss of radial symmetry, and frequent reversal of the normal topographic pattern of progressive flattening of corneal contour from the center to the periphery. A correlation was noted between the initial corneal topography and the resting position of the contact lens on the cornea for nine of the 16 eyes with rigid contact lenses. Initial topography for each of these corneas showed relative flattening of the corneal contour underlying the resting position of a decentered contact lens. Superior-riding lenses produced a topography that simulated early keratoconus. After cessation of contact lens wear, 16 of 21 eyes had a change in corneal shape to a topography that was consistent with a normal pattern. Five corneas stabilized with an abnormal topographic pattern. A much longer time without contact lenses than had been previously reported, up to 5 months, was required for a return of a stable corneal topography in eyes with contact lens-induced corneal warpage caused by rigid lenses.

Corneal nerve disruption reactivates virus in rabbits latently infected with HSV-1.

Trauma, inflammation, and neuronal stimulation or damage can reactive latent herpes simplex virus type 1 (HSV-1). The innervation density of the corneal epithelium is 300-600 times that of skin and, therefore, corneal nerve disruption could provide a strong stimulus for HSV-1 reactivation. This study has documented HSV-1 ocular reactivation following three methods of corneal nerve disruption in rabbits. Twenty HSV-1 latently infected rabbits (26 eyes) were divided into three groups: 7 rabbits received uniocular cryogenic injury, 7 rabbits underwent uniocular anterior superficial keratectomy, and 6 rabbits had binocular transection of the corneal nerves at the corneoscleral limbus which, in contrast to the other treatments, produced minimal epithelial change. Opposite eyes in the first two groups of rabbits were left undisturbed to serve as HSV-1 infected controls. Three additional rabbits, not infected with HSV-1, underwent gold chloride impregnation of the corneal nerves for light microscopic documentation of corneal nerve damage induced by each procedure. On all HSV-1 infected eyes, daily HSV-1 ocular cultures were obtained for 7 consecutive days. All three procedures resulted in marked corneal nerve destruction and degeneration. HSV-1 shedding occurred in 5/7 (71%) of the eyes that underwent cryogenic lesioning; in 5/7 (71%) of the eyes that underwent anterior keratectomy; and in 8/12 (67%) of the eyes that had the corneal nerves transected at the corneoscleral limbus. Only 4 (29%) of the 14 control eyes had positive HSV-1 ocular cultures. This investigation provides strong evidence that corneal nerve disruption is correlated with ocular HSV-1 reactivation.