Alice Y. Matoba

Herpetic Eye Disease Study: A Controlled Trial of Oral Acyclovir for Herpes Simplex Stromal Keratitis

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.

The Autoimmune Nature of Aqueous Tear Deficiency

Twenty-two patients with aqueous tear deficiency (ATD) were examined for the presence of the following autoantibodies: immunofluorescent antinuclear antibody (ANA) and Sjögrens syndrome antibodies A and B (SS-A and SS-B). These autoantibodies were found in 17 (82%) patients but not in control subjects, and they correlated with the severity of symptoms and ocular surface changes. Bacterial keratitis, often recurrent and bilateral, and progressive sterile corneal stromal melting developed in six autoantibody-positive ATD patients. Eight antibody-positive patients had labial salivary or lacrimal gland biopsies, and all showed similar histologic features with marked destruction of the glandular architecture by lymphocytic infiltration. Immunoglobulin and complement were not detected in the glandular tissue. Circumstantial evidence suggests that an abnormal immunologic reaction, possibly related to Epstein-Barr viral (EBV) infection, is the cause of the glandular destruction and tear deficiency.

Clinical and microbiological characteristics of fungal keratitis in the United States, 2001-2007: a multicenter study.

OBJECTIVE To study the epidemiology, clinical observations, and microbiologic characteristics of fungal keratitis at tertiary eye care centers in the United States. DESIGN Retrospective multicenter case series. PARTICIPANTS Fungal keratitis cases presenting to participating tertiary eye care centers. METHODS Charts were reviewed for all fungal keratitis cases confirmed by culture, histology, or confocal microscopy between January 1, 2001, and December 31, 2007, at 11 tertiary clinical sites in the United States. MAIN OUTCOME MEASURES Frequency of potential predisposing factors and associations between these factors and fungal species. RESULTS A total of 733 cases of fungal keratitis were identified. Most cases were confirmed by culture from corneal scraping (n = 693) or biopsies (n = 19); 16 cases were diagnosed by microscopic examination of corneal scraping alone; and 5 cases were diagnosed by confocal microscopy alone. Some 268 of 733 cases (37%) were associated with refractive contact lens wear, 180 of 733 cases (25%) were associated with ocular trauma, and 209 of 733 cases (29%) were associated with ocular surface disease. No predisposing factor was identified in 76 cases (10%). Filamentous fungi were identified in 141 of 180 ocular trauma cases (78%) and in 231 of 268 refractive contact lens-associated cases (86%). Yeast was the causative organism in 111 of 209 cases (53%) associated with ocular surface disease. Yeast accounted for few cases of fungal keratitis associated with refractive contact-lens wear (20 cases), therapeutic contact-lens wear (11 cases), or ocular trauma (21 cases). Surgical intervention was undertaken in 26% of cases and was most frequently performed for fungal keratitis associated with ocular surface disease (44%). Surgical intervention was more likely in cases associated with filamentous fungi (P = 0.03). Among contact lens wearers, delay in diagnosis of 2 or more weeks increased the likelihood of surgery (age-adjusted odds ratio = 2.2; 95% confidence interval, 1.2-4.2). CONCLUSIONS Trauma, contact lens wear, and ocular surface disease predispose patients to developing fungal keratitis. Filamentous fungi are most frequently the causative organism for fungal keratitis associated with trauma or contact lens wear, whereas yeast is most frequently the causative organism in patients with ocular surface disease. Delay in diagnosis increases the likelihood of surgical intervention for contact lens-associated fungal keratitis.

Pathogenesis and outcome of Paecilomyces keratitis.

PURPOSE To examine the clinical pathology and management of Paecilomyces lilacinus keratitis. DESIGN Observational case series, literature review, and laboratory study. METHODS Characteristics and outcome of 17 patients with laboratory-confirmed Paecilomyces keratitis treated at 2 referral centers were combined with 25 previously reported cases. Experimental models were developed by topically inoculating a human corneal isolate of P. lilacinus onto murine eyes and onto human donor corneas. RESULTS Of 42 reported eyes with Paecilomyces keratitis, 13 (31%) were associated with chronic keratopathy or previous ocular surgery, 11 (26%) followed corneal trauma, and 10 (24%) occurred in soft contact lens wearers. Medical cure occurred in 13 (31%), including 9 of 31 eyes (29%) treated with natamycin or amphotericin B. Penetrating keratoplasty or other surgery was performed in 29 (69%). In vitro testing of P. lilacinus indicated resistance to natamycin and amphotericin B but susceptibility to ketoconazole and voriconazole. Experimental inoculation after superficial scarification established moderately severe corneal paecilomycosis by hyphae and conidia in immunosuppressed mice and in explanted donor corneas. CONCLUSIONS P. lilacinus is an emerging fungal pathogen that infects corneal tissue by filamentous invasion with occasional intrastromal sporulation. P. lilacinus keratitis does not reliably respond to natamycin or amphotericin B and has often required therapeutic keratoplasty, but topical azole antifungal agents such as voriconazole appear promising.

