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Purpose: Epithelial keratitis is the most common presentation of ocular infection by herpes simplex virus (HSV). Quantitative assessment of available therapy is needed to guide evidence-based ophthalmology. This study aimed to compare the efficacy of various treatments for dendritic or geographic HSV epithelial keratitis and to evaluate the role of various clinical characteristics on epithelial healing., Methods: Following a systematic review of the literature, information from clinical trials of HSV dendritic or geographic epithelial keratitis was extracted, and the methodological quality of each study was scored. Methods of epithelial cauterization and curettage were grouped as relatively equivalent physicochemical therapy, and solution and ointment formulations of a given topical antiviral agent were combined. The proportion healed with 1 week of therapy, a scheduled follow-up day that approximated the average time of resolution with antiviral therapy, was selected as the primary outcome based on a masked evaluation of maximum treatment differences in published healing curves. The proportion healed at 14 days was recorded as supplemental information. Fixed-effects and random-effects meta-analysis models were used to obtain summary estimates by pooling results from comparative treatment trials. Hypotheses about which prognostic factors might affect epithelial healing during antiviral therapy were developed by multivariate analysis of the Herpetic Eye Disease Study dataset., Results: After excluding 48 duplicate reports, 14 nonrandomized studies, 15 studies with outdated or similar treatments, and 29 trials lacking sufficient data on healing or accessibility, 76 primary reports were identified. These reports involved 4,251 patients allocated to 93 treatment comparisons of dendritic epithelial keratitis in 28 categories and 9 comparisons of geographic epithelial keratitis in 6 categories. For dendritic keratitis, idoxuridine was better than placebo at 7 days (combined odds ratio [OR], 3.59; 95% confidence interval [CI], 1.92-6.70), and at 14 days (OR, 4.17; 95% CI, 1.33-13.04), but pooling was limited by lack of homogeneity and low study quality. Direct comparisons at 1 week of treatment showed that trifluridine or acyclovir was significantly better than idoxuridine (OR, 3.12 and 4.56; 95% CI, 1.55-6.29 and 2.76-7.52, respectively), and indirect comparisons were also consistent with a clinically significant benefit. Vidarabine was not significantly better than idoxuridine in pooled treatment comparisons at 1 week (OR, 1.20; 95% CI, 0.72-2.00) but was better in 2 indirect comparisons (OR, 4.22 and 4.78; 95% CI, 1.69-10.54 and 2.15-10.65, respectively). At 14 days, trifluridine (OR, 6.05; 95% CI, 2.50-14.66), acyclovir (OR, 2.88; 95% CI, 1.39-4.78), and vidarabine (OR, 1.24; 95% CI, 0.65-2.37) were each better than idoxuridine. Trials of geographic epithelial keratitis also suggested that trifluridine, acyclovir, and vidarabine were more effective that idoxuridine. Other topical antiviral agents, such as bromovinyldeoxuridine, ganciclovir, and foscarnet, appeared equivalent to trifluridine or acyclovir. Oral acyclovir was equivalent to topical antiviral therapy and did not hasten healing when used in combination with topical treatment. Antiviral agents did not increase the speed of healing when compared to debridement but reduced the risk of recrudescent epithelial keratitis. The combination of physicochemical treatment with an antiviral agent seemed to be better than either physicochemical or antiviral treatment alone, but the heterogeneous cauterization and curettage techniques and the various treatment combinations limited valid quantitative summary effect measures. The combination of topical interferon with an antiviral agent was significantly better than antiviral therapy at 7 days (OR, 13.49; 95% CI, 7.39-24.61) but not at 14 days (OR, 2.36; 95% CI, 0.82-6.79). Finding apparent heterogeneity for some pooled estimates suggested that dissimilarities in patients, interventions, outcomes, or other logistical aspects of clinical trials occur across studies., Conclusions: The available evidence on the acute treatment of presumed HSV epithelial keratitis demonstrates the effectiveness of antiviral treatment and shows the log-logistic healing curve of treated dendritic epithelial keratitis. Topical trifluridine, acyclovir, and vidarabine were significantly more effective than idoxuridine but similar in relative effectiveness for dendritic epithelial keratitis. Physicochemical methods of removing infected corneal epithelium are effective, but adjunctive virucidal agents are needed to avert recrudescent epithelial keratitis. Whether debridement in combination with antiviral therapy is more beneficial than antiviral chemotherapy alone appears likely but remains inconclusive. The combination of topical interferon with an antiviral agent significantly speeds epithelial healing. Future trials of the acute treatment of HSV epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome and should consider the effect of lesion size and other characteristics on treatment response.

