Nucci P (ed): Pediatric Cataract. Dev Ophthalmol. Basel, Karger, 2016, vol 57, pp 40–48 (DOI: 10.1159/000442500)
Incidence of and Risk Factors for Postoperative Glaucoma and Its Treatment in Paediatric Cataract Surgery Asimina Mataftsi 2nd Department of Ophthalmology, Paediatric Ophthalmology and Strabismus, Medical School, Aristotle University of Thessaloniki, ‘Papageorpiou’ Hospital, Thessaloniki, Greece
Abstract Postoperative glaucoma is perhaps the most feared complication after paediatric cataract surgery, as it is difficult to control. Paediatric glaucoma is also challenging to diagnose, and different definitions of glaucoma have led to a rather big range of reported incidences of this disease. It can occur soon after surgery, in which case it is usually closed-angle glaucoma, or it can have a late onset, even more than a decade after surgery, and its aetiopathogenesis remains unclear to this day. There is significant controversy as to what the risk factors are for developing it, especially regarding intraocular lens implantation. The vast majority of studies show that an earlier age at surgery confers a higher risk. Medical and surgical treatment of aphakic/pseudophakic glaucoma can be successful; however, management often requires repeated procedures with or without multiple medications, and the prognosis is guarded. The visual outcome depends on sufficient intraocular pressure control © 2016 S. Karger AG, Basel and management of concurrent amblyopia.
The reported incidence of postoperative glaucoma after paediatric cataract surgery varies largely among studies. This is because authors report their findings based on cohorts that differ largely. First, studies sometimes include various types of paediatric cataract, e.g. grouping infantile, developmental and traumatic cataracts, which are basically separate entities. Secondly, they often group together children with different ages at surgery. Third, some include and others exclude ocular comorbidities, such as persistent foetal vasculature (PFV) or microcornea. Fourth, the surgical technique; the type of implanted intraocular lens (IOL), if any; the site of IOL positioning (bag
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Incidence
Postoperative Glaucoma and Its Treatment in Paediatric Cataract Surgery
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versus sulcus); the postoperative medical regimen; etc., also vary considerably in different studies. Finally, and most importantly, the definition used for glaucoma diagnosis and the length of follow-up duration vary immensely among published reports. In addition, the incidence is sometimes calculated as a percentage of eyes and other times as a percentage of patients. A selection of studies reporting the incidence of postoperative glaucoma is shown in table 1. The incidence literally varies from 0 to 100%. Since glaucoma seems to be more prevalent in children operated on at a younger age, as will be detailed below, it would make sense to study this younger subgroup of patients separately. Even if there is no clear age cutoff above which glaucoma risk is significantly different, some authors recognise the first 6 or 12 months as bearing a significantly higher risk for postoperative glaucoma [17, 18, 28]; thus, infantile cataract surgery outcomes should perhaps not be merged with outcomes at older paediatric ages. However, this is not always the case, as authors sometimes do not report the percentage of infants in their large cohorts (table 1). The most important issue is perhaps the definition of glaucoma itself. It is sometimes only based on the measured intraocular pressure (IOP) being above a certain limit, maybe as a consequence of the majority of studies being retrospective, whereby the collection of data from notes is limited by the quality and quantity of the documented data. Some authors use the initiation of permanent antihypertensive medical treatment or the antiglaucomatous surgical treatment as the criterion for glaucoma occurrence, and this is probably a conservative approach that underestimates the true incidence to a certain extent. In a recent report, the World Glaucoma Association published a consensus on the definitions of glaucoma and suspected glaucoma in children (table 2) [29]. It is important that all clinical researchers use the same definition in the future, so that reported results can be compared, meta-analysed, etc., and thus useful conclusions can be drawn. This definition requires a vigilant and thorough clinical examination. When dealing with young children with limited cooperation or with amblyopic eyes with unsteady fixation or nystagmus, clinical examination can be truly challenging and may necessitate sedation or anaesthesia. Although not mentioned in the above definition, it is crucial to also measure and take into account the central corneal thickness (CCT) during IOP evaluation. It has been found that the CCT increases significantly postoperatively in pseudophakic eyes and even more so in aphakic eyes [30–34]. The pathophysiology of this change is not known. Eyes with infantile cataract that are not operated on do not have an increased CCT compared to normal control eyes, so it appears that the increased CCT is not related to the ocular dysgenesis, but rather to the changes that surgery causes in the eye. Another subtle point to make regarding this definition is that one has to differentiate glaucomatous ocular growth from the ocular growth expected at a very young age. Infantile eyes undergo rapid elongation, and this high rate of growth is altered by the aphakic or pseudophakic state [35, 36].
