Journal of Pediatric Ophthalmology Strabismus 2004;41:271-288.
Primary Congenital glaucoma
Abstract
Background:
Primary congenital glaucoma (PCG) is the most frequent childhood glaucoma and is an important cause of childhood blindness. The current understanding and the evaluation of children with this disease and its treatment are described in this report.
Methods:
Information derived from review of the authors' 287 PCG patients and current published data related to PCG was accessed for this report.
Results and Conclusions:
The nomenclature for childhood glaucoma has been inconsistent and is clarified for children with primary congenital glaucoma. The epidemiology of PCG notes a variable incidence of PCG worldwide. Familial occurrence supports autosomal recessive transmission, chromosomal loci have been identified, and the CYP1B1 gene has been identified and clinically correlated. The histopathology of PCG eyes confirms the presence of a variable trabecular meshwork anomaly and absence of an imperforate membrane. Children with PCG are diagnosed after recognition of corneal signs and symptoms of glaucoma. The examinations of PCG patients must be thorough to distinguish this glaucoma from other causes of childhood glaucoma, to prepare for surgery, and to follow progress with treatment. Medical treatment must be tailored for the pediatric patient. Surgery for PCG utilizes the potential of goniosurgery to definitively cure and other procedures, refined for children, to control their eye pressures. The future will be determined by those physicians who chose to work to sustain continued progress for children with glaucoma.
Introduction
Primary congenital glaucoma (PCG) is a hereditary childhood glaucoma secondary to abnormal development of the filtration angle, which occurs unassociated with systemic abnormalities. Glaucoma surgery has dramatically improved the visual prognosis of this important cause of childhood blindness; however, late recognition can result in permanent and severe visual morbidity. Associated amblyopia and secondary refractive errors are common. Clinical monitoring of PCG is demanding and often carried out for an uncooperative group of patients. It is best managed by ophthalmologists who possess focused training, clinical experience with childhood glaucoma, and specialized surgical and examination skills. Its affliction of young children makes glaucoma control a life-long goal requiring motivation and perseverance by the patients, parents, and their care-givers. The purpose of this report is to describe the progress made in understanding and caring for children with this primary childhood glaucoma.
Definition and Terminology
The nomenclature for childhood glaucoma is plagued with confusing terminology. Developmental glaucoma is a term used to broadly encompass all glaucomas resulting from abnormal development of the aqueous outflow system, which may or not be associated with a systemic anomaly. Hoskins classified the developmental glaucomas anatomically related to involvement of the trabecular meshwork alone (isolated trabeculodysgenesis), in combination with the iris (iridotrabeculodysgenesis), or with the cornea (corneotrabeculodysgenesis).1 Congenital glaucoma is also broadly used when responsible developmental anomalies are suspected. The label primary newborn glaucoma (isolated trabeculodysgenesis or iridotrabeculogenesis ) is used when primary congenital glaucoma (PCG) is clinically apparent at birth. When PCG is recognized between the first month and 2 years of age, it is termed primary infantile glaucoma, and is labeled late-recognized primary infantile glaucoma when recognized after 2 years of age. Primary congenital glaucoma (PCG) is the term used in this paper to refer to all 3 age groups described above with the clinical features, gonioscopic abnormalities, and genetics of isolated trabeculodysgenesis or iridotrabeculodysgenesis. The designation juvenile glaucoma is best reserved for patients with Primary juvenile glaucoma (PJG) who have normal gonioscopic findings, myopia, and acquired glaucoma associated with autosomal dominant inheritance.
The glaucomas in infancy and childhood are classified into primary and secondary groups. The primary category is sub-classified according to the presence or absence of systemic or other ocular anomalies, and the secondary category is classifiable according to their etiologies (Table1).
Epidemiology
Primary congenital glaucoma (PCG) is hereditary with a variable incidence in different populations but with an overall occurrence of 1 in 10,000 births.2 A greater incidence occurs in populations with higher rates of consanguinity: 1 in 2,500 in Saudi Arabia3 and 1 in 1,250 in Romanian gypsies, which supports autosomal recessive inheritance.4 It accounts for approximately 55% of primary pediatric glaucomas and is the most common type.5 PCG accounted for 5.7% and 10.9% of all glaucoma patients seen in tertiary eye clinics over a 2-year period in China and Japan respectivetly,6 and occurs worldwide having no racial or geographic predilection. Girls are more commonly affected in Japan with a ratio of males to females of 2 to 3, whereas boys are more commonly affected in United States and Europe with a ratio of 3:2.7, 8 The majority (about 75%) of PCG cases are bilateral and asymmetric expression should be suspected in clinically apparent unilateral cases.9 More than 80% present within the first year of life, with 25% diagnosed in the neonatal period, and 60% within the first 6 months of life.9
Genetics
The majority of PCG cases are sporadic but 10-40% are familial with frequent association with consanquinity.10 In the most familial cases transmission is autosomal recessive with variable expression and penetrance of 40-100%.10 Unequal sex distribution, lower than expected number of affected siblings in familial cases, and transmission of the disease to successive generations has put into question the autosomal recessive mode of inheritance.10 Genetic heterogeneity of PCG confirmed by linkage studies has been postulated to explain these discrepancies.10,11
Three loci for PCG) have been found.10, 12, 13 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.10,14 Genetic heterogeneity was confirmed when a second locus on chromosome 1p36 (GLC3B) was found.12 Genetic family analysis identified a third locus(GLC3C) on chromosome 14q24.3.13Although three chromosomal loci have been linked to PCG only the gene CYP1B1 in locus GLC3A has been identified.15 Mutations in this gene have been described as the predominant cause of PCG in Turkish and Saudi Arabian families.16 The mutant alleles co-segregated with the disease phenotype in an autosomal recessive manner. In cases of parent-child transmission molecular analysis invariably found homozygosity or compound heterozygosity for the mutant alleles in the affected parent and gene carrier status in the normal parent.17 These are examples of pseudo-dominance with an autosomal recessive trait.
