Faculty Bibliography

A healthy 10-year-old girl developed synchronous, bilateral, temporal redness of the eyes regarded as sectoral conjunctivitis for 5 years that was unresponsive to topical steroids and antihistamines. Finely vascularized, minimally elevated, amelanotic or faintly focally pigmented, epibulbar conjunctival lesions were present bilaterally. The lesions were completely excised. Histopathologic and immunohistochemical evaluations confirmed that they were both predominantly junctional nevi with conspicuous chronic inflammation. Juvenile conjunctival nevi frequently have atypical histopathologic traits that in an adult could be suggestive of melanoma. The differential diagnosis of much less likely disorders includes leukemia, lymphoid tumor (salmon patch), and conjunctival sarcoidosis, among other conditions. The patient has had no recurrence 3 years after surgery.

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.

INTRODUCTION/BACKGROUND:Management of corneal scarring following herpes zoster ophthalmicus (HZO) is challenging due to the dense corneal anesthesia that results from viral damage to the subepithelial nerve plexus. These patients have significant risk of graft failure following traditional corneal transplantation. We present a case of a 74-year-old white woman with counting fingers vision from HZO-associated corneal scarring and mature cataract where visual rehabilitation was accomplished with a Type I Boston keratoprosthesis (KPro) and concurrent extracapsular cataract extraction and posterior chamber intraocular lens placement (the "KPro Triple"). One month following surgery, the patient's uncorrected visual acuity improved to 20/25; this level of vision has been maintained for 7 months at present. SURGICAL TECHNIQUE (SEE VIDEO)/UNASSIGNED:The keratoprosthesis is assembled by creating a sandwich composed of the KPro front plate, the donor cornea, and the KPro backplate that is secured with a locking ring. The host cornea is then trephined and posterior synechiae lysed to allow access to the mature cataract. The cataract is manually expressed and a posterior chamber intraocular lens implanted. The assembled keratoprosthesis is then sutured into position with 9.0 nylon. A bandage contact lens is placed. COMMENT/CONCLUSIONS:In patients with severe neurotrophic keratopathy, traditional penetrating keratoplasty is fraught with problems, including poor epithelial healing and corneal ulceration. The Boston KPro can provide rapid visual rehabilitation, despite corneal anaesthesia in these patients, and is currently our treatment of choice as a primary procedure for HZO patients who need corneal transplantation.

This report describes the corneal pathology in an infant with newborn primary congenital glaucoma and discusses whether these findings could be due to a developmental anomaly. The corneal specimen of a 4-month-old infant with newborn primary congenital glaucoma and cloudy corneas who had undergone penetrating keratoplasty was evaluated by light and electron microscopy. Light microscopy showed a thinned epithelium, areas of thickened Bowman's layer (approximately 27 mum thick) interspersed with nuclei, and a thickened and disorganized stroma. Descemet's membrane was intact, and the endothelium was mildly attenuated. The corneal changes seen in this patient may be specific to primary congenital glaucoma and may contribute to the corneal clouding seen so frequently in these patients.

OBJECTIVE:To evaluate with immunohistochemical methods 5 atypical melanocytic conjunctival lesions. METHODS:This was a retrospective clinicoimmunopathologic study. Routine histochemical staining was performed with multiparametric immunohistochemical analysis with monoclonal antibodies immunoreacted on paraffin sections to identify the following cell antigens: S-100, MART-1, HMB-45, CD45, CD68, CD1a, lysozyme, and Ki-67 (nuclear proliferation protein). RESULTS:A unique granular cell nevus contained periodic acid-Schiff-positive, diastase-resistant granules and immunoreacted with monoclonal antibodies against S-100 protein and melanocytic-associated antigens MART-1 and HMB-45. Results for CD45, CD1a, CD68, and lysozyme immunostaining of the granular cells were negative. Two epithelioid cell (clonal or inverted) nevi exhibited an identical immunohistochemical profile. Only the balloon cell nevus was MART-1-positive and HMB-45-negative. The granular cell and blue nevi immunoreacted negligibly with Ki-67 (approximately 1% of cells). CONCLUSIONS:S100 and MART-1 reliably immunostained all nevocytic morphologic variants. HMB-45 immunoreactivity of the granular, epithelioid/clonal, and blue nevi did not indicate a more active or proliferative lesion but instead suggested abnormal melanogenesis. Ki-67 was the most valuable immunohistochemical adjunct to morphology for the diagnosis of these benign variant conjunctival nevi, because melanomas display a much higher proliferation index (>10% nuclear positivity among all cells counted) than the current nevi (approximately 1%).

