Congenital glaucoma: diagnosis and treatment

Congenital glaucoma is a rare but potentially severe form of glaucoma in children, in which maldevelopment of the anterior chamber angle and trabecular meshwork causes persistently elevated intraocular pressure, deformation of the growing eye, and damage to the optic nerve. Classically, infants present with a triad of lacrimation, photophobia, and blepharospasm; on examination, they show bupfalmos, corneal opacity, and ruptures of Descemet's membrane (Haab's lines). Treatment is, in the vast majority of cases, surgical, with medications serving as a "bridge" to surgery. [1]

It is important to distinguish between primary congenital glaucoma (PCG), caused by an isolated angle anomaly, and childhood secondary glaucomas associated with other anterior segment defects (Axenfeld-Rieger syndrome, aniridia), systemic diseases (Sturge-Weber syndrome), or surgical sequelae (e.g., aphakia after congenital cataract surgery). This differentiation determines the treatment strategy, prognosis, and genetic counseling. [2]

What is it: terms and age of onset

PCG is a condition called "trabeculodysgenesis": drainage structures are malformed, aqueous humor outflow is impeded, and in the elastic membranes of children, increased pressure leads to their stretching. Three windows are distinguished based on the age of symptom onset: neonatal (<1 month), infantile (1-24 months), and late childhood/juvenile (>24 months). The earlier the onset, the more aggressive the course. [3]

Table 1. Age of onset of PCG and clinical clues

Subtype	Age	The clinic is at the start	Frequent Finds
Neonatal	<1 month	Severe photophobia, milky cornea	Corneal diameter >11 mm, Haab lines
Infantile	1-24 months	Classic triad; slower	Corneal diameter >12 mm by 1 year
Late childhood	>24 months	A less "loud" debut	A higher proportion of "hidden" neuropathy

[4]

Epidemiology: How common is it?

PCG is rare, but its contribution to childhood blindness is high. In Western populations, its incidence is estimated at 1 in 10,000–30,000 newborns; in regions with a high proportion of consanguineous marriages, it is significantly more frequent: up to 1 in 2,500 (Saudi Arabia), 1 in 8,200 (some Arab populations), and is uniquely high among the Roma population of Slovakia—about 1 in 1,250. PCG accounts for up to 5–18% of all cases of childhood blindness. The disease is usually bilateral (approximately 70%). [5]

Data from national registries confirm the rarity and high “cost” of the disease: cohorts with long-term observation show that more than half of the eyes require multiple surgeries, and a good functional outcome with active tactics is achieved in ~58% of eyes. [6]

Table 2. Examples of PCG epidemiological estimates

Region/population	Indicator
Western countries	1: 10,000-30,000 newborns
Saudi Arabia	~1: 2,500
Palestinian Arabs	~1: 8 200
Roma population of Slovakia	~1: 1 250
Contribution to childhood blindness	~5-18% of cases

[7]

Genetics and risk factors

The most common gene associated with PCG is CYP1B1. The frequency of pathogenic variants varies greatly by region, from approximately 5% to 80%+ of patients with PCG (depending on the population). Early neonatal onset is more often associated with CYP1B1 and is associated with a more severe course. Rare but significant genes include LTBP2 (in consanguineous populations), TEK/ANGPT1, and genes of the "anterior segment dysplasia" spectrum (FOXC1, PITX2) - more often in secondary childhood glaucoma. [8]

Inheritance is usually autosomal recessive, but other patterns also occur. Familial cases, consanguineous marriages, and early onset are reasons for genetic counseling of the family with a discussion of testing and risks in future pregnancies. [9]

Table 3. Genes associated with childhood glaucoma

Gene	Typical association	Clinical notes
CYP1B1	Primary congenital glaucoma	Frequent variations; wide regional variation (≈5-86%)
LTBP2	PCG in case of consanguinity	Frequent severe forms
TEK / ANGPT1	Angle anomalies	Rare; TIE2 pathway
FOXC1 / PITX2	Axenfeld - Rieger	More often secondary glaucoma

[10]