Mutations in the CYP1B1 gene were found responsible for 87% of familial cases, but only present in 27% of sporadic cases of PCG.10 Approximately 45 mutations of this gene have been identified and include deletion, insertion, point mutation, missense, nonsense, frameshift, and terminator mutations.18 Genotype-phenotype correlation was described related to the success of glaucoma management and abnormalities secondary to elevated intraocular pressure and the most severe phenotype was associated with frameshift mutations.18
CYP1B1 is a member of the cytochrome P450 gene family of drug-metabolizing enzymes and is expressed in a wide range of tissues in the body including the anterior uveal tract of the eye, the
trabecular meshwork, iris, and ciliary body.19 This family of enzymes encodes monoxygenases and participates in the metabolism of exogenous hormones and drugs such as steroids. Its ocular substrate in the pathogenesis of PCG has not been identified. A reasonable postulate is that the
CYP1B1 enzyme protein is involved in the metabolism of a molecule which plays an important role in the development of the anterior chamber angle. PCG is genetically distinct from a group of conditions classified as anterior segment dysgenesis or Axenfeld-Rieger syndrome/anomaly which are transmitted by autosomal dominant inheritance resulting from mutations in the transcription factor genes PITX2 or FOXC1.20.21. PCG is also phenotypically unrelated to juvenile or adult-onset open angle glaucoma for which the MYOC (TIGR) gene has been identified at locus (GLC1A) on chromosome 1q25.22 In a small percent of these cases a CYP1B1 mutation has also been found suggesting a modifier role.23
Pathogenesis and pathology
PCG results from an abnormality of the trabecular meshwork which may represent a developmental arrest or relative immaturity of the trabecular tissue causing increased resistance to aqueous outflow.24, 25 The defect was thought initially to be an imperforate membrane (Barkan's membrane) lining the anterior chamber angle based on its gonioscopic appearance suggesting a Òclothed membrane with a shagreened surfaceÓ.26, 27 Evidence of this membrane has not been found.28
The histopathology of PCG is characterized by:
1. An anterior insertion of the iris and ciliary body in an open-angle configuration with variable exposure of the trabecular meshwork to the anterior chamber.28
The anterior iris insertion may cover a variable amount of ciliary body band and trabecular meshwork. The anterior portion of the ciliary body overlaps the posterior portion of the trabecular meshwork with underdevelopment of the angle recess. The longitudinal fibers of the ciliary muscle insert directly into the corneoscleral meshwork passing in front of the internal tip of an underdeveloped scleral spur. In one study (77.8%) of eyes with PCG had either an invisible or narrow ciliary body band compared to only 13.8% of control eyes.29
2. Thickened and taut trabecular beams in the meshwork.
Anderson's work showed that the trabecular meshwork is perforate and the intertrabecular spaces are present but the trabecular beams in between these spaces were found abnormally thickened.28 Maul et al found an increased amount of collagen fibrils in the core of the trabecular beams.30
3. A thicker and less porous juxtacanalicular meshwork
The juxtacanalicular meshwork in eyes with PCG had been found to be thicker than in normal eyes.28, 30,31 Unlike the corneoscleral meshwork, this external layer of the meshwork is normally compact with a lack of intertrabecular spaces.31 The cells in this layer are normally round with short cytoplasmic processes and are surrounded by extracellular materials comprising of collagen, elastic fibers, and amorphous substances, giving it a compact appearance30,31. Enucleated eyes of premature infants reveal that the trabecular sheets first appear on the anterior
chamber side of the trabeculum and gradually progress with fetal age towards Schlemm's canal.32 The trabecular meshwork at 42 weeks of gestation shows intertrabecular spaces similar to that seen in adult eyes, with only a few layers of cells in the juxtacanalicular area. Hence, it has been postulated that the thicker-compact juxtacanalicular meshwork seen in PCG is perhaps the result of relative immature differentiation.32
4. A paucity of vacuoles in the endothelium of Schlemm's canal
Decreased vacuoles compared to normal functioning angles has been described in PCG eyes and thought to be either an artifact or the result of reduced aqueous flow through the trabecular meshwork in the glaucomatous eyes.28, 30, 31
5. Absence of Schlemm's canal Absence of Schlemm's canal has also been described in cases of PCG but this is an exception and probably indicates more severe maldevelopment.32, 33 Immaturity of the juxtacanalicular meshwork, and/or underdevelopment of Schlemm's canal or collector channels may explain failure of goniotomy in some cases.34 Similarity of the angle histopathology in PCG, glaucoma with the Sturge-Weber syndrome, and in the maternal rubella syndrome with glaucoma,9 suggests that a common pathway for angle development is affected in these diverse conditions. The underlying mechanism of trabecular dysgenesis is still unknown. The most probable postulated mechanism is offered by Anderson who felt that excessive formation of collagen in the trabecular tissue results in thickened and taut trabecular beams that prevents posterior sliding of the peripheral iris and ciliary body along the inner eye surface resulting in the anterior location of the uveal tract and underdevelopment of the angle recess.28 The success of goniotomy in PCG may be explained by the relief of tension in the thickened and compact trabecular meshwork, with resultant decreased resistance to the outflow of aqueous.28
Clinical Features
The signs and symptoms of PCG are variable dependent on the child's age, and the severity of glaucoma and secondary corneal abnormalities (Table 2). Some children are asymptomatic while others develop intense photophobia and blepharospasm.
Infants are most likely to present with diffuse corneal opacification and be recognized promptly by physicians or parents. The classic symptoms of epiphora, photophobia and blepharospasm are secondary to corneal edema, opacification, and breaks in Descemet's membrane. Some infants may exhibit irritable behavior which may be mistakenly attributed to colic or formula intolerance. Acquired epiphora occurs and is commonly misinterpreted as evidence of a congenital nasolacrimal duct obstruction, or a Òred eyeÓ mimicking conjunctivitis may occur, leading to further delay in diagnosis. The corneas may be diffusely thick due to stromal edema or thin with buphthalmos. Alternatively, focal stromal thickening and opacification occur in association with breaks in Descemet's membrane, which develop Haab's striae after endothelial cells lay down a new basement membrane and form hyaline ridges. These defects are typically horizontal, curvilinear, and parallel to the limbus in the peripheral cornea. Corneal and ocular enlargements are usual presentation in toddlers. Progressive enlargement usually ceases by 3 to 4 years of age. Both parents and physicians may accept corneal enlargement as a normal aesthetically pleasing variation. The stretching of the cornea occurs mainly at the limbus and is associated with corneal thinning and a remarkably deep anterior chamber. The posterior segment also enlarges with overall increase in axial length and the development of clinical buphthalmos in severe cases.
In older children, astigmatism and progressive
axial myopia cause symptomatic decreased uncorrected visual acuity and
refractive amblyopia. These children with late-recognized primary congenital glaucoma may be asymptomatic and
discovered to have elevated IOP or optic nerve cupping on routine ocular
examination or when examined for unrelated ocular conditions. While cupping of
the optic nerve in glaucoma is generally a gradual process in older children
and adults, it can occur rapidly in infants. Reversibility of the cupping with
normalization of IOP in young children occurs due to suspected relative
immaturity and elasticity of the lamina cribosa.
