Consensus 9

9^th Consensus Meeting: Childhood Glaucoma

Vancouver, Canada, July 16, 2013

Edited by: R.N. Weinreb, A. Grajewski, M. Papadopoulos, J. Grigg and S. Freedman
2013. Many photos and figures. Hardbound.
ISBN-10: 90 6299 239 0.
ISBN-13: 978 90 6299 239 3
Published by: Kugler Publications.
Click here for more information on all publications in the Consensus series.

See meeting photos

Summary Consensus Points

• Definition, classification, differential diagnosis
• Establishing the diagnosis and determining glaucoma progression
• Genetics
• Medications
• Glaucoma surgery in children
• Primary congenital glaucoma and juvenile open-angle glaucoma
• Glaucoma associated with non-acquired ocular anomalies
• Glaucoma associated with non-acquired systemic disease or syndrome
• Glaucoma associated with acquired conditions
• Glaucoma following cataract surgery

Section 1 – Definition, classification, differential diagnosis

1. Childhood glaucoma is intraocular pressure (IOP) related damage to the eye.
   Comment: In addition to the IOP, optic disc appearance and visual fields, the definition of glaucoma also reflects the effect of IOP on other ocular structures in infancy.
2. The interpretation of IOP measurement in infants and young children, especially during examination under anesthesia, can potentially be affected by many factors.
   Comment: Other signs of glaucoma in infants and young children, such as ocular enlargement, Haab striae and increased cup-to-disc ratio, may be more important than the IOP value in the assessment.
3. Childhood glaucoma is classified as primary or secondary. Secondary childhood glaucoma is further classified according to whether the condition is acquired after birth or is present at birth (non-acquired). Non-acquired childhood glaucoma is categorized according to whether the signs are mainly ocular or systemic.
   Comment: Terms such as ‘developmental’, ‘congenital’ or ‘infantile’ glaucoma lack clear definition and their use is to be discouraged.
4. A child should not be labeled as having glaucoma or subjected to surgical treatment unless one is reasonably sure of the diagnosis and has excluded other conditions that may mimic glaucoma.

Section 2 – Establishing the diagnosis and determining glaucoma progression

1. Prompt diagnosis of childhood glaucoma and appropriate prompt treatment can minimize the degree of visual impairment.
   Comment: Examination under anesthesia or sedation may be appropriate to make the diagnosis, perform surgery or plan further treatment.
2. A child should not be labeled as having glaucoma or subjected to surgical treatment unless one is reasonably sure of the diagnosis and has excluded other conditions that may mimic glaucoma.
   Comment: If doubt exists about the diagnosis or evidence of progression cannot be determined, then appropriately timed follow-up or examination under anesthesia or sedation is advisable.
   Comment: Children should be encouraged onto the slit lamp for more accurate evaluation [intraocular pressure (IOP) measurement and optic disc assessment] when it appears this may be possible.
3. Glaucoma in children is characterized by the presence of elevated IOP and characteristic optic disc cupping. In addition to these features, glaucoma in infancy is associated with ocular enlargement, buphthalmos.
   Comment: IOP measurement and optic disc appearance are fundamental features of the examination throughout the life of a child with glaucoma. In an infant whose eye is still vulnerable to other effects of elevated IOP, proxies of persistent elevated IOP (enlarging corneal diameter, increasing axial length and progressive myopia) also need to be taken into consideration and regularly assessed.
   Comment: In children, the conclusion with regard to the diagnosis or progression of glaucoma must be based on the overall clinical findings and investigation results.
4. IOP measurement in infancy and early childhood can be influenced by many factors so is often unreliable when used in diagnosis and management.
5. IOP response to anesthetic agents is unpredictable. All inhaled agents lower IOP, sometimes rapidly and profoundly.
   Comment: Chloral hydrate, ketamine and midazolam appear not to lower IOP.
   Comment: Use the same anesthetic for serial examinations.
6. Increasing corneal diameter is the hallmark of all forms of glaucoma in infancy and early childhood.
   Comment: Corneal enlargement due to elevated IOP usually occurs before three years of age. Serial corneal diameter measurements are useful in establishing the diagnosis and in the monitoring of progression of glaucoma up to the age of three years.
   Comment: Central corneal thickness (CCT) should not be used to adjust IOP measurements as its role in childhood tonometry remains to be determined.
7. Gonioscopy is crucial in making the correct diagnosis and for planning surgical treatment. It should be performed at least once when possible.
8. Optic disc appearance is an important and sensitive parameter for both diagnosis and determination of progression in childhood glaucoma.
   Comment: Optic nerve size, the cup-disc ratio, focal areas of rim loss, and nerve fiber layer defects should be documented, preferably through a large pupil.
   Comment: A magnified binocular view is preferable, so attempt to examine a child on the slit lamp as soon as they are cooperative.
   Comment: Documenting the appearance of the disc at baseline and follow-up is desirable in determining both diagnosis and response to treatment.
   Comment: Cupping reversal is common in successfully-treated childhood glaucoma.
   Comment: Automated optic nerve imaging (e.g., OCT) is limited by the lack of normative data and portability of the devices.
9. Rapid changes in refractive status and axial length (AL) determination are helpful in both diagnosing the disease and determining response to treatment while the sclera remains vulnerable to the effects of elevated IOP.
   Comment: AL outside normal limits is strongly suggestive of glaucoma.
   Comment: Continued enlargement of AL beyond the normal range suggests inadequately-treated glaucoma.
   Comment: Progressive myopia is additional evidence of glaucoma progression.
10. Assessment of the visual field in children can be useful but is challenging.
    Comment: It may be helpful to use the shortest possible test (e.g., program 24-2 Sita Fast).
    Comment: Repeat visual fields to confirm deficits. If repeated testing shows consistent findings, the measurements are probably valid.
    Comment: Although there is no normative database for children, age correction of the mean deviation for standard automated perimetry is small (0.7 db/decade). Moreover, useful metrics, such as pattern standard deviation, glaucoma hemifield test and glaucoma change probability, are largely unaffected by age.

