FormalPara Key Points

Almost all anti-glaucoma medications are not licensed for use in children.

Serious side effects can occur, even from topical drops, and measures to reduce systemic absorption should be taken in children.

Treatment algorithms can be useful to help manage pediatric glaucoma.

1 Introduction

Pediatric glaucoma encompasses a diverse group of conditions affecting infants and young children, traditionally characterized by raised intraocular pressure (IOP), optic neuropathy, and visual field defects. Whereas optical coherence tomography (OCT) is increasingly being used to evaluate glaucomatous nerve fiber layer damage, robust reliable normative data in children are not widely available. Glaucoma is the second leading cause of visual impairment in all age groups and is estimated to cause a significant percentage of blindness in children, from 1.2 % the UK to 3–7 % in India. In a recent population-based survey in the USA, the incidence of pediatric glaucoma was 2.29 per 100,000 residents, and secondary glaucoma was the predominant type [1].

The World Glaucoma Society has recently classified pediatric glaucomas into primary and secondary childhood glaucomas. Primary childhood glaucoma includes primary congenital glaucoma (PCG: neonatal, infantile, late onset) and juvenile open angle glaucoma (JOAG). Secondary childhood glaucoma encompasses glaucoma associated with non-acquired ocular abnormalities, non-acquired systemic diseases, or an acquired condition, and glaucoma following cataract surgery. A relatively wide range of anti-glaucoma drugs are commercially available, including β-blockers, topical and systemic carbonic anhydrase inhibitors, prostaglandin (PG) analogs, α-adrenergic agonists, parasympathomimetics, and combined preparations. We review the pharmacotherapeutic options available for pediatric glaucoma, their safety considerations and efficacy data, and suggest possible treatment algorithms for different types of glaucoma (see Fig. 1). It is important to remember that systemic absorption of ocular medications may have a greater impact in infants than in adults, with potentially higher plasma levels for a longer period, leading to a greater risk of serious systemic adverse effects [2]. PCG accounts for one-third of all cases of childhood glaucoma [3, 4]. It is an important cause of visual impairment due to optic neuropathy, along with amblyopia secondary to progressive myopia and corneal scarring. Surgical intervention, in the form of either goniosurgery or filtration or Seton surgery, is the mainstay of treatment for primary congenital glaucoma. Medical therapy plays an important role in temporarily reducing IOP prior to surgery [5]. Whereas control of congenital glaucoma has been previously reported in 12 % of eyes in the short term and 10 % eyes in the long term with medication alone [6], surgical intervention is usually the mainstay of treatment for PCG.

Fig. 1
figure 1

Possible treatment algorithms for different types of glaucoma. ASDA anterior segment developmental anomalies, JOAG juvenile open angle glaucoma, PCG primary congenital glaucoma, PGA prostaglandin analog

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2 Anti-Glaucoma Drugs

2.1 Adrenoceptor Antagonists

Timolol is by far the most commonly prescribed β-blocker for pediatric glaucoma worldwide (Table 1) and is commercially available at concentrations of 0.1, 0.25, and 0.5 %. It is available in aqueous and gel-forming solution. The gel formulation is preferred because the systemic absorption is lower and application is once daily; its lowest concentration is preferred to reduce systemic side effects [6, 7]. Timolol reduces IOP by 20–30 % by decreasing the rate of aqueous production. Other β-blockers currently used in children are betaxolol (0.25 % suspension and 0.5 % solution twice daily, e.g. Betoptic®), levobunolol (0.5 % twice daily, e.g. Betagan®), and carteolol (1 and 2 % twice daily, e.g. Teoptic®) [8].

Table 1 Prescribed medications for glaucoma
Full size table

Topical betaxolol 0.25 %, a cardioselective β1 blocker is preferred in children with a history of asthma to reduce the risk of bronchospasm, although the published studies that confirm this have investigated adult populations. The randomized controlled trial by the BETOPTIC Pediatric Study Group reported comparable results with betaxolol hydrochloride ophthalmic suspension 0.25 % (betaxolol) and timolol maleate ophthalmic gel-forming solution (TGFS) (0.25 and 0.5 %), in subjects aged <6 years. However, all three drugs were found to be less efficacious in aphakic glaucoma [9].