Table 1. Postoperative glaucoma incidence First author [Ref.], year
Mean age at surgery, years
Aphakic glaucoma cases/ aphakic cases
IOL glaucoma Infants, n cases/IOL cases
Number of years after surgery at glaucoma diagnosisa
Mean followup, years
Asrani [1], 2000
5.06
14/124 (11%)*
1/377 (0.26%)* 73
Not reported
3.9 for IOL 7.2 for aphakic
Astle [2], 2009
5.5
N/A
0/110, 0/150*
18
N/A
Not reported
Chak [3], 2008
Not reported
23/185 (12%)
4/90 (4%)
Not reported
1.34
7
Chen [4], 2006
1.83
150/258 (58%)
N/A
Not reported
Not reported
10.37
Comer [5], 2011
0.25
18/75 (24%)*
N/A
46
2.5
6.45
Egbert [6], 2006
Not reported
12/63 (19%)
N/A
Not reported
Not reported
15.1 (median)
Freedman [7], 2015
0.15
20/57 (18%)
9/56 (16%)
114
Not reported
4.8
Haargaard [8], 2008
Not reported
66/619 (10.6%)*
6/327 (1.8%)*
267
6.6
4.2
Khan [9], 2009
0.28
31/121 (25%), 55/210 (26%)*
N/A
121
4.6 ± 3.2
Not reported
Khan [10], 2010
0.63
N/A
0/31, 0/36*
31
N/A
5.58
Kirwan [11], 2010
0.25
25/77 (33%)*
7/67 (10%)*
110
0.75 ± 0.75
7.1
Lawrence [12], 2005
0.48
13/67 (19.4%)*
0/49
Not reported
1.28
2.7
Lim [13], 2012
4.58
12%
1%
Not reported
Not reported
7.45
Lundvall [14], 1999
0.25
13/83 (15.6%)*
N/A
57
Not reported
3
Lundvall [15], 2006
0.2
N/A
2/31 (6.45%)*
28
Not reported
3
Magnusson [16], 2000
0.37
17/146 (11.6%)*
1/1 (100%)*
Not reported
2.57
9.6
Mills [17], 1994
1.9
13/82 (15.8%)
N/A
Not reported
6.01
Not reported
Rabiah [18], 2004
2.9
118/570 (21%)*
N/A
Not reported
5.4 ± 3.1
9
Ruddle [19], 2013
3.15
31/101 (30.7%), 47/147 (32%)*
N/A
101
7.2 (2.0 – 9.5)
9.9
Sahin [20], 2013
0.6 for aphakic 3.9 for IOL
12/249 (4.8%)*
0/220 (0%)*
Not reported
0.79
5.1
Swamy [21], 2007
2.4
48/261 (18.4%)*
0/96 (0%)*
Not reported
4.9 ± 2.2
6.3
Tatham [22], 2010
4.33
2/59 (3.4%)*
0/41 (0%)*
29
11.6
6.4
Trivedi [23], 2006
Not reported
8/47 (17%)*
10/266 (3.8%)
Not reported
0.72 for IOL 7.7 for aphakic
Not reported
Urban [24], 2010
0.95
5/12 (41.6%)*
6/101 (5.9%)*
Not reported
3.2
6.2
Vishwanath [25], 2004
0.16
13/80 (16.2%)
N/A
80
Not reported
5
Watts [26], 2003
0.08
12/55 (22%)
N/A
55
8.9 ± 13.5
2.85
Wong [27], 2009
0.24
10/61 (16.4%)*
5/37 (13.5%)*
62
0.43
2.5
as mean ± standard deviation or median (interquartile range).* This result regards eyes, not cases. N/A = Not applicable.