Background: Approximately 15-20% of Streptococcus pneumoniae clinical isolates in the United States are not susceptible to penicillin. Isolates with a minimum inhibitory concentration (MIC) of 0.12-1.0 mg/ml are intermediately resistant, and those with an MIC > 2.0 microg/ml are classified as having high-level penicillin resistance., Purpose: We determined the proportion of penicillin-resistant S. pneumoniae recovered from ocular and periocular infections from 1976 through 1995, compared these cases with penicillin-susceptible controls, and evaluated the susceptibility of penicillin-resistant isolates to selected cephalosporins and fluoroquinolones., Methods: MICs for cephalothin, ceftazidime, ciprofloxacin, and ofloxacin were determined for available isolates by the E test. We performed a case-comparison study to evaluate differences between patients with penicillin-susceptible and -nonsusceptible ocular pneumococcal infections., Results: Of 173 ocular isolates of S. pneumoniae isolated in the 20-year period, 12 (7%) were not susceptible to penicillin, including eight (5%) intermediate isolates and four (2%) highly resistant isolates. Penicillin-intermediate and -resistant pneumococci were recovered at a rate of none of 46 isolates from 1976 through 1980, one (4%) of 25 from 1981 through 1985, one (2%) of 51 from 1986 through 1990, and 10 (20%) of 51 from 1991 through 1995 (p < 0.0004). We found no significant differences in presenting characteristics between patients with ocular infections due to penicillin-susceptible pneumococci and those caused by nonsusceptible strains. All retested isolates with intermediate susceptibility to penicillin had a cephalothin MIC < or = 1.5 microg/ml, and all retested isolates with high-level penicillin resistance had a cephalothin MIC > or = 4 microg/ml. The ceftazidime MIC for all penicillin-resistant isolates was > or = 24 microg/ml. All penicillin-nonsusceptible isolates had MICs < or = 1.5 microg/ml for ciprofloxacin and < or = 3 microg/ml for ofloxacin., Conclusion: Penicillin resistance has recently emerged among ocular S. pneumoniae. Cephalothin, ciprofloxacin, and ofloxacin have good activity against some ocular isolates with intermediate penicillin susceptibility, although another agent such as vancomycin may be needed for pneumococci with high-level penicillin-resistance.

Purpose: This study sought to determine whether the use of an antimicrobial removal device (ARD) to process intraocular fluids increases microbial detection compared with conventional cultures., Methods: The authors retrospectively reviewed all cases of endophthalmitis submitted to their laboratory from January 1982 through December 1996. Aqueous or vitreous specimens or both that were cultured on conventional media (blood agar, chocolate agar, anaerobic blood agar, and thiol broth) and by ARD processing were included in the study. Specimens were inoculated into tubes with ARD for 5 to 10 minutes. The fluid was then withdrawn and cultured using conventional media; thioglycolate broth was added to the tube containing the resin beads. The conventional and ARD-processed cultures were incubated at 35 degrees C for at least 7 days., Results: Of the 338 endophthalmitis cultures processed using both conventional cultures and a parallel ARD, 166 (49.1%) yielded positive microbial growth on one or more media. Of the 166 culture-confirmed cases, 127 (76.5%) were positive in both the ARD-processed and direct cultures, 17 (10.2%) were positive by conventional culture only, and 22 (13.3%) were positive by the ARD-processed sample alone (P = 0.52). The spectrum of microorganisms was similar among all culture groups. The detection of coagulase-negative staphylococci and micrococci by ARD alone was slightly better than detection by conventional culture only (P = 0.06). Of 93 positive cultures from 179 patients in whom prior antibiotic use was documented, 75 (80.6%) were positive by both methods, 8 (8.6%) by conventional cultures only, and 10 (10.8%) only by the ARD-processed specimen (P = 0.81)., Conclusion: Use of an antimicrobial removal device does not significantly increase the microbial yield of endophthalmitis cultures compared with conventional culture techniques, whether or not antimicrobial therapy is being used.

