Corneal perforation in ocular graft-versus-host disease.

PURPOSE: Corneal perforation is a rare, vision-threatening complication of ocular graft-versus-host disease (GVHD) and is not well understood. Our objective was to examine the clinical disease course and histopathologic correlation in patients who progressed to this outcome. METHODS: This study is a retrospective case series from four academic centers in the United States. All patients received a hematopoietic stem cell transplant (HSCT) prior to developing ocular GVHD. Variables of interest included patient demographics, time interval between HSCT and ocular events, visual acuity throughout clinical course, corticosteroid and infection prophylaxis regimens at time of corneal perforation, medical/surgical interventions, and histopathology. RESULTS: Fourteen eyes from 14 patients were analyzed. Most patients were male (86%) and Caucasian (86%), and average age at time of hematopoietic stem cell transplant was 47 years. The mean interval between hematopoietic stem cell transplant and diagnosis of ocular graft-versus-host disease was 9.5 months, and between hematopoietic stem cell transplant and corneal perforation was 37 months. Initial best-corrected visual acuity was 20/40 or better in 9 eyes, and all eyes had moderate or poor visual outcomes despite aggressive management, including corneal gluing in all patients followed by keratoplasty in 8 patients. The mean follow-up after perforation was 34 months (range 2-140 months). Oral prednisone was used prior to perforation in 11 patients (79%). On histopathology, representative specimens in the acute phase demonstrated ulcerative keratitis with perforation but minimal inflammatory cells and no microorganisms, consistent with sterile corneal "melt" in the setting of immunosuppression; and in the healed phase, filling in of the perforation site with fibrous scar. CONCLUSIONS: In these patients, an extended time interval was identified between the diagnosis of ocular graft-versus-host disease and corneal perforation. This represents a critical window to potentially prevent this devastating outcome. Further study is required to identify those patients at greatest risk as well as to optimize prevention strategies.

Toxic Keratoconjunctivitis.

Toxic keratoconjunctivitis (TK) is an underrecognized complication of ophthalmic drug use and various environmental or occupational exposures. A detailed history and clinical examination are important to identify the offending agent(s). Common drug-related causes of TK include preservatives in ophthalmic medications, topical antimicrobials, and topical anesthetics. Alternatives to benzalkonium chloride as well as preservative-free formulations should be considered in patients requiring long-term topical medication. More advanced cases of TK may require preservative-free topical steroids and/or antibiotics, and occasionally surgical intervention. Early recognition and appropriate management of TK may help prevent permanent ocular and visual damage.

Unilateral Posterior Interstitial Keratitis as a Clinical Presentation of Herpes Simplex Virus Disease.

PURPOSE: To describe a case series of patients with unilateral, posterior interstitial keratitis presumed to be caused by herpes simplex virus. METHODS: Retrospective case series. RESULTS: Five patients were found to have unilateral, posterior interstitial keratitis. Three of the involved eyes had decreased corneal sensation, and 2 eyes had corneal stromal neovascularization. All patients were treated with topical steroids and an oral antiviral, and among those with long-term follow-up, clinical improvement required treatment over an extended duration. A review of the literature revealed 1 reported case with a similar clinical appearance, although that case was attributed to Lyme disease. CONCLUSIONS: The clinical presentation of unilateral, posterior interstitial keratitis may be a rare manifestation of herpes simplex virus keratitis.

Corneoscleral Laceration and Ocular Burns Caused by Electronic Cigarette Explosions.

PURPOSE: To report cases of acute globe rupture and bilateral corneal burns from electronic cigarette (EC) explosions. METHODS: Case series. RESULTS: We describe a series of patients with corneal injury caused by EC explosions. Both patients suffered bilateral corneal burns and decreased visual acuity, and one patient sustained a unilateral corneoscleral laceration with prolapsed iris tissue and hyphema. A review of the scientific literature revealed no prior reported cases of ocular injury secondary to EC explosions; however, multiple media and government agency articles describe fires and explosions involving ECs, including at least 4 with ocular injuries. CONCLUSIONS: Given these cases and the number of recent media reports, ECs pose a significant public health risk. Users should be warned regarding the possibility of severe injury, including sight-threatening ocular injuries ranging from corneal burns to full-thickness corneoscleral laceration.

