It is often surprising to hear that glaucoma is not just a disease of ageing. In fact, it may be diagnosed at birth, or in the first decades of life. Early onset glaucoma is a term often used for those diagnosed with glaucoma before age 40. Those with onset <18 years of age are considered to have childhood glaucoma.
Dr Jonathan Ruddle
Primary glaucoma can be divided into primary congenital glaucoma (PCG) and juvenile open angle glaucoma (JOAG).
Secondary glaucomas are divided according to their underlying pathology. Such pathologies include non-acquired ocular anomalies, such as Axenfeld-Rieger spectrum (ARS) and iris hypopolasia, non-acquired systemic disease such as connective tissue disease like Marfan syndrome, and glaucoma associated with acquired conditions like uveitis or trauma.
A ‘syndrome-detecting mindset’ is essential for optometrists who take a particular interest in paediatric myopia management
Glaucoma following childhood cataract surgery falls under a separate classification.1
Although individually rare, the lifelong burden of these conditions detrimentally affects quality of life for individuals with glaucoma, their parents, and family members. The toll of regular medication use, as well as caregiver time for appointments that can intrude on school and work, can be significant. Lifelong vision loss can occur from both the glaucoma and from complications of secondary ocular issues like high myopia, refractive amblyopia, and refractive error.2
This article describes the major subtypes of childhood glaucoma, keys to making a diagnosis, and provides an update on modern management techniques.
PRIMARY CONGENITAL GLAUCOMA
Primary congenital glaucoma can present with sudden onset corneal clouding (Figure 1), and it may be bilateral or unilateral. It can be noticed at birth, or shortly thereafter. Infants with corneal clouding are irritable, photophobic, and have watery eyes. Light sensitivity, which should be seen as a large red flag, makes it difficult for primary care professionals to assess these infant’s eyes. If it is not possible to assess corneal clarity, then urgent referral for examination under anaesthetic should occur. Heightened parental concern should also be considered.
Figure 1. Infant with corneal clouding. Photograph kindly provided by Prof Mariya Moosajee, Creator of Gene Vision and Moorfields Eye Hospital, London, UK.
Intraocular pressure (IOP) is measured under sedation or anaesthesia, along with careful anterior segment examination for corneal clouding, splits in Descemet’s layer (known as Haab striae), iris, angle or lens anomalies, the degree of refractive error and of optic nerve change.
There are forms of slower onset childhood glaucoma, the major features of which are ocular enlargement or buphthalmos. In these cases, pressure will increase more slowly, and corneal clouding may not occur. This appearance will become increasingly obvious to caregivers, especially if asymmetrical corneal enlargement occurs.
Cupping of the optic nerve can be reversible, and this is one instance where glaucoma can be diagnosed without characteristic optic nerve rim thinning or cupping.
GREATER RISKS
Are non-acquired ocular and syndromic conditions at greater risk of childhood glaucoma?
Anterior segment dysgenesis is the overarching term used to group several phenotypic conditions that all carry a greater risk of childhood glaucoma. Findings can vary from subtle iris hypoplasia to marked iris anomalies, and to marked polycoria and corectopia of Axenfeld-Reiger anomaly (Figure 2). Often included under this description are Peters anomaly (with corneal opacity) and aniridia (where rudimentary iris stump may lead to angle closure).
Figure 2. Infant with corectopia. Photo provided by Angela Chappell, Flinders University, Department of Ophthalmology.
Glaucoma is often described as occurring 50% of the time in anterior segment dysgenesis. However I think it is better to say it is 100% inevitable. The exact genotype can guide the age of onset, which could be during school years or in later decades. This knowledge underlies the importance of regular monitoring, at least yearly, which is well before the classic age for monitoring adult-onset glaucoma.
