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Primary congenital glaucoma: for patients

Overview

Primary congenital glaucoma (PCG) is the most common type of glaucoma that affects babies and young children (1 in 1,250-1,10,000 people affected), with a higher occurrence in marriages where the parents are related.[1] It is caused by changes to one of a number of genes involved in normal eye development leading to increased pressure in the eye, which in turn damages the optic nerve, and eventually cause visual impairment (glaucoma) if left untreated. PCG tends to present at birth or during early infancy but it can occur later in some children. Increased pressure within the eye at such an early age has various effects, including bulging of the eyes, also known as buphthalmos (Greek for “ox-eye”) and clouding of the cornea. These features tend to be quite striking, which usually prompt parents to seek urgent medical attention. Along with these features, parents may also notice that their child has excessive watering of the eyes, eyelid twitching and/or sensitivity to light.[2]

Treatment is aimed at lowering eye pressure, which therefore halt continuous damage to the optic nerve. This is mainly achieved through surgery. The visual prognosis varies between patients, depending on the age of onset, the severity of the condition prior to treatment and response to treatment. In general, earlier onset disease is usually associated with worse visual outcome.[3]

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The condition

Symptoms

1) Large eyes (buphthalmos)

As the sclera (outer wall of the eye) in a child is much softer and more flexible compared to adults, increased pressure in the eye will stretch the sclera, causing the eye to look enlarged/bulging. This is medically known as buphthalmos and is one of the characteristics of primary congenital glaucoma. Reducing the eye pressure does not usually bring the eye back to its normal size, though it can reduce slightly.

The right eye of an infant is enlarged due to primary congenital glaucoma
A child affected by primary congenital glaucoma presenting with buphthalmos in the right eye

Credit: Prof Sir PT Khaw, consultant ophthalmologist, Moorfields Eye Hospital, London

2) Cloudy cornea

The cornea needs to be clear in order for us to see things in focus. The clarity of the cornea is normally maintained by pumps in the endothelial layer of the cornea, which constantly pumps fluid out of the stroma. If the eye pressure is increased significantly, these pumps are overwhelmed and fail to function normally. As a result, the cornea becomes waterlogged or hazy, which causes blurry vision. The cloudiness normally clears when the eye pressure is lowered with treatment but it may take several months. Furthermore, the cornea may expand when fluid accumulates in it, causing small cracks to appear in the inner layers of the cornea. This is known as Haab striae.

The cornea of the right eye is hazy due to uncontrolled high eye pressure.
The cornea is hazy due to uncontrolled eye pressure

Credit: Prof Sir PT Khaw, consultant ophthalmologist, Moorfields Eye Hospital, London
The three main layers of the cornea. The thick stromal layer is sandwiched in between the superficial epithelium and the deep endothelial layer.
Different layers of the cornea

3) Other symptoms

In addition to the characteristic features typically associated with PCG, parents may also notice that their child has a number of these symptoms:

Nystagmus
  • Sensitivity to light
  • Excessive watering of the eyes
  • Eyelid twitching
  • Near sightedness (myopia) which requires glasses to improve
  • Nystagmus (involuntary wobbling of the eyes) due to impaired vision from the hazy cornea and damage to the optic nerve

Both eyes tend to be affected by PCG but quite often, one eye is more affected than the other. The severity of symptoms varies considerably between children. Some may have better visual function and milder symptoms, others worse. The visual prognosis varies between patients, depending on their age, how advanced the disease is before treatment and their response to treatment. Treatment is mainly aimed at reducing the pressure in the eye.

In addition to visual symptoms, some children may also have symptoms affecting other parts of the body as some of the genes responsible for PCG are also involved in the development of other organs. For example, children with mutations in the FOXC1 gene may be affected by Axenfeld-Reiger syndrome and those with certain mutations in the LTBP2 gene may display some features similar to Marfan Syndrome.[4]

Cause

Glaucoma is a condition that progressively damage the optic nerve and eventually leading to visual impairment. It can occur in adults or children, and is usually caused by higher-than-normal pressure inside the eye. The mechanisms in which the high eye pressure occur differs between different types of glaucoma.

Primary congenital glaucoma is the most common form of glaucoma among babies and young children. It is often caused by mutations in genes that are involved in eye development when we are still in the womb, particularly the formation of the drainage channels of the eye, known as the trabecular meshwork.  Harmful mutations to these genes cause the drainage channels to be poorly developed, which subsequently lead to dysregulation of normal eye pressure.

Several genes have been implicated to cause PCG. Of these genes, CYP1B1 is the most common.[5,6] Other genes that are known to be associated with PCG include LTBP2, MYOC, FOXC1 and TEK.[7] There are still other genes that are yet to be identified.

How is it diagnosed?

