J. Oscar Croxatto

Clinically Atypical Granular Corneal Dystrophy with Pathologic Features of Lattice-like Amyloid Deposits: A Study of Three Families

Four patients from families in Pennsylvania, Massachusetts, and Argentina were diagnosed clinically as having granular dystrophy. Results of pathologic examination of the corneal buttons from each patient after penetrating keratoplasty confirmed granular deposits in the anterior third of the stroma. Amyloid was demonstrated within some of these granular deposits by Congo red staining with birefringence and dichroism and by electron microscopy. In addition to the morphologically granular deposits, numerous fusiform deposits identified as amyloid by histochemistry and electron microscopy and morphologically identical to those seen in lattice corneal dystrophy were detected deep to the granular deposits. It was further shown that the histochemical pattern of staining of the granular material by a series of lectins was similar to that present in corneas with lattice dystrophy. Although a relationship between these patients cannot be definitively proven, each family traces its origins to the Italian province of Avellino.

Hydatid Cysts of the Orbit: A Review of 35 Cases

The authors reviewed 35 cases of orbital hydatid cysts, which represented 5% of orbital surgical cases seen from 1944 to 1985. The average age was 16 years (range, 2-57 years). Slowly progressive unilateral exophthalmos, with or without pain, was the most frequent clinical manifestation. Computed tomography (CT) of the orbit demonstrated a well-circumscribed mass. Ultrasonography showed an anechoic cystic mass. The parasitic membrane and contents were surgically removed through an orbital approach. Hydatid cysts should be included in the differential diagnosis of unilateral exophthalmos in patients from countries where echinococcosis is endemic. Preoperative recognition is important for planning an appropriate surgical treatment in avoiding complications.

Local and Systemic Toxicity of Intravitreal Melphalan for Vitreous Seeding in Retinoblastoma: A Preclinical and Clinical Study

PURPOSE Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model. DESIGN Clinical and preclinical, prospective, cohort study. PARTICIPANTS In the clinical study, 16 patient eyes received 107 intravitreal injections of 30 μg melphalan given weekly, a median of 6.5 times (range, 5-8). In the animal study, 12 New Zealand/Dutch Belt pigmented rabbits were given 3 weekly injections of 15 μg of intravitreal melphalan or vehicle to the right eye. METHODS Electroretinogram (ERG) responses were recorded in both humans and rabbits. For the clinical study, ERG responses were recorded at baseline, immediately before each injection, and at each follow-up visit; 82 of these studies were deemed evaluable. Median follow-up time was 5.2 months (range, 1-11). Complete blood counts (CBCs) were obtained on the day of injection at 46 patient visits. In the animal study, ERG responses were obtained along with fluorescein angiography, CBCs, and melphalan plasma concentration. After humane killing, the histopathology of the eyes was evaluated. MAIN OUTCOME MEASURES For the clinical study, we measured peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation with comparisons between ERG studies before and after intravitreal melphalan. For the animal study, we collected ERG parameters before and after intravitreal melphalan injections with histopathologic findings. RESULTS By linear regression analysis, over the course of weekly intravitreal injections in retinoblastoma patients, for every additional injection, the ERG amplitude decreased by approximately 5.8 μV. The ERG remained stable once the treatment course was completed. In retinoblastoma patients, there were no grade 3 or 4 hematologic events. One week after the second injection in rabbits, the a- and b-wave amplitude declined significantly in the melphalan treated eyes compared with vehicle-treated eyes (P<0.05). Histopathology revealed severely atrophic retina. CONCLUSIONS Weekly injections of 30 μg of melphalan can result in a decreased ERG response, which is indicative of retinal toxicity. These findings are confirmed at an equivalent dose in rabbit eyes by ERG measurements and by histopathologic evidence of severe retinal damage. Systemic toxicity with intravitreal melphalan at these doses in humans or rabbits was not detected.

Neurofibromatosis Associated with Nevus of Ota and Choroidal Melanoma

A 68-year-old woman who had generalized neurofibromatosis and nevus of Ota developed a choroidal mass in her right eye. Pathologic examination disclosed a choroid melanoma of mixed cell type. The association of oculodermal melanocytosis and von Recklinghausens neurofibromatosis, although unusual, is not surprising because both disorders originate in the neural crest cells.