It is sometimes missed that the genes causing these ocular findings can have systemic effects. FOXC1, in particular, can have related sensorineural hearing loss, and cardiac anomalies, like large atrial septal defects. These related effects blur the classification line between ocular-only and systemic diseases associated with childhood glaucoma, like Marfan syndrome and Stickler syndrome. Lesser known groups of genes that contribute to anterior segment dysgenesis include TGFB4 and CPAMD8.
SECONDARY GLAUCOMAS OF CHILDHOOD
Secondary glaucomas of childhood are rare in a general optometric or ophthalmology practice. But in the setting of previous trauma, previous uveitis, and certainly previous cataract surgery, monitoring is essential.
A ‘syndrome-detecting mindset’ is essential for optometrists who take a particular interest in paediatric myopia management. In early onset myopia, anisomyopia, and progressive disease, it’s important to take baseline optic nerve imaging and check IOP at least yearly, particularly if myopic progression is occurring.
Referral to a paediatric ophthalmologist should be considered if Stickler vitreous phenotypes and angle anomalies are suspected or detected. Fortunately, genetic knowledge and the mainstreaming of genetic investigation is making identification of syndromic patients easier.2
Rebound tonometry e.g., the iCare Home tonometer (Icare, Finland), has made it easier to measure infant and early childhood intraocular pressure without the need for in-your-face proximity, larger devices, or topical anaesthesia. It is important to note that the newer, more precise iCare Home models e.g., the iCare-200 (Figure 3), may not be as helpful as the older iTAO model, when examining a relatively uncooperative child.
Figure 3. The iCare ic200 tonometer is suitable for patients of all ages.
Normal infant intraocular pressure is typically less than typical adult IOPs. One shoud expect readings within the 8–12mmHg range when using rebound tonometry for these patients.
MANAGEMENT OF CHILDHOOD ONSET GLAUCOMA
Once the clinical diagnosis is made, initial medical management is commenced, which frequently includes oral acetazolamide. Medical therapy may need to be intense, but will be temporary. Diamox is dosed by weight and made into a palatable oral form.
Medical therapy can maintain control of secondary glaucoma for some time, however beta-blocker eye drops can induce side effects of asthma or cough. It must be remembered that timolol is frequently prescribed in combination with other agents. Brimonidine is to be avoided for patients under the age of six as it crosses the blood brain barrier and frequently induces sedation.
In primary congenital glaucoma, attention quickly turns to surgical management. Angle surgery – traditionally an ab interno goniotomy or external approach with trabeculotomy – was the first line step to managing this form of glaucoma. In recent years, the iTrack device with augmented 360° trabeculotomy, has been performed with increasing success rates. All procedures on children under 12 months of age require specialised infant anaesthetic and recovery nursing care, which is limited to major paediatric centres.
On occasion, low dose transscleral cyclodiode laser can be used to assist with pressure control. Should initial surgery fail to control pressure, then more invasive surgery is required. This will usually involve a smaller plate glaucoma tube shunt for aggressive early onset disease. Careful post-operative flow control is needed as younger eyes are more susceptible to the ravages of hypotony. In slower onset childhood glaucoma, typical of slightly older infants and children with PCG, a trabeculectomy with adjuvant mitomycin C is preferred. This avoids the future risks of an implant, but will usually require several further short anaesthetics for suture removal and antifibrotic 5FU injection.
There is no established role for smaller, minimally invasive devices in primary congenital glaucoma. Limited studies, approved by the United States Food and Drug Administration, have been performed using Preserflo (Glaukos). These have demonstrated reduced success compared to older patients treated for POAG with the same device.
The degree of difficulty in all childhood glaucoma surgeries is increased by the heightened anxiety in children postoperatively, especially if sutures removal or anti-fibrotic agent administration is needed. There may be a need for repeated examination under anaesthetic.
Careful communication with parents and caregivers is essential. So too is the need for the whole care team – reception staff, orthoptists, anaesthetists, and recovery nursing staff – to build a strong rapport with the carers and patient, as this can make the journey less intimidating.
