Jan M. McDonnell

Holmium Laser Thermokeratoplasty

PURPOSE Corneal curvature can be altered by shrinking stromal collagen with a pulsed solid-state holmium: YAG laser in a procedure termed laser thermokeratoplasty. METHODS The authors performed laser thermokeratoplasty in 40 human cadaver eyes using a ring pattern of 32 spots, each spot having a diameter of 300 microns. RESULTS The amount of induced corneal steepening decreased as ring diameter was increased in 1 mm increments, with 22.2 +/- 3.3 and 3.7 +/- 2.0 diopters (D) of central steepening with diameters of 3 and 7 mm, respectively. Results of histologic examination showed a cone-shaped zone of increased stromal hematoxylin uptake extending posteriorly for 90% of stromal thickness. Energy levels greater than those needed to induce topographic changes produced limited endothelial injury in rabbit corneas and, in some cases, intraocular inflammation. A computerized, finite element model of the globe demonstrated central corneal steepening as a result of heat-induced stromal contraction to a depth of 75% corneal thickness. CONCLUSIONS These data support previous studies indicating that central corneal topography can be modified by heating corneal stroma in a controlled fashion with the mid-infrared holmium:YAG laser.

Conjunctival melanocytic lesions in children.

Seventy-one conjunctival melanocytic proliferations in patients 20 years of age or younger were examined. Sixty-five (91.5%) were nevi; there were three cases (4.2%) of racial or acquired melanosis, and three patients were identified who had malignant melanoma of the conjunctiva. The melanoma patients are presented in detail, and additional cases of conjunctival melanoma in children and adolescents reported in the literature are reviewed to determine factors that might influence prognosis. The number of cases is so small, however, that factors cannot be identified with confidence. Follow-up data are presented. Conjunctival nevi are relatively common in children, and appear to carry no risk for the development of melanoma during childhood. However, -conjunctival melanomas do occur rarely in children and have a variable prognosis.

Mechanism of Corneal Topographic Changes

Pterygia induce irregular corneal astigmatism that sometimes necessitates surgical removal before the lesion has advanced close to the visual axis. This astigmatism may occur either due to traction generated by the pterygium mechanically pulling on and distorting the cornea, or by the pooling of tears in advance of the pterygium, or both. To evaluate the effect of localized tear pooling on pterygium-induced astigmatism, corneoscope photographs were obtained before and after absorbing excess tears at the pterygium-corneal interface with a cellulose sponge. Pterygia from these patients were then excised and examined with transmission electron microscopy for the presence of myofibroblasts. The absence of myofibroblasts in these lesions as well as the alterations in corneoscopy induced by localized removal of tears at the advancing edge of the pterygia suggest that corneal distortion in the presence of pterygia is caused in part by local changes in the tear film.

Human Papillomavirus Type 16 DNA in Ocular and Cervical Swabs of Women With Genital Tract Condylomata

Human papillomavirus type 16 is associated with dysplasias and carcinomas of the conjunctiva and of the uterine cervix. To explore the relationship between cervical and ocular human papillomavirus infection, we examined DNA from bilateral limbal swabs and cervical swabs from 17 women (age range, 17 to 46 years; median, 31.7 years) with biopsy-proven human papillomavirus-related cervical dysplasia who had a normal ocular surface. Using polymerase chain reaction, we identified human papillomavirus 16 DNA in one or both eyes of 13 (76.5%) patients, six (46.2%) of whom had demonstrable human papillomavirus 16 DNA in cervical swabs as well. It thus appears that human papillomavirus 16 is present in the conjunctivae of some patients with human papillomavirus-related genital warts who have no ocular manifestations of infection. Although autoinoculation of conjunctiva may be the source of some ocular human papillomavirus, data suggest that other modes of transmission to the eye also exist. Additional study of the epidemiologic characteristics of ocular human papillomavirus, a widely prevalent virus known to be associated with dysplasias/atypias and cancer, is warranted.

Combined Localized Current Field Hyperthermia and Irradiation for Intraocular Tumors

Ten patients with large melanomas and one patient with recurrent retinoblastoma were treated with combined localized current field (LCF) hyperthermia and iodine 125 irradiation delivered by episcleral plaque. Tumors were heated to 43 degrees to 45 degrees C for 28 to 45 minutes. Localized current field hyperthermia when combined with irradiation appeared to induce rapid tumor necrosis. One eye enucleated 17 hours after treatment showed only focal necrosis of the melanoma, while another eye demonstrated extensive necrosis 60 hours after treatment. In all remaining eyes, tumor regression occurred within the first month of treatment. Complications included cataract formation in six eyes, hemorrhagic retinal detachment in five eyes, and phthisis in two eyes. Complications from combined therapy of large intraocular tumors in this series appeared to result from the rapid necrosis of the tumor and secondary intraocular inflammation. Intraocular temperature dosimetry measurements demonstrated a temperature gradient of not more than -0.23 degrees C/mm-1 per axial millimeter from the episcleral plaque surface to the apex of the tumor. The authors believe that LCF hyperthermia could be a suitable means of application of hyperthermia in patients with intraocular tumors if further modifications were performed to reduce ocular complications.

