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ABSTRACT The paediatric glaucomas present some of the greatest clinical challenges. We review the advances in the management of the paediatric glaucomas, which have improved the outlook for
these patients and their families. These advances include improvements in diagnosis, investigations, anaesthetic techniques, medical, surgical, and laser therapies. INTRODUCTION Paediatric
glaucoma is a relatively rare, potentially blinding condition caused by elevated intraocular pressure (IOP). It is classified into primary, where there is a developmental anomaly of the
angle alone, and secondary, where outflow obstruction is due to an ocular or systemic condition.1 Primary congenital glaucoma (PCG) due to isolated trabeculodysgenesis is the commonest
glaucoma seen in infancy.2, 3 Conditions commonly causing secondary glaucoma include Axenfeld–Reiger Anomaly, Peters Anomaly, uveitis, aphakia, aniridia, and Sturge–Weber syndrome. The
management of children with glaucoma presents the ophthalmologist with some of the most anxious but at the same time incredibly rewarding periods in clinical practice. It is so challenging
that most cases are managed in tertiary institutions.4 The goal of preserving a lifetime of vision for these children involves early, prompt control of IOP, correction of ametropia and
rigorous amblyopia treatment. The control of IOP in PCG is primarily surgical with medical therapy playing a supportive role, whereas in secondary glaucomas, medical therapy is first line
except in congenital cases where surgery is often required to control IOP. Untreated or suboptimally treated the outcome of paediatric glaucoma is known to be poor.5, 6 However, over the
last 60 years, there has been a dramatic improvement in the prognosis of this disease following the introduction of new surgical techniques and the recognition of amblyopia as an important
cause of poor vision. The introduction of angle surgery revolutionised the prognosis of PCG. Goniotomy was first reported in children in 1942 by Barkan,7 followed by trabeculotomy in the
1960s independently described by both Smith8, 9 and Burian10, 11 and popularised by Harms and Dannheim.12 Subsequently, techniques widely used in adults such as trabeculectomy and drainage
implant surgery have increasingly played a role in refractory cases of paediatric glaucoma. There have been numerous recent advances in the management of paediatric glaucoma. Many have again
occurred in the field of surgery, but there also have been significant advances in medical therapy and investigations which will also be briefly discussed. INVESTIGATIONS The use of axial
length measurement in infants whose eyes are still vulnerable to the effects of IOP was recognised by Sampaolesi,13 who reported its value in making the diagnosis and by Buschmann and
Bluth,14 who described its significant role in determining progression. Subsequently, the routine use of ultrasound was established for both diagnosis and follow-up of infantile glaucoma.
More recently, the importance of pachymetry in the assessment of children with glaucoma has been highlighted, as evidence has become available regarding the role of central corneal thickness
in glaucoma.15, 16 There is evidence that children with aniridia have thickened but healthy corneas, which may have important implications regarding IOP measurements.17, 18 This emphasises
the fact that monitoring of children with glaucoma should not rely just on IOP, which is subject to many influences such as anaesthesia and corneal properties, but more importantly on
regular optic nerve examination. Children can also be examined when sleeping if adequate facilities are available in the clinic (Figure 1). MEDICAL THERAPY Medical therapy in paediatric
glaucoma often plays a supportive role. In PCG cases, preoperatively it may reduce IOP and allow the corneal oedema to clear and so improve visualisation of the angle at the time
goniosurgery. Postoperatively, it can be used as an adjunct to maximise IOP lowering. It also plays a role if surgery is very high risk or not possible due to medical problems where
anaesthesia poses a serious threat to life. In secondary glaucoma, it is often used as a first line therapy but in congenital or some infantile cases, surgery is often inevitable. Children
are usually not included in studies for the approval of glaucoma medication by regulatory agencies, but evidence has become available in the literature regarding their use in children. The
use of timolol in paediatric glaucoma patients has been extensively studied in comparison with other agents. Plasma timolol levels in children after 0.25% greatly exceed those in adults
after 0.5%, especially in infants19 and are presumed to increase the risk of side effects such as bronchospasm and bradycardia. In light of this, betaxolol (_β_1 selective antagonist) and
timolol gellan 0.25%, as an alternative because of less systemic absorption and the advantage of once a day dosing, have been widely prescribed in children. However, the recent introduction
