John W. Gittinger

Selective Immunohistochemical Staining in the Paraneoplasdc Retinopathy Syndrome

BACKGROUND The mechanism leading to visual loss in paraneoplastic retinopathy is not known. An autoimmune process has been imputed based on immunologic investigations of several patients and by analogy to certain other paraneoplastic syndromes. METHODS Two patients with documented small cell carcinoma of the lung who had clinical evidence of paraneoplastic retinopathy are described. Histopathologic examination of the retina from one patient and immunohistochemical staining of human retina with serum from control subjects and both patients were performed. RESULTS Electroretinograms demonstrated dysfunction of photoreceptors in both patients, with predominant loss of rod function in one patient. Post mortem examination showed patchy loss of photoreceptors of the extramacular retina and relative sparing of cones, findings consistent with the clinical and electrophysiologic test results. Serum from both patients stained the retina in an identical manner, with restriction of the stain to the outer retina. Stain was present over the outer plexiform layer, the outer nuclear layer, and the inner and outer segments of most photoreceptors. A sharp demarcation was present between those areas that did and did not stain. All rod inner and outer segments appeared to stain, and many cone inner segments were not stained. Immunologic tests obtained elsewhere did not show serum antibody to the 23 kD protein. CONCLUSION These findings support the concept of an autoimmune pathogenesis by showing selectivity of the immune response and correlation between the apparent target of the immune response and the clinical and pathologic findings. The mechanism by which cell loss occurs in the retina is not answered by this study. The absence of antibody to the 23 kD protein does not exclude the diagnosis of paraneoplastic retinopathy.

Foscarnet-ganciclovir cytomegalovirus retinitis trial: 5. Clinical features of cytomegalovirus retinitis at diagnosis

PURPOSE To examine associations of systemic and ocular characteristics with severity of cytomegalovirus (CMV) retinitis at time of diagnosis and to compare ocular characteristics of eyes with and without CMV retinitis. METHODS Eleven clinical centers, a data coordinating center, and a fundus photograph reading center participated in a randomized, controlled, multicenter clinical trial comparing foscarnet and ganciclovir as primary therapy for previously untreated CMV retinitis in 240 patients with AIDS. RESULTS The systemic characteristics marginally associated with the percentage of retina affected by CMV in a patients worse eye at diagnosis were chronic fever, weight loss, and number of HIV-related illnesses. A positive CMV blood culture at diagnosis was similarly associated with bilateral disease. Laboratory measures of disease did not correlate well with measures of CMV retinitis severity. Many eyes with CMV retinitis had no or minimal lesion hemorrhage, but most had signs of inflammation. Patients often reported visual symptoms for involved eyes. The worse eyes (the eye with lesions covering the most retinal area) of patients with bilateral disease had greater retinal involvement, more lesions, and fewer degrees of visual field than did involved eyes of patients with unilateral disease. Visual symptoms, inflammation, indolent retinitis, and hemorrhagic lesions were associated with a greater percentage of retina affected by CMV. CONCLUSIONS The findings support viremia as a mechanism of spread for untreated disease. Visual symptoms and signs of ocular inflammation were indicators both of the presence of CMV retinitis and of greater extent of retinal area covered by CMV retinitis lesions.

Acquired oculomotor synkinesis

Paradoxical patterns of pupillary, lid and eye movement may follow oculomotor nerve palsy or they can develop spontaneously in patients with no known history of oculomotor palsy. The mechanism of this condition, known variously as aberrant regeneration of the third nerve, oculomotor misdirection or acquired oculomotor synkinesis, is not known, although the prevailing opinion has held that it occurs when axons regenerating within an oculomotor nerve become misdirected and innervate muscles for which they were not intended. However, there is evidence against this hypothesis. The authors critically review the various hypotheses and elucidate the controversy concerning the pathogenesis of acquired oculomotor synkinesis.

Congenital adduction palsy and synergistic divergence.

Electromyography of the medial and lateral recti muscles in the right eye of a 7-year-old boy with congenital variable exotropia demonstrated cocontraction. This explained the observed simultaneous abduction on attempted levoversion. Abduction of the right eye increased intraocular pressure to 25 mm Hg from 15 mm Hg. This synergistic divergence should be considered a variant of Duanes syndrome, and, like Duanes syndrome, may occur as the result of anomalies of the peripheral oculomotor nerves or of central synaptic alterations, or of a combined central and peripheral mechanism.

Macular abnormalities in papilledema from pseudotumor cerebri

Three young women with papilledema secondary to pseudotumor cerebri evolved mottled macular pigmentation with preservation of normal visual acuity. Choroidal folds or macular star figures were observed. These macular changes could represent the sequelae of either macular edema or a mechanical disruption of the retinal pigment epithelium. The mechanism of choroidal folds in papilledema remains uncertain.

Functional Monocular Temporal Hemianopsia

Four patients, two men 25 and 43 years old and two women 20 and 40 years old, had complete monocular temporal hemianopsias, suggesting that it may be a more common functional deficit than has been recognized. The initial symptoms were visual loss and headache, and eye pain also occurred. Correct diagnosis is possible if the absence of a relative afferent pupillary defect and the persistence of a hemianopsia on binocular testing are demonstrated.

Glaucomatous cupping — Sine glaucoma☆

A 72-year-old man presented with transient episodes of gradually descending vision loss in either eye. Both discs showed marked cupping, but applanation tensions were normal. Carotid occlusions were present. The etiology of the transient visual disturbances, the relationship of carotid disease to low tension glaucoma, and the management of such patients are discussed.

The Visual-Evoked Potential in the Diagnosis of Congenital Ocular Motor Apraxia

Three infants initially thought to be blind by behavioral criteria had normal visual acuities measured by visual-evoked potentials. Contraversive deviation of the eyes on rotation of the head was present. All three later developed the characteristic head thrust of congenital ocular motor apraxia. Thus, a normal visual-evoked potential provides a significant diagnostic clue in infants with normal ophthalmoscopic findings but abnormal visual behavior.

Ocular Involvement in Castleman's Disease

A 21-year-old man with known Castlemans disease, a lymphoproliferative disorder with both local and systemic manifestations, presented with decreased vision in the left eye and chromatopsia. He had infiltration of the left disc and choroid with elevation of the retina, multiple bilateral depigmented areas at the level of the choroid or retinal pigment epithelium (RPE) (also thought to represent infiltrates), and left exophthalmos. A serious retinal detachment (RD) evolved, but then responded to radiotherapy, with recovery of good vision. Occult leptomeningeal involvement resolved during a period of observation. There was no systemic evidence of malignant lymphoma.

Optic Neuritis - Etiology?

A 44-year-old otherwise healthy woman was referred to Washington University with previous diagnoses of para planitis and retrobulbar neuritis, and with a current complaint of markedly decreased vision (light perception only) in the right eye. Among the findings at the time of this evaluation were posterior uveitis and evidence of optic neuropathy and of a disordered immune system. The patient responded to pulsed high-dose corticosteroid therapy. A subsequent similar episode in the left eye also was resolved with such treatment. Dr. Burde describes the case in detail and asks Drs. Keltner, Gittinger and Miller to offer diagnoses. Their answers vary considerably.