(vitamin A) level was reduced at 0.09 mg/L (normal 0.30–1.20). The patient received a diagnosis of retinal dysfunction due to hypovitaminosis A related to prior gastric bypass surgery. He was treated with 100 000 units of oral vitamin A per day, and over the next six weeks experienced progressive recovery of vision. A repeat ERG showed an increase in the scotopic amplitudes bilaterally (Figure 1.18B).

Discussion: Vitamin A is a fat-soluble vitamin that is absorbed across the small intestinal mucosa and transported to the liver, where it is stored in its esterified form (retinol) and available in protein-bound form to reach target tissues. In the retina it is stored in the retinal pigment epithelial cells and converted to the aldehyde form (retinal), which then combines with opsin to form rhodopsin. Vitamin A deficiency can result from inadequate nutritional intake (common in underdeveloped countries), poor intestinal absorption, impaired liver storage capacity or inadequate enzymatic conversion of retinol to retinal (a process that is dependent upon zinc as a co-factor). Causes of malabsorption include intestinal bypass surgery, regional enteritis and cystic fibrosis. Liver disease may cause hypovitaminosis A by a variety of mechanisms: decreased production of retinol-binding protein, inadequate storage of retinol, malabsorption due to decreased bile salts and depletion of zinc stores. Occasionally, deficiency is caused by the use of a synthetic vitamin A analog such as isotretinoin.

Ophthalmic manifestations of vitamin A deficiency typically include dry eyes and retinopathy. The earliest symptom is usually nyctalopia due to the greater dependency of rods on rapid transport with retinal pigment epithelial (RPE) cells. If the deficiency is not corrected, this is followed by visual field loss, photophobia and decreased acuity. Severe loss of visual acuity and color vision is unusual. Visual field testing may show central and paracentral defects that affect the superior field more than the inferior field.

Funduscopic examination is often normal, especially in early vitamin A deficiency, thus causing confusion with neurologic visual loss. With pro-

longed deficiency, multiple yellowish-white dots may appear in the mid-peripheral retina, giving it a stippled appearance. Fluorescein angiography may demonstrate numerous punctate RPE defects which correspond to these retinal lesions. These clinical abnormalities are present to varying degrees and are generally reversible within several months after vitamin repletion. Electrophysiologic tests such as dark adaptometry and full-field ERG are quite sensitive in this condition, revealing abnormal rod function even in the absence of visual symptoms. Eventually there is elevation of the threshold and loss of waveform amplitude for both rods and cones, though rod function is more severely affected. The diagnosis should be suspected on clinical grounds and confirmed by testing the vitamin A level. Following treatment, the electrophysiologic abnormalities are faster to improve than the fundus abnormalities, and the final visual prognosis is generally good although in cases of prolonged depletion permanent damage may occur.

Diagnosis: Hypovitaminosis A

Tip: Even in the absence of ophthalmoscopic abnormalities, a history of acquired, progressive nyctalopia should suggest a retinal disorder.

Swirling vision

Case: A 60-year-old plumber developed visual loss in the right eye accompanied by intermittent “swirling clouds of smoke” and occasional dim flashes of light. He did not have eye pain but did have prominent photophobia and noted that his vision was much worse in bright light. Visual acuity was count fingers OD and 20/25 OS. The visual field in the right eye showed a ring scotoma and was normal in the left eye. Dilated fundus examination and fluorescein angiography were normal. A retrobulbar optic neuropathy was suspected but an MRI of brain and orbits with gadolinium was normal. He received a tentative diagnosis of posterior ischemic optic neuropathy. Two months later, similar though milder visual loss developed in the left eye

(Figure 1.19). As before, the fundus appearance was normal.

A full-field ERG was nearly unrecordable under both scotopic and photopic conditions, indicating severe dysfunction of both rods and cones. Serologic testing showed antibodies to recoverin, diagnostic of cancer-associated retinopathy (CAR). A chest radiograph was normal but a chest computerized tomography (CT) scan revealed a small lesion which, on biopsy, proved to be a small cell lung carcinoma. His primary tumor was treated with radiation and chemotherapy and he received a course of high-dose intravenous corticosteroids followed by rituximab. Vision stabilized but unfortunately showed minimal improvement.

Discussion: Cancer-associated retinopathy (CAR) is a paraneoplastic syndrome in which antibodies directed toward a neoplasm also attack specific sites in the retina. It is most commonly associated with small cell lung carcinoma but has been described with various other malignancies including

non-small cell lung cancer, breast and gynecologic malignancies, prostate and bladder cancer. In half of patients with the syndrome, the presence of a malignancy is unsuspected at the onset of visual loss. The typical presentation consists of subacute, bilateral visual deterioration associated with photopsias and a variety of other entoptic phenomena including swirls, clouds, smoke and floaters. Early in the disease, the fundus appearance is normal. Later, attenuated arterioles, mottling of the retinal pigment epithelium, disc pallor and vitreous cells may be seen. The triad of photosensitivity, ring scotomas and attenuated retinal arterioles, particularly in an older patient, should suggest a diagnosis of CAR syndrome.

The autoimmune mechanism of CAR has been established with the discovery of auto-antibodies directed toward retina-specific antigens. To date, more than 15 auto-antibodies to the retina have been identified. The most common is the antirecoverin antibody, which targets a 23 kD protein (recoverin) found in rods and cones. As with other