Signs and Symptoms
Pediatric glaucoma is a term that includes any form of glaucoma that presents between birth and age 18 years.1,2 Pediatric glaucomas can be either primary or secondary and the angle may be open or closed. However, there is confusing and overlapping terminology. Primary congenital and primary infantile glaucoma occur secondary to trabeculodysgenesis, a developmental angle anomaly. This can be diagnosed any time between birth and early childhood. Pediatric developmental glaucomas are also classified by the time that they appear in a patient; primary congenital glaucoma occurs between birth and two months of age, primary infantile glaucoma between two months and two years of age, and late-onset primary infantile glaucoma (also known as juvenile glaucoma) after two years of age.1
Primary infantile glaucoma overlaps with juvenile-onset open-angle glaucoma (JOAG), a non-developmental glaucoma similar to primary open-angle glaucoma in adults, which develops late in childhood in the absence of angle anomalies.1,2 It is most commonly accepted that the term primary congenital glaucoma refers to patients in all three age groups in the presence of developmental anterior chamber angle abnormalities.1,3
Patients with primary congenital and infantile glaucoma typically manifest a classic triad of photophobia, lacrimation and blepharospasm.1,3,4 These occur due to corneal changes such as edema secondary to elevated intraocular pressure (IOP). Buphthalmos develops from the distensibility of immature collagen within the infant corneal stroma. Horizontal breaks in Descemet’s membrane known as Haab’s striae commonly occur. These findings strongly suggest the presence of primary congenital glaucoma; they are not present if glaucoma develops after the age of three. In older children, glaucoma is diagnosed in the same way it is in adults; that is, by observing optic disc damage, elevated intraocular pressure and structural and functional changes consistent with glaucoma, in the absence of trabeculodysgenesis.
In patients with primary congenital glaucoma, abnormalities in the anterior chamber angle are diagnostic. The iris and ciliary body are anteriorly located, with iris tissue inserting into and overlapping the trabecular meshwork, impeding the outflow of aqueous.
Primary congenital glaucoma is the most common form of pediatric glaucoma.1-4 The second most common form occurs in aphakic or pseudophakic children following congenital cataract surgery.1,5-12 The mechanism in aphakic glaucoma is unclear, but gonioscopy may reveal a blockage of the trabecular meshwork secondary to an acquired repositioning of the iris against the posterior trabecular meshwork. There is often associated abnormal pigmentation and synechiae formation within the meshwork.5 Beyond these conditions, glaucoma can occur in a pediatric patient from a number of other causes, including but not limited to trauma, inflammation, episcleral venous pressure elevation (as seen in Sturge-Weber syndrome), tumor, pupil block from subluxation, retinopathy of prematurity and infectious disease.1,13-18
The totality of pediatric glaucoma results in a diverse pathophysiology due to the wide range of possible associated conditions. Primary congenital and infantile glaucoma, however, clearly results from a developmental arrest of the iris and ciliary body in the seventh month of gestation.19 These structures insert in an anterior location with iris tissue overlapping the trabecular meshwork, impeding aqueous outflow resulting in subsequent IOP elevation.1,19 There is also developmental immaturity of the trabecular meshwork, with thickened trabecular tissue and an abnormal ground matrix.1
Primary congenital glaucoma appears to be autosomal recessive.3 Two genetic loci—GLC3A and GLC3B—have been identified in a majority of hereditary cases.20,21 An autosomal dominant JOAG has been linked to the GLC1A gene. Mutations in the trabecular meshwork inducible glucocorticoid response protein (TIGR) gene have also been identified in families with JOAG.3,22
Proper management of any pediatric glaucoma begins with accurate diagnosis and categorization of the glaucoma. In older children with JOAG, IOP measurement, disc analysis, visual field testing and diagnostic retinal nerve fiber layer imaging can all be beneficial. In infants and younger children, these tests may not be possible or practical. In such cases, IOP measurement, along with observation of corneal clouding, corneal diameter measurement and inspection for Haab’s striae become more important. Examination under sedation or general anesthesia may be necessary. Gonioscopy is critically important, as recognizing abnormal angle anatomy (trabeculodysgenesis) plays a significant role in the development of the management plan.
