REVIEW ARTICLE Medical management of pediatric glaucoma: lessons learned from randomized clinical trials Matteo Sacchi 1 & Rosario Alfio Umberto Lizzio 1 & Edoardo Villani 1 & Gianluca Monsellato 1 & Stefano Lucentini 1 & Elena Cremonesi 1 & Saverio Luccarelli 1 & Massimiliano Serafino 1,2 & Paolo Nucci 1 Received: 25 March 2020 /Revised: 18 May 2020 /Accepted: 20 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Purpose To critically discuss the randomized clinical trials (RCTs) on glaucoma medical therapy for the management of pediatric glaucoma. Methods RCTs on glaucoma drugs carried out on pediatric subjects with ocular hypertension and glaucoma were identified through systematic searches. The methods of the RCTs and the safety and the efficacy of the glaucoma drugs were reviewed and discussed. Results We included five RCTs. One study compared dorzolamide with 0.5% timolol gel; one brinzolamide with 0.5% levobetaxolol; one 0.25% betaxolol, 0.25% timolol gel, and 0.5% timolol gel; one latanoprost with 0.5% timolol; and one travoprost with 0.5% timolol. The primary outcome was safety for two studies and efficacy for three studies. None of the RCTs was powered to detect statistically significant differences in intraocular pressure (IOP) between treatments. In total, 658 subjects received at least one dose of study medication. Beta-blockers were administered to 359 patients, carbonic anhydrase inhibitor (CAI) to 154, and prostaglandins to 145 patients. IOP-lowering efficacy ranged from 20 to 23% for CAI, from 9 to 36% for beta-blockers, and from 26 to 27% for prostaglandins. The percentage of responders was 50% for CAI, ranged from 38 to 74% for beta-blockers and from 60 to 83% for prostaglandins. Two patients receiving timolol experienced a systemic, drug-related serious adverse event (one patient bradycardia and one pneumonia). Systemic, nonserious drug-related events occurred in 15 patients randomized to beta-blockers and in 8 patients randomized to CAI. No adverse events occurred in children treated with prostaglandins. Conclusion RCTs that are available on medical therapy for glaucoma are few and underpowered. The proportion of responders is lower in children; however, in subjects who are responders, the efficacy of glaucoma drugs seemed to be comparable to that in adults. As systemic adverse events have been reported, including serious events with timolol, a particular attempt to minimize the absorption of the drug (using the lowest dose and the gel formulation of beta-blockers or considering the lacrimal punctum occlusion) and a follow-up that is more frequent and more focused on safety should be considered in pediatric subjects who are on topical glaucoma medications. Keywords Pediatric glaucoma . Topical medication . Randomized clinical trial Introduction According to a recent classification, the term “pediatric glaucoma ” refers to a wide variety of conditions, including primary congenital and juvenile glaucoma, sec- ondary glaucoma including glaucoma following cataract surgery, glaucoma associated with nonacquired systemic disease, glaucoma associated with nonacquired ocular anomalies, and glaucoma associated with acquired condi- tions. Glaucoma suspect has also been included in the classification [1]. Primary congenital glaucoma is the most common form in both Asian and West countries [2, 3] and is the second leading cause of treatable childhood blindness worldwide with a prev- alence among children of 2.7% in Europe [4] and up to 8.1% in South Asia and India [5]. * Matteo Sacchi matteosacchi.hsg@gmail.com 1 University Eye Clinic, San Giuseppe Hospital, University of Milan, Via San Vittore 12, 20123 Milan, Italy 2 Department of Neuroscience, Unit of Ophthalmology, Istituto Giannina Gaslini, Genoa, Italy Graefe's Archive for Clinical and Experimental Ophthalmology https://doi.org/10.1007/s00417-020-04767-9