To the Editor:
A previously fit and well 27-year-old Caucasian male presented with loss of visual acuity to a medical post in Pheriche, Nepal (4270 m).[sn1] There was no family or personal history of eye problems, eye surgery, or contact lens use. Several weeks before presentation, he trekked in the Annapurna region, where he experienced acute mountain sickness at 4200 m. In spite of his symptoms he proceeded to 4800 m until the symptoms became severe. Although there was no ataxia, he reported “disorientation.” He self-medicated with acetazolamide and dexamethasone, resulting in improvement of his symptoms, and began descent. He experienced no adverse effects from the medication. His presentation at Pheriche was preceded by a trek to Gyokyo via Phortse. En route from Gyokyo over Cho La pass (5330 m), he stopped for the night at Thangnak (4700 m). There he developed dry, persistent cough that was aggravated by lying down. He suffered extreme fatigue and shortness of breath. He took a 250-mg dose of acetazolamide and reported that the symptoms improved somewhat. There was no headache, nausea, or dizziness, but his sleep was disturbed.
The following morning he noted that his distance vision had deteriorated and described not being able to see his guide ahead of him until he noticed movement. He stated that various signs around the lodge appeared blurred. In spite of feeling exhausted and short of breath and suffering from loss of visual acuity, he decided to proceed over Cho La Pass while self-medicating with acetazolamide 250 mg and dexamethasone in 0.5-mg increments (taking a total of 2 mg). When he arrived in Pheriche, he was alert and without signs of ataxia. His chest was clear, oxygen saturation was 91%, and pulse rate was 88 per minute. There was no suggestion of snow blindness or ocular injury. Inspection of his retinas revealed no hemorrhages or papilledema. Without Ishihara and Snellen charts, formal assessment of color vision or acuity was not possible. However, he demonstrated bilaterally decreased acuity with respect to distance vision, while near vision was unaffected when objectively tested (by asking the patient to read small-print text). A trial of oxygen did not result in improvement of acuity, nor was there any resolution overnight. The patient was advised to descend. Email follow up revealed that acuity returned to normal within 48 hours of his attendance at the clinic, as he descended to Lukla, and that formal ophthalmologic assessment in Kathmandu revealed no abnormalities.
Loss of visual acuity at high altitude may have dire consequences, as illustrated by the misfortunes of Dr Beck Weathers in his attempt to climb Everest. 1 The knowledge of eye pathology relating to high altitude has grown over the years, and the physiologic changes affecting intraocular pressure, corneal thickness, and retinal vasculature have been well described. 2 A change in refraction, and thus transient myopia, may arise from 1 of 2 mechanisms: via anterior displacement of the lens, as a consequence of alteration in vitreous volume (osmotically driven), or alteration in curvature of the lens secondary to edema or ciliary muscle spasm. Transient myopia may therefore arise in the context of poorly controlled diabetes, severe dehydration, blunt trauma leading to localized swelling, connective tissue disorders, surgery, contact lens use, or secondary to drugs. Transient myopia has been reported with a wide variety of medications, including aspirin, 3 quinine, 4 tetracyclines, 5 metronidazole, 6 sulphamethoxazole/trimethoprim,7,8 dapsone, 9 topiramate, 10 –12 triamterene, 13 and carbonic anhydrase inhibitors, and in particular acetazolamide. 14 –17 The mechanism proposed involves allergic-type reaction localized to the ciliary body. 18 The resolution of symptoms is usually longer than the half-life of the drug would suggest, and although cessation of medication is probably adequate treatment, cycloplegia may be tried.
Acetazolamide, a carbonic anhydrase inhibitor, is widely used for treatment and prevention of acute mountain sickness due to its effect on ventilation. Carbonic anhydrase inhibitors can also be employed in treatment of raised intraocular pressure, but this should have no effect on acuity. Our patient is likely to have suffered high-altitude pulmonary edema while at Thangnak, but after descent the symptom of concern was his loss of visual acuity. In the absence of previous corneal surgery or other systemic illness and given the absence of any neurologic deficit, retinal pathology, or psychologic problem, our presumption was that the patient's altered visual acuity was due to an adverse reaction to acetazolamide. The reaction may be absent at first dose and occur only with subsequent use, supporting the sensitization hypothesis. Recurrence has been demonstrated on further dosing. 17 Resolution in most of the reported cases occurred over a period of 2 to 7 days, which is longer than the timeline expected, given the half-life of acetazolamide.
Other possible contributing factors to the development of transient myopia in our patient include altitude-related hypoxia causing corneal swelling and dehydration associated with both exercise and inadequate fluid intake.
Awareness of this uncommon side effect of acetazolamide is important to all users and prescribers, especially when consequences at extreme altitude have the potential to be disastrous. A trial of acetazolamide before ascent, to minimize the likelihood of deleterious side effects, should be considered. This should be done bearing in mind a risk of sensitization.