Update in Genetics and Surgical Management of Primary Congenital Glaucoma

Abstract

Primary congenital glaucoma (PCG) continues to be an important cause of visual impairment in children despite advances in medical and surgical treatment options. The progressive and blinding nature of the disease, together with the long lifespan of the affected population, necessitates a thorough understanding of the pathophysiology of PCG and the development of long-lasting treatment options. The first part of this review discusses the genetic features and makeup of this disorder, including all currently identified genetic loci (GLC3A, GLC3B, GLC3C and GLC3D) and relevant protein targets important for trabecular and Schlemm canal dysgenesis. These target molecules primarily include CYP1B1, LTBP2, and TEK/Tie2 proteins. Their potential roles in PCG pathogenesis are discussed with the purpose of bringing the readers up to date on the molecular genetics aspect of this disorder. Special emphasis is placed on functional implications of reported genetic mutations in the setting of PCG. The second part of the review focuses on various modifications and refinements to the traditional surgical approaches performed to treat PCG, including advances in goniotomy and trabeculotomy ab externo techniques, glaucoma drainage implant surgery and cyclodiode photocoagulation techniques that ultimately provide safer surgical approaches and more effective intraocular pressure control in the 21 st century.

Primary Congenital Glaucoma: An Update

“…Occurrence is sporadic with familial inheritance in 10-40% cases (autosomal recessive with incomplete or variable penetrance). 3,19 Genetic loci identified are GLC3A, 3B, 3C and 3D. 19 • GLC3A loci (chromosome 2p21): Around 120 mutations have been described with mutations in CYP1B1 gene, encoding cytochrome P450 enzyme being commonest at 42%.…”

“…3,19 Genetic loci identified are GLC3A, 3B, 3C and 3D. 19 • GLC3A loci (chromosome 2p21): Around 120 mutations have been described with mutations in CYP1B1 gene, encoding cytochrome P450 enzyme being commonest at 42%. [20][21][22][23][24] Gene effect has been traced to monooxygenase enzyme in endogenous steroid metabolism 25 with Tyrosinase deficiency concurrence resulting in severe phenotype.…”

“…88 Keeping in mind anticipated growth of child's eye with high incidence of tube retraction, some recommend adult size implants if it can fit the paediatric eye. 19 Efficacy of tube shunts in PCG has been reported to be high from 87-90% at 1year [87][88][89][90][91][92] however survival declines over time, from 80-97% during first year to 58-66 % by 2-4 years and 20-40% by 5 -10 years. 87,89,93 Comparative studies score GDD to perform better than trabeculectomy with success of 87 to 53% (at 1 and 6 year) compared to 36 and 19% with trabeculectomy.…”

Epidemiological pattern of Primary Congenital Glaucoma among Egyptian Children aged 0-4 years Attending Minoufia University hospital

“…Among 92 cases, 80.4% of the cases had successful classic SST trabeculotomy furthermore, goniotomy and combined trabeculotomy and trabeculectomy shared the same number of patients of 8.7% and only 2% of the cases had classic SST trabeculotomy & Ahmed valve. Although goniotomy is known as the most popular glaucoma surgery to manage IOP in PCG, combined trabeculotomy-trabeculectomy has been once used with a significant success and safe profile in younger ages (5,24) .…”

Animal Model Contributions to Primary Congenital Glaucoma

“…GLC3B was the second locus, identified in 8 families, 17 of whom had PCG [ 7 ]. Cornea-derived transcript 6 ( CDT6 ) is a probable candidate gene at the GLC3B locus and may regulate the deposition of specific extracellular matrix (ECM) components in glaucoma [ 12 – 14 ]. In addition, GLC3C and GLC3D were reported to be associated with PCG.…”