of timolol 0.1% has been useful in neonates and infants due to its superior risk profile. Blotting off of excess drops and punctal occlusion and may also greatly reduce systemic absorption
and should be taught to parents.20 Topical carbonic anhydrase inhibitors are useful as second-line drugs, or when _β_-blockers are contraindicated. In a short randomised, controlled, double
masked, multicentre trial, dorzolamide was found to be well tolerated and effective for up to 3 months in children less than the age of 6 years.21 Similarly, topical dorzolamide was found to
significantly reduce mean intraocular pressure from baseline, but less so when compared with systemic acetazolamide (27 _vs_ 36%) in a paediatric glaucoma population.22 Furthermore, the use
of systemic acetazolamide was limited because of a significant incidence of systemic side effects. Brinzolamide tends to be better tolerated, as it is less irritant. However, care must be
taken with topical carbonic anhydrase inhibitors when corneal endothelial function is compromised. It is possible that latanoprost may be less efficacious in children both as a monotherapy
and in combination with other medications.23 There is evidence to suggest that it is less effective in Sturge–Weber patients24 and a decline in success over time occurs when used as
adjunctive therapy.25 However, more data are required in children. Parents should be advised about the possibility of longer, thicker hyperpigmented eyelashes and the potential for permanent
iris colour change, which has been reported in a 1-year-old child with blue–grey irides following 5.5 months of treatment.26 Its very long-term side effects are largely unknown. SURGERY
ANGLE SURGERY Angle surgery is the procedure of choice for PCG. The safety of goniotomy depends largely on adequate corneal clarity, but also on maintenance of a deep anterior chamber (AC)
to visualise the angle structures and minimise intraocular trauma. The introduction of viscoelastics27, 28, 29, 30 has contributed to the safety of goniotomy by providing a deep and stable
AC throughout the procedure, particularly at the extremes of the incision when distortion of the wound can lead to shallowing of the AC. However, they do increase the duration, complexity of
the procedure and put the patient at risk of postoperative IOP spikes if they are not thoroughly removed. Large lenses with a wide angle of view considerably improve the view during
goniotomy (Figure 2). In an attempt to avoid invasive intraocular surgery, photodisruptive goniotomy has been performed with Q-switched Nd:YAG laser, which is quick and relies less on
corneal clarity. Despite encouraging early results,31 it has not proven to be a useful tool for goniotomy. In an attempt to improve visualisation of the angle in the presence of a hazy
cornea, coaxial endoscopic goniotomy has been described in a case, which resulted in clearing of the cornea sufficiently enough to subsequently perform conventional goniotomy.32 Conventional
angle surgery incises 90–120° of the angle, but success is known to improve with repeat surgery in the non-operated part of the angle by intorting or extorting the eye. It is in this
context that the technique of suture trabeculotomy was described as an alternative to conventional angle surgery. It involves the use of 6/0 polypropylene suture to achieve a 360°
trabeculotomy and is claimed to be more successful along with avoiding some of the difficulties encountered with a trabeculotome, such as false passages.33, 34 However, success is not always
possible with a single incision and other technical difficulties along with severe hypotony35 and subretinal positioning of the suture have been reported. The use of a fine illuminated
fibre optic probe has been described, which may increase the ease and safety of this procedure. FILTERING SURGERY Trabeculectomy is the operation of choice in secondary paediatric glaucomas
and in PCG cases in whom angle surgery has failed, or when angle surgery is not possible because of limited experience. It may also be more appropriate when a very low target pressure is
required due to advanced disease or where the severity is associated with a poor prognosis, for example, corneal diameter greater than 14 mm. The main challenges in performing filtering
surgery in children relate to the fact that: (i) they are more prone to failure, due to a more aggressive healing response and thicker Tenon's capsule with its large reservoir of
fibroblasts and (ii) they are more prone to complications intra- and postoperatively, largely due to the anatomical reasons of a buphthalmic eye with its thin sclera and low scleral
rigidity. The former explains why the long-term success rates of an unenhanced trabeculectomy in children are poor.36, 37 Mitomycin-C (MMC) has been used in an attempt to improve surgical