Section 3 – Genetics

1. Genetic evaluation of childhood glaucoma is especially important in those types of glaucoma when genotype phenotype correlations are known to exist.
   Comment: The results of these tests may be important in counseling, prognosis and management.
2. There is a known correlation between primary congenital glaucoma (PCG) and mutations in the CYP1B1 gene.
   Comment: Performing carrier testing for at risk relatives is possible if both disease causing alleles of an affected family member have been identified.
3. Families affected by autosomal dominant juvenile open angle glaucoma (JOAG) have been found to have mutations in the MYOC gene.
   Comment: Genetic screening and genetic counseling could be considered in these patients to help diagnose pre-symptomatic cases among first and second degree relatives of these patients.
4. Axenfeld-Rieger anomaly and syndrome have been associated with PITX2 and FOXC1 mutations.
   Comment: PITX2 mutations are more likely to be associated with systemic findings, while the risk of glaucoma is increased with FOXC1 duplications and PITX2 mutations.
   Comment: Prospective parents may consider genetic counseling for risk calculation.
5. Aniridia is usually inherited in an autosomal-dominant fashion with high penetrance and variable expressivity, and it is almost exclusively caused by PAX6 mutations.
   Comment: A child with sporadic aniridia should have ultrasound surveillance for Wilms tumor unless genetic testing rules out a microdeletion involving the Wilms tumor gene.
6. The LTBP2 mutations seem to be involved in complex ocular phenotypes including ectopia lentis, megalocornea (unrelated to elevated intraocular pressure), microspherophakia and associated secondary glaucoma.
7. To optimize genetic counseling for families, accurate clinical ophthalmic diagnosis is critical.
   Comment: Marked variation in penetrance and expression in primary and secondary childhood glaucomas exist, so parents and siblings of an affected child should be examined to provide maximally accurate phenotypic diagnoses for the clinical geneticist.
8. General pediatric assessment forms an important part of the management for children with glaucoma and can greatly assist in identifying systemic associations and initiating early management.
9. Genetics review plays a number of important roles including confirming or identifying syndromic diagnoses, recurrence risk assessment, genetic diagnosis, interpretation of molecular data, and reproductive counseling where this may be requested by the family after appropriate genetic counseling.