Levobetaxolol, the (S)-isomer of betaxolol, was approved by the US FDA in 2000, and has also been shown to be safe and effective in children aged <6 years. A double-masked randomized controlled trial indicated it provided clinically relevant IOP reduction (2.9 mmHg at 12 weeks) in those patients entering the study without a prior anti-glaucoma medication, especially in children with PCG [10].

2.1.1 Side Effects

It is important to take a detailed history about cardiac and respiratory problems while prescribing β-blockers in children because of the increased risk of hypotension, bradycardia, bronchospasm, and apnea, especially when using nonselective agents such as timolol maleate and timolol hemihydrate [7–9, 11].

Other more rare systemic side effects include hallucinations, light headedness, depression, fatigue, diarrhea, and masking of symptoms of hypoglycemia in children with diabetes mellitus [10, 12]. Serious adverse events such as central nervous system (CNS) depression, cardiogenic shock, and—rarely—apneic spells have also been reported in young infants in sporadic cases [11, 13]. Parents should be informed about these potential side effects, and the lowest available concentration dosage should be used in neonates and infants.

Local adverse reactions to β-blockers are mild, occurring in up to 8–12 % of patients, and include stinging, conjunctival injection, punctate keratitis, photophobia, abnormal eye sensation, lid margin crusting, itching, sticky sensation, and discharge [8, 14–16]. Although long-term treatment with 0.5 % timolol has been reported as reducing tear secretion in two or three children, leading to keratoepitheliopathy [17], the authors of this review have not seen any such case in over 25 years of practice.

2.2 Carbonic Anhydrase Inhibitors

Carbonic anhydrase inhibitors (CAIs) are sulfa-containing drugs that reduce IOP by decreasing the rate of aqueous production. It is the only class of anti-glaucoma drug available in systemic and topical forms, but neither intravenous acetazolamide (Diamox®) nor topical dorzolamide 2 % (e.g. Trusopt®) or brinzolamide 1 % (e.g. Azopt®, Alcon Laboratories Inc., Fort Worth, TX, USA) are licensed for use in children.

Topical CAIs are used as first- or second-line treatment in young children. In a double-masked randomized trial that investigated timolol maleate gel-forming solution (0.25 % for patients aged <2 years and 0.5 % for patients aged ≥2 but <6 years) once daily plus placebo twice daily compared with topical 2 % dorzolamide three times daily, the latter was found to be efficacious and well-tolerated in patients with glaucoma aged <6 years, and the mean decrease in IOP was more than that found in adults [18]. In another randomized study comparing the efficacy of brinzolamide versus levobetaxolol in pediatric glaucomas, brinzolamide was found to be more efficacious for glaucoma associated with systemic or ocular abnormalities than for PCG [10]. Systemic CAIs are usually started as an additional medication to topical treatment, but their use can be limited because of systemic side effects when compared with topical medication. The dosage in children aged 1 month to 12 years is 10–20 mg/kg/day in two to four divided doses. In children aged 12–18 years, the recommended dosage is 0.5–1 gm daily, given in either two or four divided doses [8]. Portellos et al. [19] demonstrated effective IOP reduction in pediatric patients (36 %, n = 11) with a target dose of approximately 10 mg/kg/day divided into a twice-daily to four times daily schedule. Whether the frequency is two or four times daily depends on how cooperative the child is with swallowing and drinking the medications.

Sabri and Levin [20] reported additional reduction of IOP with the addition of oral acetazolamide to topical dorzolamide in a series of 22 pediatric glaucoma patients (aged 8 months to 15 years). Therefore, topical CAIs are comparable to beta blockers, are well-tolerated, and have a greater IOP-lowering effect in children than in adults; the effect can be augmented with the addition of oral CAIs if needed [20].