Clinical
Examination The clinical examination (Table 3) of
a child with glaucoma requires patience, time, and skill. A detailed examination
utilizing a slit-lamp for tonometry and biomicroscopy of the anterior segment
and optic nerve head is not possible in most children under 5 years of age but
an informative office evaluation can still be obtained. Sedation of a
particularly fractious child may be helpful. Oral chloral hydrate appears not
to alter the IOP levels and be the safest choice for children between 1 and 5
years of age,35 but is still not risk-free and monitoring of the
patient until recovery is necessary. An appropriate medical and
family history is essential to make the
diagnosis for every patient due to the genetic basis of some types of childhood
glaucoma and the occurrence of primary and secondary childhood glaucomas with various
systemic or ocular conditions, A general physical examination is also indicated when evidence of a systemic and/or
ocular developmental defect suggests diagnoses other than isolated glaucoma, or
when general anesthesia is planned. Because children resist being held down or
touched in the eye region clinical information must be gained by careful inspection
before laying on hands. The presence of glaucoma may be obvious on inspection
alone by observing the presence of hazy, enlarged or asymmetrical corneas,
light sensitivity, and abnormal visual behavior. The inspection and examination
of the anterior segment is facilitated by
the use of a pen-light and a handheld slit-lamp which allow maneuverability
regardless of the child's position. Magnification obtained with loupes or with
the oculars present on hand-held slit-lamps is useful. The corneal size and
clarity should be studied. Asymmetry in cornea size is usually more obvious on
inspection than by measurement. Breaks in Descemet's membrane should be identified
and differentiated from other abnormalities such as the more vertically-oriented
defects seen after forceps-induced birth trauma, or the irregular- scattered
defects seen with posterior polymorphous dystrophy. The iris and pupil should
be carefully studied for abnormalities such as iris stromal
hypoplasia, pupillary ectopia, and pupillary enlargement as seen with newborn congenital
glaucoma and aniridia. The anterior chambers are deep and the lenses uniformly
clear in PCG patients. Tonometry is an essential component of the examination and can
be the most difficult part with a fractious child. The best IOP measurements
are taken with a sleeping or relaxed child using topical anesthesia. IOP
readings are variably altered by sedation and general anesthesia, and falsely
elevated with a struggling patient. Time and patience are the most important
requirements for success. Repeated measurements during at the same or return
office visits may be necessary. Parents can help by holding the child to
provide reassurance and to distract the patient with a toy or a bottle.
Tonometry efforts should be initially directed to the eye which appears more normal
as IOP measurements are more critical in determining if this eye has glaucoma. Various
instruments have been used in the measurement of IOP in children. The Perkins
applanation tonometer probably ranks highest in terms of accuracy and the
Tono-Pen (Medtronic Solan, Jacksonville, Florida, USA) highest in ease of use.
The corneal thickness should be measured when possible and always estimated to
assist with the interpretation the eye pressure measurements. The Schiotz
tonometer is still useful to give an indication of the IOP in the young or
struggling child examined in the supine position, although its accuracy is most
affected by corneal thickness and curvature, and scleral rigidity. In older,
co-operative children, the familiar slit-lamp mounted Goldman tonometer may be
used. Gonioscopy is indispensable for determining the type of
glaucoma and choice of surgery. When corneal clarity permits, simultaneous
bilateral examination of the angles may be performed with Koeppe lenses. A
handheld microscope and a customized illuminator for gonioscopy are
recommended. Direct gonioscopy by this method can often be performed in the
office with a sleeping/feeding infant or a co-operative child lying supine after
topical anesthesia. Older child may permit indirect gonioscopy at the
slit-lamp. However, a detailed gonioscopic examination of a young child most often
requires general anesthesia. Epithelial removal can be performed to obtain a
clear view when the cornea is cloudy due to epithelial edema.
The angle appearance in PCG can vary
according to the severity of angle anomalies. Typically, the iris inserts more
anteriorly than normal with variable obscuration of the ciliary body band.
There is an altered translucency of the angle face causing indistinct definition
of the different angle structures (ciliary body band, scleral spur, trabecular
meshwork). The peripheral iris often appears hypoplastic with scalloping at its
insertion and with visibility of the peripheral iris pigment epithelium. In
more severe variants, the angle may be so underdeveloped that minimal visible
angle structures anterior to the iris insertion can be identified. Presence of multiple
abnormal iris processes and iridocorneal bands suggest the diagnosis of
anterior segment dysgenesis. Optic nerve head examination may be performed with a direct or indirect
ophthalmoscope. Examination with an indirect ophthalmoscope allows 3-D
assessment of the optic disc as well as detection of posterior segment
abnormalities which are usually absent PCG. An A-scan ultrasound examination is
useful to obtain the axial length of each eye, which increases with the
severity and duration of the glaucoma. B-scan ultrasound of the posterior
segment may yield useful information when cloudy corneas preclude a good view
of the fundus. Advanced cupping can be recognized and unexpected retinal
defects ruled out.
Examination
under anesthesia (EUA) A complete office examination is
usually sufficient to either exclude glaucoma, or to diagnosis or suspect glaucoma
and justify general anesthesia for a more detailed examination and probable
surgery. The role of the EUA is to add to rather than replace the office
examination. It should follow the office examination and precede any planned
glaucoma surgery. The essential information that can be obtained during the EUA
is listed in Table 4. Unfortunately, most anesthetic
agents, narcotics, and sedatives have a lowering effect on IOP measurements.35
Hence, IOP readings taken under anesthesia should never solely decide the
diagnosis of glaucoma or its management without taking other parameters such as
corneal clarity and diameter and optic nerve head findings into account.
Tonometry with a Schiotz, Perkins or Tono-Pen tonometer is best performed as
soon as possible after the induction of anesthesia. Corneal diameters are measured with
a millimeter ruler or calipers and recorded for follow-up evaluation of
glaucoma control. Detailed hand slit-lamp examination of the anterior segment
is followed by gonioscopy, which is most reliable and informative in young
children with PCG when performed during the EUA. The view through the cornea
for gonioscopy and for the posterior segment examination may be obscured by
epithelial edema. Limited epithelial removal restores the view remarkably. The
severity of the angle defect found on careful gonioscopy helps in the
preparation for angle surgery and the findings should be carefully recorded. The
EUA also gives a good opportunity for fundoscopy including optic nerve head evaluation,
which can be viewed through the gonioscopy lens, and retinoscopy. Differential
Diagnosis The diagnosis of PCG is made when
signs and symptoms of glaucoma including a persistently elevated IOP are found
in a child who has no other related ocular or systemic abnormalities and who has
no other ocular disorders that can result glaucoma. The differential diagnoses
include other childhood glaucomas (Table 1), as well as disorders presenting
with the signs and symptoms of congenital glaucoma (Table 5). Other Primary and Secondary Glaucomas Diagnosis of PCG is made by exclusion
as other causes of glaucoma given in Table 1. Other primary glaucomas are excluded
by the presence of associated congenital systemic and/or ocular abnormalities.