Angle Closure Glaucoma as Initial Manifestation of Melanocytoma of the Optic Disc

A 44-year-old man had progressive visual loss and pain due to angle-closure glaucoma associated with a papillary pigmented lesion. The eye was enucleated because of intractable pain and the suspicion of a malignant tumor. Histologic and electron microscopic examination of the enucleated eye revealed a partially necrotic melanocytoma of the optic nerve. There was histologic evidence of vaso-occlusive disease within the optic nerve that resulted in ischemic necrosis of the tumor, hypoxic retinopathy and neovascular glaucoma. This report emphasizes that significant complications may occur in otherwise typical intraocular nevi.

Unusual Ciliary Body Tumor: Mesectodermal Leiomyoma

A 23-year-old white woman presented with a pigmented ciliary body mass in the left eye. The tumor appeared to transilluminate when observed with indirect illumination. Clinically the tumor was considered to represent either a malignant melanoma or a cyst and was excised by iridocyclectomy. Electron microscopic examination established the smooth muscle nature of the tumor. The literature on this unusual tumor is reviewed. Furthermore, this report serves to emphasize the value of iridocyclectomy in the diagnosis and treatment of ciliary body tumors.

Malignant Melanoma of the Conjunctiva: Report of a Case

Malignant melanomas of the conjunctiva are extremely rare in children. The authors report an 11-year-old boy who had a nodule at the limbus in a pigmented area since early childhood. The lesion was excised and the diagnosis of atypical compound nevus was made. Five months later, the patient returned with multiple nodules in the bulbar and palpebral conjunctiva. One of the lesions was excised, and the diagnosis was malignant melanoma. He was lost for follow-up for 6 months; then he presented a large pigmented, vascularized mass protruding through the palpebral aperture. Results of systemic workup for metastatic disease were negative, and an exenteration was performed. A few months later, cervical lymphadenopathy developed followed by extensive metastatic disease.

Primary cystadenocarcinoma of the lacrimal gland

PURPOSE To report a patient with a cystadenocarcinoma of the lacrimal gland, a tumor not previously described in the ophthalmic literature. Salivary gland cystadenocarcinomas constitute a distinct group of epithelial malignancies characterized by an invasive, predominantly cystic pattern of growth that have an indolent behavior and a low incidence of metastases and recurrences. DESIGN Single interventional case report. METHODS The clinical findings, results of imaging studies, and pathologic findings are presented. RESULTS A 67-year-old man presented with a 5-year history of ptosis in the right upper eyelid. A lacrimal fossa tumor was found. The tumor was excised with an intact capsule, and the histopathologic diagnosis was primary cystadenocarcinoma of the lacrimal gland. The patient received no other form of treatment and has been observed for 1 year without evidence of recurrence or metastatic disease. CONCLUSIONS Until recently, primary adenocarcinomas of the lacrimal gland were not further subclassified. Current knowledge gained from salivary gland tumors indicates that primary adenocarcinoma encompasses a group of tumors with separate morphologic features and varied biologic behavior.

Corneal dystrophies and keratoconus

Several well-conducted clinical studies of corneal dystrophies, herein reviewed, were published during the last year. Basic sciences, including modern molecular biology techniques, contributed to the understanding of the genetics and physiopathology of these diseases. Recently incorporated surgical techniques and indications of current surgical approaches in keratoconus are discussed.

Bilateral and Massive Lipoidal Infiltration of the Cornea (Secondary Lipoidal Degeneration)

A 41-year-old white man presented with bilateral white infiltration of the cornea from limbus to limbus. Extensive examination revealed no manifestations of disorders of lipid metabolism and the patient gave no history of previous ocular disease. VDRL and other serological tests were negative. The corneal button removed by penetrating keratoplasty from the right eye was studied by light microscopy, histochemistry and electron microscopy. The light microscopic appearance was consistent with lipoidal degeneration of the cornea associated with stromal vascularization and chronic keratitis, more likely a secondary lipoidal degeneration. Cholesterol clefts were seen in all levels of the stroma focally surrounded by a foreign body giant cell reaction. Lipid vacuoles were observed in extracellular and intracellular locations within histiocytes and fibroblasts in vascularized and inflammed areas. Lipid stains disclosed cholesterol crystals, neutral fats, and phospholipids.