2.2.1 Side Effects

Oral or intravenous CAIs are known to cause various systemic adverse effects, including gastrointestinal disturbance, headache, dizziness, paresthesia, asthenia, sinusitis, rhinitis, metabolic acidosis, and poor weight gain. In infants and toddlers, metabolic acidosis usually presents as poor feeding and poor weight gain; however, Sharan et al. [21] retrospectively reported that oral acetazolamide did not cause weight loss in cases of pediatric glaucoma. Therefore, any loss of appetite or weight loss should alert the clinician to a potential problem. Oral or intravenous CAIs are contraindicated in patients with renal failure, hypokalemia, metabolic acidosis, or hyponatremia. Rarely, in adults, they have been known to cause hematopoietic toxicity, leading to aplastic anemia, neutropenia, and thrombocytopenia; however, no such cases have been reported in children [7].

A history of allergy to sulfa drugs should be checked before prescribing CAIs, and special attention should be paid to possible hypersensitivity. Allergic reactions can occur with topical CAIs, manifesting as urticaria, angioedema, or pruritus. Other common ocular side effects are ocular discomfort, stinging, bitter taste, superficial punctuate keratitis, transient blurry vision, tearing, and transient myopia. Care should be taken while prescribing topical CAIs in children with compromised cornea, as there is a risk of corneal decompensation [22]. Systemic side effects are rare with topical CAIs, but can include metabolic acidosis, which may present as lethargy and poor feeding [23]. Brinzolamide may be better tolerated than other topical CAIs.

2.3 Prostaglandin Analogs

PG analogs reduce IOP by increasing uveoscleral outflow. Whereas various preparations of PG analogs, such as topical preparations of latanoprost (e.g. Xalatan® 0.005 %; 50 µg/ml), travoprost (e.g. Travatan® 0.004 %; 4 µg/mL), and bimatoprost (e.g. Lumigan® 0.001% and 0.003%) are available in the market, latanoprost still accounts for more than 65 % of PG analog prescriptions. Tafluprost (0.0015 %) is a new PG analogue developed in a preservative-free (PF) formulation that has been recently approved by the US FDA [24]. The use of tafluprost in pediatric populations has not yet been reported. All PG analogues are administered once daily, with maximum reduction in IOP in 8 h, maintained for 24 h [25]. Latanoprost has been the subject of several studies when used for pediatric glaucoma management. These studies seem to show a good efficacy and safety profile, with higher response rates for JOAG followed by aphakic glaucoma and poorer response rates for PCG or glaucoma associated with other ocular disorders. The drug appeared to be effective in around 30 % of PCG cases [26–28].

A recent 12-week randomized trial in adult patients who did not reach target IOP with latanoprost monotherapy found it was possible to achieve additional IOP lowering and maintain monotherapy by replacing latanoprost with bimatoprost. Whereas reductions in IOP from latanoprost baseline were larger with bimatoprost 0.01 % than with bimatoprost 0.03 %, bimatoprost 0.01 % had better tolerability in terms of less frequent and severe conjunctival hyperemia [29]. Whether this holds true for pediatric cases remains to be seen.

Travoprost 0.004 % has been commercially available since 2001 but has not been approved for pediatric use. We found only one report describing the use of travoprost in 75 eyes of 57 children, where it was used as an adjunctive therapy. The IOP data were available in 26 children and showed a mean reduction of IOP of 6.5 mmHg after 1.5 years of treatment (12 eyes). Eyelash thickening and elongation was observed in 100 % of the eyes. Apart from inadequate IOP control, conjunctival injection and ocular irritation were the most common reasons for discontinuing treatment. Other side effects were eyelid swelling and subjective blurring of vision, seen in only 1 % of the eyes. No systemic side effects were observed [30]. PG analogs are popular because of their once-daily administration; they appear generally well-tolerated and reasonably effective.