success rates, but there is conflicting evidence in the literature as to its usefulness,38 due to the various definitions of success, age of patients and duration of follow-up. However, what
is not disputed is the association of antimetabolite trabeculectomies with thin avascular cystic blebs. These are known to be a major risk factor for chronic complications such as
potentially blinding bleb-related infections with a reported incidence as high as 17% in children.39 Chronic bleb-related complications are particularly significant in children due to their
considerable lifetime risk (Figure 3). Our recent understanding of the importance of trabeculectomy technique to bleb morphology (Figure 4), has led to a dramatic reduction in chronic
bleb-related complications.40 A number of modifications to the filtering technique have been described in achieving favourable bleb morphology.41 An ideal bleb is one which is elevated and
diffuse, without any restricting scar, the so-called ‘ring of steel’. A combination of the following three techniques is likely to achieve this: (i) fornix-based conjunctival flap,40 as it
minimises the chance of a posterior scar restricting aqueous diffusion, often seen following the posterior incision of limbal-based conjunctival surgery, (ii) large antimetabolite treatment
area,42 which results in a greater area for diffusion, and (iii) posterior flow encouraged through a large, scleral flap with short side incisions, with thoughtful placement of a combination
of fixed, adjustable and releasable sutures to avoid anterior limbal aqueous jets (Figure 5). Furthermore, the realisation that buphthalmic eyes are more prone to complications due to low
scleral rigidity and thin sclera has led to the intraoperative use of an anterior chamber maintainer on a three-way tap to minimise anterior chamber shallowing and the risk of intraoperative
choroidal effusions and suprachoroidal haemorrhage to which these eyes are particularly susceptible. It also allows one to judge flow through the scleral flap and place extra sutures for
tight closure to reduce the risk of postoperative hypotony (Figures 6, 7 and 8). DRAINAGE SURGERY Tube drainage surgery remains an important part of the therapeutic repertoire in paediatric
glaucoma as it offers the best chance of long-term IOP control in a small proportion of patients whose disease relentlessly progresses despite conventional surgical treatment. Furthermore,
it is indicated if future intraocular surgery such as cataract extraction is contemplated, as it is more likely to control IOP postoperatively than filtering surgery (Figure 9). The
threshold for drainage surgery in challenging refractory paediatric glaucoma cases has lowered over the years. The reasons being that results are more predictable and definitive than
cyclodiode treatment and possibly better than filtering surgery in infants.43 Furthermore, they allow the use of contact lenses in aphakia and the long-term risk of infection is
theoretically lower than that of trabeculectomy. There are no prospective, randomised trials comparing filtering surgery to drainage implants in children, and the retrospective data
currently published are contradictory.43, 44 The prevailing current opinion is that tubes are best implanted sooner rather than later in the hope of achieving early, definitive IOP control
and in doing so optimising long-term visual prognosis. With regards success, comparison of the available retrospective case series is difficult because of the varying criteria for success
and duration of follow up but certain conclusions can be drawn (i) success approximates 80% in the first year regardless of implant type, similar to adults (ii) success declines with
duration of follow up, again as in adults, and (iii) the definition of success invariably includes medical treatment as most patients require these to control IOP after surgery.38 Currently
there are no data available regarding the adjunctive use of MMC in paediatric implants, although smaller plates without antimetabolite, such as the single-plate Molteno, are much more likely
to encapsulate with poor pressure control (Figures 10 and 11). Although it may be argued that drainage devices offer the most effective long-term treatment for IOP control in refractory
cases, they are associated with significant complication rates. The problems usually relate to hypotony or to the tube itself (eg occlusion, retraction, corneal, or iris touch) and can
result in visual loss. Buphthalmic eyes are especially prone to hypotony-related complications because reduced scleral rigidity allows leakage around the tube at its entry site, making
subsequent problems such as choroidal effusions and suprachoroidal haemorrhage more likely, even with the use of valved implants. There are a number of modifications that can minimise intra-
and postoperative hypotony: an anterior chamber maintainer (Lewicky cannula); a relatively long and ‘snug’ limbal tunnel incision with a 25 gauge needle; the use of an intraluminal suture