Section 4 – Medications

1. Medications alone rarely show sustained efficacy as primary treatment for glaucoma in infants and young children, especially in primary congenital glaucoma (PCG).
   Comment: Medical therapy is frequently needed as temporizing intraocular pressure (IOP) lowering treatment before surgery or as adjuvant therapy after partially successful surgical procedures in childhood glaucoma.
   Comment: IOP-reducing medication may help reduce corneal edema prior to surgery for childhood glaucoma.
   Comment: Medical therapy should be considered first-line for some cases of childhood glaucoma (e.g., uveitis-related, glaucoma after cataract removal).
2. Childhood glaucomas are heterogeneous in their causation as well as in their responses to different glaucoma medications.
3. Systemic pharmocokinetics for glaucoma medications are different in children than in adults.
   Comment: Systemic absorption can be significant and may be reduced by advising parents to close the lids (if possible), remove excess periocular liquid and perform naso-lacrimal occlusion.
   Comment: Use minimum frequency and concentration to achieve target IOP.
4. Potentially serious or fatal systemic adverse reactions which are rarely seen in adults may occur in young children after exposure to glaucoma medications.
   Comment: Adverse side effects may manifest atypically in children (e.g., nocturnal cough with beta blockers rather than wheeze with reactive airways).
   Comment: Brimonidine should be avoided in young children.
   Comment: Children are more vulnerable to adverse effects of medications as they may be unable to verbalize symptoms and parents may not readily recognize them.
   Comment: Parents must be informed of the potential side effects.
5. Compliance and adherence issues are greater and more complex in children due to their dependence on caregivers or parents, possible lack of cooperation in the administration of treatment, as well as concurrent medical conditions that may complicate medical therapy.
6. Target pressure must be chosen and reassessed with all available information concerning whether glaucoma is adequately controlled.
   Comment: Limitations on ability to perform structural and functional testing of optic nerve make verification of glaucoma control more difficult in children.
7. Consider surgery when medical treatment fails to control glaucoma.
   Comment: Glaucoma therapy in children has to be individualized, especially in situations where the risk of surgery outweighs the benefits of continuing medical therapy.

Section 5 – Glaucoma surgery in children

1. Surgery is a critical component of the management of childhood glaucoma.
   Comment: It is important to prepare patients and parents or caregivers for lifelong follow-up and possible future surgeries.
2. Glaucoma surgery should preferably be performed by a trained surgeon in centers where there is sufficient volume to ensure surgical experience and skill, and safe anesthesia.
   Comment: A long-term surgical strategy including choice of procedures should be based on training, experience, logistics, and surgeon’s preference.
   Comment: The first chance for surgery is often the best chance, and it is important to choose the most appropriate operation.
3. Glaucoma surgery in children is more challenging than in adults with a higher failure and complication rate than in adults.
4. Angle surgery (goniotomy and trabeculotomy – conventional or circumferential) is the procedure of choice for primary congenital glaucoma with the exact choice dictated by corneal clarity and the surgeon’s experience and preference.
   Comment: Angle surgery success rates for secondary childhood glaucomas are generally not as good as for primary congenital glaucoma (PCG) with certain exceptions [e.g., glaucoma with acquired condition (uveitis) in juvenile idiopathic arthritis (JIA)].
5. Trabeculectomy, when performed by experienced childhood glaucoma surgeons, can be associated with good outcomes in appropriate cases.
   Comment: Anti-scarring agents and other adjunctive techniques may be beneficial.
6. Glaucoma drainage devices (GDD) may offer the most effective long-term intraocular pressure (IOP) control in many childhood glaucomas especially those that are refractory to other surgical treatment.
   Comment: There is no prospective evidence that anti-scarring agents influence drainage device outcomes.
7. Cyclophotocoagulation with the diode laser has limited long-term success and often requires re-treatment and the continuation of medications.
8. Other glaucoma procedures advocated in children for the treatment of glaucoma have not been widely adopted either because of the technical challenges in buphthalmic eyes or because they are yet to be proven efficacious or safe in children.
9. Concurrent with glaucoma therapy, visual development needs to be evaluated and optimized with ametropic correction and amblyopia therapy.
10. With childhood glaucoma surgery, one needs carefully to consider the risks and benefits of each intervention, especially in refractory cases when the fellow eye is healthier, and in only eyes.
    Comment: Whenever possible, the assent of the child should be sought when making these difficult decisions.