2.3.1 Side Effects

Systemic side effects are extremely rare for PG analogs [30, 31]. We found only one case report of heavy sweat secretion over the entire body within 1–2 h of latanoprost application in a child with aniridia and glaucoma [32]. In a recent phase I open-label pilot study, a higher plasma level of latanoprost acid was reported in younger children versus adolescents and adults, attributed primarily to lower body weight and smaller blood volume. However, this higher systemic exposure was not accompanied by any systemic side effects [23].

Eyelash growth is the most common side effect of latanoprost exposure and has been reported to occur in 100 % of subjects exposed to the drug for ≥6 months [26]. Elgin et al. [33] found the mean growth of eyelash length in children was higher than in adults, but the result was not statistically significant (p = 0.678) [33]. Other side effects reported in children include conjunctival hyperemia, follicular conjunctivitis, irritation, headache, focusing difficulty, iris pigmentation, and sleep disturbance [24]. There is no current evidence to establish a link between latanoprost use and ocular or cutaneous melanoma [34]. There is evidence in adults of upper eyelid fat atrophy with the use of PG analogue, but no such report exists in children [35, 36].

Other ocular adverse events related to latanoprost reported in adults include ocular surface problems and irritation, periocular skin pigmentation, cystoid macular edema, anterior uveitis, and reactivation of herpes simplex keratitis due to potential inflammatory excitation. The incidence of conjunctival hyperemia, periocular skin pigmentation, and hypertrichosis is higher with bimatoprost and travoprost than with latanoprost. Of these, hyperemia is a significant cause for treatment discontinuation with the PG analogs [32, 33]. Ocular surface events, including irritation, dry eye, itching, blurred vision, burning, discharge, allergy, and blepharitis, occur at a similar incidence with all PG analogs. A link between bimatoprost and intraocular inflammation has been reported as a single case report [34]. However, Fortuna et al. [38] studied the rate of flare in patients with uveitic glaucoma treated with topical bimatoprost and suggested it did not increase flare in the anterior chamber in these patients. However, this cohort was receiving immunomodulatory therapy so it is difficult to draw any firm conclusions. At this point, we advise caution when using PG analogs in uveitic glaucoma in children [37, 38]. PG analogs are commonly used as an adjunctive therapy in port-wine stain-related pediatric glaucoma [39]. However, caution must be taken in eyes with diffuse choroidal hemangiomas because of the risk of uveal choroidal effusion. Prompt discontinuation of PG analogs usually resolves signs and symptoms [40–42].

2.4 Alpha-Adrenergic Agonists

Topical brimonidine tartrate and apraclonidine are the two α-adrenergic agonists available for the treatment of glaucoma in children. Both the drugs lower IOP through a dual mechanism of action, reducing aqueous humor production and increasing uveoscleral outflow. Brimonidine is available as Alphagan® 0.2 % and Alphagan® P 0.15 and 0.1 % and is administered twice daily. Apraclonidine is available as Iopidine® 0.5 and 1 % and is a second- or third-line drug mainly used to reduce IOP before surgery or anterior segment laser therapy.

Although brimonidine is not approved by the US FDA for use in children, it has been used in infants and children with congenital glaucoma and has been shown to have a beneficial ocular hypotensive effect, with a decrease in IOP ranging from 6.7 to 21 % [43–45]. Its use in infants is contraindicated, as serious life-threatening events have been reported [46]. Apraclonidine 0.5 % is not licensed for use in children aged <12 years, and the 1 % preparation is not licensed for use in children [14]. Apraclonidine is generally used to decrease bleeding during angle surgery and for long-term IOP control in selected eyes with glaucoma refractory to other medications [47].

2.4.1 Side Effects

Given the known side effects of α-agonists, brimonidine more so than apraclonidine, they are contraindicated in infants aged <2 years and in children with severe cardiovascular disease, cerebral or coronary insufficiency, Raynaud’s syndrome, postural hypotension, depression, or hepatic or renal impairment [7].