Purpose: To identify the characteristics and outcomes of infectious crystalline keratopathy caused by gram-negative bacteria., Methods: We reviewed all patients treated at a university eye center for infectious crystalline keratopathy from 1978 through 1995 and performed a nested case-comparison study by comparing patients with keratitis caused by gram-negative rods and those with keratitis caused by gram-positive cocci., Results: Eighteen patients (mean age +/- SD, 59 +/- 17 years) displayed unilateral culture-positive infectious crystalline keratopathy. Among 18 eyes with crystalline keratopathy, five occurrences (28%) were caused by gram-negative rods (Acinetobacter lwoffi, Citrobacter koseri, Enterobacter aerogenes, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia), 10 (55%) were caused primarily by gram-positive cocci, and three (17%) were caused primarily by yeasts. Four cases grew two different isolates. No significant difference in predisposing factors, clinical appearance, or visual outcome was found between infections caused by gram-negative bacteria and those caused by gram-positive bacteria., Conclusions: Gram-negative bacteria can cause infectious crystalline keratopathy but have no distinguishing features from infectious crystalline keratopathy caused by streptococci and other gram-positive bacteria. Appropriate laboratory evaluation is therefore necessary to guide specific antimicrobial therapy.

Objective: To describe patterns of conjunctivitis caused by ophthalmic decongestants., Design: Case series., Setting: Outpatient eye clinic., Patients: We selected patients with conjunctival inflammation who were using nonprescription decongestant eyedrops, who had no other cause for conjunctivitis, and whose conditions improved after discontinuing the incriminated preparations., Main Outcome Measures: Clinical characteristics of conjunctival inflammation and time to resolution of symptoms and signs after discontinuing the use of eyedrops., Results: Seventy patients (137 eyes) were identified. Preparations containing the vasoconstrictors naphazoline, tetrahydrozoline, or phenylephrine were associated with 3 clinical patterns of conjunctivitis: conjunctival hyperemia (50 cases), follicular conjunctivitis (17 cases), and eczematoid blepharoconjunctivitis (3 cases). Decongestants were used daily for a median of 3 years (range, 8 hours to 20 years) prior to presentation. The median time to resolution of symptoms and signs was 4 weeks (range, 1-24 weeks), and patients remained asymptomatic for a median follow-up of 6 months (range, 0-12 years)., Conclusion: Nonprescription decongestant eyedrops can produce acute and chronic forms of conjunctivitis by pharmacological, toxic, and allergic mechanisms. Once recognized, conjunctival inflammation often takes several weeks to resolve.

Infectious crystalline keratopathy is a chronic infection of the cornea, characterized by branching intrastromal opacities without inflammation. These changes are usually due to accumulations of bacterial colonies, most commonly viridans streptococci, but this entity has previously been reported in association with Candida albicans and Candida tropicalis. We present the case of a 66-year-old man who had previously undergone penetrating keratoplasty and developed infectious crystalline keratopathy due to Candida parapsilosis. Histopathology showed interlamellar accumulations of viable yeasts with no inflammation. Chronic topical corticosteroid use in this patient produced relative immunosuppression, allowing for the infection by Candida parapsilosis and the lack of inflammation in the cornea. The spectrum of causative organisms in infectious crystalline keratopathy continues to grow, emphasizing the need for laboratory evaluation in the management of this disorder.

A man with acquired immunodeficiency syndrome developed a generalized rash and bilateral dendritic epithelial keratitis without retinitis. Cytologic examination of superficial corneal scrapings showed many megalosyncytial giant cells that were highly characteristic of cytomegalovirus (CMV) infection. Viral cultures yielded CMV from 2 separate specimens obtained by corneal epithelial debridement from both eyes. The slightly elevated, opaque, branching, nonulcerative epitheliopathy recurred after corneal scrapings and persisted despite oral and topical antiviral therapy. Stromal keratouveitis subsequently developed. This case report confirms that CMV can produce corneal involvement and suggests that CMV keratitis may be an emergent complication of acquired immunodeficiency syndrome.

Objectives: To determine if the number of ocular infections associated with Stenotrophomonas maltophilia is increasing, to identify predisposing factors, and to evaluate antimicrobial susceptibility., Methods: Retrospective review of ocular microbiology laboratory records from January 1, 1972, through December 31, 1995., Results: Stenotrophomonas maltophilia was recovered from 15 cases of ocular infection, at a rate of one in every 1339 ocular specimens in the 1970s, one in 413 in the 1980s, and one in 363 in the 1990s through 1995. The organism was the predominant isolate in five cases and was part of a polybacterial infection in the remaining 10 cases. Eight of the 15 cases had bacterial keratitis, including one with infectious crystalline keratopathy. Of the remaining seven infections, S maltophilia was recovered from two cases of acute conjunctivitis, two infected scleral buckles (one with orbital cellulitis), two cases of infantile dacryocystitis, and one case of preseptal cellulitis. Ocular isolates of S maltophilia were resistant to the aminoglycosides and most beta-lactams, and showed variable susceptibility to the fluoroquinolones., Conclusions: Stenotrophomonas maltophilia is emerging as an important opportunistic ocular pathogen. Most infections by this organism occur in patients with ocular compromise, and the characteristically resistant antibiogram of S maltophilia limits the therapeutic options.