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a Shown
Table 2. Glaucoma and glaucoma suspect definitions [29] Glaucoma
IOP >21 mm Hg plus at least one of the following: – optic disc change – corneal findings, e.g. Haab striae, oedema – ocular enlargement by progressive myopia or increased axial length – visual field defect consistent with glaucoma
Glaucoma suspect
– – – –
IOP >21 mm Hg on 2 separate occasions suspicious optic disc suspicious visual field increased corneal diameter or axial length with a normal IOP
The pathophysiology of postoperative glaucoma is unclear for both aphakic and pseudophakic eyes. It is tempting to assume that glaucoma could be the consequence of a dysgenesis of the iridocorneal angle that accompanies the dysgenesis of the lens. However, eyes with congenital cataract that are not operated on do not develop glaucoma, except for some eyes with PFV, a condition that per se predisposes one to glaucoma [37]. Along with PFV, other associated ocular anomalies have been shown to cause predisposition to postoperative glaucoma, including aniridia, microcornea/microphthalmia, and anterior segment developmental anomalies [16, 17, 38, 39]. In addition, there are systemic conditions that infer a higher risk, such as Lowe syndrome and congenital rubella syndrome [17, 40]. Ocular hypertension has been found to often precede the diagnosis of glaucoma [6, 7]. Both angle-closure and open-angle glaucoma have been described, the former being more likely to have an early onset [39]. However, in the majority of studies, gonioscopic findings are not reported, as most often they are not available, given the limited compliance for gonioscopy in a child [17, 39]. In most cases, aphakic glaucoma is reported to be open angle, with pupillary block being relatively infrequent [28, 34, 41, 42]. In a study of 65 patients with aphakic glaucoma, Walton [28] describes, in most cases, an open angle with acquired forward insertion of the iris over the trabecular meshwork in the absence of detectable chronic inflammation. The presence of significant residual lens tissue in 78% of patients and the need for secondary lens surgery in half of them are documented [28]. Kang et al. [39] report a closed-filtration-angle configuration in 10/33 eyes with postoperative glaucoma, while in the remaining 23 eyes, consistent gonioscopic findings, peripheral anterior synechiae, a poorly developed angle recess, translucent tissue overlying the meshwork, and areas of increased pigmentation or increased vasculature were present [39]. Histopathology in an enucleated eye confirmed incomplete development of the angle recess and showed a thickened hypercellular trabecular meshwork, with an indistinct Schlemm’s canal and scleral spur [39].
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Postulated mechanisms for postoperative glaucoma are many and diverse, including genetic predisposition; immaturity of the angle, which renders it more susceptible to surgical trauma; significant postoperative inflammation; perioperative complications; a steroid-induced mechanism; and finally, an interaction between retained lens material or the anterior vitreous with the developing angle [43]. Of all these, there is some evidence to support the last: many of the histopathological changes seen in trabecular meshwork cell culture after exposure to lens epithelial cells resemble alterations observed in primary open-angle glaucoma, and this implies a possible role for lens epithelial cells in the development of aphakic glaucoma [44]. This finding reveals a very exciting area for research. If confirmed, it would explain the higher risk for glaucoma in younger eyes, when the angle is still immature and under development, and the possibly higher risk for glaucoma in aphakic (versus pseudophakic) eyes. The influence of IOL implantation on the risk for glaucoma is perhaps the most debatable issue in infantile cataract. Some published studies suggest that implantation reduces this risk, while some suggest that it does not [1, 2, 27]. A population-based study on 165 infants identified a younger age at detection as the only independent risk factor for the development of glaucoma when assessed after 7 years of follow-up, while an association with aphakia existed in univariate but not multivariate analysis [3]. Recently, the Infant Aphakia Treatment Study, a prospective controlled trial randomising 114 infants 1â&#x20AC;&#x201C;6 months of age with unilateral cataract to either aphakia or pseudophakia, published 5-year results. The authors found no association between aphakia/IOL and the risk for postoperative glaucoma [7]. In contrast, an independent patient data meta-analysis that studied retrospective data on 470 infants 0â&#x20AC;&#x201C;12 months of age with unilateral or bilateral cataract found a significantly higher risk among aphakic eyes compared to pseudophakic eyes, with a median follow-up of 6 years [45]. These results should be interpreted with caution, given that each study has its own strengths and limitations. For now, it appears that the evidence is not clearly in favour of the presence or absence of an association. The influence of age at surgery on risk for postoperative glaucoma is a much less controversial issue. The vast majority of studies have found that the younger the age at surgery, the higher the risk, even among only infants (<12 months) [7, 19]. Studies so far present evidence for a number of thresholds: 4.5 months [23], 9 months [8, 21], 2.5 months [11], 3 months [46], 10 days [16], and 12 months [4, 17, 28]; thus, it is probably safest to say there is no proven cutoff above which the lowest risk exists. In a meta-analysis by Mataftsi et al. [45], additional intraocular procedures after cataract surgery were found to confer a higher risk for the development of glaucoma, and the association remained when other risk factors were adjusted for, i.e. this was an independent risk factor. This finding confirms a previous report by Rabiah [18] that found secondary membrane surgery as a predictor of glaucoma. The result implies that repeated episodes/an increased amount of surgical trauma to the angle or postoperative inflammation may eventually lead to glaucoma. Alternatively, it may be an additional indication that lens epithelial cell proliferation (significant enough to
require surgical treatment of visual axis opacification) is aetiopathologically associated with glaucoma. Unfortunately, no study exists that accounts for the (small) size of the eye, the anatomy of the iris and the angle, the surgeonâ&#x20AC;&#x2122;s experience, the gravity of the operative manoeuvres and the protracted surgical trauma, the use of perioperative steroids, etc. These factors may possibly play a role but are hard to quantify, standardise and study in adjusted groups.