Primary congenital glaucoma is best managed surgically, with medications only used adjunctively. The most performed and successful surgeries for primary congenital glaucoma are the angle surgeries—goniotomy and trabeculotomy. The former involves inserting a goniotomy knife into the anterior chamber and incising the anterior aspect of the middle third of the trabecular meshwork over 120°.1 In trabeculotomy, an external dissection of Schlemm’s canal is performed over 180° of the anterior chamber angle.1
Goniotomy and trabeculotomy are typically very successful for primary congenital glaucoma. Goniotomy is performed when a clear cornea allows angle visualization, while trabeculotomy is preferred in cases involving a cloudy cornea. However, these procedures are less successful for cases of pediatric glaucoma other than primary congenital and infantile forms. In these cases, trabeculectomy with adjunctive antimetabolite application is a common procedure. In refractory cases, combined trabeculectomy with glaucoma drainage implant devices offer the most successful and predictable option.23-30
More recently, deep sclerectomy and circumferential trabeculotomy have met with success in managing congenital and childhood glaucoma.31,32 Even more recently, transscleral cyclophotocoagulation and endoscopic cyclophotocoagulation have been seen to be safe, effective and comparable treatments that may be considered first-line therapy to achieve control of IOP in all forms of pediatric glaucoma. These procedures, when effective, can allow the patient to avoid a penetrating procedure.33
While surgery is the preferred treatment for pediatric developmental glaucoma, there are times where medications may be necessary, either prior to or adjunctively with surgery. For the majority of glaucoma meds, pediatric use is considered off label and safety and efficacy have not been studied; clinical guidance has been obtained through case series and retrospective analyses. Topical beta-blockers have been deemed safe and effective when used in children.34-36 Prostaglandin analogs are safe and well tolerated, but unfortunately not very effective in the pediatric glaucoma population. Older children with JOAG demonstrate the best efficacy response.37-39
When used in children, topical carbonic anhydrase inhibitors (CAIs) are safe and effective in lowering IOP.40,41 Brimonidine, though effective in lowering IOP in children, crosses the blood/brain barrier and can potentially affect the central nervous system. This medication has demonstrated an unacceptable level of adverse events in children and should be avoided if possible.42-44
Upon lowering IOP in infants, reversal of cupping as well as corneal clearing has been observed. However, once buphthalmos has occurred, the globe will not return to normal size.4,45
• Aphakic and pseudophakic children must be followed life-long for the development of glaucoma. However, the presence of an intraocular lens seems to reduce the incidence of glaucoma development, though the reasons are unclear.
• IOP does not have to be dramat-i-cally high in a child for glaucoma to develop. IOP above 20mm Hg is concerning.
• Congenital, infantile and developmental glaucoma implies trabeculodysgenesis. A child with glaucoma but without angle abnormalities has JOAG or another secondary glaucoma.
• In rare instances where topical glaucoma medications in children are indicated, preferences include CAIs and beta-blockers. Prostaglandins are reserved only for cases involving older children with JOAG. Brimonidine should always be avoided.
1. Beck AD. Diagnosis and management of pediatric glaucoma. Ophthalmol Clin North Am. 2001;14(3):501-12.
2. Luntz MH. Congenital, infantile, and juvenile glaucoma. Ophthalmology 1979; 86(5):793-802.
3. Ho CL, Walton DS. Primary congenital glaucoma: 2004 update. J Pediatr Ophthalmol Strabismus. 2004;41(5):271-88.
4. DeLuise VP, Anderson DR. Primary infantile glaucoma (congenital glaucoma). Surv Ophthalmol 1983;28(1):1-19.
5. Walton DS. Pediatric aphakic glaucoma: a study of 65 patients. Trans Am Ophthalmol Soc. 1995;93:403-13.
6. Magnusson G, Abrahamsson M, Sjostrand J. Glaucoma following congenital cataract surgery: an 18-year longitudinal follow-up. Acta Ophthalmol Scand. 2000;78(1):65-70.
7. Chen TC, Walton DS, Bhatia LS. Aphakic glaucoma after congenital cataract surgery. Arch Ophthalmol. 2004;122(12):1819-25.
8. Egbert JE, Christiansen SP, Wright MM, et al. The natural history of glaucoma and ocular hypertension after pediatric cataract surgery. J AAPOS. 2006;10(1):54-7.
9. Asrani S, Freedman S, Hasselblad V, et al. Does primary intraocular lens implantation prevent “aphakic” glaucoma in children? J AAPOS. 2000;4(1):33-9.
10. Trivedi RH, Wilson ME Jr, Golub RL. Incidence and risk factors for glaucoma after pediatric cataract surgery with and without intraocular lens implantation. J AAPOS. 2006;10(2):117-23.
11. Bhola R, Keech RV, Olson RJ, et al. Long-term outcome of pediatric aphakic glaucoma. J AAPOS. 2006;10(3):243-8.
12. Brady KM, Atkinson CS, Kilty LA, Hiles DA. Glaucoma after cataract extraction and posterior chamber lens implantation in children. J Cataract Refract Surg. 1997;23 Suppl 1:669-74.
13. Di Rocco C, Tamburrini G. Sturge-Weber syndrome. Childs Nerv Syst. 2006;22(8):909-21.
14. Sijssens KM, Rothova A, Berendschot TT, et al. Ocular hypertension and secondary glaucoma in children with uveitis Ophthalmology. 2006;113(5):859.e1-2.
15. Freedman SF, Rodriguez-Rosa RE, Rojas MC, et al. Goniotomy for glaucoma secondary to chronic childhood uveitis. Am J Ophthalmol. 2002;133(5):617-21.
16. Kafkala C, Hynes A, Choi J, et al. Ahmed valve implantation for uncontrolled pediatric uveitic glaucoma. J AAPOS. 2005;9(4):336-40.
17. Taylor RH, Ainsworth JR, Evans AR, et al. The epidemiology of pediatric glaucoma: the Toronto experience. J AAPOS. 1999;3(5):308-15.