A careful ocular history, examination, and systemic assessment should also
detect cases of secondary glaucoma, hence, the importance of a complete general
physical examination and ocular examination for all pediatric glaucoma
suspects. Differential diagnosis of the
glaucomas is accomplished by considering the anterior segment findings. The
presence of glaucoma related corneal abnormalities support that diagnosis and
may suggest its severity and duration. Enlargement of the cornea may be exaggerated
with early infantile glaucoma associated with neurofibromatosis or with a nevus
flammeus. A small cornea may be seen at the onset of aphakic glaucoma or
glaucoma complicating advanced retinopathy of prematurity. The depth of the
anterior becomes abnormally deep with early childhood glaucoma, but will be
shallow in the presence of a pupillary block secondary glaucoma. Evaluation
of the iris can be helpful in differentiating the glaucomas.
Recognition of the newborn variant of PCG may depend on this because the angle
features typically may not be seen well in the presence of the corneal opacity.
In this condition, iridotrabeculodysgenesis, the iris is thin and flat associated with abnormally large pupils
often large enough to suggest aniridia. Examination of the iris should be
continued during the gonioscopic assessment of the anterior segment. When iris
and other anterior segment abnormalities exist, as in anterior segment
dysgenesis, differentiation from primary congenital glaucoma is relatively
easy. In Rieger syndrome, for instance, associated iris atrophy, iris processes
in the angle, anterior termination of the Schwalbe's line and characteristic faces
makes the diagnosis clear-cut. In aniridic glaucoma, there are conspicuous iris
defects as well as prominent angle abnormalities consisting of progressive shifting
of the iris stump onto the angle face. Severe underdevelopment of the
filtration angles and pupillary iris ectropion occur with glaucoma associated
with neurofibromatosis (NF 1), and in the congenital iris ectropion syndrome. An angle anomaly resembling that
found in PCG may be present with glaucoma associated with certain systemic
syndromes such as Sturge-Weber syndrome, cutis marmorata telangiectatica
congenita, the maternal rubella syndrome, oculocerebrorenal syndrome of Lowe,
Down syndrome, Cranio-cerebello-cardiac syndrome, and Stickler syndrome. Hence,
these conditions and others must be recognized by their non ocular features. Disorders with corneal edema or
opacity Corneal haze or opacification is
the sign which most often initiates an evaluation for childhood glaucoma, but
is also seen in other conditions in the newborn or infant (Table 5). Forceps
induced obstetric trauma with resultant Descemet's membrane tears and corneal
edema and clouding is in the differential diagnosis; this is differentiated
from PCG by the presence of periorbital soft tissue trauma, normal IOP,
frequently vertical orientation of the Descemet's tears, and the absence of
corneal enlargement, abnormally deep anterior chamber, and abnormal filtration
angle. Viral keratitis such as herpetic or rubella keratitis can result in a
cloudy cornea in the newborn. Rubella keratitis in the newborn may particularly
resemble PCG because it can be bilateral and associated with glaucoma. Peters'
anomaly is characterized by corneal opacities which may coexist also with
glaucoma, but characteristic corneal abnormalities and associated anterior
segment anomalies help distinguish them from PCG. . Diffuse stromal thickening
with absence of corneal enlargement help to distinguish the congenital
endothelial dystrophies.40 Corneal clouding secondary to storage
diseases seldom cause confusion due to the plethora of associated systemic
signs. Disorders with corneal enlargement Any infant with corneal enlargement
should be evaluated for glaucoma (Figure 1.) and repetitively reexamined for an
elevated IOP in cases of doubt. Axial myopia is both in the differential
diagnosis and is a presenting sign of glaucoma in childhood; signs such as
peripapillary crescent, tilted optic nerve head insertion, choroidal mottling
or retinal tessellation in the posterior pole are helpful distinguishing
features not seen in PCG. In hereditary megalocornea, the strikingly enlarged
corneas are associated with very deep anterior chambers at the expense of the
posterior segments, absence of Descemet's membrane breaks or corneal opacities,
presence of iris transillumination and pigment dispersion on the lens, cornea,
iris surfaces and in the angle, as well as X-linked recessive inheritance in
the majority of cases. 37 Disorders with epiphora and a
Ôred eye' The ocular examination must
distinguish conditions showing epiphora and/or the Ôred eye' from glaucoma.
Congenital nasolacrimal duct obstruction is a common early cause of persistent epiphora
and is always associated with discharge. Acute onset of epiphora with red eye should
also suggest a corneal injury, infection, or intraocular inflammation. Principles
of Management The management of a child with
glaucoma is challenging. Primary congenital glaucoma is a chronic disease
affecting infants and young children with normal life expectancies. The IOP-reducing
benefit of each treatment modality may not persist. Treatments should be
carefully tailored with the goal of long term control of the IOP with minimum
risk to the eye to enable meaningful vision for life. Surgery constitutes the mainstay of
therapy for PCG. Medications alone are rarely effective but play an important
secondary role as adjunctive treatment. Because angle surgery enjoys striking
success rates in PCG, it should be considered first and will often be the initial
procedure of choice. Other surgical procedures must be considered when
appropriate angle surgery has failed or is unlikely to succeed because of
gonioscopic evidence of a severe filtration angle anomaly. Medical treatment PCG responds poorly to medical
therapy alone. However, medications are important and are used before surgery
as a temporizing measure in infants unfit for surgery or anesthesia, to prepare
a patient for goniosurgery by clearing the cornea, and mainly for adjunctive
therapy in complicated cases unsuitable or only partially controlled by
surgical therapy. Medications can have different risk and benefit profiles in
children compared to adults, and ophthalmologists using them in infants and
children should be aware of these differences. Ocular surface toxicity and
allergy are also real problems complicating continuous topical treatment
started at a young age. Children are also often unable to communicate adverse
effects which give importance to the observations of parents and physicians to
assess the appearance of the eye, and the systemic signs, behavior, appetite
and growth. Oral carbonic anhydrase
inhibitors (CAIs), acetazolamide and
methazolamide are the most effective and potent IOP lowering drug for children
with primary congenital glaucoma. At acetazolamide dosages of 10 Ð 15 mg/kg/day
by mouth it is generally safe for use in the short term and often reduces IOP
by a third.39 It is useful to clear the cornea before goniosurgery
and to improve IOP control after a surgical procedure failed to lower IOP
satisfactorily, prior to further glaucoma surgery. Acetazolamide is
administered by mouth utilizing a mixture prepared from pulverized tablets, and
is usually well-tolerated by young children. Inhibition of carbonic anhydrase
in the kidneys results in decreased hydrogen ion and increased bicarbonate in
the urine. The resultant metabolic acidosis may be associated with noticeable
hyperpnea, decreased appetite, increased fatigue and failure to thrive with
prolonged use. These symptoms can be reduced by decreasing the acetazolamide
dosage and by the addition of oral sodium bicarbonate at 1 Ð 2 mEq/kg/day.40.
