Primary congenital glaucoma (PCG)

Congenital glaucoma is a developmental glaucoma occurring before the age of three years due to an obstruction that prevents adequate drainage of aqueous humor caused by abnormal development of the trabecular meshwork (TM) and anterior chamber angle.

History:

Primary congenital glaucoma (PCG) was first described by Hippocrates (460–377 BC) when he noticed abnormal enlargement of the eyes in infants but did not relate the condition to elevated IOP. PCG was not well understood until the early 18th century when Berger first linked the elevated IOP to enlargement of the globe. In 1869, von Muralt established the classical form of buphthalmos as a form of glaucoma. In the late 1800s, the Manual of Human and Comparative Histology published in 1873 described the angle drainage system, including the anatomical structure of Schlemm’s canal and Descemet’s membrane, referring to them as an anterior lymphatic drainage system. Thereafter, the Atlas of the Pathological Anatomy of the Eyeball translated to English from German by William Gowers in 1875, established that angle structure malformation as the culprit for PCG. In the early 1900s, congenital glaucoma seemed untreatable and Anderson commented: “The future of patients with hydrophthalmia is dark” and “one seeks in vain for a best operation in the treatment of hydrophthalmia”. However, the introduction of goniotomy in 1938 by Barkan has dramatically changed the poor prognosis of congenital glaucoma. In addition, the introduction of new diagnostic tools, IOP-lowering medications, and improvement of surgical techniques has improved the prognosis of this devastating disease and preserved the vision of affected children.

---

Classification

Glaucoma:

Collection of related disorders with complex optic nerve atrophy and characteristic loss of larger retinal ganglion cells (RGC) leading to a consequent carbon copy pattern of loss of visual field and vision

World Glaucoma Association classification for childhood glaucoma:

Childhood/Developmental glaucoma: Glaucoma associated with developmental anomalies of the eye present at birth.

• Primary Childhood Glaucoma: Resulting from maldevelopment of the aqueous outflow system
  • Congenital glaucoma: At/before birth (M/C non-syndromic glaucoma in infancy)
  • Infantile glaucoma: Birth until 3 years of life.
  • Juvenile glaucoma: After 3 years to teenage
• Secondary Childhood Glaucoma: Resulting from damage to the aqueous outflow system due to maldevelopment of some other portion of the eye
  • Angle closure due to pupillary block in a small eye
  • Microspherophakia: Dislocated lens
  • Persistent hyperplastic primary vitreous or retinopathy of prematurity: Forward shift of the lens-iris diaphragm

Hoskins and Shaffer classification system:

Anatomical approach to classification based on the area of dysgenesis.

• Trabeculodysgenesis:
  • Flat iris insertion defects: Anterior/posterior/mixed
  • Cocave (wrap-around) iris insertion defects
• Iridotrabeculodysgenesis
  • Stromal defects: hypoplasia, hyperplasia
  • Anomalous iris vessels
  • Structural defects: coloboma, aniridia
• Corneotrabeculodysgenesis
  • Anomalies, such as Axenfeld’s, Rieger’s and Peters

---

Etiology

CYP1B1:

CYP1B1 is a member of the cytochrome P450 family of membrane-bound oxidase enzymes that have broad roles in metabolism and produce hormones and other metabolic intermediates during development. Autosomal recessive mutations in CYP1B1 are the most common known cause of PCG.

Other genetic mutations:

• Latent transforming growth factor beta binding protein 2 (LTBP2)
• Tunica interna endothelial cell kinase (TEK)

Syndromic glaucomas:

• Axenfeld-Rieger syndrome: Autosomal dominant genetic condition characterized by anterior segment dysgenesis and systemic abnormalities.
• Aniridia: Rare developmental eye disease characterized by an underdeveloped iris

---

Presentation

Clinical triad:

1. Epiphora: Excessive tearing
2. Photophobia: Hypersensitivity to light
3. Blepharospasm: Inflammation of eyelids

Other findings:

• Buphthalmos: Enlargement of the eyeball
• Iris covering a variable portion of ciliary body and trabecular meshwork
• Juxtacanalicular with less number of pores
• Sinus venosus eye: Absence of Schlemm’s canal
• Haab’s striae: Breaks in Descemet’s membrane

---

Management

Aim of treatment is to lower the elevated IOP to a level that preserves visual function without causing extensive damage to the optic nerve and/or the retina. Late presentations in which a significant amount of irreversible damage had already occurred, the treatment aims to preserve the current visual status and prevent the fellow eye from subsequent deterioration.

Medical treatment:

IOP-lowering medications work either by decreasing aqueous humor secretion or increasing its elimination. They are, in almost all cases, used topically in the form of eye drops.

• Decreasing aqueous humor secretion: α-agonists, β-blockers, and carbonic anhydrase (CA) inhibitors
• Increasing elimination of aqueous humor: Adrenaline derivatives, parasympathomimetics, and prostaglandin analogues

Surgical management:

Surgical treatment is the mainstay of management in cases of PCG. Early surgical intervention is of prime importance in the management of patients with PCG. The primary goal of all surgical procedures is to eliminate the resistance to aqueous outflow caused by the anatomical anomaly in the anterior chamber angle.

• Internal approach: Goniotomy
• External approach: Trabeculotomy or trabeculectomy (can be performed even in the presence of a cloudy cornea)
• Glaucoma drainage devices (GDD) and cyclodestructive procedures: Failure of the primary surgical procedure