1) Eye examination

An ophthalmologist is able to diagnose PCG based on the presenting features, examination and the results of various tests that assess the structure and function of the eye. Examination is usally performed under general anaesthetic as it is often difficult to carry out a detailed evaluation in babies and young children. The examination usually involves checking the eye pressure (tonometry), assessing the architecture of the drainage channels of the eye including the trabecular meshwork (gonioscopy) and taking a photograph of the optic nerve (for future comparisons to detect glaucoma progression). Once a child is old enough (usually about the age of 7 years), automated measurements of the side vision (perimetry) are performed as well to monitor visual function.  Occasionally, the ophthalmologist may also want to examine the parents and siblings as well even though they may be unaware of any visual problems. This is because either parent or sibling(s) may have a very mild condition which does not affect his/her vision. This is more likely if the parents are related.

2) General medical assessment

As PCG may involve other parts of the body as well, an assessment by a paediatrician may need to be carried out to detect if there are any systemic involvement.

3) Genetic testing

Genetic testing will help identify if there is a faulty gene so that families can have a better-informed genetic counselling session and more accurate advice on prognosis. It can also help inform the team to refer your child to a paediatrician for further assessment if the gene responsible is known to cause symptoms in other parts of the body.

Families should be aware that the responsible gene is only identified in 13-25% of PCG cases using current genetic testing techniques.[7,8]

How is it inherited?

Most of the genetic changes associated with PCG are inherited in an autosomal recessive manner. This means that both parents are usually unaffected carriers (only have one faulty gene copy) while the patient has two faulty gene copies (inherited one each from each parent). Other inheritance patterns that have been observed in PCG are autosomal dominant and de novo sporadic. De novo sporadic means that the changes in the genes that cause the condition can arise randomly for the first time in the child and is not inherited from either parent. Depending on the responsible gene, the changes might be passed down to subsequent generations in an autosomal recessive or autosomal dominant manner. Genetic testing will be able to provide a clearer picture.

If your child is affected by PCG, it is advisable to see a genetic counsellor to obtain more information and advice on inheritance and family planning options.

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Treatment

Is there any treatment?

1) Surgery

The main aim of treatment in PCG is to lower the eye pressure and therefore halting the progression of glaucoma. Compared to glaucoma in adults, eye drops and medications are often not very effective in lowering eye pressure in PCG. Therefore, surgery remains the first line of treatment in PCG. Eye drops are usually used to lower the eye pressure temporarily while waiting for surgery or after surgery to achieve better control of the eye pressure.

There are various surgical options available, which are briefly outlined here. Your child’s ophthalmologist will be able to explain to you in further detail.

(a) Goniotomy and trabeculotomy

These are usually the first procedures performed in PCG. Goniotomy involves making an opening through the front of the eye to open up the trabecular meshwork (the drainage system of the eye), which are previously not opened properly when the eye was developing. Goniotomy however requires the cornea to be clear.  

If the cornea is hazy, a trabeculotomy may be performed instead. This involves making a flap in the conjunctiva and sclera into the drainage channel, and then using a fine probe to open up the trabecular meshwork. The flap is then closed with tiny stitches that dissolve on their own. Both goniotomy and trabeculotomy are associated with high success rates in lowering eye pressure with relatively few complications.[9]

(b) Trabeculectomy

This is a more complex procedure that involves making an entirely new drainage channel. Similar to trabeculotomy, a small flap is made in the conjunctiva and sclera, which is then stitched closed after the channel has been created. The fluid in the eye flows through this new opening and accumulate in the flap, giving the appearance of a little “bump”, which is known as a bleb. The fluid in the bleb gets re-absorbed by blood vessels surrounding the eyeball. The stitches used to close the flap tend to stay in there permanently. Trabeculectomy is not usually performed initially as it may involve more follow-ups (some of which have to be performed under general anaesthetic if stitches need to be removed) and higher risk of bleb-related complications such as infections and scarring, which may require further operations to revise the bleb.[10]

(c) Drainage tubes

Drainage tubes are also an option for lowering eye pressure in PCG. However, there is a higher risk of requiring further procedures due to implant-related complications such as migration of the tube or erosion of the tube through the conjunctiva.[11]

(d) Laser procedures

Laser is usually used in cases where the eye pressure does not reduce adequately with the above operations, or in children who are unable to undergo prolonged general anaesthetic due to other health issues.

These are just basic information about the common procedures used to treat PCG and by no means serve as a recommendation. The selected surgical option is highly individualised based on the ophthalmologist’s assessment and expertise. You should speak to the treating doctor if you have further queries about the different procedures.

2) Supportive measures

It can be difficult to predict how good a child’s eyesight will be after surgery. Many children with treated PCG usually have good vision in adulthood. The main focus is to make sure the eye pressure is well controlled. In addition, some of the following measures can be used to further optimise eyesight after surgery:

  • Regular monitoring of visual function and prescribing glasses (if required)
  • Treating a “lazy eye” (if discovered during follow-ups) by patching the good eye for a few hours a day
  • Tinted glasses to help alleviate light sensitivity
  • Regular lifelong monitoring of the eye pressure in case of further elevation
  • Visual aids and assistive technology if vision remains poor despite treatment

3) Systemic treatment

As some children with PCG may have conditions affecting other parts of the body, they might need input from various specialists co-ordinated by a paediatrician. If vision remains poor despite treatment, it can have a negative impact on early childhood development. Therefore, children may sometimes be referred to practitioners familiar with developmental surveillance and intervention for children with visual impairment, such as developmental paediatricians as well as advisory teaching services for children with visual impairment (e.g. sensory support serviceswithin local authority). This will enable provisions to be made within the educational and home settings to so that they child can reach their developmental potential and develop skills to achieve independence.