Renal calculi formation secondary to the alkaline urine potentiated by
acetazolamide may complicate long-term use and this risk is increased with the
use of sodium bicarbonate.41 Myelosuppression is a rare idiosyncratic
life-threatening complication of CAI usage, and has not been reported in
children less than 6 years of age.42 If the CAI is prescribed for
more than a month, blood counts should be obtained and the drug immediately
ceased if a fall in the level of any single formed blood element is observed. The topical CAIs, dorzolamide and
brinzolamide, constitute a welcome alternative with less risk of systemic side
effects compared the oral CAIs. They are generally less effective than the oral
CAIs as they reduce IOP by a quarter, but are better tolerated,43,44
and are therefore used extensively in children with glaucoma. They are
administered topically 3 times a day for maximum effectiveness, and can be
expected to have an additive benefit when used in conjunction with
beta-blockers even though both drugs are suppressors of aqueous production.45 Beta-adrenergic antagonists (beta-blockers) have been used extensively for the
treatment of glaucoma in infancy to adolescence and adulthood. Studies have
found IOP-lowering efficacy of 20-30% in responsive cases of childhood glaucoma
but none has looked at its efficacy in PCG.46,47 Severe systemic
side effects from topical timolol are rare in infants and children but bronchospasm
and bradycardia have been reported,47-49 especially with the higher
concentration of 0.5% . Apnea has been described in neonates and a toddler although
other factors such as co-existent congenital disorders could also have
contributed to the apneic spells.49, 50 Passo et al have
demonstrated that plasma timolol levels are much higher in children receiving
timolol 0.25% compared to adults receiving 0.5% timolol, and ranged from 10
times higher in a 5-year old (3.5 ng/ml) to up to 100 times higher in a neonate
(34 ng/ml).51 Punctal occlusion after topical timolol decreased the
mean 1-hour plasma timolol level by approximately 40%.51 Hence, in
the treatment of glaucoma in the young, it is prudent to start with a lower
concentration of timolol (0.25%) at a lower frequency of once daily, begin
treatment with only one eye initially in bilateral glaucoma, and advise
single-drop application with the use of punctal occlusion after every
application. It is wise to avoid beta-blockers in patients with significant
asthma and bradycardia, and to use them with caution in neonates. Brimonidine, a relatively selective
alpha-agonist, reduces intraocular pressure (IOP) by decreasing aqueous
production and increasing uveoscleral outflow.52 Brimonidine passes
through the blood-brain barrier, potentially causing central nervous system
(CNS) toxicity.53 There are reports of bradycardia, hypotension,
hypothermia, hypotonia, apnea and unresponsiveness in infants after topical
brimonidine.54-57 A study on the safety and efficacy of brimonidine
in older children 2.4 to16.8 years of age reported somnolence and extreme
fatigue following brimonidine administration and also showed a 6.7% average IOP
reduction in a group of pediatric patients aged 2.4 to 16.8 years, which is much
less than that shown in adult studies.58 Brimonidine should be
avoided in infancy and toddlers and be used with caution in older children. The prostaglandin analogues latanoprost, travoprost, and bimatrost have been
shown to be very effective in the treatment of adult glaucoma, have similar
chemical structures, and reduce intraocular pressure primarily by enhancing
uveoscleral outflow.59 They also have very similar side effects, the
most prominent of which are conjunctival hyperemia, iris and skin pigmentation,
and accelerated eyelash growth.59 Their use and efficacy in children
has not been widely reported. Disappointingly little IOP lowering and a high
non-respond rate in children has been reported although they are safe
systemically.60,61 A significant IOP-lowering effect was found in
some older children, with primary juvenile glaucoma or Sturge-Weber related
glaucoma.60,61 The average age of non-responders was 5 years versus
11 years for responders.61 Miotics such as pilocarpine are ineffective for PCG. Symptoms
of ciliary spasm and visual blurring from the induced myopia occur in older
children. They can be useful for aphakic glaucoma where they are better
tolerated, as are indicated preoperatively before angle surgery (goniotomy and
trabeculotomy) for PCG to achieve miosis and prevent peripheral anterior synechia
formation.
Goniotomy Barkan developed the goniotomy technique and described its successful
use for infants with glaucoma.62, 63 This seminal
accomplishment offered for the first time a successful therapy for infantile glaucoma heretofore considered a
hopeless disease. Indications. Goniotomy is the procedure of choice
for children with this PCG when planned by a physician familiar with the technique and when the cornea
is clear enough to enable confident viewing of the filtration angle. Pre-operative
gonioscopic evaluation is essential preparation for goniosurgery and may reveal encouraging or potential
discouraging findings to support a successful outcome. Inadequate pressure control
after an initial goniotomy often indicates the need for repeat
goniosurgery. Repeat goniotomy should also be considered with a reoccurrence
of glaucoma irrespective of the patient's age even into adulthood. The severe
angle anomaly with extreme forward insertion of the iris and minimal
development of the trabeculum typically seen with primary newborn glaucoma decreases the potential for a successful goniotomy.
The indication for goniotomy is also much less certain for other primary glaucomas
including glaucoma with a nevus flammeus, Rieger syndrome, and
neurofibromatosis so these. Late-recognized PCG can be difficult to distinguish from primary
juvenile glaucoma, but fortunately
goniotomy is indicated for both of these conditions. Results. The expected outcome of goniotomy surgery
for PCG overall is very favorable with a reported success rate over 80%.64 Patients recognized
to have glaucoma between birth and 2 months of age have a lower success rate with goniotomy,65-68
which may correlate with their severe filtration angle anomaly. Goniotomy
surgery was performed for 335 eyes and glaucoma control was achieved with single goniotomy
in 71% (239) of eyes and by one or more goniotomies in 94% (313) of eyes.69 Relapse
following successful goniotomy is unusual68 and occurred more frequently when the
glaucoma was first recognized at birth (36%), compared to results in children recognized before 6 months
of age (16%).68 History of repeat goniotomy procedures and glaucoma bilaterality
also were found to be risk factors for elapse.68 Review of the functional
results in patients with successful goniotomy determined that only 47% (34) of eyes achieved an acuity of
20/50 or better, associated with an increased incidence of anisometropia and strabismus.70
Technique. Goniotomy is performed utilizing a light source,
magnification instrument, fixation forceps, operating gonioscopic lens and a suitable
goniotomy needle or knife. Following the positioning
of the globe and with the trabecular meshwork in view through an operating lens,
the cutting instrument is entered into the anterior chamber through the peripheral
cornea and brought into contact with the mid section of the trabeculum. A
circumferential incision is then made in the trabeculum (Figure 2), and the
instrument is removed without causing injury to the cornea or lens.71
Surgical complications after goniotomy surgery are rare. A post operative
hyphema is a constant finding and usually of no clinical significance.