Outside the tertiary hospitals that treat congenital glaucoma, a team approach is required to ensure these patients receive the care needed. They are the ‘frequent-flyers’ of clinics, providing post-operative refractive and amblyopia care. Not infrequently, the disease itself, and surgery to remedy it, can leave children with significant irregular astigmatism and anisometropic refractive outcomes. Given their age and limits of cooperation, careful cycloplegic refraction may be an iterative process. Regular occlusive patching and weekly atropine penalisation are part of the treatment for many. Topical medications and monitoring of IOP is required, at least every four to six months. If more than one medication is needed, or a medication is required more than twice a day, it is likely that further surgery will be proposed.
Alongside the child’s glaucoma, the burden of other paediatric conditions needs consideration. Managing the impact of low vision on development and educational interactions necessitates a team approach involving paediatricians, GPs, and vision care professionals. More common paediatric conditions, like autism-spectrum disorder, speech delay, and gross motor delays can accompany vision loss, though not necessarily in greater frequency than expected in the population.
THE ROLE OF GENETICS
Primary congenital glaucoma is increasingly recognised as having a genetic basis. Although the proportion varies by ethnicity across population studies, genetic investigation is considered part of the work-up in this condition. The most commonly associated gene is CYP1B1, a cytochrome P450 enzyme thought to have a coordinating role in the developing trabecular meshwork.
We now know that other genes do contribute, and Flinders University Adelaide researchers are leading the world in gathering evidence of their effect.3 Broadly, genes can play a role in angiogenesis, anterior segment development, and connective tissue stability. Generally, as expected for a disease with major impact at a young age, these are large genetic disruptions, and usually recessively inherited. Identifying disruptive changes in these genes can contribute to a greater understanding of the milder variants of the same or similar genes. This will contribute to our knowledge about the polygenetic causes of adult-onset forms of glaucoma.
Referral of congenital glaucoma patients to clinical genetics services is important. This should take place soon after diagnosis to help parents think about recurrence risks in their future family planning. It is sensible to assess siblings and parents for glaucoma at least yearly.
SUMMARY
We have the tools to identify, treat, and manage the complications of childhood glaucoma. With a collaborative team approach, patients and their families can be best supported to understand and navigate this condition, maintaining vision and quality of life as much as possible. Eye care providers need to be alert to the clinical findings and the risks for developing glaucoma in childhood and early adulthood.
Dr Jonathan Ruddle is an ophthalmologist with advanced training in all aspects of glaucoma and cataract management. He graduated from medicine at Melbourne University in 1998 and undertook Ophthalmology training at the Royal Victorian Eye and Ear Hospital. After being awarded Fellowship of the Royal Australian and New Zealand College of Ophthalmologists in 2007 he undertook further advanced training in complex glaucoma and cataract surgery both in Melbourne and overseas at Moorfields Eye Hospital London.
Dr Ruddle has appointments at the Glaucoma and Genetics clinics of the Royal Victorian Eye and Ear Hospital and at the Royal Children’s Hospital. He has been invited to speak at national and international meetings in the management of challenging glaucoma.
References
1. Beck A., Chang T.C.P., Freedman S., Section 1: Definition, classification, differential diagnosis. In: Weinreb R.N., Grajewski A.L., Papadopoulos M., et al.,(eds.) World Glaucoma Association (WGA) Consensus Series 9 – Childhood Glaucoma. Amsterdam: Kugler Publications; 2013:3e10.
2. Knight L.S.W., Ridge B., Staffieri S.E., et al., Quality of life in children with glaucoma: a qualitative interview study in Australia. BMJ Open. 2022 Jul 0;12(7):e062754.
3. Knight L.S.W., Ruddle J.B., Taranath D.A., et al., Childhood and Early Onset Glaucoma Classification and Genetic Profile in a Large Australasian Disease Registry. Ophthalmology. 2021 Nov;128(11):1549-1560. doi: 10.1016/j.ophtha.2021.04.016. Epub 2021 Apr 20. PMID: 33892047.