Purpose: Topical corneal anesthetic abuse is a self-inflicted injury, causing profound corneal morbidity. Superimposed infection is an important complicating factor. The authors report four patients with confirmed topical anesthetic abuse of the cornea, in whom Candida keratitis developed., Methods: A retrospective review of the medical records of four patients with confirmed topical corneal anesthetic abuse and fungal keratitis., Results: A 21-year-old woman, two 28-year-old women, and a 35-year-old man were included in the study. All these patients sustained a corneal injury, prompting the chronic use of topical anesthetics (0.5% proparacaine hydrochloride in 3 patients, and 0.5% tetracaine hydrochloride and 0.4% benoxinate hydrochloride in the other). Corneal findings included epithelial defects in all patients, focal infiltrate in one patient, and ring-shaped stromal infiltrate in three patients. Topical anesthetic was discontinued, all patients initially were treated empirically with antibacterial agents, and three patients received topical corticosteroids. Subsequent corneal cultures grew Candida spp, Candida albicans specifically in three patients, and local and systemic antifungal therapy was started. Corneas in two patients re-epithelialized; a conjunctival flap was performed on another patient with a descemetocele; and the remaining patient was lost to follow-up, although repeat fungal cultures yielded no growth., Conclusions: Corneal superinfection with Candida may occur during topical anesthetic abuse. Therapy includes discontinuation of the anesthetic and institution of antifungal therapy.

Objectives: To describe a national eye banking registry and to assess the effects of donor age, cause of donor death, time from death to procurement, storage time, and distance between the points of recovery and transplantation on the reported occurrence of primary corneal graft failure., Design: We performed a retrospective case-control study to estimate the odds ratios of five donor factors for cases of primary graft failure voluntarily reported to a national registry using controls from selected eye banks. We also performed a nested case-control cohort study to compare cases of primary graft failure that occurred in both corneas from the same donor with those of nonmated corneas in which primary graft failure was reported to assess odds ratios for the same donor factors., Patients: One hundred forty-seven patients developed primary graft failure in penetrating keratoplasty transplantations performed between January 1, 1991, and December 31, 1993. These cases were reported to the Adverse Reaction Registry of the Eye Bank Association of America, Washington, DC. Controls included 7240 donor corneas distributed by nine eye banks during 1992., Results: Of the 147 donor corneas that developed primary graft failure, 17 (12%) were obtained from donors who were aged 70 years and older, 39 (27%) came from donors who died of trauma, 13 (9%) had a cadaver time longer than 12 hours, 10 (7%) had a storage time longer than 7 days, and 38 (26%) were distributed outside the eye bank's region. Compared with controls, these donor corneas were more likely to have a storage time longer than 7 days (odds ratio, 2.4; 95% confidence limits, 1.2 and 4.6) and to come from donors aged 70 years and older (odds ratio, 2.4; 95% confidence limits, 1.4 and 4.0). The 22 corneas (15%) in which primary graft failure occurred in both recipients from the same donor were 8.5 times (95% confidence limits, 1.1 and 51.5) more likely to be preserved beyond 1 week than were nonmated corneas with primary failure but were not from significantly older donors. Logistic regression analysis showed that the association between prolonged storage time and primary graft failure in mated corneas remained significant even when the analysis was controlled for other donor factors., Conclusions: No clearly defined donor or eye banking factor accounted for most cases of primary graft failure, although prolonged corneal storage and advanced donor age may increase its risk. Ophthalmologists are urged to report to their eye bank all cases of primary graft failure and other adverse events that might be attributable to donor eye tissue.