Occasionally a significant amount of blood will reflux into the anterior chamber
during the first 72 hours after surgery, and when this becomes complicated by an
elevated IOP washout of the blood should be considered. Endoscopic goniotomy
has been successfully preformed utilizing a coaxial ocular endoscope in the
presence corneal opacification which prevented a standard goniotomy procedure.72
Trabeculotomy Trabeculotomy ab externo is an
alternative procedure to goniotomy for PCG. Its successful use for infantile glaucoma was
recognized early and favorable results reported.73, 74 The efficacy
of this newer operation compared favorably with goniotomy.74 The
results of trabeculotomy and goniotomy for infantile glaucoma were compared and
found equally effective and safe, and the significant advantage of
trabeculotomy for those cases with a cloudy cornea limiting visualization of
the angle was described.75 Primary combined
trabeculotomy-trabeculectomy was performed for 144 eyes with PCG and based on a
success rate of over 90% at 6 months recommended for cases with significant
corneal edema.76 Trabeculotomy rather than goniotomy
may be a more appropriate choice for surgeons not experienced with goniotomy especially
when the cornea is so cloudy secondary to edema and/or scarring that the angle
can not be comfortably visualized. It requires more operating time than goniotomy
and a quadrant of the limbus must be used for this surgery. The operative technique for
trabeculotomy has been modified very little.77 The superior
quadrants are best saved for alternative surgery. A limbus based scleral flap
is created to expose the sclerolimbal junction, followed by a radial incision
centered over this landmark to unroof and expose Schlemn's canal.
Trabeculotomy probes are then introduced into Schlemn's canal and then brought
into the anterior chamber in a plane parallel to the iris to create a fistula
between the canal and the anterior chamber.78
Following removal of the probes the scleral flap and conjunctiva are
repositioned.
An alternative variation of this procedure
is to thread a suture circumferentially through Schlemn's canal followed by its
removal into and out of the anterior chamber which creates a communication
between these structures which has been effective for PCG.79
Study of the long-term
effectiveness of trabeculotomy has confirmed its efficacy for PCG.
Trabeculotomy for 99 eyes reported a probability of success after one or more surgeries
at 5 and 10 years to be 92% and 82% respectively.80 Trabeculotomy
for 46 children with PCG and a mean age of approximately 4 years
(range13-88months) achieved success in 87%(68) eyes using custom probes for 102
procedures.81 Complications after standard trabeculotomy are
unusual. A small reflux hyphema of no consequence is common. Trabeculectomy Before the use of
goniosurgery for PCG filtering surgery was performed with little expectation
for success. Procedures done included limbo-scleral trephine and posterior lip
sclerectomy. Beauchamp studied the use of trabeculectomy for 7 children with refractory
PCG following angle surgery; four patients were followed and 3 of the 8
operated eyes were adequately controlled.82 Introduction of
trabeculectomy lessened the risk of filtration surgery in young children but
had not significantly improved glaucoma control. The addition of
antimetabolites administration during trabeculectomy surgery for children
followed and improved the surgical outcome in terms of more effective IOP
control. 83 The indication for
trabeculectomy surgery for PCG is persistence of an unacceptable eye pressure
elevation following an appropriate number of angle incision operations. The
condition of the superior conjunctiva related to previous surgery, patient age,
potential for follow-up examinations, post operative contact lens use, and the
risk of postoperative infection, all must be considered. Children under one
year of age show a significantly lower success rate than older patients.84
An explanation for this is not clear. The surgery is not more complicated
and the use of an antimetabolite has not improved the outcomes. Postoperative
care is difficult for these young patients. Their post operative course is characterized
by decreasing evidence of external filtration even in patients who achieve
improved IOP control following the trabeculectomy procedure. Favorable outcome
with combined trabeculotomy-trabeculectomy for PCG patients under 1 month of
age has been described.85 The trabeculectomy
surgical procedure for PCG does not vary significantly from the technique
performed for adults. A limbus based or fornix based flap is manufactured.
The fornix based flap spares the surgeon the need to enter through the youthful
conjunctiva and Tenon's layers which are substantially thicker than found with
adult eyes. If used, mitomycin-C 0.2-0.4 mgm/cc. is applied to the scleral flap
region and broadly more posteriorly.86 A scleral flap is created
with adequate extension anteriorly to facilitate entry into the anterior
chamber in front of the abnormal anterior insertion of the iris. After removal
of a small section of trabeculum the iridectomy is performed. The flap is
closed with nylon or absorbable sutures and the conjunctiva is closed tightly.
Absorbable 10-0 stitches allow tension on the scleral flap to be released
at a time 2-4 weeks following the procedure. The results of
trabeculectomy procedures are encouraging with 60-70% of patients successfully controlled
during the first 2 years after surgery83, 84, 87. Continued
failures are to be expected to with continued observation. Complications
after trabeculectomy with use of adjunctive anti-fibrosis agents are frequent83,
84,87 After surgery shallowing of the anterior is frequent and choroidal
expansion occurs variably in proportion to the degree and duration of hypotony.
Chronic postoperative hypotony with maculopathy occurs infrequently. Non- progressive
subcapsular lens opacities occur even after only a few weeks of hypotony.
Failure is associated with decreasing evidence of subconjunctival filtration
often without evidence internally of blockage of the sclerostomy. Ciliary
processes can be seen in the internal sclerostomy with both functioning and
nonfunctioning results. Late-onset bleb-related endophthalmitis occurs
acutely with an expected occurrence rate of (7-17 %)83, 84, 88 and
typically occurs within a three year period following surgery.88 Candidate
patients remain at risk when thin-avascular blebs are present even in the absence
of leakage. Following trabeculectomy for PCG thin-avascular blebs were observed
after 18 months in 33% and 67% of eyes following use of 0.2 mgm./cc. and
0.4mgm/cc. of mitomycin-C, respectively.89 Bleb excision followed by
conjunctival advancement is necessary for blebs which become at risk for
infection and is fortunately associated with a low incidence of bleb failure.90 Aqueous drainage devices Implant surgery is an important treatment alternative for
PCG patients who are poor candidates for angle incision therapy and trabeculectomy or who have
proven to be a refractory to these procedures. Molteno pioneered the
contemporary translimbal glaucoma implant and reported favorable results. Their use for
PCG has been widely adopted and their efficacy and complications better understood.91,
