Primary Congenital Glaucoma

What is Primary Congenital Glaucoma?

Hippocrates, an ancient Greek physician, first mentioned congenital glaucoma when he saw babies with unusually large eyes. He later connected this condition with increased pressure in the eye and abnormalities in the eye’s drainage angle. Congenital glaucoma is sometimes called developmental glaucoma, as it may not always show up right after birth. There are different types of this condition based on when symptoms first appear.

One is True congenital glaucoma, often called newborn glaucoma. In this type, the baby is either born with larger than normal eyes or the enlargement becomes noticeable within the first month after birth. The belief is that the eye pressure increases while the baby is still in the womb. This type makes up about 25% of congenital glaucoma cases.

Infantile glaucoma appears in babies and toddlers between 1 and 36 months old and makes up about 65% of these conditions. Juvenile glaucoma affects older children and teenagers who show signs of increased eye pressure after three years of age but before they become adults. This type accounts for about 10% of cases.

There’s another way to classify these conditions based on what part of the eye has not developed correctly, it is called the Hoskin classification. Type 1, Trabeculodysgenesis, involves a defect in the development of the trabecular meshwork, the drainage system in the eye. Type 2, Iridotrabeculodysgenesis, includes underdevelopment or overgrowth of the stroma (the supportive tissue of the eye), abnormal iris vessels, or structural defects resulting in conditions like coloboma or aniridia. Finally, Type 3, Corneotrabeculodysgenesis, involves complex cases of congenital glaucoma like Axenfield, Rieger, or Peters anomaly.

Within this classification, Type 1 is known as primary congenital glaucoma, while Types 2 and 3 are referred to as secondary congenital glaucoma.

What Causes Primary Congenital Glaucoma?

Most cases of a type of eye condition known as primary congenital glaucoma happen randomly without any family history of the disease. This means it can occur in anyone, not only those with a genetic predisposition or relatives who have the condition. About 90% of cases are like this. However, there are times when this type of glaucoma runs in families, which makes up about 10% of cases.

This familial type of glaucoma is usually inherited in what’s called an ‘autosomal recessive’ pattern, where you need to get the faulty gene from both your mother and your father to have the disease. But even if you do inherit the faulty gene from both parents, it doesn’t always mean you will get the disease. This chance can vary from 40% to 100%.

Scientists have identified five areas in your DNA, or loci, that are linked with primary congenital glaucoma. They’re called GLC3A, GLC3B, GLC3C, GLC3D, and GLC3E. Among them, GLC3A is tied to a specific gene named CYP1B1.

Changes or mutations in this CYP1B1 gene are the most commonly found reason in cases where the disease is inherited from both parents. There’s another gene, called the latent transforming growth factor-beta – or LTBP2 for short – which is close to the GLC3C loci. This gene is also closely associated with primary congenital glaucoma.

Risk Factors and Frequency for Primary Congenital Glaucoma

Primary congenital glaucoma (PCG)’s occurrence changes a lot among different ethnic groups. For example, in western countries, the incidence can vary from around 1 in every 10,000 to 1 in 30,000 live births. In contrast, in countries like Saudi Arabia, it can be as high as 1 in 2,500 live births. Additionally, glaucoma can be the reason behind 7% of children’s registration in special schools for the blind.

Why the difference? The higher occurrence in some countries and ethnic groups is usually because there are more consanguineous – or closely related – marriages. Though it’s less common, we know this because around 65 to 80% of PCG cases affect both eyes. Typically, more males are affected than females, with the ratio being around 3:2 in studies from the United States and Europe. In Slovakia, it’s even higher, with about 1 in every 1,250 births resulting in PCG. A particular study in Japan found the male-to-female ratio to be 6:5 in patients with a particular genetic mutation (CYP1B1), but without this mutation, the ratio rose to 19:2.

• PCG occurrence varies greatly among different ethnic groups.
• In western countries, its incidence is 1 in every 10,000 to 30,000 live births.
• In countries like Saudi Arabia, it can be as high as 1 in every 2,500 live births.
• Glaucoma accounts for 7% of children registered in schools for the blind.
• The higher occurrence in certain regions is due to more closely related marriages in those areas.
• 65 to 80% of PCG cases affect both eyes.
• The typical male-to-female ratio is around 3:2.
• A specific genetic mutation (CYP1B1) affects the male-to-female ratio.

