Retinal toxicity after high-dose cisplatin therapy.

Because of increasing complaints of visual dysfunction, 13 patients with refractory or recently diagnosed ovarian carcinoma were evaluated for possible cisplatin-induced ophthalmologic toxicity. All patients had received high-dose cisplatin (200 mg/m2 in five divided daily doses) over two to four cycles. Eight patients (62%) developed symptoms of blurred vision and three (23%) also developed altered color perception. Retinal toxicity in the form of cone dysfunction was documented by electroretinography and color vision testing in 11 patients. Three patients were studied prospectively. Two patients who developed cone dysfunction had normal ophthalmologic exams before the initiation of chemotherapy or after one cycle of cisplatin, suggesting a causal relationship between cisplatin therapy and subsequent retinal abnormalities. Though visual acuity improved off therapy, color vision abnormalities persisted as long as 16 months beyond therapy.

Choroideremia: a clinical, electron microscopic, and biochemical report.

An asymptomatic 19-year-old male with choroideremia had diffuse loss of retinal pigment epithelium (RPE) and choroid except for the periphery and macula. Fluorescein angiography of the arteriovenous phase showed absence of retinal pigment epithelium and exaggerated visualization of choroidal vessels in involved areas. The mother was a typical carrier with pigment stippling of the midperipheral retina. Histopathologic examination of affected areas of one eye showed marked degeneration of the outer and midretina with loss of retinal pigment epithelium and Bruch's membrane, absence of choriocapillaris, chorioretinal adhesions and gliosis. Atrophy of inner and mid-choroid was also observed. Pigmented macrophage-like cells had migrated into the outer and midretinal layers. Electron microscopy disclosed macrophage-like cells with trilaminar structures and photoreceptor phagosomes in the RPE and outer retina. Remnants of photoreceptor outer segments were adherent to the plasma membranes of the macrophage-like cells. Biochemical analysis of retinal tissue samples for interphotoreceptor retinoid-binding protein (IRBP) showed marked reduction in the 146K bands in the equator and posterior pole in the patient compared to controls. Cyclic nucleotide content was altered in the retinal equator. Cyclic AMP was several-fold higher in the RPE-choroid complex of the affected eye than in the control.

Phototransection of vitreal membranes with the carbon dioxide laser in rabbits.

An intravitreal CO2 laser probe phototransected vitreal membranes in rabbits with short pulses of infrared energy delivered through either an optical fiber or an articulated arm. The potential use of the CO2 laser probe appears to be as an adjunct to the mechanical vitrectors.

Rarity of diabetic retinopathy in patients with acromegaly.

We studied 44 acromegalic patients with the use of fluorescein angiography to detect the presence of diabetic retinopathy. We found elements of diabetic retinopathy in only one patient (2.2%). The average patient had a growth hormone concentration of 32 ng/mL (range, 1 to 275 ng/mL) for a duration of 10.5 years (range, three to 26 years). Forty-five percent (20) of our group had glucose intolerance and 14% (six) had elevated fasting blood glucose levels for an average duration of two years (range, one to four years). We conclude that diabetic retinopathy is an uncommon finding in patients with acromegaly and that fluorescein angiography does not reveal cases that were not detected by conventional funduscopic examination.

Increased incidence of retinopathy in diabetics with elevated blood pressure. A six-year follow-up study in Pima Indians.

The incidence of retinopathy was assessed in 188 diabetic and 284 nondiabetic Pima Indian adults six years after an initial examination had shown each to be free of retinopathy. Exminations included direct ophthalmoscopy through dilated pupils. The incidence of retinal lesions was strongly related to the presence of diabetes and, among the diabetic subjects, to insulin treatment, disease duration, plasma glucose concentration, and presence of other complications such as proteinuria, loss of deep tendon reflexes, and increased vibration-sensation threshold. In diabetic subjects not taking insulin, the incidence of exudates in those with systolic blood pressures of at least 145 mm Hg was more than twice that of those with pressures of less than 125 mm Hg. This association persisted when assessed within categories of subjects stratified according to 13 potentially confounding variables, suggesting that control of blood pressure may reduce the incidence of retinal exudates in diabetics not treated with insulin.

Cellular immune responsiveness of uveitis patients to retinal S-antigen.

S-antigen, an organ-specific substance isolated from the retinal photoreceptor region, was shown to be a potent agent for the induction of experimental autoimmune uveitis. S-antigen and other ocular antigens were tested for their ability to induce blast transformation of lymphocytes from patients with a variety of ocular inflammatory diseases. Lymphocytes from 22% of patients tested manifested a positive memory response to the S-antigen prepared from bovine eyes. Responses to human S-antigen paralleled those found with the bovine. All of those with a positive response had active or inactive retinal lesions. Some posterior uveitis patients responded to crude retinal extracts but not to S-antigen, indicating the possible role of other retinal antigens still to be purified. Control subjects did not manifest a positive immune response to the S-antigen, nor did patients with anterior uveitis. Possibly, these responses play some role in the pathogenesis of the disease.

Analysis of the systemic corticosteroid sensitivity of patients with primary open-angle glaucoma.

Patients with primary open-angle glaucoma have an ocular and systemic sensitivity to corticosteroids. We adapted a cellular assay that used peripheral blood lymphocytes to detect this corticosteroid sensitivity in vitro in a microtiter assay. It reduced the time, cost, and amount of blood required to examine a patient. We examined ten subjects on three separate days and demonstrated that the reliability of one 50% inhibitory concentration was about 76%. We then studied 25 patients with primary open-angle glaucoma and 25 control subjects using this in vitro assay. The patients with primary open-angle glaucoma were significantly more sensitive to corticosteroids than the control subjects (P less than .001).

Retinopathy in Pima Indians. Relationships to glucose level, duration of diabetes, age at diagnosis of diabetes, and age at examination in a population with a high prevalence of diabetes mellitus.

The occurrence of retinopathy and its relationship to diabetes in 1,640 Pima Indians age 15 and over has been determined. Eighteen per cent of those with two-hour postload plasma glucose levels of equal to or greater than 200 mg./dl. had some evidence of retinopathy. Of those with retinopathy and diabetes, 7 per cent were found to have proliferative or neovascular changes, the remainder having microaneurysms and/or exudates. The frequency of retinopathy increased from 3 per cent among newly diagnosed diabetics to 47 per cent among those with diabetes of 10 or more years duration. No relationship was found with sex, age at diagnosis of diabetes, or age at time of examination when duration of diabetes was taken into account. The occurrence of retinopathy was confined largely to those who fell into the second or hyperglycemic component of the frequency distribution of plasma glucose levels in the population, indicating the significance of the bimodal glucose tolerance frequency distribution.