Topical Fumagillin Research Articles

Efficacy of fumagillin bicyclohexylamine on experimental corneal neovascularization in rat model.

Fumagillin has been previously used to treat corneal microsporidial keratitis and also identified as an angiogenesis inhibitor. This study aimed to evaluate efficacy of fumagillin bicyclohexylamine on the rat model of corneal neovascularization induced by silver nitrate cauterization. Twenty-four Albino Wistar rats (n = 24) were divided into three groups. Following silver nitrate-induced corneal injury, eyes in Group 1 received one drop of 5mg/mL topical fumagillin bicyclohexylamine four times daily for 10days. Group 2 received subconjunctival injection of 0.1mL fumagillin bicyclohexylamine (2.5mg/mL) on day 1 and day 5. Group 3 received artificial tears and lubricants four times daily for 10days as control. On day 10, animals were sacrificed. Corneal specimens were obtained and prepared to assess vascular endothelial growth factor (VEGF-C) levels and corneal angiogenic microvessel density. There was no significant difference in VEGF-C levels between the groups (P = 0.994). Assessment of angiogenic microvessel density for peripheral corneal zone also did not reveal significant difference between the groups (P = 0.113). However, mean vascular density in Group 1 and Group 2 was significantly higher for both midperipheral and central corneal zones in comparison with Group 3 (P = 0.003, P = 0.015). Previously proved to be effective for treatment of microsporidial keratitis in humans, topical and subconjunctival concentration or dosing of fumagillin bicyclohexylamine failed to reduce corneal neovascularization induced by silver nitrate in this study. Further studies comparing different concentrations and dosing may detect inhibitory effects of fumagillin on corneal neovascularization without inducing toxicity.

Emerging Prevalence of Microsporidial Keratitis in Singapore: Epidemiology, Clinical Features, and Management

To investigate the incidence and epidemiologic factors involved in the development of microsporidial keratitis. The association of host immune status and clinical pattern, clinical features, and the role of fluoroquinolone monotherapy in treatment are also examined. Retrospective, noncomparative case series. All cases (124 patients, 134 eyes) of microsporidial keratitis confirmed with modified trichrome stain positive of corneal scrape over a 4-year period. Epidemiologic factors were observed. Host immune status with human immunodeficiency virus (HIV) serology and CD4/CD8 analysis was performed when consent was obtained. Visual acuity (VA) and slit-lamp examination throughout the course of keratitis was recorded. Treatment used included topical fluoroquinolones (ciprofloxacin 0.3%, moxifloxacin 0.5%, gatifloxacin 0.5%, levofloxacin 0.5%, or norfloxacin 0.3%) as monotherapy or in combination with topical fumagillin and/or systemic albendazole. Where corneal edema developed, ultrasound corneal pachymetry was recorded. Demographic features and epidemiologic factors, including host immune status. Clinical features and disease course, including the response to different therapeutic regimes. Patients ranged in age from 11 to 68 years (mean, 31.9; median, 30) with a male:female ratio of 8:1 (females n = 17 [13.7%]). We performed HIV serology and CD4/CD8 in 45.9% of cases (n = 57); all the cases tested were negative with normal T-cell indices. Epidemiologic factors included soil exposure (50%), contact lens wear (21.1%), and topical steroid treatment (17.1%). The VA on presentation ranged from 20/20 to 20/100 (median, 20/30) with no loss in lines of VA on resolution. Common features were follicular papillary conjunctivitis and coarse punctate epithelial lesions in 3 patterns--diffuse, peripheral, and paracentral--evolving into nummular keratitis before resolution. Resolution occurred in 99% of cases on topical fluoroquinolone monotherapy. Four patients had recurrent disease that resolved with repeat fluoroquinolone or fluoroquinolone/oral albendazole combination. Two new clinical features were identified--diffuse endotheliitis (19.4%) with corneal edema and limbitis. This study identifies an increasing incidence of microsporidial keratitis in Singapore with a strong correlation with prior soil exposure. Diffuse endotheliitis and limbitis have not been described and resolves with topical steroid therapy. Topical fluoroquinolone monotherapy is a valid treatment option.