We evaluated the efficacy of topical cyclodextrin-encapsulated FK-506 in the prevention of experimental corneal allograft rejection. Two weeks after inducing corneal inflammation and neovascularization with 8-0 silk sutures, 23 albino rabbits received a unilateral 8-mm diameter central penetrating corneal allograft from pigmented donors. Rabbits were randomly assigned to no treatment (eight eyes), topical cyclodextrin four times daily for 28 days (seven eyes), or topical FK-506 0.3 mg/ml in a cyclodextrin suspension (eight eyes) four times daily for 28 days. Grafts were examined daily for degree of inflammation, neovascularization, edema, and signs of rejection for up to 100 days. Seven of eight (88%) untreated grafts and five of seven (71%) cyclodextrin-treated grafts rejected at a median of 3 weeks after transplantation, whereas only two (25%) of eight FK-506-treated grafts rejected and did so at a significantly longer interval (p < 0.005). Topical FK-506 prevents or delays corneal allograft rejection after experimental corneal transplantation.

A 33-year-old woman had keratoconus and retinal cone dystrophy, an association that has not been reported previously. The family history suggested a recessive inheritance pattern. Genetic probes for these conditions are needed to determine whether the coincidental occurrence of keratoconus and cone dystrophy is due to a genetic relationship or was a chance event.

Purpose: Certain drugs bind to anionic phospholipids of lysosomal membranes and produce progressive intracellular accumulation of lamellar inclusions. We studied two patients treated for opportunistic infections associated with the acquired immunodeficiency syndrome (AIDS), who developed bilateral ocular surface changes suggestive of drug-induced corneal lipidosis., Methods: Two patients with AIDS had translucent vacuoles within the corneal epithelium and mild conjunctival hyperemia. Because the differential diagnosis included microsporidial keratoconjunctivitis, biopsies of the ocular surface were performed for histopathologic analysis., Results: Transmission electron microscopy of corneal epithelial debridement and conjunctival biopsy specimens showed intracellular, electron-dense lipoidal bodies and multilaminated lysosomal inclusions suggestive of a drug-induced lipidosis. Both patients also had tubuloreticular inclusions in conjunctival capillary endothelial cells. The ocular surface changes resolved within one to three months after dosage reduction or discontinuation of systemic ganciclovir and acyclovir., Conclusions: Drug-induced phospholipidosis is a cause of punctate corneal epitheliopathy during AIDS, but the responsible agent remains to be identified.

Background: Histopathologic studies of this unusual keratitis caused by Capnocytophaga species have not been reported previously., Methods: The authors report the light microscopic and ultrastructural findings of three patients with a distinctive necrotizing keratitis caused by an anaerobic gram-negative bacillus. In three patients, ages 19, 81, and 91 years, a necrotizing stromal keratitis developed; two of these patients had a previous penetrating keratoplasty for pseudophakic bullous keratopathy. The first patient did not have ocular surgery previously and was treated initially for presumed Acanthamoeba keratitis., Results: By light microscopy, all three keratectomy specimens were strikingly similar and showed a necrotizing and/or suppurative stromal keratitis displaying myriad slender, fusiform, gram-negative bacilli located anterior to Descemet's membrane and extending into the deep corneal stroma, assuming a "picket fence" appearance. Cultures of the cornea in case 1 grew Capnocytophaga ochracea. For the remaining two patients, a diagnosis presumptively was made based on characteristic histopathologic features. Results of electron microscopic examination showed numerous bacilli that were mostly extracellular; occasional organisms were phagocytosed by macrophages., Conclusion: The histopathologic features of Capnocytophaga keratitis are unique; therefore, a presumptive diagnosis can be made based on the morphology and location of the bacilli in the keratectomy specimens. To the authors' knowledge, this is the first study describing the typical histopathologic and electron microscopic findings of Capnocytophaga keratitis.

Purpose: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis., Methods: The authors performed a randomized, double-masked, placebo-controlled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization., Results: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups., Conclusions: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Purpose: To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine., Methods: The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial., Results: The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group., Conclusion: There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.

Background: Infectious crystalline keratopathy is a distinctive clinical entity characterized by bacterial replication within the corena without inflammation. The authors report on a patient with infectious crystalline keratopathy due to Streptococcus pneumoniae serotype 11F. They used this isolate to study the contribution of the pneumococcal polysaccharide capsule to the pathogenesis of the infectious crystalline keratopathy., Methods: Aliquots containing 10(6) colony-forming units of pneumococci serotype 11F, serogroup 9 or 15, were inoculated into New Zealand white rabbit corneas. The corneas were examined at 24, 48, and 72 hours. Representative corneas were excised at 24 hours and processed for histopathologic analysis., Results: Pauci-inflammatory crystalline lesions developed in all corneas inoculated with the serotype 11F ocular isolate by 24 hours. Suppurative keratitis developed in control corneas inoculated with serogroup 9 or 15 pneumococci. The nonocular 11F isolates produced lesions with some features compatible with infectious crystalline keratopathy., Conclusion: Different pneumococcal serotypes vary in their ability to produce infectious crystalline keratopathy. Because serotype differences reflect differences in the antigenic polysaccharides of the bacterial capsule, this study suggests that properties of the pneumococcal capsule may influence the initial development of infectious crystalline keratopathy.

