Stromal microsporidial keratitis successfully treated with medical therapy.

PURPOSE: To report a case of severe stromal microsporidal keratitis successfully treated with oral albendazole and topical voriconazole. OBSERVATIONS: A 71-year-old man presented with progressive vision loss and corneal opacification for one year. Initial visual acuity was counting fingers attributed to a dense subepithelial opacification. Confocal microscopy and subsequent corneal biopsy lead to the diagnosis of microsporidial keratitis. The patient completed a four-week course of oral albendazole and topical voriconazole which resulted in resolution of the corneal opacification and improvement in visual acuity to 20/250. CONCLUSIONS AND IMPORTANCE: A four-week course of oral albendazole and topical voriconazole was an effective treatment for severe stromal microsporidial keratitis.

Widespread Ocular Surface Squamous Neoplasia Treated with Topical Interferon Alpha-2b.

PURPOSE: To emphasize the importance of staging ocular surface squamous neoplasia when contemplating use of topical interferon alpha-2b alone. CASES: Two patients with 360 degrees of limbal involvement. RESULTS: Two patients with in situ squamous cell carcinoma of the conjunctiva and clinical involvement of the entire limbus were treated with topical interferon alpha-2b. Thorough examination and multiple biopsies excluded invasive disease. The patients had complete response to therapy. CONCLUSION: Widespread intraepithelial squamous neoplasia involving the entire limbus can be successfully treated with topical therapies. Biopsy plays a role in excluding invasive disease. Interferon alpha-2b is a preferable agent to start with because it is well tolerated. Since long-term risks of recurrence are unknown, appropriate monitoring is essential.

Candida Endophthalmitis After Descemet Stripping Automated Endothelial Keratoplasty With Grafts From Both Eyes of a Donor With Possible Systemic Candidiasis.

PURPOSE: To report 2 cases with late postoperative Candida albicans interface keratitis and endophthalmitis after Descemet stripping automated endothelial keratoplasty (DSAEK) with corneal grafts originating from a single donor with a history of presumed pulmonary candidiasis. METHODS: Two patients underwent uncomplicated DSAEK by 2 corneal surgeons at different surgery centers but with tissue from the same donor and were referred to the Bascom Palmer Eye Institute with multifocal infiltrates at the graft-host cornea interface 6 to 8 weeks later, and anterior chamber cultures that were positive for the same genetic strain of C. albicans. Immediate explantation of DSAEK lenticules and daily intracameral and instrastromal voriconazole and amphotericin injections failed to control the infection. Thus, both patients underwent therapeutic penetrating keratoplasty with intraocular lens explantation, pars plana vitrectomy, and serial postoperative intraocular antifungal injection. RESULTS: Both patients are doing well at 2 years postoperatively with best-corrected vision of 20/20 and 20/30+ with rigid gas permeable lenses. One patient required repeat optical penetrating keratoplasty and glaucoma tube implantation 1 year after the original surgery. Literature review reveals that donor lenticule explantation and intraocular antifungals are often inadequate to control fungal interface keratitis, and a therapeutic graft is commonly needed. CONCLUSIONS: Interface fungal keratitis and endophthalmitis due to infected donor corneal tissue is difficult to treat, and both recipients of grafts originating from the same donor are at risk of developing this challenging condition.

Ocular Surface Squamous Neoplasia Associated with Atopic Keratoconjunctivitis.

PURPOSE: To describe 2 cases of invasive squamous cell carcinoma that originated in the setting of severe atopic keratoconjunctivitis (AKC). METHODS: Case one involved a 73-year-old male with atopic eczema and severe AKC who developed a limbal lesion suspicious for ocular surface squamous neoplasia (OSSN). Slit-lamp examination was significant for a new sessile lesion in the temporal limbal region of the left eye. The lesion was treated with excisional biopsy and cryotherapy. Topical therapy with mitomycin C, topical interferon alpha 2b, and topical 5-fluorouracil provided only partial control. Exenteration was eventually needed. Case two involved a 53-year-old male with history of severe AKC and eczema. Computed tomography imaging showed an infiltrative mass of the right orbit. Incisional biopsies confirmed conjunctival squamous cell carcinoma of both sides (invasive in the right eye, in situ in the left eye). Exenteration was needed for control of invasive carcinoma in the right eye. RESULTS: Squamous cell carcinoma was treated without success in spite of surgical excision and aggressive treatment with multiple topical agents and multiple applications of cryotherapy. Orbital exenteration was needed in both cases. CONCLUSION: Chronic inflammation associated with AKC may be a risk factor for the development of bilateral, diffuse, invasive, and recurrent OSSN that may require exenteration.

Occult Fungal Scleritis.