PURPOSE/OBJECTIVE:The purpose of this study was to report a case of Phomopsis fungal keratitis that was diagnosed 2 months after a rose thorn injury that occurred while gardening. METHODS:The authors conducted a retrospective case report with literature review. RESULTS:Deep stromal keratitis with extension of hyphae through Descemet's membrane was treated by therapeutic keratoplasty combined with oral and topical antifungal medications. The causative organism, a Phomopsis species, was identified by culture of the surgical specimens. Phomopsis, a plant fungus, has not been previously reported as a cause of human fungal keratitis. One year after the initial surgery, visual rehabilitation was accomplished with a repeat cornea transplant and cataract extraction with return of vision to 20/25. CONCLUSIONS:Advanced fungal keratitis can be successfully treated by a combination of surgery to debulk the infectious organisms and pre- and postoperative medical therapy. Prompt recognition of fungal keratitis will increase the likelihood of cure. Phomopsis species, ubiquitous plant fungi, can cause infectious keratitis in humans.

Conjunctival melanoma patients often follow an unpredictable course with significant rates of recurrence and metastases despite optimal treatment. Can we better understand conjunctival melanomas by applying the cancer stem cell hypothesis? The cancer stem cell hypothesis posits that cancers exist as a hierarchical system where cancer stem cells generate and maintain tumors. Targeting cancer stem cells may be the key to future treatments. Directed treatments need to focus on key differences between cancer stem cells and normal tissue stem cells. These directed treatments may lead to curative therapies and decrease the number of recurrences and metastases.

PURPOSE/OBJECTIVE:To describe changes in demographics and pathogens for fungal keratitis cases diagnosed at the Massachusetts Eye and Ear Infirmary. METHODS:Patient demographics, clinical and laboratory findings, treatment and outcomes of 46 cases of culture-proven fungal keratitis diagnosed from January 2004 through November 2007 were compared with 23 cases of fungal keratitis previously collected over a similar period from January 1999 through November 2002. RESULTS:During 2004-2007, the rate of fungal keratitis was 1.0 cases per month, an increase from the baseline rate of 0.5 cases per month during 1999-2002. The proportion of cases caused by filamentous fungi increased from 30% (1999-2002) to 65% (2004-2007) (P = 0.01). Soft contact lens wear accounted for 41% of fungal keratitis cases in 2004-2007, as compared with 17% in 1999-2002. The majority of patients (70%) received oral antifungal treatment in addition to topical amphotericin B and natamycin. Seventeen patients (40%) required therapeutic keratoplasty. Patients with a history of corneal transplant had the highest rate of therapeutic keratoplasties (67%) and had the poorest visual outcome (40% counting fingers or less). In the contact lens group, 94% of patients maintained vision of at least 20/40 and only 12% required surgery to control the infection. CONCLUSIONS:There has been an increase in fungal keratitis in the Boston area and a change in the causative pathogens and risk factors for infection. Filamentous fungi now account for the majority of fungal keratitis cases, whereas yeasts were the predominant pathogen in the past. Soft contact lens wear is currently the most common risk factor for development of fungal keratitis.

PURPOSE/OBJECTIVE:To investigate the differential expression of the glycoprotein clusterin/apoJ (CLU) in normal and Fuchs' endothelial dystrophy (FED) corneal endothelium and to compare the expression of various forms of CLU in normal and FED tissue. METHODS:FED and pseudophakic bullous keratopathy (PBK) corneal buttons were removed during transplantation, and normal corneas were obtained from tissue banks. Human corneal endothelial cells and Descemet's membrane (HCEC-DM) complex was dissected from the stroma. Proteins were separated on 2-D gels and subjected to comparative proteomic analysis. Relative expression of presecretory CLU (pre-sCLU), secretory (s)CLU, and nuclear (n)CLU were compared between normal and FED HCEC-DM by Western blot analysis. Expression of CLU mRNA was compared by using RT-PCR. Subcellular localization of CLU was compared in corneal wholemounts from normal eyes and eyes with FED by immunocytochemistry followed by confocal microscopy. RESULTS:Proteomic analysis revealed an apparent increase in CLU expression in FED HCEC-DM compared with the normal control. Western blot analysis demonstrated that pre-sCLU protein expression was 5.2 times higher in FED than in normal samples (P = 3.52E-05), whereas the mature form modified for secretion (sCLU) was not significantly elevated (P = 0.092). Expression of nCLU protein was significantly elevated in FED (P = 0.013). RT-PCR analysis revealed that CLU mRNA was significantly increased (P = 0.002) in FED samples, but not in PBK samples. CLU also had a distinctive localization in FED samples with enhanced intracellular staining around the guttae and in the nuclei of endothelial cells. CONCLUSIONS:CLU expression is markedly elevated in FED-affected tissue, pointing to a yet undiscovered form of dysregulation of endothelial cell function involved in FED pathogenesis.