Corneal transplantation, the most common transplantation procedure done in the United States, requires access to a sufficient number of donor eyes. We examined how laws governing tissue donation affect availability of corneal tissue by reviewing records of the Lions Eye Bank of Texas, Houston, from 1961 through 1990 (43,696 eyes from 21,898 donors). Relevant Texas statutes included the Uniform Anatomical Gift Act of 1970, the Justice of the Peace/Medical Examiner Law of 1977, and the Routine Inquiry Law of 1988. Before 1970, the mean (+/- SD) number of donated corneas was 72 +/- 38 per year; enactment of each statute above was associated with increased mean annual donations of 215 +/- 87, 1329 +/- 562, and 1958 +/- 33 corneas, respectively. The Justice of the Peace/Medical Examiner Law yielded significantly younger donors (who died of trauma), and the Routine Inquiry Law increased the number of hospitalized donors. Data from this eye bank were compared with current state laws nationwide. Effective legislation is a means to meet national ophthalmic surgical needs.

Objective: To determine the efficacy and safety of topical 0.3% ciprofloxacin hydrochloride ophthalmic ointment in the treatment of bacterial keratitis., Design: Prospective case series with a nonrandomized comparison of culture-positive, evaluable cases (ciprofloxacin ointment group) with culture-positive, concurrent patients (nonenrolled group) treated with conventional therapy., Setting: Multicenter clinical study., Patients: After informed consent was obtained, 253 eligible patients underwent corneal scrapings and received topical ciprofloxacin ointment; 145 (57%) had positive cultures and completed the follow-up schedule. Forty (70%) of 57 apparently eligible patients had culture-positive bacterial keratitis but were not enrolled in the ciprofloxacin ointment study during the same period., Intervention: Ciprofloxacin ophthalmic ointment instilled every 1 to 2 hours for 2 days, then every 4 hours for 12 days., Main Outcome Measures: Clinical evaluation of signs at 1, 3, 7, and 14 days of treatment and the overall condition classified as clinical success (cured or improved) or failure (unchanged or worse) during and after therapy., Results: Clinical success with the initial treatment occurred in 135 patients (93%) in the ciprofloxacin ointment group and in 28 patients (70%) in the nonenrolled group. Of the 10 ciprofloxacin clinical failures, seven were staphylococcal; two, pneumococcal; and one, polybacterial. The 90% minimum inhibitory concentration of ciprofloxacin was 3 mg/L or less for corneal bacterial isolates. No serious adverse event attributable to ciprofloxacin ointment occurred, although 32 (13%) of 253 patients developed a transient white crystalline corneal precipitate shown with liquid chromatography in two cases to be ciprofloxacin., Conclusion: Ciprofloxacin ophthalmic ointment is an effective and safe topical antimicrobial agent for the treatment of bacterial keratitis caused by susceptible microorganisms.

Laser iridotomy is generally a safe and effective procedure for narrow-angle glaucoma. However, since surgical success with the argon laser depends on a focal thermal effect, a corneal burn is a possible complication. I describe five patients with occludable anterior chamber angles and bilateral corneal guttata who developed uniocular progressive corneal edema with visual loss following argon laser iridotomy. These five patients underwent iridotomy with a total laser energy of 63, 48.5, 7, 25, and 25 J, respectively, and began to lose vision due to corneal edema immediately, and 5, 2, 4, and 2 years later, respectively. Following penetrating keratoplasty with cataract surgery, histopathology of the corneal buttons showed generalized endothelial cell loss in all five. Microstructural findings of guttata and thickened Descemet's membrane implied that prior endothelial dystrophy had predisposed these patients to laser-induced damage. Risk factors for immediate or delayed-onset bullous keratopathy after argon laser iridotomy include prior angle closure, preexisting endothelial guttata, and high laser energy with multiple applications. Recognizing the potential of this complication offers opportunities for preventive strategies.

