Sir,

Famotidine is a competitive inhibitor of histamine H2-receptors. The primary clinically important pharmacological activity of famotidine is inhibition of gastric secrection. It is widely used due to its relatively limited side effect profile compared to other H2-antagonists. While transient and mild blurred vision has been reported, particularly with cimetidine,1 severe and permanent visual loss induced by H2-antagonists has not been reported. We describe the first case report of severe retinopathy as an adverse effect of famotidine.

Case report

A 57-year-old man was referred to our clinic with the complaint of sudden visual loss in both eyes after taking two doses of famotidine (20 mg/tab bid). He had no relevant underlying diseases, or family history of hereditary ocular diseases. He was not taking any other medications, and had no history of smoking. Regular health examination performed 1 month ago showed visual acuity of 20/15 in both eyes. He had suffered from a gastric ulcer for more than 1 year and had taken lansoprazole for about 6 months. No ocular side effect was noted using lansoprazole. Five days prior to visiting our clinic, his internist changed the prescription from lansoprazole to famotidine (20 mg/tab bid). After taking two doses of famotidine, he noticed sudden onset of blurred vision and darkening in both eyes. No photopsias was noted. He stopped taking famotidine, but no recovery in his vision occurred.

On visiting our clinic, best-corrected visual acuity was 20/200 in the right eye and 20/40 in the left eye. Automatic static perimetry showed severe generalized depression in both eyes (Figure 1). Slit-lamp examination was normal in both eyes. Indirect ophthalmoscopy and fluorescein angiography revealed no abnormalities (Figure 2). Electroretinogram demonstrated severely depressed response in both eyes (Figure 3a). Electrooculogram showed decreased Arden ratio (Figure 3b), and visual-evoked potential testing revealed poor waveform (Figure 3c). Severe retinopathy due to famotidine was impressed. Although cancer-associated retinopathy was not likely, computerized tomography of the chest was arranged and revealed negative findings. Visual function had not improved 6 months after the cessation of famotidine.

Figure 1
figure 1

Automatic static perimetry showed severe generalized depression in both eyes. (60 degree Quantify Missed Points exam, DICON, Division of Vismed, Inc.)

Full size image
Figure 2
figure 2

Indirect ophthalmoscopy and fluorescein angiography revealed no abnormalities.

Full size image
Figure 3
figure 3

(a) Electroretinogram demonstrated severely depressed response in both eyes. (b) Electrooculogram showed decreased Arden ratio. (c) Visual-evoked potential testing revealed poor waveform.

Full size image

Comment

H2-receptors are widely distributed throughout mammalian tissues and organ systems. They are also present on human ocular surfaces and retinal vessels.2, 3 Abelson and Udell2 suggested a vasodilatory effect through the H2-receptor, which can be blocked by cimetidine. Antihistamine has been reported to reduce blood–retinal barrier permeability in diabetes.3, 4 Thus, use of an H2-histamine antagonist might affect the blood flow of retinal vessels and perhaps result in side effects of transient headache or blurred vision.

In this case, the patient had taken lansoprazole for about 6 months without ocular side effects. The sudden loss of vision occurred after taking two doses of famotidine and he denied any recent dietary changes or special events around that time. These circumstances suggest that the retinopathy resulted from famotidine use. However, it is unlikely that the retinopathy was caused by change in vascular permeability or decrease in blood flow, because the fluorescein angiography was normal. Instead, the findings in ERG, EOG, and VEP suggest that the retinopathy derived from direct toxic effects to the photoreceptors-RPE (retinal pigment epithelium) complex. It is not clear whether this adverse effect occurred through histamine H2 receptors or not.

The results of several cohort studies do not suggest a major increased risk for eye disorders associated with use of antiulcer drugs, including famotidine.5, 6, 7, 8 However, those studies might fail to demonstrate exceedingly rare complications and therefore do not guarantee ocular safety. Although the exact mechanism in this patient remains unclear, we would like to remind physicians of the potential for this rare complication of famotidine.