HMB-45 Immunohistochemical Staining of Conjunctival Melanocytic Lesions

HMB-45 is a monoclonal antibody recently described as being highly specific for melanocytic proliferations of the skin and in metastases of melanotic lesions. To determine a possible role for HMB-45 in ophthalmic pathology, 45 conjunctival lesions, including 23 melanomas, were analyzed using immunohistochemical techniques with anti-S-100 and HMB-45 as primary antibodies. Nineteen (82.6%) of the melanomas exhibited HMB-45 positivity, and 19 (82.6%) contained S-100 protein, with concordance of all but two cases. Seven cases of primary acquired melanosis were studied; one (33%) of three with atypia was HMB-45 positive, as were two (50%) of four without atypia. Among nevi, 1 (9.1%) of 11 showed faint staining with HMB-45. Fifteen conjunctival epithelial dysplasias were negative with HMB-45. At present, HMB-45 appears to offer no great advantage over S-100 protein in the analysis of conjunctival melanomas. Its role in the distinction of benign from atypical or malignant junctional melanocytic proliferations remains unclear.

Histopathologic changes following irradiation for uveal tract melanoma

Histopathologic studies were performed on 38 eyes in patients with uveal melanoma who had enucleation. Of the 38 eyes examined, enucleation was required in 11 (29%) following episeleral radioactive plaque therapy (RPT), which was performed in 83 patients. The reasons for enucleation in the 11 patients who had RPT were progressive tumor in 5 and treatment complications in 6 eyes. The histologie findings in these 11 patients were compared to those seen in 7 patients (18%) who received a planned course of preoperative external beam radiotherapy (RT) prior to enucleation and with 20 uveal melanoma patients (53%) who were treated with enucleation alone. Tumor necrosis was found in the eyes of patients from all three groups examined. It was, however, seen more frequently and to a greater extent in the 11 RPT patients as compared to the 7 preoperative RT and 20 enucleation alone patients, p = .01. There was no difference in the incidence or extent of tumor necrosis in the 7 preoperative RT patients as compared to the 20 primary enucleation patients, p = .18. In all 3 study groups, no correlation was found between tumor size and necrosis. In the 11 RPT patients, necrosis was independent of cell type and the radiation dose. As expected, the RPT patients had a greater incidence of neovascularization on the iris and scleral necrosis than those of the other two study groups (70 vs. 12.5% and 33 vs 0%, respectively), p = .004. A major effort needs to be made to optimize episeleral RPT in order to reduce treatment complications and increase the incidence of primary tumor control.

Keratitis as a complication of bilateral, simultaneous radial keratotomy.

During a one-month period, we examined four patients referred for evaluation of probable microbial keratitis after bilateral, simultaneous radial keratotomy. Each patient had midstromal infiltrates compatible with microbial keratitis that involved one or more of the radial incisions. In two patients the keratitis was bilateral. All patients had been treated empirically with antibiotic agents; superficial cultures with cotton-tipped applicators and corneal scraping by inserting a platinum spatula into the radial incisions were negative. Corneal biopsy of one patient disclosed gram-positive rods and culture of the biopsy specimen grew diphtheroids. The infiltrates gradually resolved over a period of several months with intensive antibiotic therapy. Sight-threatening infectious keratitis can occur after radial keratotomy, and we believe that simultaneous bilateral ocular surgery of any kind should be discouraged.

Infectious crystalline keratopathy with ring opacity

A 41-year-old physician was treated for 3 months with antiviral medications, antibiotics, and steroids for presumed herpetic keratitis. When seen by us, an annular infiltrate was observed, along with crystalline-like opacities in the superficial one third of the stroma. Cultures of scrapings and of subsequent biopsies were positive for Streptococcus mitis of the viridans group; histopathology demonstrated large aggregates of cocci between the stroma lamellae. Tapering of topical corticosteroids and treatment with topical penicillin resulted in resolution of the infiltrates. The clinical appearance and findings in this patient suggest that infectious crystalline keratitis can produce an annular infiltrate. Injection of the organism into rabbit corneas produced a crystalline infiltrate, but no annular opacity was observed. Corticosteroids altered the clinical and histopathologic appearance of the lesions in rabbits.

Fibrous histiocytoid leprosy of the cornea.

We describe a 50-year-old man with a 10-year history of gradually enlarging limbal tumors and conjunctival injection. An excised limbal mass presented a diagnostic challenge histopathologically and was initially believed to be a fibrous histiocytoma. Special stains, however, revealed acid-fast organisms in the fibrous histiocytes, and the diagnosis was changed to corneal leproma. This case confirms the existence of fibrous histiocytoma-like lesions in leprosy, which in this form can be termed fibrous histiocytoid leprosy. Furthermore, it suggests the need for special stains to rule out infectious cause in lesions believed to be atypical fibrous histiocytomas.