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Current research in PCG

The development of the anterior segment is a complex process that involves an intricate network of genes interacting with each other. Although some genes responsible for PCG have been identified, research currently focuses on finding the remaining genes involved in this process and understanding their mechanisms in human eye development. As genetic testing becomes increasingly available in routine eye care, it is hoped that more new genes can be identified by testing more patients with PCG.[12]

There is currently no gene-based therapy that can reverse the structural malformations induced by the genetic changes. It is possible that such therapeutic approaches may be able to improve the movement of fluid in the eye in the future. Advances in glaucoma therapies can potentially lead to further improvement of outcomes in children affected by PCG.

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Practical advice

Living with PCG

It can be difficult to predict how good a child’s eyesight will be after surgery. Many children with PCG who was treated have good vision in adulthood. For the small minority of children whose eyesight remain sub-optimum despite treatment, they can still lead an independent life through maximising their available vision and having access to social support. Here are some ideas:

  • Attending the low vision clinic which provides access to low vision specialists, Eye Clinic Liaison Officers (ECLOs), visual aids and visual rehabilitation services
  • Utilising assistive technologies that can improve quality of life
  • Getting in touch with the local education authority for access to qualified teachers for children with visual impairment (QTVI) and special educational needs co-ordinator (SENCO)
  • Preferential seating in classroom such as in the front row
  • Registering as sight impaired (SI) or severely sight impaired (SSI) if eligible for access to social support and financial concessions
  • Getting in touch with national or local charities for advice and peer support

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Referral to a specialist centre

If you are based in the UK and would like to be seen in the nearest specialist centre for your eye condition, either to receive a more comprehensive genetic management or just to find out more about current research, you can approach your GP to make a referral or alternatively arrange for a private appointment. 

More information can be found in our “How to see a genetic eye specialist?” page.  

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Further information and support

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A patient’s perspective

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References

  1.  Aponte EP, Diehl N, Mohney BG. Incidence and clinical characteristics of childhood glaucoma: a population-based study. Arch Ophthalmol. Apr 2010;128(4):478-82
  2.  Badawi AH, Al-Muhaylib AA, Al Owaifeer AM, Al-Essa RS, Al-Shahwan SA. Primary congenital glaucoma: An updated review. Saudi J Ophthalmol. Oct-Dec 2019;33(4):382-388
  3.  Ko F, Papadopoulos M, Khaw PT. Primary congenital glaucoma. Prog Brain Res. 2015;221:177-89
  4.  Morlino S, Alesi V, Cali F, et al. LTBP2-related “Marfan-like” phenotype in two Roma/Gypsy subjects with the LTBP2 homozygous p.R299X variant. Am J Med Genet A. Jan 2019;179(1):104-112
  5.  Nishimura DY, Searby CC, Alward WL, et al. A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye. Am J Hum Genet. Feb 2001;68(2):364-72
  6.  Kaur K, Mandal AK, Chakrabarti S. Primary Congenital Glaucoma and the Involvement of CYP1B1. Middle East Afr J Ophthalmol. Jan 2011;18(1):7-16
  7.  Patel A, Hayward JD, Tailor V, et al. The Oculome Panel Test: Next-Generation Sequencing to Diagnose a Diverse Range of Genetic Developmental Eye Disorders. Ophthalmology. Jun 2019;126(6):888-907
  8.  Jackson D, Malka S, Harding P, Palma J, Dunbar H, Moosajee M. Molecular diagnostic challenges for non-retinal developmental eye disorders in the United Kingdom. Am J Med Genet C Semin Med Genet. Sep 2020;184(3):578-589
  9.  Abu-Amero KK, Edward DP. Primary Congenital Glaucoma. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews(®). University of Washington, Seattle Copyright © 1993-2020, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993
  10.  Chakrabarti S, Kaur K, Komatireddy S, et al. Gln48His is the prevalent myocilin mutation in primary open angle and primary congenital glaucoma phenotypes in India. Mol Vis. Feb 4 2005;11:111-3
  11.  Medina-Trillo C, Aroca-Aguilar JD, Méndez-Hernández CD, et al. Rare FOXC1 variants in congenital glaucoma: identification of translation regulatory sequences. Eur J Hum Genet. May 2016;24(5):672-80
  12.  Black GC, MacEwen C, Lotery AJ. The integration of genomics into clinical ophthalmic services in the UK. Eye. 2020/06/01 2020;34(6):993-996

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Updated on November 30, 2020
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