A 76-year old woman developed an intracorneal cyst following uncomplicated cataract surgery. Progressive enlargement led to partial visual loss. Following drainage of the cyst, cytopathologic examination showed epithelial cells. The cyst subsequently reformed and caused acute pupillary block. Repeat drainage and cryotherapy were performed. Vision was limited by corneal edema, and penetrating keratoplasty was performed.

Two patients developed corneal opacities resembling infectious crystalline keratopathy. Predisposing factors included a recent corneal transplant with suture replacement in one patient and postradiation keratoconjunctivitis with disposable therapeutic contact-lens wear in the other patient. Both patients were using a topically applied corticosteroid and an aminoglycoside antimicrobial. Smears of corneal scrapings showed numerous yeasts without inflammatory cells. Culturing yielded Candida albicans and Staphylococcus haemolyticus in the first case and C. albicans and S. epidermidis in the second case. Combined antifungal and antimicrobial therapy, with initial withdrawal of corticosteroid use, was effective. The microbial cause of pauci-inflammatory keratitis includes not only viridans streptococci and other bacteria but fungi as well.

We treated five patients, aged 26, 4, 6, 13, and 7 years, who developed disciform stromal keratitis one, four, four, eight, and ten weeks, respectively, after the onset of the acute vesicular exanthema. Serologic testing confirmed recent varicella and excluded other infectious causes in two cases. After initial improvement with a topical corticosteroid, three patients developed recurrent corneal inflammation resembling zoster keratitis. These cases and previous reports indicate that varicella-zoster virus is a cause of disciform stromal keratitis that may occur and recur several weeks or months after the primary skin rash has resolved.

A 65-year-old man with recurrent herpetic keratitis underwent corneal transplantation for persistent nonimmunologic graft failure. Histopathologic examination of the corneal button revealed an epithelial dendrite containing Cowdry type A inclusion bodies, moderate stromal edema, and a retrocorneal fibrous membrane. Immunohistochemical studies demonstrated herpes simplex virus antigens in epithelial cells bordering the dendritic defect and in stromal keratocytes. The mean width of corneal epithelium displaying herpes simplex virus-positive epithelial cells on either side of the dendritic defect measured 200 +/- 46 microns. By electron microscopy, herpesvirus particles were identified in epithelial cells lining the dendrite as well as in stromal keratocytes. Infected keratocytes were scattered throughout the stroma but were not observed subjacent to the epithelial dendrite. This study demonstrates that a recurrent epithelial dendrite can be associated with subclinical stromal infection of the graft.

Amebic keratitis presents a therapeutic dilemma because Acanthamoeba, unlike Naegleria, encysts in infected tissues. To date, the results of medical therapy have been disappointing, and the optimal medical regimen for acanthamoeba keratitis is yet to be defined. Clinical cure necessitates eradication of the encysted amebae with medications known to have ocular toxic effects in combination with surgical maneuvers. Antiinfective agents possessing in vitro cysticidal activity include paromomycin, neomycin, ketoconazole, natamycin, and ciclopirox olamine, but no agent has been shown to be uniformly effective against all isolates of Acanthamoeba. Treatment of amebic cysts with propamidine isethionate plus either paromomycin or neomycin has produced slightly additive cysticidal effects. Multiple factors, including the varied clinical presentation and the lack of standardized in vitro techniques for the assay of cysticidal activity, account for the lack of correlation between in vitro activity and in vivo efficacy.

Four patients with chronic open-angle glaucoma developed a dendriform corneal epithelial lesion. Two were associated with the use of topical betaxolol for 2 months and 6 weeks, and two were related to topical levobunolol. Resolution occurred within 2 weeks of discontinuation of the beta-blocker eyedrop. The distinctive pattern of dendritic epithelial keratopathy associated with these topical medications may be due to epithelial toxicity with subsequent regeneration.

Cellufluor, a fluorochrome with affinity for chitin and cellulose, was retrospectively compared to gram and giemsa stains for detection of human oculomycoses. From culture-proven specimens, this chemofluorescent stain detected hyphae or yeasts on 50% of smears previously considered negative. Cellufluor is a useful adjunct in the detection and confirmation of fungal elements from ocular specimens.

Of 92 enucleated eyes with scleral inflammation and 114 eyes from 81 patients with scleritis, 45 (49%) and 20 (18%), respectively, showed evidence of increased intraocular pressure. Damage to the trabecular meshwork of iridocyclitis, overlying corneoscleral inflammation, or peripheral anterior synechiae was the most common cause of increased intraocular pressure. Other causes included topical corticosteroid use, angle neovascularization, and posterior scleritis with secondary angle closure.