The most important concern when prescribing brimonidine in the pediatric age group, especially infants, is the risk of serious life-threatening adverse events. Bradycardia, hypotension, excessive sleepiness, lethargy, irritability, breathing difficulty, cyanosis, decreased body temperature, dry mucous membranes, failure to thrive, and weakness are the most commonly reported systemic side effects after administration of topical brimonidine. The majority of the adverse events occur within a few hours of administration of the drops. Increased sensitivity to brimonidine in infants could be attributed to their small size, immature ability to metabolize and excrete drugs, immature blood–brain barrier, or to increased receptor sensitivity [13, 44, 48]. It has been suggested that, if possible, alternative glaucoma therapy should be considered, especially in children weighing <20 kg and those aged <6 years [41].

Apraclonidine appeared systemically safe in children, with minimal side effects compared with brimonidine [14, 48]. In a retrospective study by Wright and Freedman [49], 115 eyes of 75 pediatric glaucoma patients received apraclonidine 0.5 % drops. The majority of the patients received apraclonidine during and after angle surgery. Overall, 6 of 75 subjects experienced side effects. Local adverse events were topical allergy in two children, presenting with erythema, itching, and follicular conjunctivitis; systemic side effects occurred in infants aged <6 months and included lethargy (three children) and decreased appetite (one child) [49].

Although apraclonidine is less α-selective than brimonidine, it is contraindicated in patients with cardiovascular and cerebrovascular disease, vasovagal attack, chronic renal failure, or depression as well as those who are pregnant or breastfeeding [7]. Commonly occurring local adverse effects with brimonidine include stinging/burning, blurring of vision, red eye, eye itching/rubbing, conjunctival follicles, and eye discharge. Corneal erosions, eyelid inflammation, and photophobia can occur but are rare [8, 13, 43–46]. Although a recent report [14] indicated that α-agonists (brimonidine 2 % and apraclonidine 0.5 %) accounted for 22 % of all prescriptions in a heterogeneous pediatric glaucoma group and 33 % of prescriptions as an additional therapy, the use of brimonidine in particular is contraindicated in young children and should be used with caution in any child given the reports of lethargy and syncope in teenagers [45, 46]. Even the authors of the previously mentioned retrospective review acknowledged that brimonidine ought not to have been prescribed as often as it was and was contraindicated according to the institution’s own guidelines [14].

2.5 Parasympathomimetics (Miotics)

Parasympathomimetics lower IOP by direct cholinergic action on the longitudinal ciliary muscle within the eye, which leads to an increase in the aqueous outflow facility and also causes constriction of the pupil. These drugs are not very effective in developmental glaucoma, most likely because of abnormal insertion of ciliary muscle into the trabecular meshwork; in fact, it may cause a paradoxical rise in IOP. Pilocarpine, a direct-acting parasympathomimetic, is the most widely used drug in this class and is available in 0.5–4 % eye drops and 4 % gel form as Pilogel®. The recommended dosage for children aged 1 month to 2 years is one drop of 0.5 or 1 % solution three times daily. For children aged 2–18 years, one drop of 0.5 % four times daily has the desired effect; 4 % Pilogel® can be used once daily at night [8]. The rate-limiting factor on its use is headache induced for 3–4 days after initial commencement.

Although, pilocarpine is rarely used as monotherapy, it may be beneficial in children with aphakic and pseudophakic glaucoma. It is commonly prescribed to induce miosis before angle surgery and filtering surgery in PCG [4, 14]. In a recent study, pilocarpine 2 or 4 % constituted 14 % of all types of prescriptions for pediatric glaucoma and was mostly used in combination with surgical treatments (primarily after goniotomy surgery). When used as monotherapy, 7 % of patient experienced a mean reduction in IOP of only 2.2 mmHg, but the pediatric glaucoma group was heterogeneous in etiology [14].