Section 6 – Primary congenital glaucoma and juvenile open-angle glaucoma

1. Primary congenital glaucoma (PCG) is the most common non-sydromic glaucoma in infancy and is classified according to onset of signs. Its worldwide incidence is variable and influenced by consanguinity.
2. PCG is usually inherited in an autosomal recessive manner, with a family history reported in 10-40% of cases and is more common in consanguineous populations.
   Comment: Mutations in the CYP1B1 gene have been identified and show variable expressivity and phenotypes.
   Comment: Clinical screening of current and future siblings is essential if there is parental consanguinity.
3. The pathogenesis of PCG remains uncertain but the immature angle appearance seen clinically is thought to result from the arrested maturation of tissues derived from cranial neural crest cells.
4. PCG is a surgical condition and the surgical procedure of choice is usually angle surgery (goniotomy or trabeculotomy) with high rates of success reported for both in favorable cases and after multiple procedures.
   Comment: Combined trabeculotomy with trabeculectomy as an initial procedure is suggested by some to be more successful than either procedure performed alone in certain populations. There are no supporting prospective comparisons in the literature.
5. Once angle surgery fails, the next procedure of choice is either trabeculectomy or a glaucoma drainage device.
6. Juvenile open-angle glaucoma (JOAG) is a relatively rare form of childhood glaucoma usually presenting after the age of four years, with a normal angle appearance and no signs of other ocular anomalies or systemic disease.
7. Depending on age, medical therapy is the first-line treatment for JOAG, although surgery is often required.
8. Evidence remains weak for the optimum first-line surgical intervention for JOAG.

Section 7 – Glaucoma associated with non-acquired ocular anomalies

1. Children who have non-acquired ocular anomalies often have systemic conditions that require pediatric evaluation and/or treatment.
2. Many non-acquired ocular anomalies are genetic in nature.
   Comment: Screening of family members in such cases and genetic counseling is indicated.
3. Glaucoma related to non-acquired ocular anomalies may be present at birth or may develop over time, so regular lifelong monitoring is necessary.
4. Before glaucoma develops, one should consider treating elevated intraocular pressure (IOP) associated with non-acquired ocular anomalies (secondary ocular hypertension).
5. Infantile onset of glaucoma related to non-acquired ocular anomalies is associated with buphthalmos and the risk of Descemet membrane breaks.
6. Medical treatment is usually first-line, but surgery is often required early for congenital/infantile presentations and should not be delayed.
   Comment: Angle surgery in infants may be effective although the results are usually not as good as for primary congenital glaucoma (PCG).
   Comment: Often trabeculectomy with anti-scarring agents or primary tube surgery is necessary for IOP control.
   Comment: Cyclodestruction may be considered after faiIed trabeculectomy or tube surgery.
7. There is considerable phenotypic variability associated with genetic mutations recognized in children with non-acquired ocular anomalies.
8. Axenfeld-Rieger (AR) anomaly is recognized now to represent a spectrum of disease previously referred to as Axenfeld anomaly and Rieger anomaly. Axenfeld-Rieger syndrome includes the ocular fi ndings of Axenfeld-Rieger anomaly with the addition of systemic abnormalities.
   Comment: Examination of family members including gonioscopy is important to determine whether the patient is part of a larger pedigree or a new case.
9. Peters anomaly is usually seen as an isolated ocular disorder but can be associated with systemic abnormalities of neural crest origin and is referred to as Peters plus syndrome.
   Comment: It is important to exclude the presence of systemic involvement and when it is present, to co-manage it with a pediatrician.
   Comment: Assessing for glaucoma can be challenging as typical IOP measurement over the central cornea may be inaccurate and the optic discs may not be visible. Measure the IOP in a clear area of cornea if possible.
10. Aniridia is commonly associated with glaucoma and is due to both open- and closed-angle mechanisms.
    Comment: Children with sporadic aniridia should be screened for Wilms tumor.
11. Management of persistent fetal vasculature can be challenging because of the heterogeneity of clinical presentation.
    Comment: Surgical treatment is aimed towards obtaining useful vision and preventing or treating secondary complications such as glaucoma.