Signs and Symptoms of Primary Congenital Glaucoma

Glaucoma is a serious eye condition that can occur even in children. It is important to be aware of any family history of glaucoma or closely related parents, as these are significant factors to consider. Symptoms of this condition can range from being present in one or both eyes. Common signs of glaucoma include teary eyes, sensitivity to light, and uncontrolled blinking. Parents may also notice their child’s eyes appearing blue or larger than usual, or a sudden whiteness appearing on the child’s corneas. This can also lead to vision issues like significantly reduced vision sharpness, nearsightedness, uneven vision, and “lazy eye”.

During a clinical examination for glaucoma, the following aspects should be evaluated:

• Light Fixation – The child’s ability to focus on and follow light with each eye separately. Squint in some cases may be due to trouble with fixation, and there may also be uncontrolled eye movements in longstanding cases.
• Sclera – The “white” of the eye might show a bluish tint due to extreme nearsightedness, thinning of the sclera, and exposure of underlying eye tissue.
• Cornea – The cornea may appear enlarged, also known as buphthalmos. Between birth and 6 months, normal corneal size should be between 9.5 to 11.5 mm. A size of more than 12 mm could suggest glaucoma. After that, a corneal diameter of more than 13 mm also suggests enlargement. The cornea may show tears or breaks in its inner layer, or be swollen. This swelling usually starts in the outermost layer and can eventually involve deeper layers, causing permanent cloudiness and severely impacting vision.
• Anterior chamber – The front part of the eye is usually deep. Iris should be examined for shaking, inward curling, underdevelopment, or any signs of thinning.
• Pupil – May appear oval, bigger and lack sufficient blood supply.
• Lens – Should be examined for cloudiness or any misplacement due to excessive stretching of the supporting fibers.
• Optic disc – This typically shows reversible cupping in the early stages. Later stages may present with an enlarged optic disc ratio or even deterioration.
• Intraocular pressure – Usually raised for children with glaucoma, this measurement can be taken using a pneumatic instrument during an outpatient visit.

Testing for Primary Congenital Glaucoma

If your doctor suspects that your child has congenital glaucoma, they’ll need to do a detailed examination under anesthesia. This allows the doctor to plan out the best treatment and management plan.

During this procedure, the doctor will look at the cornea (the clear front surface of the eye) in great detail. This includes measuring the size of the cornea and using a special handheld device known as a slit lamp to further examine it.

They will also carry out a detailed ophthalmoscopy. This process involves the doctor looking at the back of the eye, paying special attention to the disc inside the eye (the optic disc). They’ll note what this looks like and if there are any abnormal blood vessels or significant findings.

The doctor will also measure intraocular pressure (IOP), which is the pressure inside the eye. This can be done using a few different types of tools, including a Schiotz or handheld Perkin’s applanation tonometer or a pneumotonometer/tonopen. Children with congenital glaucoma typically have an IOP within the range of 30 to 40 mmHg, which can lead to swelling of the clear front surface of the eye.

The next steps include a gonioscopic examination, which helps the doctor see the eye’s internal drainage system, and a pachymetry, which involves measuring the thickness of the cornea. This is important because the pressure readings can be affected by the cornea’s thickness.

Another crucial metric in this examination is the axial length, the length of the eye from front to back. This is often increased in children with primary congenital glaucoma due to pressure-induced stretching. Your doctor will also carry out cycloplegic retinoscopy, a test to determine the refractive defect and the need for corrective lenses if the axial length increases.

In children around 7 to 8 years old with good vision, the doctor might check for peripheral visual field loss using a test called perimetry. When the child is able to cooperate in regular eye tests, the doctor can use optical coherence tomography (OCT) to look at the nerve and sensory layers of the eye in detail. This is often done under anesthesia.

Finally, the doctor could conduct genetic screening and look at the family’s eye health history if necessary.

Treatment Options for Primary Congenital Glaucoma

Managing primary congenital glaucoma, an eye condition that affects infants, depends largely on the severity and the patient’s age at diagnosis. The main treatment process revolves around surgery, but in some cases, a course of medicine may be an initial step.

The gold standard or most effective method of treating primary congenital glaucoma is angle surgery. There are two types of angle surgeries: goniotomy and trabeculotomy, both aimed at improving the flow of a fluid in the eye called aqueous humor, thus reducing the pressure inside the eye. If these surgeries do not yield the desired results, more invasive procedures, such as trabeculectomy with mitomycin C (a kind of medication), or the use of a device to facilitate fluid drainage, may be tried. For stubborn cases, cycloablation could be attempted, a process that uses a special type of laser or a cool probe. Medication can also be used alongside these treatments to control the pressure inside the eye and improve visibility for the surgeon.

