Albert & Jakobiec's Principles & Practice of Ophthalmology, 3rd Edition

CHAPTER 198 - Primary Congenital Glaucoma

Sharon F. Freedman

Key Features: Primary Congenital Glaucoma

  

.   

Rare, usually bilateral, inherited defect in the trabecular meshwork.

  

.   

Commonly presents between 3-9 months of age (less often presenting at birth or up to ~3 years of age), and causing buphthalmos and blindness if not treated.

  

.   

Classic 'triad' of presenting symptoms (photophobia, epiphora and blepharospasm) relate to rapid ocular expansion of the infant eye under high pressure, causing corneal enlargement, and frequently also producing breaks in Descemet's membrane (Haab's striae) and resultant corneal edema and opacification.

  

.   

Associated signs of high pressure in the infant eye (in addition to the corneal stretching and opacity) include deep anterior chamber, buphthalmos, myopia, and optic nerve cupping. In extreme cases the lens can actually dislocate.

  

.   

Primary treatment modality is surgical, medications adjunctive.

  

.   

Goniotomy or trabeculotomy (angle surgery) are usually first-line surgical modalities that successfully control IOP in majority of cases (best prognosis with onset at 3-9 months of age).

  

.   

Additional surgical procedures for refractory cases include trabeculectomy (sometimes combined with trabeculotomy by some surgeons), glaucoma implant surgery, and cycloablation, in addition to medication use.

  

.   

Visual loss can result from corneal scarring and optic nerve damage, but often also occurs due to amblyopia in unilateral or asymmetrical cases.

  

.   

Vision in the better seeing eye is at least 20/50 in most cases where glaucoma is stabilized after initial angle surgery.

  

.   

Aggressive early control of glaucoma and attention to refractive errors and amblyopia, as well as life-long follow-up of glaucoma, maximize visual outcome and quality of life in affected children.

DEFINITION

Primary congenital open-angle glaucoma, often termed congenital or infantile glaucoma, is a rare, inherited, developmental defect in the trabecular meshwork and anterior chamber angle. This disease, which has also been called trabeculodysgenesis, usually presents in the newborn or infant with an 'open', albeit abnormal, angle; elevated intraocular pressure (IOP); corneal enlargement or edema, or both; and optic nerve cupping.[1,2] Enlargement of the entire globe in primary infantile glaucoma (buphthalmos, derived from the Greek for ox-eye) was noted early on by Hippocrates (460-377 bc) but only later recognized by von Muralt in 1869 as a form of glaucoma.[3] Although usually diagnosed in the first year of life, primary infantile glaucoma may begin in the second or third year of life, often without prominent corneal edema or enlargement. Before Barkan's application of angle surgery (goniotomy) to treat primary congenital glaucoma in 1938,[4] the visual outlook for affected children was bleak. Although patients with primary infantile glaucoma make up less than 0.01% of ophthalmic patients, they were stated to account for 2-15% of populations in institutions for the blind.[3] Control of IOP is only one challenge in treating children with primary infantile glaucoma; visual loss may occur not only from corneal scarring and optic nerve damage but also as a result of amblyopia related to anisometropia or strabismus, or both (Table 198.1).


TABLE 198.1   -- Causes of Visual Loss in Primary Infantile Glaucoma

Corneal scarring

Cataracts

Optic nerve damage

Anisometropic amblyopia

Strabismic amblyopia

Retinal pigmentary changes, detachment (possible complication after filtration, seton, or cycloablative surgery)

 

Although primary infantile glaucoma is the most common childhood glaucoma, this disease must be distinguished from other primary and secondary glaucomas in children. The presence of associated ocular and systemic abnormalities, either congenital (in other primary glaucomas) or acquired (in secondary glaucomas), helps rule out primary infantile glaucoma. Juvenile open-angle glaucoma, a distinct inherited disease with onset in middle childhood to early adulthood, must also be separately considered (see Chapter 199). A detailed classification system for the childhood glaucomas is presented in Chapter 305.

 

 

DEMOGRAPHICS AND GENETICS

Primary infantile glaucoma occurs in ~1 in 10 000 births.[5] It is bilateral in 65[3]-80%[6] of cases. The ratio of the incidence of males:females is 3:2 in the United States and Europe, but it is 2:3 in Japan.[2,7]This disease is found worldwide without known racial predilection. More than 80% of all patients have an onset of disease within the first year of life, with ~25% diagnosed as newborns and more than 60% presenting by 6 months of age.[8,9]

Although the majority of primary infantile glaucoma cases are sporadic (no known family history), ~10% are familial, usually transmitted as an autosomal recessive trait, with penetrance varying from 40% to 100%.[10,11] This variable penetrance may make it difficult to determine the exact mode of inheritance of this disease; multifactorial and even autosomal dominant mechanisms have been proposed.[2]

Several investigators have localized primary infantile glaucoma-related genes.[12-14] Two loci, GLC3A, linked to the 2p21 region and GLC3B, linked to 1p36 region, have been identified, and the presence of at least a third locus in the human genome responsible for congenital glaucoma is suspected. Mutations in the CYP1B1 (cytochrome P4501B1) gene have been identified in those cases of congenital glaucoma linked to GLC3A.[12,13] Although the role of its gene product in recessively inherited congenital glaucoma is yet to be defined, the CYP1B1 gene codes for cytochrome P4501B1, a monooxygenase that may be responsible for the metabolism of one or more compounds that perform vital functions in the developing eye.[15]