Section 8 – Glaucoma associated with non-acquired systemic disease or syndrome

1. Syndromes with system anomalies or systemic diseases that are present at birth can be associated with ocular signs that include glaucoma.
   Comment: Patients should be regularly monitored for glaucoma throughout life and elevated intraocular pressure (IOP) treated, should it occur.
   Comment: Patients also should be assessed for systemic manifestations of their disease.
2. Sturge-Weber syndrome (SWS) is commonly associated with glaucoma.
   Comment: Periocular port-wine marks are associated with ipsilateral glaucoma. Lid involvement and/or episcleral capillary vascular malformation appear to further increase the risk of glaucoma.
   Comment: Choroidal hemangioma increases the risk of serous choroidal effusion and suprachoroidal hemorrhage with surgery, especially if the IOP drops precipitously or hypotony develops. Modifications to the surgical technique must be employed to minimize risk of hypotony.
   Comment: Patients should be assessed, perhaps including neuroimaging, for other manifestations of SWS.
3. Neurofibromatosis (NF1) is uncommonly associated with glaucoma.
   Comment: Optic pathway gliomas affect 12-15% of patients with neurofibromatosis and can present with decreased vision distinct from glaucoma.
4. Ectopia Lentis (EL) can present as an isolated ocular anomaly or be associated with other ocular or systemic findings.
   Comment: Patients with EL are at risk of acute pupillary block.
   Comment: All patients without a proven or obvious cause of EL should be tested for homocystinura by urine analysis and investigated for blood homocyteine levels prior to any anesthesia or sedation because of life-threatening vascular risks.
   Comment: Patients with Marfan syndrome should have echocardiography and cardiology consultation prior to surgery.
5. Maintain close follow-up for infants with known or suspected congenital rubella, since glaucoma signs might be less evident at birth in some cases.
   Comment: Rubella keratitis should be differentiated from corneal findings associated with IOP related corneal edema.

Section 9 – Glaucoma associated with acquired conditions

1. Managing uveitic glaucoma in children is challenging. The control of intraocular inflammation with adequate immunosuppression, topical and/or systemic agents, is a crucial part of management.
   Comment: Hypotony is a particular concern with surgery and modifications to the surgical technique must be employed to minimize its risk.
2. Traumatic glaucoma pathogenesis is multifactorial.
   Comment: Patients with sickle cell disease (not trait) are at higher risk for rebleed and are likely to develop glaucomatous optic nerve damage, even with only moderately raised intraocular pressure (IOP).
   Comment: Management is aimed at controlling IOP and minimizing damage to the cornea and optic nerve. Consider surgical intervention with sustained elevated IOP > 30 mmHg unresponsive to maximum medical therapy or if corneal staining is present.
3. Steroid-induced elevated IOP is not uncommon and may be severe in children treated with ocular and systemic corticosteroids .
   Comment: Consider discontinuing the corticosteroid if possible or switching to a steroid sparing agent to ensure underlying disease control, which takes priority.
   Comment: IOP elevation may persist for months, years or even become permanent, requiring medical or surgical intervention.
4. Glaucoma secondary to intraocular tumors in children is a relatively rare event.
   Comment: Patients can be symptomatic with acute glaucoma due to the fast growth of the tumor, or symptom free in the case of a progressive, slow growing tumor.
   Comment: In cases of unexplained glaucoma, the possibility of an intraocular tumor should be considered, especially when a child presents with a severe chronic uveitis associated with high IOP.
   Comment: Incisional surgical intervention to lower IOP is contra-indicated for glaucoma secondary to malignant ocular lesions.
5. The causes of retinopathy of prematurity (ROP) induced glaucoma are multifactorial in nature but largely due to secondary angle closure.
   Comment: Glaucoma may develop years or decades later in patients with treated or untreated Stage-4 or -5 ROP, so long-term surveillance is warranted.
   Comment: IOP elevation may follow laser therapy for threshold ROP.

Section 10 – Glaucoma following cataract surgery

1. Glaucoma following cataract surgery is that which occurs after pediatric cataract removal of either congenital idiopathic cataract, cataract associated with ocular or systemic syndromes and acquired cataract.
2. Glaucoma can occur in aphakic and pseudophakic eyes.
3. Young age at the time of cataract surgery and microcornea increase the risk of glaucoma.
4. Glaucoma usually occurs in eyes with open angles but angle closure can occur, and it is important to elucidate the underlying mechanism when possible (e.g., by gonioscopy).
5. The risk of glaucoma following cataract surgery in children is lifelong, so regular monitoring is necessary.
6. Medical intraocular pressure (IOP) lowering therapy is usually first line treatment for glaucoma following cataract surgery. When medical therapy fails, surgical therapy is indicated but there is no consensus on the preferred approach.