Before a surgical procedure, medication is typically used to decrease the fluid causing the elevated eye pressure. The medications come in the form of eye drops, and either reduce production or improve the outflow of this fluid. Some examples of such medications include apraclonidine and timolol. However, it’s important to use some medications like these with caution in very young children as they could cause excessive sleepiness or breathing difficulties.

Surgery remains the most common treatment for primary congenital glaucoma, with the type of surgery decided based on the disease severity and surgeon’s preference. The two main categories of surgery are angle procedures and filtration procedures.

Angle procedures increase the aqueous outflow by mulipulating the angle at which the fluid leaves the eye. Two techniques are commonly used, Goniotomy and Trabeculotomy. Goniotomy requires a clear view of the eye’s interior and has a success rate of 70 to 90%. Trabeculotomy, on the other hand, is used when the cornea is cloudy or previous surgeries have been ineffective. This method has a success rate of 75 to 90%.

Filtration procedures, including trabeculectomy and deep sclerectomy, create an alternative pathway for fluid to leave the eye. However, trabeculectomy isn’t as successful in children due to their body’s strong healing responses, but using certain medications can improve the outcomes. Sclerectomy involves removing part of the eye’s drainage system without penetrating the eye.

Finally, if standard treatments are ineffective, Glaucoma Drainage Devices or Combined Trabeculotomy and Trabeculectomy could be considered. These procedures create an artificial channel to drain the fluid in the eye, reducing pressure. In worse case scenarios, with poor or no gaze, a cycloablation is recommended. A modification of this process using a micropulse laser is a safer and better option.

What else can Primary Congenital Glaucoma be?

When diagnosing primary congenital glaucoma, doctors use a handy acronym to remember other possible conditions that cause similar symptoms – STUMPED:

• S – Sclerocornea
• T – Trauma, tears in Descemet membrane
• U – Ulcer: viral, fungal, bacterial, neurotrophic, pythium
• M – Metabolic disorders: mucolipidoses, mucopolysaccharidosis, tyrisinosis
• P – Peters anomaly
• E – Endothelial dystrophy, congenital hereditary endothelial dystrophy, Posterior polymorphous dystrophy, Fuch dystrophy
• D – Dermoid

Apart from these, doctors also keep in mind the following conditions:

• Interstitial keratitis
• High myopia
• Megalocornea
• Corneal abrasion
• Messman dystrophy
• Reis Buckler dystrophy
• Retinoblastoma
• Retinopathy of prematurity
• Persistent primary hyperplastic vitreous
• Traumatic glaucoma
• Congenital rubella syndrome
• Sturge Weber syndrome
• Aniridia
• Optic disc pit
• Optic atrophy
• Coloboma

What to expect with Primary Congenital Glaucoma

The success of treating primary congenital glaucoma, a type of eye disease often present from birth, depends on several factors. These include how early the condition is noticed, its severity, and the clarity of the cornea, which is the clear front surface of the eye. The quicker the diagnosis and treatment, the better the chances of preserving good vision. Corneal edema (swelling of the clear front surface of the eye) and changes to the optic nerve head (the spot where the optic nerve enters the back of the eye) can be reversed if prompt medical attention is given.

Children with this condition need to be regularly checked for vision issues caused by the lengthening of the eyeball and managed appropriately. Regular lifelong check-ups that focus on intraocular pressures (the fluid pressure inside the eye) and the optic nerve head are also necessary. Late detection of the disease could lead to complications that risk vision loss.

Research from the United States shows the effectiveness of proper treatment and regular checks. In this study, nearly 91% of patients did not see the disease advance after one year of solid treatment; this success rate remained relatively high even after several years. Additional research confirmed the benefit of early detection, showing a 90% success rate for interventions on patients between 2 months to 1 year old. In contrast, the success rate was only 50% amongst those who discovered the disease later or noticed it late.

Possible Complications When Diagnosed with Primary Congenital Glaucoma

The complications associated with primary congenital glaucoma can stem from the glaucoma itself or from the surgery or anesthesia involved in treatment. If people don’t seek help soon enough, they may suffer from severe vision problems, damage to the eye’s optic nerve, or defects in their visual field. When the cornea develops stripes, known as Haab’s striae, it can opacify, or become cloudy, causing serious vision issues. High eye pressure can stretch the eye, leading to nearsightedness or irregular vision. Lifelong treatment is essential to correct these vision changes and prevent vision loss. Moreover, these patients may be susceptible to complications such as lens dislocation or retinal issues.

