Alan M. Roth

Cancer-Associated Retinopathy (CAR Syndrome) with Antibodies Reacting with Retinal, Optic-Nerve, and Cancer Cells

A VARIETY of neurologic disorders are associated with different forms of cancer.1 2 3 4 5 6 7 Secondary neurologic effects that become manifest in the absence of metastasis are collectively called ...

Clinical and Pathologic Description of 17 Cases of Corneal Intraepithelial Neoplasia

In 17 patients with corneal intraepithelial neoplasia (dysplasia), the epithelium formed a gray plaque at the corneal limbus adjacent to a conjunctival papilloma in seven cases, leukoplakia in six cases, a pterygium in one case, and a pinguecula in one case. The lesion was an extension of a similar neoplastic process of the conjunctiva in 15 cases, was associated with chronic conjunctivitis in one case, and was isolated to the cornea in one case. Fine white dots mottled the opalescent, ground-glass sheet, whose fimbriated leading edge consisted of sharply demarcated gray fingers that extended to the visual axis in some cases. The disorder can wax and wane spontaneously, shown in one case observed for 16 years. Histopathologically, the thick, hypercellular corneal epithelium abutted sharply against adjacent normal epithelium and demonstrated both cellular pleomorphism and poor intercellular adhesion in the deeper layers. The adjacent conjunctival neoplastic lesions ranged from mild dysplasia to invasive squamous cell carcinoma. Ultrastructurally, the corneal epithelium showed a marked decrease in desmosomal attachments, an abundance of intracytoplasmic filaments characteristic of keratin, and a loss of epithelial basement membrane and hemidesmosomes. The lesion did not extend into Bowmans zone. We classify this dysplastic process as a mild form of corneal intraepithelial dysplasia, a term used to designate the spectrum of epithelial changes ranging from dysplasia to carcinoma in situ. The virulence of the corneal lesion itself is low.

Clinicopathologic Correlation of Microphthalmos with Cyst

Three patients had microphthalmos with cyst in one orbit and contralateral congenital cystic eye, microphthalmos alone, or microphthalmos with cyst. Four eyes were examined histopathologically. The microphthalmic eye demonstrated a spectrum of anterior segment abnormalities, retinal disorganization and gliosis, and a choroidal and scleral colomboma. The cyst connected to the colobona consisted of an outer fibrovascular layer and inner gliotic neuroectodermal layer. The cyst probably originated from proliferation of neuroectodermal tissue at the edge of a persistently open embryonic fissure. Treatment consisted of multiple aspirations of the cyst, excision of the cyst alone, and excision of both the microphthalmic eye and cyst.

Long-Term Effects of Intravitreal Injection of GMP-Grade Bone-Marrow–Derived CD34+ Cells in NOD-SCID Mice with Acute Ischemia-Reperfusion Injury

PURPOSE To determine long-term safety of intravitreal administration of good manufacturing practice (GMP)-grade human bone-marrow-derived CD34(+) cells in NOD-SCID (nonobese diabetic-severe combined immunodeficiency) mice with acute retinal ischemia-reperfusion injury, a model for retinal vasculopathy. METHOD Acute ischemia-reperfusion injury was induced in the right eye of adult NOD-SCID mice (n = 23) by transient elevation of intraocular pressure. Seven days later, 12 injured eyes and 5 normal contralateral eyes were injected each intravitreally with 5 × 10(4) CD34(+) cells isolated under GMP conditions from a healthy human donor bone marrow using an immunomagnetic cell isolation system. The remaining 11 injured eyes were not treated and served as controls. Mice were euthanized 1 day, 4 months, and 8 months later. Both eyes were enucleated and examined by immunohistochemical analysis and hematoxylin and eosin staining. Among mice followed for 8 months, electroretinography (ERG) was performed on both eyes before euthanization. All major organs were examined grossly and histologically after serial sectioning. RESULTS Immunohistochemical staining 4 months after injection showed detectable CD34(+) cells in the retinal vasculature. ERG at 8 months after CD34(+) cell injection showed signals that were similar in untreated eyes. Histology of the enucleated eyes injected with CD34(+) cells showed no intraocular tumor or abnormal tissue growth after 8 months. Histologic analysis of all major organs showed no abnormal proliferation of human cells. CONCLUSIONS Intravitreal administration of GMP-grade human bone-marrow-derived CD34(+) cells appears to be well tolerated long-term in eyes with acute retinal ischemic injury. A clinical trial will start to further explore this therapy.

Optic cupping caused by an intracranial aneurysm.

A 51-year-old woman had optic disk cupping from optic nerve compression by an intracranial aneurysm. Slit-lamp stereoscopic examination of the living eye immediately post mortem revealed an optic cup vertically oral, elongated superiorly, and indistinguishable from disk changes seen early in glaucoma. The histopathological changes differed from those in glaucoma by showing no glial atrophy. Instead, the cupping was caused by loss of axons in the prelaminar region of the nerve head and collapse of glial columns.

Antibody Indications of Secondary and Superimposed Retinal Hypersensitivity in Retinitis Pigmentosa

Antibody reactions with recognized retinopathy-inducing retinal antigens may be interpreted to reflect ongoing autoimmune events responsible for some forms of vision loss. We sought evidence of secondary and superimposed retinal hypersensitivity indicated by such antibody reactivity in a random group of patients with retinitis pigmentosa. We identified patterns of immunologic reactivity within members of a group of 52 patients with retinitis pigmentosa, which suggests some patients with retinitis pigmentosa may experience consequential superimposed retinal hypersensitivity. Identifying subgroups of patients with retinitis pigmentosa who exhibit indications of retinal hypersensitivity to known uveitopathogenic retinal proteins may permit the reduction of their rate of retinal degradation by immunomodulation.

Histoplasma Capsulatum in the Presumed Ocular Histoplasmosis Syndrome

I demonstrated Histoplasma capsulatum organisms in disciform macular lesions, as well as a peripapillary lesion and peripheral atrophic scars in both eyes and in the lung of a patient with no history of active histoplasmosis. Autopsy findings were compatible with those of the presumed ocular histoplasmosis syndrome.

Intraosseous Hemangioma of the Orbital Roof

A 63-year-old woman had an osseous hemangioma of the orbital rim. Diagnosis of this primary bone tumor was made by its distinctive radiographic appearance and confirmed by pathologic, examination. Although this is a benign lesion, it is expansile and can cause ocular signs. Surgical resection is the recommended treatment.

Solitary Keratoacanthoma of the Conjunctiva

Two ranch workers had rapidly-growing crateriform conjunctival nodules excised without recurrence. Histopathologically, these lesions consisted of acanthotic epithelium characterized by prominent keratin formation both within cells and in horn pearls. Although both clinically and histologically they resemble squamous cell carcinoma, keratoacanthomas are benign tumors commonly thought to arise in hair follicles. The presence of these lesions on conjunctiva and other epithelia without hair in the two cases described was evidence against this hypothesis.

Lepromatous Iridocyclitis Diagnosed by Anterior Chamber Paracentesis

A 34-year-old man with a three-month history of intraocular inflammation after ocular trauma with a fir branch, had an acute unilateral fulminant iridocyclitis. The iris had a thick, gray, cheesy membrane composed of nodular lepromata. The patient denied a history of Hansens disease, despite the dermatologic and facial features that suggested the diagnosis. Anterior chamber paracentesis and scleral nodule biopsy demonstrated Mycobacterium lepra. The iridocyclitis resolved after treatment with dapsone, corticosteroids, and rifampin.