(3/0 Supramid); an external ligating suture (6/0 vicryl) with a venting ‘Sherwood’ slit45 and viscoelastic or intraocular gases such as 20% C3F8 in the anterior chamber if required. To
minimise the complications related to the tube itself, care should be taken to avoid: exposure by constructing a scleral tunnel 1–2 mm from the limbus; corneal-tube touch by directing the
25G needle away from the cornea, close and parallel to iris once the AC is entered; tube occlusion from iris by beveling the tube and having the bevel face the cornea and tube retraction by
leaving at least a 2 mm length of tube in the AC. Vitreous occlusion in aphakes is prevented by performing a thorough anterior vitrectomy in all cases. If viscoelastics are used and left in
the eye, sterile air is a useful adjunct to reduce postoperative pressure spikes (Figure 12). CYCLODESTRUCTION A number of cyclodestructive procedures have been described for use in: blind
painful eyes; eyes with poor visual potential, or in whom surgery either has a poor prognosis, or is technically impossible (eg severely scarred conjunctiva). Contact trans-scleral
semi-conductor diode laser (810 nm) has become increasingly more popular than Nd:YAG laser and cyclocryotherapy as a method of ciliary body ablation. Apart from being compact and portable,
diode laser has the advantageous properties of improved penetration and transmission with conjunctival and scleral compression, and more selective absorption by the ciliary body, leading to
coagulative necrosis. As a result, it is better tolerated and less complications have been reported than with Nd:YAG laser and cyclocryotherapy.46, 47, 48, 49 It has a satisfactory pressure
lowering effect in the short term with an apparently low risk of serious complications (including phthisis) and a rapid rehabilitation.48, 49 However, the disadvantages include the need to
be repeated to achieve and maintain IOP control, which probably increases the likelihood of phthisis, and also the requirement of ongoing medical treatment post laser. It is important to use
transillumination in buphthalmic eyes to avoid inadvertent treatment of the iris base as the normal anatomical landmarks are unreliable (Figure 13). The use of endoscopic diode laser
cyclophotocoagulation has been reported in a series of 36 eyes, with a cumulative success rate of 43% similar to that of diode and Nd:YAG laser but with a lower retreatment rate.50 The
biggest drawback of this technique is the intraocular approach, which may increase the risk of infection, cataract formation and other significant surgical complications such as retinal
detachment in aphakic patients. Other considerations with cyclodestructive procedures are predisposing the eye to hypotony from chronic aqueous hyposecretion if future implant surgery is
required,49 and possibly to long-term fibrotic failure from the destruction of the blood aqueous barrier and subsequent release of inflammatory mediators bathing the drainage site.
CONCLUSION There have been many advances in the management of the paediatric glaucomas particularly in the field of surgery, which have significantly improved the management of these often
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ACKNOWLEDGEMENTS Our paediatric research is supported by the Guide Dogs for the blind, Fight for Sight, the International Glaucoma Association, Moorfields Trustees, the Daily Telegraph
appeal, the Haymans Trust, Ron and Liora Moskovitz, and the Helen Hamlyn Trust in memory of Paul Hamlyn. This work was also supported by the Department of Health's National Institute
for Health Biomedical Research Centre at Moorfields Eye Hospital and the UCL Institute of Ophthalmology and the UK Ophthalmic Research Network. The views expressed in this publication are
those of the authors and not necessarily those of the Department of Health. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Paediatric Glaucoma Unit, Moorfields Eye Hospital, London, UK M
Papadopoulos * National Institutes for Health Research Biomedical Research Centre (Ophthalmology), at Moorfields Eye Hospital and the UCL Institute of Ophthalmology, Paediatric Glaucoma Unit
and ORB (Ocular Repair and Regeneration Biology), London, UK P T Khaw Authors * M Papadopoulos View author publications You can also search for this author inPubMed Google Scholar * P T
Khaw View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to M Papadopoulos. RIGHTS AND PERMISSIONS Reprints and
permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Papadopoulos, M., Khaw, P. Advances in the management of paediatric glaucoma. _Eye_ 21, 1319–1325 (2007).
https://doi.org/10.1038/sj.eye.6702850 Download citation * Received: 12 March 2007 * Revised: 31 March 2007 * Accepted: 31 March 2007 * Published: 04 October 2007 * Issue Date: October 2007
* DOI: https://doi.org/10.1038/sj.eye.6702850 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not
currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * paediatric glaucoma * goniotomy * trabeculotomy *
trabeculectomy * tube surgery