PURPOSE: To heighten awareness of occult fungal scleritis. METHOD: Case report and review of the literature. RESULTS: A 73-year-old woman with diabetes mellitus was diagnosed for 3 months with immune-mediated scleritis and subsequently treated with corticosteroids. On referral, the patient had a scleral nodule with contiguous corneal infiltrate and hypopyon. Culture grew Fusarium species not further classified. The infection could not be controlled with antifungal therapy, and the eye was removed. No exogenous or endogenous source for the infection could be identified by clinical history or examination. CONCLUSION: Fungal scleritis can develop in persons without a history of foreign body injury, minor trauma, or evidence of endogenous fungemia. A high index of suspicion for infectious scleritis must be maintained in persons with presumed immune-mediated scleritis who fail to respond to conventional therapy, particularly if they present with decreased visual acuity.

Separate Primary Melanomas of the Bulbar Conjunctiva and Eyelid Skin: Clinical Implications of Multiple Primary Melanomas.

PURPOSE: We report a patient with previous in situ melanoma of the forehead skin who was referred for treatment of a bulbar conjunctival melanoma and a separate superficially invasive melanoma of the eyelid skin, and we offer a review of the biological and clinical implications of patients who have multiple primary melanomas. METHODS: This article offers a clinicopathological correlation with a review of the relevant literature. RESULTS: An 80-year-old white man was referred for evaluation of a suspicious conjunctival tumor and a lower-eyelid lesion. Excisional biopsies revealed that both were primary melanomas arising within in situ disease. Over the span of 25 years, the patient had three separate foci of in situ melanoma, two of which spawned invasive melanoma. CONCLUSION: Separate melanomas arising from the bulbar conjunctiva and eyelid skin have rarely been reported. Multiple primary melanomas of the skin, however, are not uncommon. Based on studies of persons with multiple cutaneous melanomas, the prognosis is best predicted by the tumor with the greatest depth of invasion. Patients with multiple melanomas should be examined for dysplastic nevi, additional cutaneous melanomas, and screened periodically for future lesions. Ongoing studies enrolling patients with multiple primary melanomas are attempting to generate insights into low-penetrance susceptibility genes.

Cataract surgery in patients with chronic severe graft-versus-host disease.

PURPOSE: To evaluate the surgical outcomes of cataract extraction with phacoemulsification and intraocular lens implantation in patients with severe chronic ocular graft-versus-host disease (GVHD). SETTING: University of South Florida Eye Institute, Tampa, Florida, USA. DESIGN: Retrospective case study. METHODS: A chart review was performed to identify patients with clinically severe, biopsy-proven chronic ocular GVHD who had cataract extraction. Outcome parameters included preoperative and postoperative corrected distance visual acuity (CDVA), type of cataract, postoperative complications, type of underlying malignancy, and time from bone marrow transplant to cataract extraction. RESULTS: This study comprised 10 eyes of 6 patients with severe GVHD. Posterior subcapsular cataract accounted for all cataracts that were surgically removed in this patient cohort. The mean preoperative CDVA was 20/84, which improved to 20/30 at the 1-month postoperative visit and remained stable at 20/28 at the final visit noted in the charts (both P < .05). Two patients developed postoperative corneal melting. All but 1 patient had improved visual acuity after surgery. CONCLUSIONS: With meticulous preoperative biometric measurements and calculations and aggressive assessment and treatment of dry-eye syndrome, patients with severe ocular GVHD who had cataract extraction had excellent postsurgical refractive outcomes. Postoperative corneal melting was a complication seen with greater frequency than anticipated in this patient cohort. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Ocular manifestations of monoclonal copper-binding immunoglobulin.

The dense accumulation of copper in Descemet membrane and lens capsule is the characteristic manifestation of a circulating monoclonal antibody with strong affinity for copper. The overproduction of this monoclonal immunoglobulin may be associated with either multiple myeloma or a benign monoclonal gammopathy. Despite prolonged exposure to elevated serum copper, no other tissues in the body are adversely affected by this redox metal. We describe the clinical and pathological findings in a 46-year-old woman with this disorder.

Graft versus host disease: clinical evaluation, diagnosis and management.

Graft versus H\host disease (GVHD) can be a devastating complication following bone marrow transplantation. Acute or chronic systemic GVHD can be lethal, and severe damage of different organs and tissues can occur with both types of GVHD. Ocular involvement, either in an acute or chronic presentation, may range from mild to severe with accompanying vision loss present in 60-90 % of patients. Chronic ocular GVHD, the most common form of GVHD, affects mainly the lacrimal gland, meibomian glands, cornea and conjunctiva, mimicking other immunologically mediated inflammatory diseases of the ocular surface without specific symptoms or signs. However, dry eye disease is the main manifestation of GVHD. The long-term treatment of ocular GVHD continues to be challenging and involves a multidisciplinary approach wherein the ophthalmologist plays a major role. Besides systemic immunosuppression and ocular lubricants, topical steroids and topical cyclosporine are commonly prescribed. Newer therapeutic interventions for moderate and severe ocular GVHD include the use of serum eye drops and scleral contact lenses. In this manuscript, we review the mechanisms, clinical findings, and treatment of ocular GVHD.

