Childhood Glaucoma: An Overview: Parul Singh, Yogesh Kumar, Manoj Tyagi, Krishna Kuldeep, Parmeshwari Das Sharma
Childhood Glaucoma: An Overview: Parul Singh, Yogesh Kumar, Manoj Tyagi, Krishna Kuldeep, Parmeshwari Das Sharma
Childhood Glaucoma: An Overview: Parul Singh, Yogesh Kumar, Manoj Tyagi, Krishna Kuldeep, Parmeshwari Das Sharma
ABSTRACT
Several types of childhood glaucoma exist, and the terminology is based on the time of onset of disease and its potential
cause. Though childhood glaucoma occurs less commonly than adults but can lead to permanent visual damage due to
amblyopia, optic neuropathy or refractive error. A detailed evaluation should be done to establish diagnosis. Medical
therapy has a limited role and surgery remains main modality for treatment. Childhood glaucoma is a treatable disease,
if early diagnosis is established and therapeutic intervention done in time. In children with low vision efforts should be
there to maintain residual vision and visual rehabilitation with low vision aids should be done.
Keywords: Childhood Glaucoma; Goniotomy; Trabeculotomy
1. Introduction
Glaucoma is less common in children than in adults. Although glaucoma can lead to permanent visual damage at
any age, the consequences of the disease are more often
severe in children due to additional damage that can
happen to the developing visual system. Associated amblyopia and secondary refractive errors are common.
Primary congenital glaucoma (PCG) is hereditary childhood glaucoma secondary to abnormal development of
the filtration angle. Nonetheless, most ophthalmologists
usually encounter the wide range of secondary forms of
glaucoma in this age group. Glaucoma surgery has drastically improved the visual prognosis of children afflicted
with glaucoma. However, late diagnosis of the condition
can result in permanent and severe visual morbidity. Its
affliction of young children makes glaucoma control a
life-long goal requiring motivation and perseverance by
patients, their parents and doctors. This article is intended to provide an overview of the disease at genetic
levels, newer technological tools assisting in diagnosis,
IOP lowering medications and refined surgical techniques.
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2. Epidemiology
Primary congenital glaucoma is hereditary with a variable incidence in different populations, but an overall
occurrence of 1 in 10,000 births is seen [2]. A greater
incidence occurs in populations with higher rates of consanguinity [3,4]. Boys are more commonly affected in
United States and Europe with boys to girls ratio of 3:2.
Whereas, in Japan more girls are seen having this condition [5,6]. The majority (about 75%) of PCG cases are
bilateral and asymmetric expression should be suspected
in clinically apparent unilateral cases. More than 80%
patients present within the first year of life, with 25%
diagnosed in the neonatal period and 60% within the first
6 months of life [7].
3. Genetics
The majority of PCG cases are sporadic but 10% - 40%
are familial with frequent association with consanguinity
[8]. In the most familial cases, transmission is autosomal
recessive with variable expression and penetrance of
40% - 100% [8].
Genetic heterogenicity of PCG confirmed by linkage
studies explain discrepancies like unequal sex distribution, lower than expected number of affected siblings in
familial cases, and transmission of the disease to successsive generations [8]. Three loci for PCG have been found
[8-10]. The initial locus on chromosome 2p21 (GLC3A)
was described in 1995 by Sarfarazi et al. who identified
significant genetic linkage to this region in 11 of 17 turkish families [8,11]. Genetic heterogenicity was confirmed
when a second locus on chromosome 1p36 (GLC3B) was
found [9]. Genetic family analysis identified a third locus
GLC3C on chromosome 14q24.3 [10]. Although three
chromosomal loci have been linked to PCG, only
CYP1B1 in locus GLC3A has been identified [12]. Mutations in these genes have been described as the predominant cause of PCG in Turkish and Saudi arabian
families [13]. It has been reported that 87% of familial
and 27% sporadic case are due to mutation in this gene
[8]. Approximately 45 mutations of this gene have been
identified and include deletion, insertion, point mutation,
mis-sense, non-sense, frameshift and terminator mutation
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4. Pathogenesis
The exact mechanism involved in pathophysiology of
primary infantile glaucoma is not known. One theory
said that a pathologic membrane (known as Barkans
membrane) [19] covered and blocked the trabecular
meshwork in primary infantile glaucoma. Clinical and
histopathologic observations of the anterior chamber in
infantile glaucoma have revealed that the anatomic relationship between the iris, trabecular meshwork and
ciliary body are immature. The principal defect in primary infantile glaucoma is a failure of one or more steps
in the normal development of the anterior chamber angle.
As the genes associated with primary infantile glaucoma are characterized further and the physiological or
developmental role of the proteins they encode become
better understood; the molecular, cellular and embryological pathophysiology of this rare disorder will become
clear [12].
Among the secondary glaucomas of childhood, the
underlying pathophysiology is as varied as that in adults.