Ecothiopate iodide (EI) is a miotic long-acting cholinesterase inhibitor previously used for treatment of adult open angle glaucoma that has been used in children for the management of accommodative esotropia. In a recent study, its use in secondary glaucoma after cataract extraction in children was reported to give a significant reduction in IOP [50]. The majority of patients in this study received this drug as an additional IOP-lowering agent. The mean duration of treatment was 3.5 years. This study failed to discuss the significant side effects of EI in both children and adults. There are numerous reports of induced ocular pemphigoid with long-term use of this drug (minimum 6 years), bronchospasm, cystoid macular edema, and prolongation of anesthetic agents, specifically succinyl choline, which have been reported to cause apnea post-anesthesia [51–54]. Even when used in accommodative esotropia in children, burning, itching, brow ache, epiphora, and pemphigoid reaction have been reported [55]. Its fall from favor is likely to have been influenced by these significant side effects. Its use in aphakic and pseudophakic glaucoma should likely be reserved as a temporizing additional medication prior to considering definitive surgical intervention such as a drainage tube. Its prolonged use should be avoided.

2.5.1 Side Effects

Combined local and systemic side effects can occur in up to 4 % of patients [14]. Ocular adverse events associated with pilocarpine include soreness, stinging, itching, blurred vision due to induced myopia, conjunctival congestion, vitreous hemorrhage, and pupillary block. It should be avoided in children with uveitic glaucoma and in individuals at risk of retinal detachment.

Patients receiving pilocarpine can experience systemic symptoms related to its cholinergic action, including nausea, vomiting, diarrhea, abdominal pain, and sweating, distress, and cough [7]. It should be used with caution in patients with cardiac disease, asthma, peptic ulceration, or urinary tract obstruction [8]. The side effects of EI are outlined in the previous section.

2.6 Combined Preparations

Combined preparations are useful in children because of the likely improved compliance. The other advantages of fixed-combination eye drops include less exposure to preservatives, no washout effect of one drop over the other, and convenience for both the parents and the child.

The combination of dorzolamide (2 %) and timolol (0.5 %) (COSOPT) is a commonly used combined preparation in childhood glaucoma. The mean IOP reduction when COSOPT was used as monotherapy in pediatric glaucoma was comparable to that of its constituent components [14]. Adverse effects include stinging, pain, nausea, allergic reaction, corneal epitheliopathy, and corneal opacification. Headache, nausea, rash, wheezing, asthma, and chest pain have been reported in children receiving COSOPT [4, 49, 56]. Other currently available combined preparations include brimonidine 0.2 % and timolol 0.5 % (Combigan®, Allergan), latanoprost 50 µg/ml and timolol 0.5 % (Xalacom®, Pharmacia), bimatoprost 300 µg/ml and timolol 0.5 % (Ganfort®, Allergan), travoprost 40 µg/ml and timolol 0.5 % (Duotrav™, Alcon), and timolol 0.5 % and brinzolamide 1 % (Azarga® Alcon Laboratories, Inc.).

Tafluprost 15 µg/ml and timolol 5 mg/ml without preservatives (TTFC) is a newly introduced fixed-drug combination anti-glaucoma medication. The mean IOP decrease was in the range of 29.6–34.6 % [57]. The PF TTFC does not yet have market authorization. This drug was approved in Japan in 2013 (TAPCOM®; Santen Pharmaceuticals, Osaka, Japan) [58].

3 Discussion

The definitive management of childhood glaucoma is complex. While medical management is extremely important, surgery is often the definitive treatment, especially for congenital glaucoma. However, surgery in children can be fraught with complications because of their decreased scleral rigidity, noncompliance post-surgery, and difficulty undertaking full and proper post-operative examinations. Topical eye drops are absorbed into systemic circulation via the nasal mucosa, and to a lesser extent by the nasolacrimal duct. Children are at increased risk of systemic adverse effects because of increased systemic absorption secondary to a smaller blood volume and reduced body mass compared with adults; they are also at risk of an increase in drug elimination half-life because of their immature metabolic system [7]. Systemic absorption can be minimized by instructing the parent to administer only one drop of each topical medication and to occlude the lacrimal duct by exerting pressure over the medial canthal area for 3–4 min after drop instillation.

