Glaucoma is an irreversible cause of blindness in the world with more than 70 million affected individuals (Quigley and Broman 2006). Treatment of glaucoma warrants rigorous intraocular hypertension control by pharmacological or surgical interventions. Sometimes these pharmacological agents can produce systemic side effects. Prostaglandin analogue drops generally produce headache, flu-like symptom and myalgias (Goldberg et al. 2008). Latanoprost is reported to produce chest tightness in patients with glaucoma. Systemic PGF2α is known to produce significant cardiac effects, but the same is not reported with its ocular use. Prostaglandin-induced visceral nociceptor sensitization was thought to produce the reported side effect (Rajan et al. 2003). Topical beta blockers are known to produce several cardiac side effects like congestive heart failure, bradyarrhythmias and sinus arrest. These effects may be life threatening in some cases. Beta blockers are also known to produce respiratory side effects, even deaths have been reported in some cases with topical timolol. Hence, beta blockers are contraindicated in patients with cardiac and respiratory disorders (Shiuey and Eisenberg 1996). Alpha-2 agonists are known to cause depression and profound hypotension (especially in children). In specific, brimonidine produces somnolence, shortness of breath, dizziness, headache and low mood as its systemic side effects. Frequency of these side effects may vary from 20 to 50 % with high occurrence rate in elderly cases. Reports of apneic spells and cyanosis, hypothermia and hypotony related to CNS depression warrant avoidance of brimonidine in newborns, young infants and children with juvenile glaucoma younger than 12 years (Bowman et al. 2004; Enyedi and Freedman 2001).

In ophthalmology, mydriatics and cycloplegics are generally used for posterior segment evaluation like fundus photography, fluorescein angiography and OCT. Miotics are generally used for the management of angle-closure glaucoma. Due to their activity on the autonomic nervous system, these drugs may produce systemic side effects. Phenylephrine’s activity on alpha receptors can produce cardiovascular complications (Kanski 1969; Reilly et al. 1996; Shiuey and Eisenberg 1996). In the same manner cycloplegics have various side effects related to CNS and cardiovascular systems. Few of the reported side effects are more common in children and elderly. Shorter duration of action and tendency to produce less systemic side effects make tropicamide a drug of choice among others (Kanski 1969; Reilly et al. 1996; Shiuey and Eisenberg 1996).

These drugs are used to treat neovascular ocular disorders such as age-related macular degeneration, diabetic retinopathy etc. For the localized benefit, usually anti-VEGF compounds are injected intravitreally for ocular neovascular conditions. The systemic absorption of these compounds from vitreous humor has been attributed to their systemic adverse effects may or may not be related to their action through VEGF pathway. Intravitreal pegaptanib is considered to be a safer drug as compared to ranibizumab or bevacizumab. A retrospective study including 1173 patients receiving bevacizumab reported acute blood pressure elevations (0.59 %), cerebrovascular accidents (0.5 %), myocardial infarctions (0.4 %) and iliac artery aneurysms (0.17 %) as systemic side effects (Wu et al. 2008). Contrary to this, study done by Hwang et al. in 2012 did not find any significant difference in the safety profile of bevacizumab compared to ranibizumab (Hwang et al. 2012). Similarly a recent meta-analysis also concluded treatment from the both drugs as safe (Wang and Zhang 2014). Systemic side effects occur during treatment with these drugs should be thoroughly monitored irrespective of their safety reports.