92 Introduction of the Baerveldt implant (Pharmacia & Upjohn, Inc.
Kalamazoo, MI) in 1990 made available a silicone non-valved implant and the Ahmed Glaucoma Valve implant
(New World Medical, Inc., Rancho Cucamonga, CA) was designed with a valve to
lessen the occurrence of immediate post operative hypotony. The indications for glaucoma implant
surgery for PCG have expanded beyond being only an option to consider after other
procedures have failed. Implant surgery can follow trabeculectomy at the same
preferred superior site but should not be planned to precede it. Most patients
with PCG will have initial goniosurgery, and if unsuccessful trabeculectomy
will be considered followed by implant surgery. When pre-operative gonioscopy
reveals a severe angle anomaly in a newborn patient goniosurgery has only a
minimal chance of success, and the outcome of trabeculectomy at this age even
with antimetabolate augmentation is poor, hence, these infants are strong
candidates for primary glaucoma implant surgery. When the outcome of 32
patients with a mean age of 7 months treated with glaucoma implants and 19
patients with a mean age of 5 months treated with trabeculectomy were compared
, the success probability at 77 months was 53% and 19% respectively.93
The surgical technique is similar
for all glaucoma implants80. The superior temporal quadrant is the
preferred site to maximize the distance of the drainage plate from the optic
nerve. Following a periotomy the implant device is placed with its anterior
edge approximately 6-7 mm. from the limbus. The tube is shortened and beveled
and an incision is made into the anterior chamber to allow entry of the tube
parallel to the iris, taking into account the frequent anterior insertion of
the iris in PCG infants. Contact between the iris and the tube will result in
corectopia. The tube can be tied with a 7-0 absorbable suture to impede flow
and decrease the risk of hypotony. The tube is then protected with autogenous
sclera or pericardium and the limbal peritomy is closed.94 The results of glaucoma implant surgery the pediatric
glaucomas and for PCG are favorable.95, 96 In a cohort of 14 PCG eyes,
including 9 eyes with a history of previous cycloabalation, success was achieved in 93% (13) of eyes
with the continued use of medications.96 Importantly the potential
success of implant surgery for refractory PCG has greatly decreased the use of
destructive cycloablative procedures. Use of the Ahmed implant for 60 pediatric
glaucoma eyes, including 25 with PCG, IOP control was achieved in 73%(44 eyes)
at last examination with continued use of medications in 77%, however,
complications occurred in 50%(30 eyes).97 The complications of pediatric
glaucoma implant surgery are varied andfrequent.96, 97 Early
hypotony and tube related problems are most common and often require
intervention.96 Glaucoma implant tube exposure puts an eye at
significant risk for infection and post operative endophthalmitis and must be
corrected promptly by recovering the tube.98 Cyclodestruction Cyclodestructive procedures are
selectively used for PCG which has proven refractory to medical therapy and to
the conventional surgical procedures to improve aqueous outflow, and work by
decreasing aqueous production. The required ciliary epithelial ablation can be
clinically produced by cyclocryotherapy, or by transcleral or endoscopic diode
laser cyclophotocoagulation. The indications for using any of
these intentionally damaging procedures must also consider the long term visual
and anatomic prognosis and parents' own expectations for the affected eye. The ocular indications include, a
blind painful eye, a blind eye with a high pressure and rapidly deteriorating
cornea, an eye proven to be refractory to all more conservative treatment
alternatives, an eye with anatomic defects which preclude other glaucoma
procedures, and a patient who is not a candidate for either prolonged general
anesthesia or intraocular surgery. The cycloabalation surgical
procedures differ but have in common the direction of destructive energy
targeted for the ciliary epithelium, and the need for general anesthesia. The
cyclocryotreatment and the transcleral laser probes are applied externally to
the retrolimbal conjunctiva, while the laser endoscope is entered through the
anterior chamber to approximate the ciliary processes. The reported results of
cyclodestructive procedures for PCG patients are difficult to interpret because
of the limited number of reported cases and their use primarily for eyes with
advanced disease, but are of value. The
results of cyclocryotherapy for 37 PCG eyes with the history of previous eye
surgery was compared to 12 eyes without prior procedures and control was
achieved in 31% and 30% respectively.99 Twenty- five PCG eyes were
in a cohort of 64 eyes with pediatric glaucoma treated with cyclocryotreatment
which achieved success in 44%(28) at last examination (Mean, 4.8 ±3.3years)
with an average of 4.1±4.0 treatments for each eye.100 Twenty-six PCG eyes were in a
series of 77 refractory pediatric glaucoma eyes treated with laser diode
cyclophotocoagulation that collectively achieved a success rate of 30% after
approximately 4 years.101Four eyes of 3 patients with PCG and a
history of multiple previous conventional glaucoma procedures were treated with
endoscopic diode laser photocoagulation and success was achieved in 1 eye.102
Nineteen eyes with PCG were included in a series of 69eyes with pediatric
glaucoma treated with a mean of 2.1 sessions per eye; at one year 79% were controlled
below 21mmHg., and 48%were controlled at 5 years.103 Cyclodestructive operations are
followed by many complications including phthisis,100, 101retinal
detachment,100, 101, 103and chronic hypotony and cataracts.99 Not
yet reported is the chronic post cyclodestruction anterior segment syndrome
seen frequently in children successfully controlled by these procedures, and
which is characterized by band keratopathy, corneal edema and endothelial cell
drop out, chronic anterior chamber flare, posterior synechia and microcoria,
and slowly progressive cataracts. The
Future The potential therapeutic use of knowing
the genetic basis for PCG is appreciated. Continued progress in the development
of techniques to target and alter genetic expression of the outflow pathways is
crucial to make such beneficial intervention a therapeutic reality.104Spontaneous
resolution of PCG is clinical evidence which supports the hope that such
intervention could be successful. Evidence that the genetically determined
outflow pathway anomalies can be qualitatively influenced by pharmological
agents provides additional information to support work for medical therapy for
PCG in the future.105The possibility of a degenerative component in
PCG is suggested by the progressive iris stromal abnormalities seem in some
patients and the impaired outflow acquired in PJG which may possess a related
genetic basis.106 Inhibition of this unidentified mechanism may also
prove beneficial. Inevitably children with glaucoma will
present that requires glaucoma therapy. Continued development and utilization
of goniosurgery will be required. Filtration surgery for children unresponsive
to angle therapies must be done with greater confidence for a favorable outcome
without progressive conjunctival deterioration. Glaucoma implants have been
successful for resistant PCG but new devices which are both smaller and more
biocompatible will control IOP even more reliably.