Ocular side effects could be due to both the drug and the preservatives, such as benzalkonium chloride (BAK). BAK is the most commonly used preservative in almost all anti-glaucoma preparations and is strongly implicated as the main cause for ocular toxicity. Ocular surface damage could result in reduced tear film quality and quantity, conjunctival inflammation, impairment of the corneal epithelium barrier function, and the effect on corneal innervation [59]. Ocular surface discomfort is a common reason for poor compliance with topical anti-glaucoma treatment.

Four medications can currently be obtained in PF forms: timolol, a dorzolamide/timolol fixed combination (COSOPT® without BAK as preservative, Merck Frosst Canada Ltd, Kirkland, Canada), the prostaglandin analog tafluprost, and PF fixed-combination bimatoprost 0.03 %/timolol 0.5 % (bimatoprost/timolol PF; Ganfort SD) [60–63].

If signs or symptoms of ocular surface toxicity are noticed, PF preparations may be considered in children. However, there are currently no studies describing their use in pediatric patients.

Another way to minimize toxicity is to use eye drops with less toxic preservatives such as benzododecinium bromide 0.012 % (in Timoptic XE®), PURITE®, sofZia (Travatan Z), and travoprost with poliquaternium-1. The use of these have not been reported in children. Travoprost Z is approved in the USA, and travoprost with poliquaternium-1 is currently available in Europe [64].

It is crucial that the prescribing physician is aware of the potential side effects and their presentation and ensures the child’s caregivers are, too. Adverse reactions can be detected early by questioning parents about the specific symptoms, such as stinging and burning, and can be minimized by reducing the number of different eye drops used (via fixed-combination eye drops), reducing the frequency of administration, and also by providing proper drop instillation training to the parents or caregiver. The difference in cost of normal brand and generic topical and systemic drugs varies between world regions; nevertheless, in an increasingly health dollar aware environment, reduced drug costs should be considered [65]. Studies have shown that a switch from COSOPT to generic timolol–dorzolamide showed no change in therapeutic results [66]. Furthermore, the volume of drop also varies between brand and generic drugs. These differences should be considered before prescribing drugs for pediatric glaucoma [67].

Recently, associations between parental health literacy and adherence to pediatric glaucoma medications has been studied, with better levels of adherence found in children whose parents had higher literacy skills [68]. Parents should be educated about the chronic nature of the disease and counseled regarding keeping regular office visits.

4 Conclusions

Medical management of childhood glaucoma is challenging. It should be customized based on the age and general health of the child, the type of glaucoma, and the known efficacy and safety profiles of each drug. In conclusion, the goal of medical therapy for glaucoma in children should be to achieve target IOP while minimizing side effects and maximizing compliance. The pharmacotherapeutic options include β-blockers, carbonic anhydrase inhibitors, PG analogs, α-adrenergic agonists, parasympathomimetics, and various combined preparations. Timolol and PG analogs are the topical medications most commonly as monotherapy, with good diurnal control of IOP. Among combined preparations, the combination of timolol and dorzolamide is the most preferred therapy. Brimonidine is less favored by most pediatric ophthalmologists because of its potentially life-threatening side effects in infants. Further studies are necessary in pediatric populations with newer agents in the PG group, such as travoprost and tafluprost. It is important for the reader to check regional regulations with respect to licensure and off-label use of topical anti-glaucoma medication for children, as this can vary from region to region.

In future, existing medical therapies for glaucoma require further evaluation in well-controlled randomized clinical trials with pediatric populations in terms of effect on central corneal thickness, ocular surface stability, and effectiveness of PF preparations.