Occurrence at or shortly after birth indicates a profound
developmental abnormality of anterior chamber angle
whereas, manifestation later usually suggests a different
process.
Secondary open angle also occur in young children.
Both corticosteroid-induced and chronic uveitic glaucomas are described [20]. It is difficult to classify the underlying cause of glaucoma, that frequently follows pediatric cataract extraction. Walton examined 65 children
in whom, pre-operative gonioscopy revealed no consistent angle defect but post-operative gonioscopy revealed
filtration angle deformity [21]. Retained lens material
was one of the risk factor known another cause may be
presence of small cornea.
5. Presentation
The signs and symptoms of PCG are variable dependent
on childs age and severity of glaucoma; and secondary
corneal abnormalities. PCG is characterized by clinical
triad of epiphora, blepharospasm and photophobia, but
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7. Differential Diagnosis
6. Diagnosis and Ancillary Testing
It is important to do a complete ophthalmic examination
in a child suspected of glaucoma. This includes IOP
measurement, gonioscopy, optic nerve head examination
and refraction. Check for the childs ability to fix and
follow; and for the presence of nystagmus. Examination
of the cornea is crucial with respect to size and clarity of
the cornea and the presence of Haabs striae.
This examination can be done in clinic. With some
practice, IOP can be measured in a conscious, swaddled
infant using perkins tonometer or tonopen. Usually IOP
in infants with normal eyes is in the range of 11 - 14 mm
Hg using these devices. The measurement of IOP greater
than 20 mmHg in a calm, resting infant is suspicious for
glaucoma when other signs and symptoms also suggest
the disease. Measurements of IOP undertaken while a
child cries and resists efforts to hold the eye open are
invalid.
Examination of the optic nerve is attempted, because
obvious cupping confirms the diagnosis. Shaffer and
Hetherington noted a cup to disc ratio (C/D ratio) greater
than 0.3 in 68% of 126 eyes affected by primary infantile
glaucoma [22], whereas C/D ratio greater than 0.3 was
found in less than 2.6% of newborns with normal eyes
[23]. A Koeppe infant diagnostic lens offers good visualization of disc using direct ophthalmoscope. Gonioscopy can also be performed with it even in a conscious
infant. In the normal newborn eye, the iris usually inserts
posterior to the scleral spur. In PCG, the iris commonly
inserts anteriorly directly into the trabecular meshwork.
This iris insertion is most commonly flat, although concave insertion may be rarely seen.
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Condition
Tearing, discharge,
conjunctival injection
Nasolacrimal duct
obstruction infections
Allergic conjunctivitis
Enlarged cornea,
apparent asymmetry
of globe size
Primary megalocornea
Unilateral high myopia
Proptosis lid retraction
Contralateral microphthalmos
Enopthalmos ptosis
Photophobia,
blepharospasm
High myopia
Pathologic myopia
Vitreo-retinal degeneration
e.g. Sticklers syndrome
Enlarged cup to
disc ratio
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8. Management
The definitive treatment for primary infantile glaucoma
is surgical. Medical therapy usually provides a supportive role to reduce the IOP temporarily, to clear the cornea, and to facilitate surgical intervention. Laser therapy
has limited role in developmental glaucomas. Primary
surgical treatment is usually with goniotomy or trabeculotomy, although combined trabeculotomy with trabeculectomy may be useful in certain populations with high
risk of failure of goniotomy or trabeculotomy. Refractory
congenital glaucomas may be managed by trabeculectomy
with anti-fibrosis drugs, glaucoma drainage implants and
cyclodestructive procedures (Figure 1).
Normal Examination
Congenital Glaucoma
Follow-up
Goniotomy
Trabeculotomy
Trabeculectomy
Combined trabeculotomy and trabeculectomy
Unsuccessful
results
Successful
results
Follow-up
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glaucoma of all grades of severity, trabeculotomy controls IOP in over 90% of eyes. The efficacy of this operation compared favorably with goniotomy. The results of
trabeculotomy and goniotomy for infantile glaucoma
were compared and found equally effective and safe [35].
The significant advantage of trabeculotomy for those
cases with a cloudy cornea limiting visualization of the
angle was described [36]. A newer trabeculotomy technique with protein suture passed 360 through Schlemms
canal has been mentioned [37].
8.2.3. Trabeculectomy
A trabeculectomy involves creating a full thickness
opening in the sclera (sclerotomy) for outflow of aqueous.
A partial thickness scleral flap covers the opening and
the conjunctiva overlies the flap. Intraocular pressure can
be significantly lowered with this. Success rate in adults
is usually around 70% - 80%. In children, long term success rate is lower being around 50% [38] due to more
aggressive wound healing response in children, which
scars down sclerotomy or scleral flap. Children are also
more prone to complications such as infections due to
eye rubbing.