Deep Anterior Lamellar Keratoplasty to Treat Microsporidial Stromal Keratitis

To describe deep anterior lamellar keratoplasty (DALK) as a surgical option to treat a case of severe microsporidial stromal keratitis in an immunocompetent patient. This study is a descriptive case report. A 42 year-old Pakistani woman had an 8-year history of symptoms in the left eye. She had been previously provisionally diagnosed as suspected herpes simplex keratitis or Thygeson keratitis. At presentation, her best-corrected visual acuity was 20/20 OD and 20/200 OS. Examination of the left cornea revealed irregular, central, deep stromal opacification with keratitic precipitates and occasional cells in the anterior chamber. Investigations for mycobacteria, syphilis, and a tetraplex test were normal; all other hematological/biochemistry/virology investigations were normal-she was not found to be immunocompromised. A corneal biopsy confirmed microsporidial infiltration of the stroma. After intensive medical treatment with topical fumagillin and oral albendazole without resolution, DALK was performed with total stromal replacement using the big-bubble technique. One year postoperatively, the graft remained clear with no evidence of recurrence and best-corrected visual acuity was 20/40 OS. Microsporidial stromal keratitis is rare. Conventional surgical treatment for such a condition has been penetrating keratoplasty. DALK may be considered an option for visual rehabilitation in these cases.

Microsporidium Stromal Keratitis: In Vivo Confocal Findings

To relate the clinical signs, histopathologic features, and in vivo confocal biomicroscopy findings of a case of stromal microsporidial keratitis and to describe the use of in vivo confocal microscopy to monitor treatment effect. An immunocompetent male patient presented with unilateral indolent stromal keratitis. Stromal microsporidiosis was confirmed after corneal biopsy. He underwent examination that used in vivo confocal microscopy (Heidelberg Retina Tomograph II and Rostock Cornea Module) before and after treatment with topical fumagillin and oral albendazole. Clinicopathologic correlation of the confocal scan was performed. Corneal biopsy showed extracellular microsporidium spores aligned along keratocytes and corneal lamellae. In vivo confocal scans showed similar morphology, with bright dots aligned along keratocytes. Treatment with antimicrobials and topical steroid gave resolution of active keratitis, correlating with disappearance of the bright spores on repeat in vivo confocal scanning. The in vivo confocal microscopy appearance of microsporidial keratitis corresponds to the histologic features from biopsy material. Treatment response may be monitored by using this technique, although definitive diagnosis requires corneal biopsy.

Keratitis caused by Trachipleistophora anthropopthera

We report a case of intrastromal keratitis in a 42-year-old male with underlying human immunodeficiency virus-1 infection. Numerous microsporidial spores were found from corneal biopsy. Ultrastructural studies of corneal tissues revealed dimorphic sporophorous vesicles containing characteristic spores belonging to Trachipleistophora anthropopthera. Infection could be controlled by penetrating keratoplasty but not by topical fumagillin and systemic albendazole per se. This is the first report of human keratitis caused by this organism.

Ocular and Sinus Microsporidial Infection Cured With Systemic Albendazole

To report treatment of a patient with acquired immunodeficiency syndrome (AIDS) and ocular and paranasal sinus microsporidial infection. Case report. A patient with AIDS and ocular microsporidial infection experienced resolution of ocular symptoms with topical fumagillin, but symptoms recurred upon cessation of therapy. Paranasal sinus microsporidial infection was diagnosed. The patient received sequential systemic treatment with itraconazole followed by albendazole. Sinus symptoms resolved with albendazole. He remained symptom-free with a normal examination 17 months after concluding therapy. Although fumagillin and itraconazole may have played a role, systemic albendazole appears to be responsible for clinical resolution of microsporidial infection.