Follow-Up Issues:

• Severe vision problems
• Damage to the eye’s optic nerve
• Visual field defects
• Development of stripes on the cornea (Haab’s striae)
• Clouding of the cornea
• Nearsightedness
• Irregular vision
• Lens dislocation
• Retinal issues

Surgery can also lead to complications, including a range from minor conditions like internal eye bleeding, to serious concerns like retinal detachment or atrophy of the eyeball.

Surgery-Related Complications:

• Internal eye bleeding (Hyphema)
• Shallow front part of the eye (anterior chamber)
• Adhesions in the eye (Peripheral anterior synechiae)
• Detachment of the iris from its base (Iridodialysis)
• Tearing of ciliary body (Cyclodialysis)
• Cataract
• Growth under the cornea (Epithelial ingrowth)
• Detachment of the choroid in the eye
• Retinal detachment
• Atrophy of the eyeball (Phthisis bulbi)

Surgery is sometimes followed by over or under filtration, inflammation of the filtration bleb, or loss of jelly-like substance in the eye.

Filtering Procedure-related Complications:

• Over or under filtration
• Inflammation of the filtration bleb (Blebitis)
• Loss of jelly-like substance from the eye (Vitreous loss)
• Scleral collapse
• Scleral flap leak
• Tube lens touch
• Decomposition of the corneal endothelium from tube cornea touch
• Tube erosion
• Implant migration
• Dual vision (Diplopia) from implant-related restrictions
• Inflammation inside the eye (Endophthalmitis)

Destructive eye procedures can result in low eye pressure (Hypotony) or retinal detachment, among other complications.

Cyclodestructive Procedure-related Complications:

• Low eye pressure (Hypotony)
• Retinal detachment
• Atrophy of the eyeball (Phthisis)

Additionally, anesthesia can lead to complications such as unusual reflexes occurring during eye surgery (oculocardiac reflex), severe allergic reactions (anaphylaxis), or even heart failure.

Anaesthesia-related Complications:

• Unusual reflexes during eye surgery (Oculocardiac reflex)
• Severe allergic reactions (Anaphylaxis)
• Dangerous reaction to certain drugs used during surgery (Malignant hyperthermia)
• Heart failure (Cardiovascular collapse)
• A group of rare genetic disorders that affect the nervous system (Hepatic porphyria)
• Brain injury due to lack of oxygen (Hypoxic brain injury)

Recovery from Primary Congenital Glaucoma

Kids going through surgery should be given topical steroids, which are creams or gels that help to reduce inflammation. These might be either prednisolone 1% or dexamethasone 0.1% in reducing doses over one week. They should also be given a topical antibiotic (a medicine to fight infection that you put directly on the skin) like tobramycin 0.3%, moxifloxacin 0.3%, or gatifloxacin to be applied four times per day for 20 days. This is to avoid any infections after the surgery.

It’s important that these patients have regular check-ups after surgery to look for any signs of low eye pressure (hypotony), inflammation, or infection. It’s also crucial to measure the pressure inside their eyes (intraocular pressures) every 3 to 4 months for at least two years after the surgery.

These patients will also need vision tests with the eyes in a relaxed state (cycloplegic refraction) every six months. Regular lifelong check-ups every six months will be necessary to keep an eye on the pressure inside their eyes and to detect any complications from surgery early.

If the surgery to improve the eye’s drainage system (angle or filtration surgery) does not work, the patients should be advised about the potential need for a different surgery involving a device to drain fluid from the eye (GDD.) They should also be informed about the risks of further failure, lazy eye (amblyopia), blindness, and a shrunken, non-functional eye (phthisis bulbi).

Preventing Primary Congenital Glaucoma

Primary congenital glaucoma is a condition that typically presents at birth and can cause serious vision problems, but it can be treated effectively if it’s caught early on. This is why it’s critical for parents, regular doctors, and eye health professionals to be on the lookout for early signs. Symptoms to look for include larger than normal eyes, excessive eye watering, redness, or a child being sensitive to light. If these signs are noticed, a specialist in eye diseases, called an ophthalmologist, should be contacted as soon as possible. By being aware of these early signals, parents can help prevent vision loss resulting from this condition.

Treatment options need to be clearly explained to the parents so they can make an informed decision about what’s best for their child. Furthermore, the importance of consistent check-ups and following the prescribed treatment plan should be highlighted. Also, the child will need regular appointments with an eye health professional for the measurement of their eye’s focus, which is done through a process known as refraction. Lastly, the initial transition to clinics for children with low vision – where they are helped to adapt to vision impairment – is extremely beneficial. Here, the child and parents can learn about necessary lifestyle and educational adjustments early on.