Sir,

Amphetamine derivatives used in weight reduction regimens are considered safe for use over a several week period. Ischaemic and/or haemorrhagic infarcts and necrotizing angiitis are common neurologic complications of amphetamine abuse. Ocular side effects of amphetamine abuse include mydriasis, decreased accommodation and convergence, visual hallucinations (blue tinge to objects), retinal vasoconstriction and vasculitis, retinal microaneurysms and haemorrhage, and anterior ischaemic optic neuropathy.1 In this report a 35-year-old woman developed acute nonarteritic anterior ischaemic optic neuropathy (NAION) after two prescribed dosages of phentermine hydrochloride as part of her weight loss treatment.

Case report

This obese 35-year-old Caucasian woman developed an acute superior nasal visual field defect in her left eye 1 day after taking Adipex-P (phentermine hydrochloride) 37.5 mg p.o.q. day for 2 days. Her body mass index was 34 kg/m2. She had no history of heart disease, diabetes, hypertension, hypercholesterolaemia, or strokes.

On neuro-ophthalmologic examination her visual acuity with correction was 20/20 OD and 20/100 OS. Humphrey visual fields revealed a left superior nasal focal defect respecting the horizontal meridian. She had a left relative afferent pupillary defect and a protan defect. Extraocular motility was normal. Slit-lamp examination revealed no cells or flare in the anterior chambers. On dilated funduscopic examination, her left optic disc appeared swollen with small slit-like peripapillary haemorrhages in the superior and temporal aspect of the disc. A small petechial haemorrhage was seen at the 5 o'clock position in the peripapillary region. No cotton wool spots were observed. Her right cup-to-disc ratio was 0.3. Maculae and peripheral retina were normal.

MRI of the brain and orbits with gadolinium, MRA of the cerebral blood vessels, carotid ultrasound, and transoesophageal echocardiogram were all normal. Her cerebrospinal fluid (CSF) opening pressure was 148 mm H2O; CSF cell count, protein, glucose, VDRL, gram stain, bacterial, viral, and fungal cultures were all unremarkable. Leber's hereditary optic neuropathy mitochondrial DNA mutations for 3460, 11778, 14484, and 15257 alleles were all negative. Autoimmune profile including antinuclear antibody, double stranded DNA, anti-SSA, anti-SSB, anti-Smith, anti-RNP, scleroderma antibody, and Jo-1 antibody were all negative. Hypercoagulable laboratories including cardiolipin antibody screen with reflex testing, lupus anticoagulant, beta-2 glycoprotein I antibodies, phosphatidylserine antibodies, VDRL, and dilute Russell viper venom were all negative. Serum Chlamydia pneumoniae PCR, Lyme antibodies, and HIV 1 antibody were negative. Serum angiotensin-converting enzyme, serum methylmalonate, and urine for heavy metals were negative. Fasting plasma homocysteine test was normal and PCR for methylene tetrahydrofolate reductase was negative. Her haemoglobin A1C and HDL/LDL ratio were normal.

Three weeks later, after discontinuing the medication, her visual acuity was 20/20 OD and 20/60 OS. Disc haemorrhages resolved and the left optic disc had mild temporal pallor.

Comment

Phentermine hydrochloride is a sympathomimetic amine with pharmacologic activity similar to the prototype class of drugs, the amphetamines. It is an FDA-approved prescription medication indicated for short-term (a few weeks) adjunct to a regimen of weight reduction based on exercise, behavioural modification, and caloric restriction in the management of exogenous obesity for patients with an initial body mass index greater than or equal to 30 kg/m2 (PDR drug).

Only two other reports of amphetamine-related acute visual loss have shown a temporal relationship of acute NAION following oxymetazoline2 used in nasal decongestants3 and intranasal methamphetamine abuse. Unlike these patients who had underlying insulin-dependent diabetes, hypertension, or crowded optic nerve heads, the patient presented here was healthy. Investigation for autoimmune disorders, hypercoagulable disorders, hypercholesterolaemia, hypertension, diabetes, strokes, valvular and cardiac wall abnormalities, LHON mutation, infectious disorders, sarcoidosis, and B12 deficiency was negative. This patient also did not show any central nervous system findings or fluoroscein angiographic evidence of necrotizing angiitis related to vascular occlusion.4 Her acute unilateral visual loss is a result of ischaemia to the posterior ciliary arteries of the left eye from vasoconstriction secondary to phentermine.

This report emphasizes the possible ocular adverse effects of prescribed diet pills, such as phentermine hydrochloride. It is important to be aware that acute NAION may occur not only in patients who abuse amphetamines, but also in patients who take the usual prescribed doses of phentermine hydrochloride, a Federal Drug Administration (FDA)-approved medication for the treatment of obesity.