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The susceptibility of Candida albicans to topical amphotericin B and natamycin was evaluated in a model of stromal keratitis in Dutch-belted rabbits and compared with minimal inhibitory concentrations in vitro. Treatment was delayed 24 hr to allow invasive disease to occur and was then continued for 5 days. Ten strains of Candida albicans comprised the test panel. For amphotericin B, the minimal inhibitory concentration (MIC) by tube dilution classified the same strains as resistant or susceptible as did the in vivo response. A dose-response was observed with different concentrations of the drug. For natamycin, the MIC misclassified two strains. The rate of administration of natamycin required in this model was much higher than for amphotericin B, a therapeutic effect being observed with natamycin only when the drug was administered every 30 min during the in vivo efficacy and in vitro susceptibility with these strains is in agreement with that observed in the authors' previous studies using a model of immediate treatment.

A centralized registry of cases was established when it became apparent that an outbreak of Candida parapsilosis endophthalmitis in California was due to intrinsic contamination of a nationally distributed ocular irrigation solution. The purposes were to detect cases, to identify patients at risk, to collect and disseminate clinical information regarding the infection, and to make available information and experience regarding treatment. As a result of these efforts, all patients exposed to the solution were reviewed by their physicians and numerous cases of infection were detected. In contrast, Food and Drug Administration-mandated procedures, traditionally focused on manufacturing standards, were effective in recalling the contaminated solution but failed to provide physicians with adequate information to identify and care for patients at risk.

Two patients developed exposure keratitis in the nonoperated eye during intraocular surgery under local anesthesia. These cases demonstrate that potentially serious injuries may occur to the fellow eye even with the use of local anesthesia and that special precautions should be taken to avoid this problem.

Eleven contact lens-wearing patients presented with Acanthamoeba keratitis. Eight cases were culture- and/or stain-positive for Acanthamoeba and three were presumed to have Acanthamoeba keratitis based on history and clinical findings. Six wore daily wear soft contact lenses, two wore extended-wear soft contact lenses, one wore a polymethylmethacrylate hard contact lens, one wore a gas-permeable hard contact lens, and one wore a Saturn lens (combined hard and soft lens). Four patients used distilled water and salt tablet saline, three used tap water and salt tablet saline, two used tap water rinse, two used well water rinse or storage, and one used intravenous (IV) saline. It is apparent that all contact lens wearers are at some risk for Acanthamoeba keratitis developing if proper contact lens care is not maintained. Of great concern is the inability of most current chemical sterilization methods to kill the organism if the lens becomes contaminated. Heat disinfection will kill Acanthamoeba trophozoites and cysts but the lens must not be placed into contaminated solutions afterward. Prevention is very important because medical and surgical treatment failures are frequent. Eye care practitioners who fit contact lenses are advised to use heat disinfection for low-water content stock soft contact lenses, and to use hydrogen peroxide without a catalyst for a minimum of 6 hours for all other stock lens fitting sets, to specifically inquire about contact lens care habits used by their patients, and to discourage the use of homemade saline solutions.

A microcomputer system was developed for the Department of Ophthalmology, Vanderbilt University School of Medicine. It is being used as a measurement and analysis tool for corneal endothelial and epithelial research programs, as well as objective measurement of clinical visual field tests.

All physicians evaluating a painful red eye in a contact lens wearer should consider the diagnosis of Acanthamoeba keratitis. Although it remains relatively rare, the incidence of this infection is on the rise. Clues to the correct diagnosis include a corneal abrasion that fails to heal appropriately, pain out of proportion to the clinical findings, and a history of poor contact lens hygiene. Prompt recognition and appropriate ophthalmologic intervention can improve the visual outcome for patients with this devastating corneal infection.

Amphotericin B, 5-flucytosine (5-FC), and ketoconazole levels were estimated in vitreous and aqueous samples taken from four patients undergoing therapeutic vitrectomy for fungal endophthalmitis. The levels of amphotericin B in the vitreous of three patients were low (.04 - .17 microgram/ml). However, 5-FC was present in a concentration of 22.2 micrograms/ml in one patient. In another case the aqueous level of ketoconazole was 0.35 microgram/ml. The vitreous in the same patient contained 0.71 microgram/ml of the drug.

Thirty patients randomized to the Acyclovir (ACV) group (26 with dendritic lesions, 4 geographic lesions) and 34 patients randomized to the idoxuridine (IDU) treatment group (26 dendritic lesions, 8 geographic lesions) with epithelial herpetic keratitis were evaluated for efficacy and adverse reactions in a multi-center, double-masked, randomized, stratified trial. Patients were treated with either 3% acyclovir ophthalmic ointment or 0.5% idoxuridine ophthalmic ointment five times a day for 14 days. The results of the trial indicated no significant difference between ACV and IDU as antiviral agents in the treatment of epithelial herpetic keratitis. The overall healing patterns of ACV and IDU adjusted for lesion type and prognostic factors, including presenting condition (initial or recurrent disease), duration of symptoms, prior ophthalmic steroid use, and positive pretreatment herpesvirus culture, as well as, the healing patterns within each lesion type adjusted for these factors, were not significantly different between the two treatment groups. There was no significant difference between the two groups in the frequency of development of deeper involvement. The only significant difference (P less than 0.01) in the frequency of development of adverse reactions was found in the incidence of development of superficial punctate epitheliopathy (IDU-42%, ACV-11%).

