Trifluridine decreases ocular HSV-1 recovery, but not herpetic lesions after timolol iontophoresis.

To determine the effect of a topically applied antiviral agent on shedding of herpes simplex virus type 1 (HSV-1) into the tear film and corneal epithelial lesions, ten rabbits latently infected with HSV-1 were subjected to transcorneal iontophoresis of 0.01% timolol once a day for 3 consecutive days to induce viral shedding and lesions. Iontophoretic induction was performed similarly in five uninfected rabbits as controls. Half of the infected rabbits and all of the uninfected controls received topical 1.0% trifluridine five time a day for 9 days, beginning the day after the first iontophoresis. All eyes were examined daily for 10 days by slit-lamp biomicroscopy and tear film samples collected on swabs were analyzed for virus. In the infected rabbits, the eyes treated with trifluridine had significantly fewer swabs positive for HSV-1 than the untreated eyes (P less than 0.001); however, there was no significant difference in the numbers of lesions in the treated and untreated eyes. The uninfected controls had no positive swabs and developed no lesions. These results suggest that topical treatment with trifluridine may reduce recovery of HSV-1 from the tear film, but does not affect the incidence of iontophoretically induced corneal epithelial lesions.

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.

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).

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.

Histopathologic and scanning electron microscopic study of one type of intraocular lens.

We performed clinicopathologic analyses of 28 explanted anterior chamber intraocular lenses (Stableflex). Two factors strongly indicated that this lens can be difficult to remove: (1) the clinical histories obtained from the explanting surgeons who, with few exceptions, stated that removal was extremely difficult; and (2) our scanning electron microscopic findings, which documented extensive tissue encapsulation around loops as well as multiple sites of loop severance required at the time of lens removal. The general efficacy of this intraocular lens compared with other anterior chamber lenses was not addressed in this study.

Lens injury following iridotomy with a Q-switched neodymium-YAG laser.

By scanning electron microscopy, we studied eight lenses from eyes that had received a neodymium-YAG laser iridotomy one day prior to elective intracapsular cataract extraction. In some of these cases, pitting lesions were found on the anterior-equatorial lens surface, thereby showing that lenticular damage may occur following this procedure if the iridotomy is applied too centrally. It is recommended that care be taken to ensure that the iridotomy be placed at a site peripheral to the outer circumference of the lens.

Treatment of experimental Pseudomonas keratitis using collagen shields containing tobramycin.

To study the effectiveness of collagen shields containing tobramycin sulfate in the treatment of Pseudomonas keratitis, rabbits were infected via an intrastromal injection of Pseudomonas aeruginosa and treated 22 hours later with either collagen corneal shields rehydrated in 4% tobramycin and applied to the cornea or 4% tobramycin drops. Bacterial killing was quantitated by culturing corneal homogenates and calculating the number of viable bacteria (colony-forming units) per cornea. Corneas receiving shields rehydrated in 4% tobramycin and applied for four hours demonstrated significantly reduced numbers of bacteria compared with untreated control corneas. The collagen shields were as effective in reducing the number of viable bacteria per cornea as 4% tobramycin drops applied every 30 minutes over a four-hour period. Over a nine-hour treatment period, the addition of four drops of 4% tobramycin to shields in situ was as effective as exchange with a new shield rehydrated in 4% tobramycin. These results suggest that collagen shields rehydrated in a water-soluble antibiotic such as tobramycin may be an effective and convenient mode of therapy for Pseudomonas keratitis.

X-ray microanalysis of crystalline material in the liver of a narcotics user.

A 22-year-old athlete, who had had intravenous injections of narcotics in the past, developed a viral hepatitis with markedly altered liver enzyme values. Studies revealed evidence of a virtual cure of hepatitis B virus and a current infection with delta agent. Liver biopsy showed a mixed-cell portal inflammation and doubly refractile crystalline particles. These particles were shown by energy-dispersive x-ray microanalysis to contain calcite, silica, talc, and a variety of elements including Al, P, S, Cl, K, Ti, Cr, Fe, Ni, Br, Yb, Os, Ir, and a trace U. The predominance of Ca-containing compounds suggested that the foreign material was present as a result of the chemical preparation of the narcotic or as a narcotic diluent. The potential for pathologic alteration by the various substances is discussed. These observations support the idea of particulate-induced hepatic disease advanced previously by others.

Selective decontamination in intensive care practice: a review of clinical experience.

Acquired infection is a common problem in intensive care and in a general ICU the infection rate can exceed 80% in patients ventilated beyond 5 days. SDD, adapted from regimes used in neutropenic patients, was first introduced to the ICU situation in Groningen. This article reviews 10 published trials of SDD in ICU. The trial designs vary but all show a significant reduction in both colonisation rates and acquired infection rates. Infection rates were reduced from 10%-78% to 3%-10% in the SDD treated groups. Of the 10 trials 2 showed an overall reduction in mortality 2 showed a reduction in infection-related mortality and 1 showed a reduction in mortality amongst trauma patients. Although further evaluation of trials is required SDD now appears to be of proven efficacy in certain groups of high risk patients within ICU.

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.

Melanocytoma: nomenclature, pathogenesis, natural history and treatment.

A melanocytoma (magnocellular nevus) is a benign pigmented tumor that may arise wherever uveal melanocytes are present. The most commonly observed site is on or adjacent to the optic nerve head. In the past this tumor was frequently misdiagnosed as a malignant melanoma and many unnecessary enucleations were carried out. Its clinical features are now well recognized and, fortunately, specimens of melanocytomas are rarely received in ocular pathology laboratories today. A review of the literature concerning this tumor is presented, with special reference to the changing concepts in nomenclature, pathogenesis, natural history, and treatment that have evolved in the past one hundred years. We also define the clinical and histopathological features of this tumor.

Cyclosporine-containing collagen shields suppress corneal allograft rejection.

Thirty-seven rabbit eyes with penetrating keratoplasty grafts placed in vascularized beds to enhance the possibility of graft rejection were treated with cyclosporine delivered in collagen shields or drops of olive oil. Treatment was begun either immediately after grafting or at the first sign of immune graft reaction. Mean survival time of the grafts in the collagen shield treated eyes was significantly longer than in the eyes treated with drops. In the eyes treated at the first sign of graft reaction, cyclosporine in collagen shields halted the rejection process; seven of these eyes survived the 120-day observation period, compared to one of the eyes treated with drops. These results indicate that the collagen shield is an effective delivery system for cyclosporine and the topically administered cyclosporine is effective in suppressing the initiation of graft rejection and in reversing a graft reaction in progress.

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.

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.

Sterile hypopyon secondary to ultrasonic cleaning solution.

During a 20-week period, 21 cases of sterile hypopyon occurred 24 hours after uncomplicated extracapsular cataract extraction and in-the-bag posterior chamber intraocular lens implantation at the Valley Eye Institute. While all cases responded to steroid treatment and exhibited no residual ocular effects, the cause of the hypopyon remained a mystery despite an on-going reevaluation of the surgical procedure and sterilization techniques. Several suspected causes were investigated and eliminated. It was clinically determined that surgical instruments placed in older ultrasonic cleaning solution caused the hypopyons. Further analysis at the Center for Intraocular Research at the University of Utah revealed that the instruments were contaminated by a heat-stable endotoxin that remained on the instruments through the autoclaving process. Surgeons currently using ultrasonic instrument cleaners should be aware that, with some models, following the manufacturer's recommended fluid changing procedures could result in endotoxic contamination of surgical instruments which could, in turn, cause severe inflammatory reactions in the immediate postoperative period.

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.

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.

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.

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.

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.