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9. Conclusion
The main goal in managing primary congenital glaucoma
is early diagnosis and therefore early surgical intervention. Following successful surgery, glasses should be
prescribed and care must be taken to manage amblyopia
for optimal visual rehabilitation.
REFERENCES
[6]
[7]
A. E. Kolker and J. Hetherington, Congenital Glaucoma, In: Becker-Shaffers Diagnosis and Therapy of
the Glaucomas, 5th Edition, CV Mosby, St Louis, 1983, p.
317
[8]
M. Sarfarazi and I. Stoilov, Molecular Genetics of Primary Congenital Glaucoma, Eye, Vol. 14, 2000, pp. 422428. doi:10.1038/eye.2000.126
[9]
A. N. Akarsu, M. E. Turacli, S. G. Aktan, et al., A Second Locus (GLC3C) for Primary Glaucoma (Buphthalmos) Maps to the 1p36 Region, Human Molecular Genetics, Vol. 5, No. 8, 1996, pp. 1199-1203.
doi:10.1093/hmg/5.8.1199
[1]
[2]
S. J. H. Miller, Genetic Aspects of Glaucoma, Transactions of the Ophthalmological Society of the UK, Vol. 86,
1966, pp. 425-434.
[15] A. T. Johnson, A. V. Drack, A. E. Kwitek, et al., Clinical Features and Linkage Analysis of a Family Autosomal
Dominant Juvenile Glaucoma, Ophthalmology, Vol. 100,
No. 4, 1993, pp. 524-529.
[3]
S. C. Debnath, K. D. Teichmann and K. Salamah, Trabeculectomy versus Trabeculotomy in Congenital Glaucoma, British Journal of Ophthalmology, Vol. 73, No. 8,
1989, pp. 608-611. doi:10.1136/bjo.73.8.608
[4]
A. Gencik, Epidemiology and Genetics of Primary Congenital Glaucoma in Slovakia. Description of a Form of
Primary Congenital in Gypsies with Autosomal-Recessive Inheritance and Complete Penetrance, Develop-
OJOph
77
[34] K. M. Joos and J. H. Shen, An Ocular Endoscope Enables a Goniotomy Despite a Cloudy Cornea, Archives
of Ophthalmology, Vol. 119, No. 1, 2001, pp. 134-135.
[35] S. D. McPherson Jr. and D. MacFarland, External Trabeculotomy for Developmental Glaucoma, Ophthalmology, Vol. 87, No. 4, 1980, pp. 302-305.
[23] K. T. Richardson and R. N. Shaffers, Optic-Nerve Cupping in Congenital Glaucoma, American Journal of
Ophthalmology, Vol. 62, No. 3, 1966, pp. 507-509.
[24] R. N. Jaffar and A. K. Ghulamqadir, Effect of Oral Choral Hydrate on the Intraocular Pressure Measurement,
Journal of Pediatric Ophthalmology and Strabismus, Vol.
30, No. 6, 1993, pp. 372-376.
[25] H. D. Hoskins Jr., J. Hetherington Jr., S. D. Magee, R.
Naykhin and C. V. Migliazzo, Clinical Experience with
Timolol in Childhood Glaucoma, Archives of Ophthalmology, Vol. 103, No. 8, 1985, pp. 1163-1165.
doi:10.1001/archopht.1985.01050080075024
[26] L. B. Enyedi and S. F. Freedman, Safety and Efficacy of
Brimonidine in Children with Glaucoma, Journal of
AAPOS, Vol. 5, No. 5, 2001, pp. 281-284.
doi:10.1067/mpa.2001.117571
[27] R. J, Bowman, J, Cope and K, K. Nischal, Ocular and
Systemic Side-Effects of Brimonidine 0.25% Eye Drops
(Alphagan in Children), Eye, Vol. 18, 2004, pp. 24-26.
doi:10.1038/sj.eye.6700520
[28] L. I. Larsson and A. Alm, Aqueous Humor Flow in Human Eyes Treated with Dorzolamide and Different Doses
of Acetazolamide, Archives of Ophthalmology, Vol. 116,
No. 1, 1998, pp. 19-24.
[29] M. Portellos, E. G. Buckley and S. F. Freedman, Topical
versus Oral Carbonic Anhydrase Inhibitor for Pediatric
Glaucoma, Journal of AAPOS, Vol. 2, No. 1, 1998, pp.
43-47. doi:10.1016/S1091-8531(98)90109-4
[30] L. L. Wayman, L. I. Larsson, T. L. Maus and R. F. Brubaker, Additive Effect of Dorzolamide on Aqueous Humor Flow in Patients Receiving Long Term Treatment
with Timolol, Archives of Ophthalmology, Vol. 116, No.
11, 1998, pp. 1438-1440.
[31] R. K. Parrish, P. Palmberg and W. P. Sheu, A Comparison of Latanoprost, Bimatoprost and Travoprost in Pa-
OJOph