Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:To review emerging indications for the Boston keratoprosthesis (KPro) and to discuss current research underway to improve clinical outcomes. RECENT FINDINGS/RESULTS:In addition to multiple failed corneal grafts, other ocular conditions for which the Boston KPro has been used include herpetic keratitis, aniridia, autoimmune ocular disorders, and pediatric corneal opacities. In the recent years, the KPro has been implanted for various other conditions and has also been explored as a cost-effective treatment for severe corneal diseases internationally. Cicatricial and inflammatory ocular conditions remain the most difficult cases for KPro use but studies investigating various immunomodulators and biologic materials for improved retention are ongoing. Postoperative management of glaucoma is critical for preserving the visual gains achieved with the Boston KPro. Current studies are evaluating novel devices for intraocular pressure measurement. SUMMARY/CONCLUSIONS:Accrued experience with the Boston KPro has demonstrated its versatility but also the difficulties that remain in postoperative management. With many studies underway to improve cost-effectiveness, intra-operative and postoperative management, keratoprostheses will be made increasingly available to those countries most in need.

OBJECTIVE:To study the epidemiology, clinical observations, and microbiologic characteristics of fungal keratitis at tertiary eye care centers in the United States. DESIGN/METHODS:Retrospective multicenter case series. PARTICIPANTS/METHODS: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/METHODS: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.

PURPOSE/OBJECTIVE:To report with morphologic and phylogenetic speciation the first case from Israel of Pythium insidiosum keratitis associated with contact-lens wear. METHODS:Case report and literature review. RESULTS:A 21-year-old man with a history of contact-lens use and water exposure was hospitalized in Israel for a corneal ulcer. The ulcer progressed despite intensive antibiotics. He flew home to the United States for further care. Examination revealed a corneal ulcer with hypopyon. The infection progressed despite intensive medical therapy, and a therapeutic penetrating keratoplasty was performed. Histology and cornea cultures from the host cornea revealed sparsely septate, branching hyphae, consistent with P. insidiosum. DNA sequencing of the Pythium isolate supported the clinical history that the infection was acquired outside of the United States. Despite intensive medical therapy and a second corneal transplant, the ulcer progressed, ultimately requiring enucleation. CONCLUSION/CONCLUSIONS:This is the first reported case of culture-proven, contact lens-related Pythium keratitis originating from Israel. Pythium is a fungus-like, aquatic oomycete found in tropical climates. Human pythiosis is uncommon but associated with high morbidity. Case reports describe surgical cure of Pythium keratitis, but this case recurred despite two penetrating keratoplasties and maximal antifungal therapy. In cases of presumed fungal keratitis that do not respond to antifungals, the fungus should be sent for speciation because early surgical intervention is the only means to save the eye in ocular pythiosis.

OBJECTIVE:To evaluate retroprosthetic membranes that can occur in 25% to 65% of patients with the Boston type 1 keratoprosthesis (KPro). METHODS:Two patients with Peter anomaly and 2 with neurotrophic scarred corneas underwent revisions of their type 1 KPros because of visually compromising retroprosthetic membranes. The excised membranes were studied by light microscopy with hematoxylin-eosin, periodic acid-Schiff, and toluidine blue stains. Immunohistochemical and transmission electron microscopic examination were also used. RESULTS:Light microscopic examination revealed that the retro-KPro fibrous membranes originated from the host's corneal stroma. These mildly to moderately vascularized membranes grew through gaps in the Descemet membrane to reach behind the KPro back plate and adhere to the anterior iris surface, which had undergone partial lysis. In 2 cases, the fibrous membranes merged at the pupil with matrical portions of metaplastic lens epithelium, forming a bilayered structure that crossed the optical axis. Retro-KPro membranes stained positively for α-smooth muscle actin but negatively for pancytokeratin. Electron microscopy confirmed the presence of actin filaments within myofibroblasts and small surviving clusters of metaplastic lens epithelial cells. CONCLUSIONS:Stromal downgrowth, rather than epithelial downgrowth, was the major element of the retro-KPro membranes in this series. Metaplastic lens epithelium also contributed to opacification of the visual axis. Florid membranous inflammation was not a prominent finding and thus probably not a requisite stimulus for membrane development. Further advances in prosthetic design and newer antifibroproliferative agents may reduce membrane formation.

PURPOSE/OBJECTIVE:To report a case of corneal primary acquired melanosis (PAM) with atypia after cataract surgery. METHODS:Retrospective case report with literature review. RESULTS:Excision of an elevated pigmented conjunctival lesion was performed at the time of cataract extraction by clear corneal phacoemulsification by an outside surgeon. Histopathologic examination revealed PAM with atypia. Three months after the initial surgery, recurrent melanosis involving the peripheral corneal epithelium was noted, with extension of pigment into the corneal stroma through the paracentesis site. Excision of the involved corneal epithelium and the adjacent conjunctiva was performed, and microscopically recurrent PAM with atypia was confirmed. Adjuvant cryotherapy was applied at the time of surgery, and topical mitomycin C was given postoperatively. Repeat biopsies revealed no remaining malignancy, and the intrastromal pigment has disappeared during 18 months of follow-up. CONCLUSION/CONCLUSIONS:We present this case to illustrate the importance of complete evaluation and treatment of potentially atypical melanocytic conjunctival lesions before proceeding with elective intraocular surgery.