Microsporidial Keratoconjunctivitis Caused by Septata intestinalis in a Patient With Acquired Immunodeficiency Syndrome

To examine and treat a patient with acquired immunodeficiency syndrome (AIDS) who had mildly hyperemic conjunctiva and epithelial keratopathy in both eyes. The patient underwent conjunctival biopsy. The specimen was examined by transmission electron microscopy. Septata intestinalis was demonstrated to be the cause of keratoconjunctivitis in the patient. The keratoconjunctivitis resolved after three weeks of therapy with topical fumagillin. No organisms were seen on repeat conjunctival biopsy. Microsporidial keratoconjunctivitis in patients with AIDS can be caused by S. intestinalis. This condition appears to respond to topical fumagillin.

Diagnosis of Microsporidial Keratitis by Confocal Microscopy and the Chromatrope Stain

To illustrate the value of confocal microscopy and chromatrope stain in the diagnosis of microsporidial keratitis. In vivo confocal microscopy was performed on a man with the human immunodeficiency virus who had severe bilateral epithelial keratitis refractory to topical antibacterial medications. The results were compared to conjunctival scrapings stained with the chromatrope-based Weber stain. Confocal microscopy demonstrated many small, intraepithelial opacities of the corneal epithelium, which were suggestive of Microsporidia. Results of the chromatrope stain of conjunctival scrapings confirmed the diagnosis of microsporidial keratitis. Rapid diagnosis allowed prompt initiation of topical fumagillin, which permitted rapid, long-term control of the symptoms of microsporidial keratitis.

Topical Fumagillin in The Treatment of Microsporidial Keratoconjunctivitis in Aids

To report microsporidial keratoconjunctivitis in a patient infected with HIV who was treated with topical fumagillin. A 37-year-old white man who was experiencing redness, pain, irritation, decreased vision, and a foreign body sensation occurring in both eyes was referred to the ophthalmology clinic. The patient had a medical history significant for AIDS, Pneumocystis carinii pneumonia, and Cytomegalovirus retinitis. Conjunctival smears were taken and stained positive for the presence of Microsporidia. The patient was diagnosed with bilateral microsporidial keratoconjunctivitis and fumagillin therapy was initiated. After 5 days of therapy, the patient reported significant improvements characterized by a decrease in blurred vision with only slight blurring in the left eye, decrease in headache, and decreased foreign body sensation. The patient continued topical fumagillin therapy for more than 14 months, with only slight blurring in the left eye and no apparent ocular toxicity as a result of fumagillin therapy. Although rare in occurrence, increasing numbers of documented microsporidial infections are being reported in the medical literature, particularly in individuals who are seropositive for HIV. Clinicians need to be cognizant of microsporidial keratoconjunctivitis as another opportunistic infection in this patient population. Although a curative agent has yet to be discovered, fumagillin represents a safe, effective, low-cost, topical agent for the treatment of microsporidial keratoconjunctivitis.

Successful Treatment of Microsporidial Keratoconjunctivitis with Topical Fumagillin in a Patient with AIDS

There recently have been several reports of microsporidial keratoconjunctivitis caused by the organism Encephalitozoon hellem. However, treatment of this infection has been largely ineffective. We report a case of a 35-year-old Hispanic woman with AIDS and E. hellem keratoconjunctivitis confirmed with light, electron, and immunofluorescence microscopy that resolved promptly with topical fumagillin, a crystalline antibiotic with proven efficacy against Encephalitozoon species. No corneal or systemic toxicities were noted using the dosage and preparation employed (10 mg/ml suspension in balanced salt solution). An easily prepared, topical fumagillin suspension appears to be a safe, effective treatment for E. hellem keratoconjunctivitis.

Treatment of Microsporidial Keratoconjunctivitis with Topical Fumagillin

Encephalitozoon hellem is a newly described cause of microsporidial keratoconjunctivitis, occurring chiefly in patients with significantly diminished CD4+ T-lymphocyte levels. This disorder is symptomatically disabling and generally recalcitrant to topical antimicrobial therapy. Two homosexual men with E. hellem keratoconjunctivitis diagnosed by Gram stain, transmission electron microscopy, and specific indirect immunofluorescent assay were treated with topical fumagillin (Fumidil B). Both patients had marked symptomatic improvement with reduction of clinical findings. Symptoms and signs recurred with temporary discontinuation of the drug. Both patients, however, remained symptom-free on maintenance levels of topical fumagillin with no evidence of toxic side effects.