Topical treatment of severe ocular infections may require the use of antibiotics fortified in concentration beyond commercially available preparations. The authors studied tear pharmacokinetics, tissue bioavailability, epithelial toxicity, and comparative antibacterial efficacy of topical tobramycin concentrations ranging from 0.3-5.0%. Tear pharmacodynamics demonstrate bioassay-measurable levels with each preparation up to 6 hr after a single 50-microliter drop challenge. Comparing various fortified concentration levels yields progressive parallel-biphasic decay curves in antibiotic tear-film concentrations. Both tear and corneal data demonstrate increases in measured antibiotic levels largely proportional to the increases in drug concentration instilled. Tobramycin was undetectable in corneas treated with 0.3% tobramycin, yet measurable with higher drug levels. A rabbit epithelial wound-healing model demonstrated progressive toxicity ranging from no effect of 0.3% tobramycin on healing rates compared with paired controls, to a significant decrease in re-epithelialization rates with 1.1% (P = 0.03) and 4.0% (P = 0.02) tobramycin. Finally, a Pseudomonas aeruginosa keratitis model in the rat demonstrates the antibiotic efficacy of topical tobramycin treatment over untreated controls (P less than 0.00001), and a progressively enhanced efficacy with increasing tobramycin concentrations is suggested. Concentration enhancement of topical ocular medication is useful in the treatment of severe ocular infection.

We evaluated 31 fungal specimens obtained from equine corneas over a 10-year period, 1973 to 1983. More than half were received in late summer and early autumn, and the number tended to increase in frequency during the 1980s. These isolates included 13 different genera and 20 different species. The prevalent genus was Aspergillus (35%). On the basis of examinations for tube-dilution minimal inhibitory concentrations and minimal fungicidal concentrations of 16 fungal isolates, the imidazole antibiotics such as miconazole and ketoconazole consistently showed the lowest geometric mean titers for filamentous fungi. Because fungal sensitivities varied considerably among different species in vitro sensitivity testing is suggested as an aid in the determination of optimal therapy.

The authors identified nine patients with culture-proven keratitis after radial keratotomy (RK). Three patients became infected in the immediate post-operative period, and six patients had delayed-onset keratitis. Gram-negative rods were the predominant pathogens in late-onset keratitis (4 of 6 infections). Gram-positive cocci were implicated in all three postoperative infections. The inferior corneal quadrants were involved in seven of nine patients. Two episodes of late-onset keratitis were associated with contact lens wear. Five of these patients had transverse incisions or greater than eight radial cuts. All six patients regained visual acuity of 20/40 or better. Two additional cases of early-onset and six cases of late-onset keratitis with many features similar to these cases have been reported previously.

Supplementation of tissue culture medium with chondroitin sulfate has been shown to enhance donor corneal preservation. We assessed the efficacy of one of these chondroitin-supplemented media (K-Sol) in comparison with McCarey-Kaufman (MK) medium in maintaining corneal cellular morphology. Thirty-six human corneas, obtained within 8.6 h after death, were placed into K-Sol medium for up to 20 days preservation, and five paired control corneas were placed into MK medium for up to 6 days preservation. Specular photomicrographs were obtained every second to third day for a predetermined storage interval, then studied morphologically in a masked protocol by light microscopy, transmission electron microscopy, and scanning electron microscopy. Endothelial cell loss by specular microscopy averaged 5.8% after 1 week (6 to 8 days) and 7.4% after 13 days in K-Sol medium. Epithelial changes were erratic throughout the 20 day K-Sol preservation period. However, substantial keratocyte changes occurred after 10 days, and endothelial morphology uniformly deteriorated after 17 days. The morphologic data suggest that human corneas may be able to be preserved in K-Sol medium at 4 degrees C for up to 10 days but should be cautiously used thereafter.

Three patients had pellucid marginal corneal degeneration complicated by corneal edema. The corneal edema appeared to be a result of a break or detachment of Descemet's membrane as a result of increasing corneal ectasia. The disruption in Descemet's membrane began just above the inferior, crescent-shaped area of stromal thinning. Therapeutic modalities initially included hypertonic solution to determine whether corneal edema would resolve spontaneously, apparently by endothelial migration with healing over the break in Descemet's membrane. One patient required thermokeratoplasty and another penetrating keratoplasty for persistent stromal edema. Acute hydrops can occur with pellucid marginal corneal degeneration by a pathogenesis similar to other noninflammatory corneal thinning disorders such as keratoconus.