OBJECTIVE:Fungal keratitis is a serious ocular infection that is considered to be rare among contact lens wearers. The recent Fusarium keratitis outbreak raised questions regarding the background rate of Fusarium-related keratitis and other fungal keratitis in this population. DESIGN/METHODS:Retrospective, multicenter case series. PARTICIPANTS/METHODS:Six hundred ninety-five cases of fungal keratitis cases who presented to 1 of 10 tertiary medical centers from 2001 to 2007. METHODS:Ten tertiary care centers in the United States performed a retrospective review of culture-positive fungal keratitis cases at their centers between January 2001 and December 2007. Cases were identified using microbiology, pathology, and/or confocal microscopy records. Information was collected on contact lens status, method of diagnosis, and organism(s) identified. The quarterly number of cases by contact lens status was calculated and Poisson regression was used to evaluate presence of trends. The Johns Hopkins Medicine Institutional Review Board (IRB) and the IRBs at each participating center approved the research. MAIN OUTCOME MEASURES/METHODS:Quarterly number of fungal keratitis cases and fungal species. RESULTS:We identified 695 fungal keratitis cases; 283 involved the use of contact lenses. The quarterly number of Fusarium cases increased among contact lens wearers (CLWs) during the period that ReNu with MoistureLoc (Bausch & Lomb, Rochester, NY) was on the market, but returned to prior levels after withdrawal of the product from the market. The quarterly frequency of other filamentous fungi cases showed a statistically significant increase among CLWs comparing October 2004 through June 2006 with July 2006 through December 2007 with January 2001 through September 2004 (P < 0.0001). CONCLUSIONS:The quarterly number of Fusarium fungal keratitis cases among CLWs returned to pre-Renu with Moistureloc levels after removal of the product from the market. However, the number of other filamentous fungal keratitis cases, although small, seems to have increased among refractive CLWs. Reasons for these apparent increases are unclear.

PURPOSE/OBJECTIVE:To describe the clinical and immunopathologic features of the first convincing apocrine hidrocystoma of the caruncle that happened to be pigmented. METHODS:Case report with clinical evaluation, ultrasound biomicroscopy, and paraffin-embedded tissue stained with hematoxylin and eosin, periodic acid-Schiff, and immunohistochemical markers. RESULTS:Ultrasound biomicroscopy identified a cyst occurring in a 56-year-old white woman. Histopathologically, it was lined by an inner eosinophilic columnar epithelium that was gross cystic disease fluid protein-15-positive and evinced apical decapitation secretion and periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules. Fontana- and MART-1-positive melanin granules were demonstrated. There was an outer layer of smooth muscle actin-positive myoepithelial cells. An adjacent apocrine gland was discovered with identical staining characteristics but without melanin granules. CONCLUSIONS:Classical apocrine gland cysts can exceptionally develop in the caruncle. The light dispersion of cytoplasmic melanin found in the lining cells may have contributed to the cyst's clinical pigmentation, which is otherwise generally regarded as the result of the Tyndall effect, wherein blue wavelengths of light reflect from a colloidal solution of lipofuscin and cell debris.

PURPOSE/OBJECTIVE:In recent years, outbreaks of Acanthamoeba keratitis (AK) have been reported worldwide. The purpose of this study was to examine the clinical experience of AK at the Massachusetts Eye and Ear Infirmary. METHODS:A retrospective case review was completed on patients with infectious keratitis whose corneal cultures were positive for Acanthamoeba between January 2000 and December 2008. The clinical characteristics and visual outcomes were examined in those patients with a follow-up period greater than 6 months. RESULTS:Four cases were identified between January 2000 and December 2003, whereas 26 cases were identified between January 2004 and December 2008. Charts before 2004 were unavailable for review. A total of 15 cases between 2004 and 2008 had a follow-up period of greater than 6 months. In these cases, possible risk factors associated with AK included soft contact lens wear (12 of 15 cases), exposure to freshwater or saltwater sources (8 of 15 cases), chronic ocular surface disease (6 of 15 cases), ocular trauma (3 of 15 cases), and concomitant infectious keratitis (2 of 15 cases). Four cases were associated with the use of Advanced Medical Optics Complete MoisturePlus Multi-Purpose Solution. Many cases were recalcitrant to medical therapy alone, necessitating therapeutic penetrating keratoplasty in 8 of 15 cases. CONCLUSIONS:The number of AK cases at the Massachusetts Eye and Ear Infirmary has increased since 2004. Contact lens wear and exposure to contaminated water sources were potential risk factors for AK. Clinicians should maintain a high clinical suspicion for AK in cases of atypical keratitis with known risk factors for AK.

PURPOSE/OBJECTIVE:To report a case of pigmented deposits on a type I Boston keratoprosthesis (KPro) associated with the use of topical ibopamine as a treatment for hypotony. METHODS:Case report and literature review. RESULTS:The dopamine-like agent ibopamine caused black deposits on the bandage lens and on the front plate of the Boston KPro that resulted in reduced visual acuity. Change to a daily disposable contact lens and regular cleaning of the KPro front plate with diluted baby shampoo eliminated this problem. CONCLUSION/CONCLUSIONS:This is the first report of this complication with topical ibopamine use and should be considered when ibopamine is used chronically for hypotony.