Postoperative glaucoma after paediatric cataract surgery presents a dual challenge: timely detection and effective treatment, including amblyopia management. It is said to have the poorest visual acuity prognosis among all types of paediatric glaucoma, although management options have increased, and successful outcomes have become more common over the decades [47]. Medical treatment can sometimes prove sufficient in controlling the IOP, although surgery is necessary in many cases [5, 34, 42]. Although most ocular hypotensive eye drops that are used in adults are not licenced for use in children, they can be safely applied in children as well, with the significant exception of brimonidine [47, 48]. This alpha2 agonist can cause central nervous system depression, and it is contraindicated in children less than 2 years of age and even must be avoided in older toddlers [49]. Beta blockers, cholinergic agents (e.g. echothiophate iodide) [50], prostaglandin analogues (e.g. latanoprost) [51], and both topical and systemic carbonic anhydrase inhibitors [52, 53] have generally proven safe and effective in children, but the clinician must be aware of and promptly recognise potential side effects [48]. In pupillary block glaucoma, surgical or laser peripheral iridotomy and/or anterior vitrectomy are applied to relieve the block. Surgical treatment for aphakic/pseudophakic glaucoma includes goniosurgical (goniotomy, trabeculotomy), filtering (trabeculectomy with or without antimetabolites), cycloablative (cryocoagulation, diode laser photocoagulation, ab interno laser photocoagulation) and shunting procedures [34, 54, 55]. In many cases, more than one surgical procedure is required to control the IOP, with or without additional medication use. In many cases, these operations have dramatic complications, and the desirable IOP control may be delayed [56]. Varied success is reported for all surgical options above, with most published reports being retrospective, relatively small case series influenced by the experience and personal preferences of the authors. Goniotomy and/or trabeculotomy were found to be successful in 8 of the 14 eyes with aphakic glaucoma (57.1%) in a case series, with a mean number of angle procedures of 1.4 per eye [54]. Combined trabeculotomy/trabeculectomy with mitomycin C was successful in 34/41 eyes in a recently reported study [57]. Drainage tube implantation was the preferred primary operation for aphakic glaucoma at another cen-
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Treatment
tre, and ≥2 surgical procedures were required in 11/15 surgically treated eyes [5]. Varied surgical approaches were also used in another retrospective series, without a description of the indications for each type of intervention [11]. It is likely that postoperative aphakic or pseudophakic glaucoma encompasses different aetiologies (e.g. closed versus open-angle glaucoma), and it is possible that this condition may result from a combination of factors (e.g. anomalies/immaturity of the angle and significant surgical trauma). Better understanding of the aetiopathogenesis of glaucoma will help in the application of customised medical, and especially surgical, management in each case to optimise results. Finally, it is important to underscore the fact that the poor visual outcome in eyes with aphakic/pseudophakic glaucoma is often the result of amblyopia, so the clinician must remain vigilant to the recognition and treatment of this important element, in parallel with efforts to keep the IOP under sufficient control to avoid glaucomatous damage to the optic nerve [47].
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Asimina Mataftsi, MD, MRCOphth 2nd Department of Ophthalmology Medical School Aristotle University of Thessaloniki GR–56429 Thessaloniki (Greece) E-Mail mataftsi @ doctors.org.uk
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Nucci P (ed): Pediatric Cataract. Dev Ophthalmol. Basel, Karger, 2016, vol 57, pp 40–48 (DOI: 10.1159/000442500)
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