18. Awad AH, Mullaney PB, Al-Mesfer S, et al. Glaucoma in Sturge-Weber syndrome. J AAPOS. 1999;3(1):40-5.
19. Maumenee AE. Further observations on the pathogenesis of congenital glaucoma. Trans Am Ophthalmol Soc 1963; 55: 1163-76.
20. Sarfarazi M, Akarsu AN, Hossain A et al. Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence of genetic heterogeneity. Genomics 1995; 30(2): 171-7.
21. Sarfarazi M, Stoilov I. Molecular genetics of primary congenital glaucoma. Eye 2000; 14:422-8.
22. Richards JE, Ritch R, Lichter PR, et al. Novel trabecular meshwork inducible glucocortocoid response mutation in an eight-generation juvenile-onset primary open angle glaucoma pedigree. Ophthalmology 1998;105:1698-1707.
23. Tesser R, Hess DB, Freedman SF. Combined intraocular lens implantation and glaucoma implant (tube shunt) surgery in pediatric patients: a case series. J AAPOS. 2005;9(4):330-5.
24. Englert JA, Freedman SF, Cox TA. The Ahmed valve in refractory pediatric glaucoma. Am J Ophthalmol. 1999;127(1):34-42.
25. Sidoti PA, Belmonte SJ, Liebmann JM, et al. Trabeculectomy with mitomycin-C in the treatment of pediatric glaucomas. Ophthalmology. 2000;107(3):422-9.
26. Tanimoto SA, Brandt JD. Options in pediatric glaucoma after angle surgery has failed. Curr Opin Ophthalmol. 2006;17(2):132-7.
27. Ishida K, Mandal AK, Netland PA. Glaucoma drainage implants in pediatric patients. Ophthalmol Clin North Am. 2005;18(3):431-42.
28. Al-Hazmi A, Awad A, Zwaan J, et al. Correlation between surgical success rate and severity of congenital glaucoma. Br J Ophthalmol. 2005;89(4):449-53.
29. Morales J, Al Shahwan S, Al Odhayb S, et al. Current surgical options for the management of pediatric glaucoma. J Ophthalmol. 2013;2013: 763735: Epub 2013 Apr 24.
30. Ou Y, Caprioli J. Surgical management of pediatric glaucoma. Dev Ophthalmol. 2012;50:157-72.
31. Al-Obeidan SA, Osman Eel-D, Dewedar AS, et al. Efficacy and safety of deep sclerectomy in childhood glaucoma in Saudi Arabia. Acta Ophthalmol. 2014;92(1):65-70.
32. Girkin CA, Marchase N, Cogen MS. Circumferential trabeculotomy with an illuminated microcatheter in congenital glaucomas. J Glaucoma. 2012;21(3):160-3.
33. Kraus CL, Tychsen L, Lueder GT, Culican SM. Comparison of the Effectiveness and Safety of Transscleral Cyclophotocoagulation and Endoscopic Cyclophotocoagulation in Pediatric Glaucoma. J Pediatr Ophthalmol Strabismus. 2014 Feb 18:1-8.
34. Hoskins HD Jr, Hetherington J Jr, Magee SD, et al. Clinical experience with timolol in childhood glaucoma. Arch Ophthalmol. 1985;103(8):1163-5.
35. McMahon CD, Hetherington J Jr, Hoskins HD Jr, et al. Timolol and pediatric glaucomas. Ophthalmology. 1981;88(3):249-52.
36. Zimmerman TJ, Kooner KS, Morgan KS. Safety and efficacy of timolol in pediatric glaucoma. Surv Ophthalmol. 1983;28 Suppl:262-4.
37. Enyedi LB, Freedman SF. Latanoprost for the treatment of pediatric glaucoma. Surv Ophthalmol. 2002;47 Suppl 1:S129-32.
38. Enyedi LB, Freedman SF, Buckley EG. The effectiveness of latanoprost for the treatment of pediatric glaucoma. J AAPOS. 1999;3(1):33-9.
39. Urban B, Bakunowicz-Lazarczyk A, Mrugacz M, et al. The effectiveness of latanoprost for the treatment of pediatric glaucoma. Klin Oczna. 2004;106(1-2 Suppl):243-4.
40. Ott EZ, Mills MD, Arango S, et al. A randomized trial assessing dorzolamide in patients with glaucoma who are younger than 6 years. Arch Ophthalmol. 2005;123(9):1177-86.
41. Rehurek J, Spicarova R, Vancurova J. Effect of Trusopt on normal intraocular pressure values in children. Cesk Slov Oftalmol. 2000;56(6):366-9.
42. Al-Shahwan S, Al-Torbak AA, Turkmani S, et al. Side-effect profile of brimonidine tartrate in children. Ophthalmology. 2005;112(12):2143.
43. Enyedi LB, Freedman SF. Safety and efficacy of brimonidine in children with glaucoma. J AAPOS. 2001;5(5):281-4.
44. Berlin RJ, Lee UT, Samples JR, et al. Ophthalmic drops causing coma in an infant. J Pediatr. 2001;138(3):441-3.
45. Quigley HA. The pathogenesis of reversible cupping in congenital glaucoma. Am J Ophthalmol 1977; 84:358-70.