Bradycardia during optical timolol therapy: its delayed remission after timolol discontinuation and unexpected...

Optical betablockers (BBs), including nonselective BB timolol, are commonly used for the management of primary open angle glaucoma and ocular hypertension. About 80% of topically administered timolol is systemically absorbed, which can rarely induce such complications as bradycardia, bronchospasm and depression.

The authors describe a case of a 67-year-old female referred because of significant bradycardia and a suggestion of pacemaker implantation. She had no cardiovascular history besides hyperlipidemia and mild hyperglycemia, so her previous treatment was focused on glaucoma due to which she had been using optical timolol for several years. Moreover, she suffered from depression which was treated with venlafaxine and sertraline. Over a few months, she started feeling weak and dizzy. Her daily heart rate (HR) markedly decreased to 40-45/min. 24-hour ECG monitoring revealed multiple episodes of nodal rhythm and of sinoatrial block and the lowest HR of 33/min; bradycardia defined as HR less than 45/min constituted over 40% of the time recorded. Close observation with repeated 24-hour ECG monitoring after timolol discontinuation showed lasting several-daylong gradual bradycardia remission; after 2, 9, 16 and 23 days, bradycardia constituted 19.9%, 13.9%, 0.2% and 0% of the time recorded, respectively. Genetic testing of cytochrome P450 2D6 revealed the presence of the c.506 -1G>A variant with one non-functional allele (CYP2D6 *4/-) which might have slowed down timolol metabolism in the context of simultaneous antidepressants use, so venlafaxine and sertraline were reduced. However, during follow-up, incremental bradycardia relapse, suggestive of an underlying sinus node dysfunction, was observed.