Efforts must continue to define the pediatric safety and efficacy of
glaucoma drugs, which have been developed for adults, to make these agents more
quickly available for children and allow them to be used more confidently. Increased exposure of ophthalmology residents to the challenge and
rewards of caring for children with glaucoma should be encouraged. Support must
become more available to enable this work to be continued
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1. Primary Congenital Glaucoma. 8 month patient with symptomatic
secondary asymmetric anterior segment enlargement. Figure
2. Primary Congenital Glaucoma. Gonioscopic view of the filtration angle
following successful goniotomy procedure. Table
1. The Primary and Secondary Pediatric Glaucomas I. Developmental
Childhood glaucomas
A. Primary congenital glaucoma (PCG)
1 Newborn PCG (iridotrabeculodysgenesis)
2. Infantile PCG (trabeculodysgenesis)
3. Juvenile (Late-recognized) PCG
B. Primary juvenile glaucoma (PJG)
C. Primary angle closure glaucoma
D. Associated with systemic abnormalities
1. Sturge-Weber syndrome
2. Neurofibromatosis (NF-1)
3. Stickler syndrome
4. Oculocerebrorenal syndrome of Lowe (OCRL)
5. Rieger syndrome
6. SHORT syndrome
7. Hepatocerebrorenal syndrome
8. Marfan syndrome
9. Rubinstein-Taybi syndrome
10. Infantile glaucoma with retardation and paralysis
11. Oculodentodigital dysplasia
12. Open angle glaucoma associated with microcornea
and absent frontal sinuses
13. Mucopolysaccharidoses
14. Trisomy 13
15. Caudal regression syndrome
16. Trisomy 21 (Down syndrome)
17. Cutis marmorata telangiectasia congenita
18. Warburg syndrome
19. Kniest syndrome (skeletal dysplasia)
20. Michel's syndrome
21. Nonprogressive hemiatrophy
22. PHACE syndrome
23. Soto syndrome
24. Linear scleroderma
25. GAPO syndrome
26. Roberts' pseudothalidomide syndrome
27. Wolf-Hirschhorn (4p-) syndrome
28. Robinow syndrome
29. Nail-patella syndrome
30. Proteus syndrome
31. Fetal hydantoin syndrome
32. Cranio-cerebello-cardiac (3C) syndrome
33. Brachmann-deLange syndrome
E. Associated with ocular abnormalities
1. Primary newborn glaucoma with iris anomalies
2. Aniridia
a. Congenital onset
b. Acquired onset
3. Congenital ocular melanosis
4. Sclerocornea
5. Congenital iris ectropion syndrome
6. Peters' syndrome
7. Iridotrabecular dysgenesis (iris hypoplasia)
8. Posterior polymorphous dystrophy
9. Idiopathic or familial elevated episcleral
venous pressure 10. Anterior corneal
staphyloma
11. Congenital microcoria with myopia
12. Congenital hereditary endothelial dystrophy
13. Iridocorneal endothelial syndrome (ICE) II. Secondary
glaucomas
A. Traumatic glaucoma
1. Acute glaucoma
a. Angle concussion
b. Hyphema
c. Ghost cell glaucoma
2. Glaucoma following angle recession
3. Arteriovenous fistula
B. Secondary to intraocular neoplasm
1. Retinoblastoma
2. Juvenile xanthogranuloma
3. Leukemia
4. Melanoma of ciliary body
5. Melanocytoma
6. Iris rhabdomyosarcoma
7. Aggressive iris nevi
8. Medulloepithelioma
C. Secondary to uveitis
1. Open angle glaucoma
2. Angle blockage glaucoma
a. Synechial angle closure
b. Iris bombe with pupillary block
c. Trabecular endothelialization
D. Lens related glaucoma
1. Subluxation-dislocation and pupillary block
a. Marfan syndrome
b. Homocystinuria
c. Weill-Marchesani syndrome
d. Axial subluxation progressive myopia syndrome
e. Ectopia lentis et pupillae
2. Spherophakia and pupillary block
3. Phacolytic glaucoma
E. Aphakic glaucoma
1. Lens tissue trabecular obstruction
2. Pupillary block
3. Glaucoma following infantile lensectomy
F. Steroid glaucoma
G. Secondary to rubeosis
1. Retinoblastoma
2. Coats' disease
3. Medulloepithelioma
4. Familial exudative vitreoretinopathy
5. Chronic retinal detachment
H. Secondary angle closure glaucoma
1. Retinopathy of prematurity
2. Microphthalmos
3. Nanophthalmos
4. Retinoblastoma
5. Persistent hyperplastic primary vitreous
6. Congenital pupillary iris-lens membrane
7. Topiramate(Topamax;Ortho-McNeil Pharm. Raritan,NJ,USA)
8. Central retinal vein occlusion
9. Ciliary body cysts
I. Malignant glaucoma
J. Glaucoma associated with increased venous pressure
1. Cavernous or dural A-V shunt
2. Orbital disease
K. Maternal rubella syndrome
L. Intraocular infection
1. Acute recurrent toxoplasmosis
2. Acute herpetic iritis
3. Endogenous endophthalmitis Table
2: Signs and symptoms of glaucoma in infancy and childhood Symptoms Signs Photophobia Epiphora Blepharospasm Red eye Irritability Cloudy cornea Enlarged cornea/eye Poor vision Asymptomatic Irritability Buphthalmos Corneal enlargement Corneal edema Corneal size asymmetry Breaks in Descemet's membrane Iris and pupillary abns. Elevated IOP Visual impairment Myopia/ astigmatism Optic nerve cupping Table
3: PCG Clinical examination History and systemic examination General
inspection (for photophobia, corneal size and asymmetry, systemic defects) Vision
assessment Tonometry Anterior
segment examination (cornea, anterior chamber, iris, pupil ) Gonioscopy Fundoscopy
and optic nerve head evaluation Ultrasonography
Retinoscopy Table
4: Information to be obtained under EUA Intraocular
pressures Corneal
diameters Anterior
segment assessment Gonioscopic
observations Retinoscopy
measurements Optic
nerve head assessment Photographic
documentation Table
5: Differential diagnoses of the classical signs and symptoms of PCG 1. Corneal edema or opacity Ocular Birth trauma
Sclerocornea Keratitis
Limbal dermoid Congenital
hereditary endothelial dystrophy Posterior
polymorphous corneal dystrophy
Anterior
staphyloma Peters' anomaly Systemic Mucopolysccharidoses
I, II, III Mucolipidoses
IV Cystinosis Generalised
gangliosidosis I Infantile
Niemann-Pick disease De
Barsy syndrome Familial
dysautonomia 2. Corneal enlargement Axial myopia Hereditary megalocornea Keratoglobus 3. Epiphora and Ôred eye' Conjunctivitis Corneal abrasion Congenital nasolacrimal duct
obstruction Uveitis Keratitis 4. Photophobia Ocular
Keratitis Aniridia Iritis Cataract Achromatopsia Posterior
polymorphous dystrophy Systemic Albinism Meningitis
Posterior fossa tumor38