Fungal corneal infections can be very difficult to treat. An evolving understanding of the pharmacology of the currently available antifungal agents has led to improved medical treatment of the keratomycoses. The pharmacology, pharmacokinetics, spectrum of activity and toxicity of these agents is reviewed and promising new antifungal compounds and modes of treatment are discussed.

Staphylococcus epidermidis has been reported with increasing frequency as a cause of bacterial endophthalmitis. Over the past eight years 18 consecutive postsurgical cases have been treated by combined antibiotic-corticosteroid therapy without intravitreal antibiotics or vitrectomy. Fourteen (78%) achieved a final visual acuity of 20/50 or better. When these cases were added to similarly reported cases in the literature, 72% achieved this level of vision. By contrast, 42% of adequately documented cases in the literature treated by intravitreal antibiotics, and 42% treated additionally by vitrectomy, achieved a vision of 20/50 or better. S. epidermidis is an organism with a low order of virulence. The use of intravitreal antibiotics and vitrectomy do not appear to be necessary for effective treatment.

Infection with Fusarium solani was established by injecting spores into the anterior chambers of outbred Wistar rats. The disease produced was remarkably similar to that reported in man and progressed to a fulminating endophthalmitis. Attenuation of the disease could be accomplished by repeated animal passage of the isolate.

There is good evidence that maintenance of the structural integrity of the human cornea carries with it significant advantages over and above the preservation of normal function. The breakdown in the protective layers of the cornea and invasion by blood vessels and lymphatics would seem to add greatly to the risk of recurrent inflammatory disease. There is a solid rationale, therefore, for the development of therapeutic principles aimed at preventing these structural changes from occurring.

The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats.

Two patients had bilateral papilledema complicating acromegaly. Both patients had enlarged blind spots, but otherwise visual fields were normal. Suprasellar extension of the pituitary tumors was diligently sought with the use of visual field examination, pneumoencephalography, internal carotid arteriography, and computed axial tomography, and tumor extension did not exist. Transphenoidal and transethmoidal routes were used to perform partial hypophysectomies in these patients. The procedure was completely successful in one patient and partially successful in the other patient. After hypophysectomy, papilledema resolved in both patients. This beneficial effect may be the result of anatomical changes, the reduction in growth hormone levels, or both. These observations suggest that the acromegaly may be different from papilledema that occurs secondary to suprasellar expansion of pituitary tumors.

A prospective double-blind controlled study was undertaken to determine the effects of different compression times applied to soften the eye on normal subjects. Application of the Honan intraocular pressure reducer (HIPR) produced a significantly (p less than 0.02) greater decrease in intraocular pressure when applied for 40 minutes (14.3 mmHg SD = 1.7) when compared to a five-minute application (8.8 mmHg SD = 1.7). No untoward effects were noted in these patients. Physiologic effects of external ocular compression are discussed.

Chorioretinitis developed in the right eye of a patient with contact lens-associated Acanthamoeba keratitis in the left eye during an acute exacerbation of the keratitis. This chorioretinitis may have resulted from hematogenous dissemination from his corneal infection.

Twenty-two isolates from patients with postsurgical endophthalmitis due to infection with Candida parapsilosis as a result of exposure to a contaminated ocular irrigating solution were classified by enzyme profile analysis and antifungal susceptibility. These isolates were identical to a single isolate obtained from a contaminated vial but could be differentiated, on the basis of enzyme profile and antifungal susceptibility, from randomly selected stock isolates. The combination of these tests appears to have value in discriminating epidemic from non-epidemic strains.

In laboratory experience with a heterogenous group of 26 human ocular fungal isolates, brain-heart infusion broth proved to be the most useful medium for isolation. Although Candida and Fusarium species grew out within four days of inoculation, one fourth of the cultures did not become positive until 14 to 19 days had elapsed. In an animal model of endophthalmitis due to F. solani infection, brain-heart infusion broth again was the most useful. The highly nutritious media used for fungal isolation are prone to contamination by organisms that are difficult to distinguish from true pathogens. Sham culture studies demonstrated that this contamination can easily occur during the process of sampling the lesion and inoculating the media.

A model of deep stromal Candida albicans infection was established by injecting 25 microliters of a suspension containing 5 X 10(9) colony forming units/ml of the yeast into corneas of pigmented rabbits. In this model, the infection lasts for more than 8 days. Using quantitative techniques, the authors compared the efficacy of six topical antifungal agents in the presence of an intact epithelium and in corneas debrided of epithelium. In corneas debrided on a daily basis, the polyenes (amphotericin B 0.15% and 0.075% and natamycin 5%) exhibited a significant antifungal effect. When the epithelium was left intact, 5% natamycin and 0.075% amphotericin B were without effect, while the efficacy of the 0.15% preparation of amphotericin B was much reduced. Removal of the epithelium appeared to affect adversely the efficacy of flucytosine. The imidazoles were not efficacious in this model.

We diagnosed mycotic endophthalmitis by positive cultures in a 47-year-old man and a 42-year-old woman, both intravenous amphetamine users. Reinfection with a different fungal species was documented in one case. Rapid identification of the isolate, in vitro susceptibilities, selection of appropriate routes and dosages of antifungals, and the role of adjunctive corticosteroids are crucial factors in the management of these difficult cases. We prescribed antifungals and adjunctive corticosteroids, and our patients' vision improved.