Strategies of human corneal endothelial tissue regeneration.

Penetrating keratoplasty has previously been the only surgical treatment for patients with corneal endothelial disorders. Recently, posterior lamellar keratoplasty has become a viable and less aggressive alternative technique. However, both transplantation techniques have disadvantages, such as non-immunologic graft failure, allograft endothelial rejection or a global shortage of donor corneas. Over the past few years, several groups have established methods for the isolation, preservation, in vitro cultivation, transplantation, and in vivo stimulation of human corneal endothelial cells in animal models. It is hoped that these new strategies will allow the treatment of more than one patient with one donor cornea, performing autologous corneal endothelium transplantation from a surgical biopsy sample, or stimulating the growth of corneal endothelial cells in vivo. However, several aspects need to be addressed before commencing clinical trials.

Activation of Smad-mediated TGF-ß signaling triggers epithelial-mesenchymal transitions in murine cloned corneal progenitor cells.

Epithelial-mesenchymal transition (EMT), via activation of Wnt signaling, is prevailing in embryogenesis, but postnatally it only occurs in pathological processes, such as in tissue fibrosis and tumor metastasis. Our prior studies led us to speculate that EMT might be involved in the loss of limbal epithelial stem cells in explant cultures. To examine this hypothesis, we successfully grew murine corneal/limbal epithelial progenitors by prolonging the culture time and by seeding at a low density in a serum-free medium. Single cell-derived clonal growth was accompanied by a gradient of Wnt signaling activity, from the center to the periphery, marked by a centrifugal loss of E-cadherin and ß-catenin from intercellular junctions, coupled with nuclear translocation of ß-catenin and LEF-1. Large-colony-forming efficiency at central location of colony was higher than peripheral location. Importantly, there was also progressive centrifugal differentiation, with positive K14 keratin expression and the loss of p63 and PCNA nuclear staining, and irreversible EMT, evidenced by cytoplasmic expression of α-SMA and nuclear localization of S100A4; and by nuclear translocation of Smad4. Furthermore, cytoplasmic expression of α-SMA was promoted by high-density cultures and their conditioned media, which contained cell density-dependent levels of TGF-ß1, TGF-ß2, GM-CSF, and IL-1α. Exogenous TGF-ß1 induced α-SMA positive cells in a low-density culture, while TGF-ß1 neutralizing antibody partially inhibited α-SMA expression in a high-density culture. Collectively, these results indicate that irreversible EMT emerges in the periphery of clonal expansion where differentiation and senescence of murine corneal/limbal epithelial progenitors occurs as a result of Smad-mediated TGF-ß-signaling.

Very late-onset corneal scar triggered by trauma after photorefractive keratectomy.

A 54-year-old woman who had photorefractive keratectomy (PRK) more than 10 years earlier presented with a history of being hit in the eye by a tree branch and developing blurred vision a short time later. The corrected visual acuity was 20/100 with localized grade 3 stromal haze. The haze intensified despite initial response to corticosteroids and cyclosporine, and treatment with phototherapeutic keratectomy and 0.02% mitomycin-C (MMC) was effective in restoring corneal clarity and normal vision. Late-onset stromal scar can be triggered by trauma years after PRK. Phototherapeutic keratectomy with MMC can be an effective treatment for late-onset scar. Persistent haze or scar after trauma if PRK had not been performed previously is exceedingly rare.

Flap relift for retreatment after femtosecond laser-assisted LASIK.

PURPOSE: To analyze the results of LASIK retreatment performed by relifting the original femtosecond laser-created flap. METHODS: A retrospective analysis was performed on 1298 eyes from 688 patients treated with LASIK using the femtosecond laser to identify 88 consecutive eyes of 71 patients that underwent attempted flap lift to treat residual refractive error. The eyes were separated in groups in which the flap lift was possible or flap lift was not possible to investigate factors that could make flap lifting more difficult. The main factors evaluated were bed and side-cut energy and time between original surgery and retreatment. In addition, all retreated eyes were studied as a group to evaluate the refractive outcomes of flap lift retreatment. RESULTS: In 10 (11.3%) retreated eyes, flap lift was not possible without risk of flap injury due to strong healing of the original femtosecond laser interface. The group of eyes in which the flap could not be relifted had the attempted retreatment performed a longer time period after original LASIK (10.3±3.3 months) compared to the group in which the flap could be re-lifted (5.24±3.14 months) (P<.001). No significant differences were found between groups in any other parameters, including bed and side-cut energies. After retreatment, 82% of eyes achieved 20/20 or better uncorrected visual acuity. CONCLUSIONS: This study provides clinical evidence that flap lift retreatment after femtosecond laser-assisted LASIK achieves excellent clinical results and is significantly easier to perform in the first 6 to 8 months after primary LASIK.