Pathogenesis: What goes wrong

The main problem is angle dysgenesis: the trabecular meshwork and the transition zone to the Schlemm canal develop abnormally, remaining "imperforate" elements of embryonic tissue, and outflow resistance increases. In the growing eye, pressure deforms the delicate membranes: the corneal diameter and the length of the eye increase, and ruptures of Descemet's membrane and bulging membranes appear. Some optic nerve damage in children is reversible after pressure is reduced—this is a window of opportunity for early surgery. [11]

Secondary childhood glaucomas add their own mechanisms: in aniridia (PAX6), it's angle hypoplasia; in Sturge-Weber syndrome, it's venous hypertension and anterior synechiae; in aphakia, it's angle remodeling after cataract surgery. The approach here is different than for PCG. [12]

Clinical manifestations

The infant presents with lacrimation, photophobia, and eyelid spasms. Parents notice a "large, shiny eye," corneal opacity, and "silvery" streaks (Haab's lines). The physician notes corneal dilation (suspiciously >11 mm in a newborn; >12 mm in children under 1 year), epithelial edema, elevated pressure (adjusted for anesthesia/sedation), and/or disc excavation. The process is often bilateral but asymmetrical. [13]

In children over 2-3 years of age, symptoms are more subtle: decreased vision, myopia, strabismus, or amblyopia may predominate. Therefore, systematic screening and examination for complaints of light and tears is vital. [14]

Table 4. Norms and red flags in infants

Parameter	Norm	Suspicious on PCG
Corneal diameter at birth	~9.5-10.5 mm	>11.0 mm
Corneal diameter at 1 year	~11.0-11.5 mm	>12.0 mm
Intraocular pressure	<21 mmHg	≥21 mmHg (including sedation)
Cornea	Transparent	Edema, Haab lines

[15]

Diagnostics

1) Slit lamp examination/biomicroscopy (depending on age - manual methods): corneal condition, corneal diameter (calipers), anterior chamber depth, pupillary response. 2) Tonometry (Perkins/Tono-Pen) with mandatory recording of time, method and applied sedation. 3) Gonioscopy (if transparency allows): assessment of the angle and trabecula; in case of cloudiness - ultrasound biomicroscopy or OCT of the anterior segment. 4) Ophthalmoscopy/photography of the disc, OCT of the macula and nerve fiber layer if possible; A-scan of the length of the eye. 5) Examination under anesthesia (EUA) - the gold standard for babies: repeat measurements, angle clarification, keratometry, refraction, examination of the periphery. [16]

If secondary childhood glaucoma is suspected, an etiologic search is carried out (anterior segment dysplasia, aniridia, vascular syndromes), and in familial cases and early onset, genetic counseling/testing is carried out. [17]

Table 5. What must be documented at the initial visit

Paragraph	For what
Corneal diameter (both eyes)	Objective marker of dynamics
Intraocular pressure (method, sedation)	Comparability in dynamics
Corneal condition (edema, Haab lines)	Severity and reversibility
Photograph of the optic nerve head	Base for comparison
Eye length (A-scan)	Growth dynamics of the eye

[18]

Differential diagnosis

• Megalocornea: large but transparent cornea, normal pressure, no edema or Haab lines.
• Congenital corneal dystrophies and birth trauma of Descemet's membrane: clouding without "glaucoma" parameters; pressure is normal.
• Aniridia, Axenfeld-Rieger syndrome, Sturge-Weber syndrome: there are systemic/anterior segmental signs.
• Aphakic/pseudophakic glaucoma after congenital cataract surgery - a different mechanism and different tactics. [19]

Treatment

The key idea: PCG treatment is primarily surgical, and drops provide temporary support before and between surgeries. The goal is to sustainably reduce resistance at the trabecular level.