A masquerader? Paecilomyces must be distinguished from Penicillium in fungal keratitis: a report of two contrasting cases.

We describe the clinical outcomes of two contrasting cases of fungal keratitis due to Paecilomyces spp. The first case involving a 58-year-old woman was complicated by an initial laboratory misidentification as Penicillium and consequently a delay in treatment with an optimised antifungal regimen. The patient had a protracted clinical course that required a total of four penetrating keratoplasties. However, an accurate diagnosis was promptly made in the second case, a 46-year-old woman, which resulted in a satisfactory outcome after penetrating keratoplasty. Our principal aim was to highlight a diagnostic challenge relating to the accurate microbial identification of Paecilomyces spp. This can be difficult given its morphological similarity to Pencillium, and confusion over the two genera has resulted in misdiagnoses reported previously. Our report aims to raise awareness of this potential laboratory misidentification, which can affect clinical decision-making in guiding antimicrobial therapy.

Use of Topical Besifloxacin in the Treatment of Mycobacterium chelonae Ocular Surface Infections.

PURPOSE: To present the clinical outcome of 3 cases of ocular surface infections by Mycobacterium chelonae treated with besifloxacin (0.6%, Besivance; Bausch & Lomb, Tampa, FL). METHODS: In this retrospective review of a small case series, we reviewed the medical records of 3 clinical patients with M. chelonae infection involving the ocular surface. Besifloxacin was used as an adjunct in 2 cases of keratitis and as the principal therapeutic agent in a case of nodular conjunctivitis. RESULTS: Two patients who presented with culture-proven M. chelonae keratitis initially had been treated with topical amikacin and oral clarithromycin for 6 months in the first case and for 2 months in the second without complete resolution. Topical besifloxacin was added as an adjunct therapy to amikacin with progressive weaning of clarithromycin. Both cases of keratitis eventually resolved without recurrence after discontinuation of topical amikacin and besifloxacin. A third patient presented with nodular conjunctival inflammation, which initially had been treated with topical ciprofloxacin and corticosteroids without improvement. One nodular lesion was excised and submitted for microbial culture, which revealed the growth of M. chelonae. Marked improvement of the conjunctivitis was noted after 3 weeks of treatment with topical besifloxacin. Complete resolution of the conjunctival nodules was achieved after 10 weeks of treatment with besifloxacin. CONCLUSIONS: Topical besifloxacin seems to be a useful adjunct agent in the treatment of nontuberculous mycobacterial keratitis by M. chelonae and may be viable for use as a first-line agent in cases of nodular conjunctivitis by M. chelonae.

Novel CHST6 gene mutations in 2 unrelated cases of macular corneal dystrophy.

PURPOSE: To investigate the possible mutations in the carbohydrate sulfotransferase 6 (CHST6) gene of 2 unrelated cases of macular corneal dystrophy (MCD) and to report atypical stromal deposits in one of them. METHODS: Corneal tissues were stained with antisulfated keratan sulfate (KS), antitransforming growth factor beta 1-induced protein (TGFBIp), thioflavin-T, alcian blue, and Masson trichrome. Sequencing was performed to identify potential mutations in the CHST6 gene and the fourth and twelfth exons of the TGFBI gene. RESULTS: Alcian blue staining revealed the presence of multiple subepithelial and intrastromal mucopolysaccharide deposits, confirming the diagnosis of MCD in both cases. Immunofluorescence staining in case 1 revealed the presence of sulfated KS only in the keratocytes and select endothelial cells, consistent with MCD type IA. Preferential expression of sulfated KS was observed in keratocytes and extracellular stromal matrix in case 2, consistent with MCD type II. Atypical subepithelial and superficial stromal deposits were observed in case 1, which stained positively with alcian blue, eosin, Masson trichrome, and thioflavin-T indicating the presence of hyaline and amyloid materials. CHST6 gene sequencing revealed 2 heterozygous mutations in case 1 (a p.Arg211Gln and a novel mutation of p.Arg177Gly) and a novel homozygous mutation of p.Pro186Arg in case 2. No mutations were found in exons 4 or 12 of the TGFBI gene in case 1. CONCLUSIONS: Secondary hyalinosis and amyloidosis occur in a case of MCD type IA with a novel p.Arg177Gly mutation in CHST6. A novel p.Pro186Arg mutation in CHST6 is associated with MCD type II in an African American.