Faculty Bibliography

Corneal dystrophies are a group of heterogenous conditions that are characterized by the progressive loss of corneal transparency that results from the accumulation of deposits within the different corneal layers. Up until recently, corneal dystrophies were classified according to their slit lamp appearance, the morphology of the deposits, the depth of the corneal involvement and their histopathological features. This classification has been challenged because of the significant inter-and intra- familial variability in phenotypic expression of the corneal dystrophies and the overlapping characteristics between the different types. In addition, there are dystrophies with atypical characteristics that involve multiple corneal layers or are associated with extraocular involvement that can not be classified into a single type based on morphologic criteria. Recent developments in corneal genetics have shed light on the pathogenesis of corneal dystrophies and have led to the implementation of a new classification scheme that takes into account the responsible gene defect. The discovery that mutations in Tissue Growth factor beta inducible (TGFBI) responsive gene, BIGH3, are the cause of a group of corneal dystrophies (granular, Avellino, lattice and Reis Bucklers) has revolutionized our understanding of these conditions (Stone et al., 1994; Munier et al., 1997). Since this discovery, the genetic basis of many corneal dystrophies and a chromosomal locus for several others has been described. It has also been shown that mutations in the same gene can cause different phenotypes. The association of specific gene mutations with specific phenotypes has given the clinician the opportunity to use molecular genetic analysis to diagnose dystrophic corneal disorders. In parallel, characterization of the mutations responsible for different types of corneal dystrophies has expanded our knowledge regarding their genetic and inheritance patterns. The finding of a highly penetrant, dominantly inherited corneal dystrophy in an affected offspring of unaffected parents has confirmed the existence of spontaneous pathogenic mutations. Additionally, molecular analysis for pathogenetic mutations can confirm the diagnosis in cases with atypical presentations of corneal dystophies. On the other hand, we still know little about how interactions between the environment and the genetic composition affect the phenotype of these conditions. It is highly likely that even when our understanding of the molecular basis of the corneal dystrophies is complete, this knowledge will be used as an adjunct to clinical findings to make the diagnosis of a corneal dystrophy.

Congenital corneal opacities present in approximately 3/100,000 newborns. Many different disorders may result in corneal opacifications of infancy, including Peters' anomaly (PA), congenital hereditary endothelial dystrophy (CHED), congenital hereditary stromal dystrophy (CHSD) and posterior polymorphous dystrophy (PPMD). Current studies have localized defects using genetic testing in PA, CHED, CHSD and PPMD. Identifying mutations for specific disorders may lead to better understanding of the underlying pathogeneses and may help with diagnosis and prognosis. This article will review the clinical presentations, treatments and genetics of Peters' anomaly, congenital hereditary endothelial dystrophy, congenital hereditary stromal dystrophy and posterior polymorphous dystrophy.

OBJECTIVE:To describe the surgical procedure for placement of an implantable telescope prosthesis for end-stage age-related macular degeneration. METHODS:As part of a phase 2/3 clinical trial for patients with bilateral, irreversible age-related macular degeneration, the optimal procedure for monocular placement of the telescope prosthesis was determined. RESULTS:Because of the unique configuration of the telescope prosthesis, proper wound construction, anterior chamber management, and device insertion after phacoemulsification are critical for successful surgery. CONCLUSION/CONCLUSIONS:A unique surgical technique ensures appropriate placement of the telescope prosthesis, while reducing surgical trauma to the corneal endothelium.

The current World Health Organization classification of conjunctival melanocytic proliferations divides them into conjunctival nevi and invasive melanoma but, in contrast to other anatomic sites, does not recognize melanoma in situ. All atypical intraepithelial conjunctival proliferations are included in a heterogeneous category designated as primary acquired melanosis (PAM) with atypia. We performed clinicopathologic analysis of 29 cases of PAM with atypia. On the basis of histologic features and frequency of association with invasive melanoma and metastases, we were able to divide our cases into 2 histologic groups. The low-risk group (13 cases) included lesions composed of small to medium size melanocytes with high nuclear to cytoplasmic ratio and small to medium size hyperchromatic nuclei devoid of nucleoli showing predominantly single cell lentiginous growth pattern. Invasive melanoma occurred in only 2 cases from this group. None of these lesions metastasized. The second, high-risk group (16 cases), showed increased frequency of association with invasive melanoma (15/16 cases, 94%) and metastases (4/16 cases, 25%). These lesions were more heterogeneous architecturally but were all composed of melanocytes showing various degrees of epithelioid features such as abundant cytoplasm, vesicular nuclei, or prominent nucleoli. In 4 cases discrete areas showing high-risk and low-risk features were identified. All 4 lesions were associated with invasion. Our findings offer a practical approach for prognostically useful subclassification of PAM with atypia, which emphasizes cytologic features of intraepithelial conjunctival melanocytic proliferation.

We review the use of three topical medications for the therapy of ocular surface tumors: mitomycin C, 5-fluorouracil, and interferon alpha-2B. One hundred sixty patients with histologically or cytologically proven epithelial and melanocytic tumors were identified in the literature. Side effects occurred most often with mitomycin C, followed by 5-fluorouracil, and interferon alpha-2B. Patients most frequently experienced transient keratitis, redness, and irritation. Topical agents were used as both primary and adjuvant therapy. Rates of tumor regression for CIN and squamous cell carcinoma ranged from 80 to 96%, and 70% of pigmented tumors regressed after an average follow-up of 27 months.

Due to their indolent nature, conjunctival lymphomas have different treatment options compared to other adnexal lymphomas. Therapeutic options directed towards conjunctival lymphomas include radiotherapy (external beam radiation), brachytherapy, cryotherapy, intralesional interferon injections, systemic rituximab, and observation. Radiotherapy that has been demonstrated to be highly effective for both low and high-grade tumors, however, can be associated with a high percentage of short-term side effects and long-term complications. Brachytherapy can provide local tumor control, but can also cause many complications. Cryotherapy may be used for certain tumor locations, but has a high recurrence rate. Both interferon and rituximab show promising results for treating low-grade tumors while avoiding the complications associated with radiotherapy. Finally, reports of spontaneous regression of low-grade conjunctival lymphomas have led some investigators to advocate a course of careful observation following biopsy.

PURPOSE/OBJECTIVE:To report a case of conjunctival melanoma arising from diffuse primary acquired melanosis (PAM) with atypia in a young black woman in the context of previously published cases of this lesion in blacks. METHODS:Retrospective case report with literature review. The number and percentage of conjunctival melanomas occurring in black patients were determined from case series in which race was specified, published from 1950 to the present. RESULTS:Nodular multifocal conjunctival melanoma in a 30-year-old black woman was treated using surgical excision and adjuvant cryotherapy. Extensive PAM with severe atypia, including areas of microinvasive melanoma, was treated using topical mitomycin C. Literature review revealed 35 cases of conjunctival melanoma occurring in black patients. No previous reports of mitomycin C use in black patients with melanoma or PAM were identified. CONCLUSIONS:Conjunctival melanoma is an exceedingly rare tumor in black patients. The current case brings the total of reported cases to 36. We successfully treated nodular melanoma and diffuse PAM in a young black woman using a combination of excision with cryotherapy and topical mitomycin C, suggesting that these lesions are amenable to the same types of therapy previously described for white patients.