The Effect of Therapeutic Soft Contact Lenses on Antibiotic Delivery to the Cornea

The effects of high (71%) and low (38.6%) water content lenses on antibiotic delivery to the cornea were studied in rabbits by measuring corneal tobramycin concentrations 1, 2, 4 and 6 hours after topical application at intervals of 15 minutes. In the presence of the low water content lens corneal drug levels were higher than in control corneas for every time point assayed. This difference was only significant at 4 hours (P less than 0.05). In eyes wearing the high water content contact lens corneal drug concentration was also higher at every time point tested except one hour. The difference was significant only at 4 hours (P less than 0.01). The data suggest that in the normal, noninflammed eye, the presence of a therapeutic soft contact lens will not compromise aminoglycoside delivery to the cornea.

Epstein-Barr Viral Stromal Keratitis

We have identified seven patients with clinical and serological features suggestive of Epstein-Barr viral (EBV) stromal keratitis. Four had discrete, sharply demarcated, multifocal, pleomorphic or ring-shaped granular anterior stromal opacities with normal intervening stroma, seemingly distinct from adenoviral or herpes simplex stromal keratitis. Two had soft, blotchy, pleomorphic, multifocal infiltrates, predominantly involving the peripheral cornea at all depths, and with minimal neovascularization, resembling syphilitic stromal keratitis. One patient had features or both forms of keratitis. OUr experience suggests that EBV may be more commonly associated with stromal keratitis than recognized previously.

Rapidly Progressive Cataract and Iris Atrophy during Treatment of Acanthamoeba Keratitis

PURPOSE To identify characteristics associated with cataract occurring during the course of Acanthamoeba keratitis. DESIGN Retrospective observational case series. PARTICIPANTS Eighty-one laboratory-confirmed patients with Acanthamoeba keratitis. METHODS Review of clinical records. MAIN OUTCOME MEASURES Development of cataract during management of Acanthamoeba keratitis. RESULTS Rapidly progressive crystalline lens opacification occurred in 9 eyes within 4 to 15 weeks after diagnosis of Acanthamoeba keratitis. Three were associated with inflammatory complications, including anterior scleritis (2 eyes) and iridocyclitis (1 eye). Six others had the abrupt onset of a dense cataract, including 5 with iris atrophy, that occurred during the initial 6 months of therapy with chlorhexidine, a diamidine, and adjunctive corticosteroid. Extracapsular cataract extraction was performed with or after penetrating keratoplasty. Secondary glaucoma developed in 6 of 9 eyes subsequent to iris atrophy (4 eyes) or a cyclitic membrane (2 eyes), and 3 eyes underwent trabeculectomy. CONCLUSIONS Cataract may occur and progress during the management of Acanthamoeba keratitis in association with anterior segment inflammation, iris atrophy, and secondary glaucoma.

Bilateral Acanthamoeba Keratitis

PURPOSE To determine the prevalence and characteristics of binocular involvement among patients with Acanthamoeba keratitis. DESIGN Retrospective case series. METHODS Risk factors and outcomes of bilateral infection were explored among consecutive cases of Acanthamoeba keratitis diagnosed at a single institution from 1997 through mid 2007. RESULTS Fifty eyes were confirmed to have Acanthamoeba keratitis by microbiologic or histopathologic testing; two-thirds occurred during a regional outbreak beginning in 2004. Five (11%) of 45 patients had infection of both eyes, including three with concurrent involvement and two with successive disease of the contralateral cornea. Three binocularly infected patients used soft contact lenses, and two wore rigid gas-permeable lenses. Nine of 10 eyes achieved visual acuity of 20/30 or better after antiamebic therapy. CONCLUSIONS Bilateral Acanthamoeba keratitis is an infectious complication of contact lens wear. With laboratory confirmation, vision often can be restored with medical therapy.

Infectious Crystalline Keratopathy due to Streptococcus pneumoniae: Possible Association with Serotype

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.

Mucus fishing syndrome.

Twenty-five patients are described with a variety of external ocular diseases including keratoconjunctivitis sicca, blepharitis, and allergic conjunctivitis, who presented with persistence of symptoms of irritation, foreign body sensation, and apparent excessive mucus production, with mild conjunctival inflammation despite appropriate treatment of the underlying disease. All patients were found to have evidence of trauma to the conjunctival epithelium due to mechanical removal of the excess mucus from the surface of the globe or inferior cul-de-sac. The surface irritation created by the mechanical damage led to a further increase in mucus production, creating a cycle that we have termed mucus fishing syndrome. Cessation of this behavior coupled with ongoing therapy of the underlying disease led to resolution of signs and symptoms in all patients.