Goniotomy (ab interno) and trabeculotomy (ab externo) are the two classic first-line procedures. The choice depends on the corneal transparency: goniotomy is preferred for a clear cornea, while external trabeculotomy is preferred for cloudy corneas. In recent years, 360-degree trabeculotomy with an illuminated microcatheter, or the "thread" technique, has gained popularity: in randomized and observational studies, it often provides lower pressure and a reduced need for repeat interventions compared with segmental trabeculotomy. [20]

If control is insufficient after angle surgeries, filtration surgeries (trabeculectomy) and/or drainage devices (Ahmed valve, tubes) are used. In the pediatric population, the risk of scarring and complications is higher; antimetabolites are used with caution, preferring drainage devices in refractory cases and in secondary glaucomas. [21]

Drug therapy in infants is a bridge and complement: beta-blockers and carbonic anhydrase inhibitors are often used first, alpha-agonists are limited due to systemic side effects, and prostaglandin analogs are less effective in PCG. Prescribing, dosing, and monitoring in children require pediatric experience (bronchospasm, apnea, electrolytes). [22]

Related tasks: prevention and treatment of amblyopia, refractive correction, strabismus control, corneal protection, and parental education on the signs of decompensation. It is the combination of surgery and pediatric ophthalmology that yields the best functional results. [23]

Table 6. Surgical options for PCG

Method	When we choose	Pros	Limitations/Risks
Goniotomy (ab interno)	The cornea is transparent	Physiological, fast recovery	Requires good visibility of the angle
Trabeculotomy (ab externo)	Corneal opacity	Does not depend on transparency	Segmental effect
360° trabeculotomy	Primary/recurrent, severe cases	The greatest coverage of trabeculae, high chances of control	Technical nuances, possible ruptures of the mucous canal
Trabeculectomy	Refractory cases	A marked decrease in pressure	Risk of scarring, hypotension; use with caution with antimetabolites
Drainage devices	Multi-operational/secondary forms	Less dependent on scarring	Tube in a small eye, erosion, infection

[24]

Table 7. Drops for infants: what to remember

Class	Role	Special notes
Beta blockers	Reduce production	Risk of bradycardia/bronchospasm; caution in infants
Carbonic anhydrase inhibitors (topical/systemic)	Bridge before surgery	Systemic - control of electrolytes, appetite
Prostaglandin analogues	Addition	The effect on PCG is moderate
Alpha agonists	Reserve	Limited in infants due to sedation/apnea risk

[25]

Postoperative care and observation

In the early period, anterior chamber depth, corneal transparency, pressure, and suture/tube position are monitored. Children often require additional procedures (suture adjustment, filter pad massage, and revisions). Long-term care includes monitoring the development of amblyopia, spectacle selection, occlusion therapy, and re-evaluation of the disc and visual field as the child matures. [26]

Table 8. Observation schedule (approximate)

Postoperative period	What to check
1-2 days	Camera, pressure, leaks, cornea
1-2 weeks	Pressure, cornea, healing, refraction if possible
1-3 months	Pressure, disc, cornea; therapy adjustments
Continue regularly	Pressure, eye growth (A-scan), disc/OCT, amblyopia

(Specific intervals vary by method and flow; this is a guideline.) [27]

Forecast

Outcome is determined by the age of onset, the speed of surgery, and the anatomy of the angle. In modern series, 360° trabeculotomy and combined angle techniques offer a high chance of long-term control; however, approximately half of the eyes may require more than one operation during their lifetime. With early, appropriate management, a significant proportion of children maintain good vision into adulthood. [28]

Frequently Asked Questions

Can PCG be cured with just drops?
No. Drops are a bridge and a supplement. The mainstay of treatment is surgical restoration of the outflow. [29]

How to choose between goniotomy and trabeculotomy?
Based on corneal transparency and anatomy. If the angle is sufficiently visible, goniotomy is used; if it is cloudy, ab externo trabeculotomy is used. The 360° approach is increasingly being discussed. [30]

How reliable is 360° trabeculotomy?
Several studies show lower mean pressure and fewer reoperations compared to the segmental technique, including in complex cases. The decision is individual and depends on the center's experience. [31]

Are genetic tests necessary?
For early onset, familial cases, and high-risk populations—yes, subject to consultation with a geneticist. This is important for prognosis and family planning. [32]