A variety of CYP1B1 mutations have been identified in families with congenital glaucoma worldwide.[16-27] Reddy and colleagues examined 64 unrelated cases of primary congenital glaucoma in southern India, and noted that CYP1B1 mutations accounted for 37% of their cases.[28] Panicker and colleagues further demonstrated a correlation between genotype and phenotype for several CYP1B1 mutations in a large cohort of children with primary congenital glaucoma in the same region of India.[17]

While most of the mutations in CYP1B1 in patients with congenital glaucoma have been identified in genetically homogenous populations (with high prevalence demonstrated in the Saudi Arabian, Slovakian, and Turkish populations, Sena and colleagues recently demonstrated four founder mutations in CYP1B1 in two ethnically heterogeneous populations from the United States and Brazil. These authors propose that the identification of these founder mutations in ethnically diverse populations suggests a higher carrier frequency for these older mutations in the studies populations, such that genetic testing for the founder mutations may lead to productive genetic counseling for congenital glaucoma.[15] The routine genetic testing of children with primary congenital, a laudable goal for the near future, must await better funding of the laboratories currently equipped to do such testing, which is consuming of time and resources.

Primary infantile glaucoma and adult open-angle glaucoma appear to be unrelated diseases. Steroid-induced IOP elevation, a known risk factor for the adult disease, occurs with equal frequency in parents of infants with glaucoma and parents of infants in the general population.[10,29]

Parents of children affected with primary infantile glaucoma, regardless of prior family history, should be cognizant of the real, but small, risk that subsequent offspring will also be affected. The chance of a second child having the disease is no more than 3% but may be as high as 25% if two children have the disease (assuming autosomal recessive inheritance).[2] All siblings of any child with primary infantile glaucoma should be examined carefully; infants should be followed up closely, especially during the first year of life, to exclude this disease.

 

 

PATHOGENESIS

Despite general agreement that abnormal development of the anterior chamber angle obstructs aqueous outflow, the exact nature of this abnormality in primary infantile glaucoma has yet to be understood. Barkan and Worst described early an imperforate membrane, 'Barkan's membrane', covering the surface of the anterior chamber angle.[30,31] In the absence of histologic confirmation of this membrane, and with much subsequent study by numerous investigators, it is generally agreed that aqueous outflow obstruction occurs at the level of the trabecular meshwork itself.[2,32,33]

The normal development of the anterior chamber angle has been studied extensively but is not fully understood. The defect in this development that results in primary infantile glaucoma similarly is not fully defined. Allen and colleagues suggested that the normal angle forms after cleavage of mesodermal tissue, faulty cleavage resulting in abnormal trabecular tissue that is present in primary infantile glaucoma.[34] Mann postulated that the normal angle formed by atrophy, rather than by cleavage, of mesodermal tissue; a faulty process of atrophy was suspected in cases of primary infantile glaucoma.[35] Anderson proposed development of the anterior chamber angle by posterior sliding of uveal tissues relative to the cornea and sclera. The defect in glaucoma was hypothesized to be premature or excessive formation of collagenous beams in the meshwork, preventing the normal posterior sliding of the ciliary body and peripheral iris, and resulting in an anterior iris insertion with trabecular meshwork obstruction (Fig. 198.1).[32] Maumenee had previously documented an abnormal anterior insertion of the ciliary muscle fibers into the trabecular meshwork in cases of infantile glaucoma,[36] which might obstruct the function of this tissue.

Click to view full size figure  

 

FIGURE 198.1  Process of exposing the trabecular meshwork to the anterior chamber during development. (a) If the uveal tract simply splits away by cleavage or by atrophy of tissue, the result would be an angle configuration in which the ciliary muscle extends into the iris and the ciliary processes are on the back of the iris. (b) However, with slippage of the layers caused by a differential growth rate, the ciliary muscle and the ciliary processes that initially overlapped the trabecular meshwork surface come to lie posteriorly.
(a and b) From Anderson DR: The development of the trabecular meshwork and its abnormality in primary infantile glaucoma. Trans Am Ophthalmol Soc 1981; 79:464.

 

 

Kupfer and Kaiser-Kupfer proposed the importance of neural crest cells in the normal development of the anterior chamber angle. Faulty migration or differentiation of these cells was postulated to explain the defects noted in various types of congenital glaucoma.[37] Smelser and Ozanics explained primary infantile glaucoma as a failure of proper rearrangement of anterior chamber angle mesoderm into normal trabecular meshwork, a theory that blends with that of Kupfer and Kaiser-Kupfer.[38]

Primary infantile glaucoma may well result from a developmental arrest of neural crest cell-derived anterior chamber angle tissue, with subsequent aqueous outflow obstruction by one or more mechanisms. These may include compression of the trabecular meshwork beams by a high iris and ciliary body insertion as well as abnormal development of the trabecular meshwork itself.

 

 

CLINICAL MANIFESTATIONS

SIGNS AND SYMPTOMS

Infants with primary infantile glaucoma usually present for ophthalmic evaluation because the parents or pediatrician have noted something unusual about the appearance of the patient's eyes or behavior. Often corneal opacification or enlargement, or both (resulting from elevated IOP), is the sign that signals glaucoma in the infant (Fig. 198.2). In other cases, the child's glaucoma manifests itself as one or more of the 'classic triad' of findings: epiphora, photophobia, and blepharospasm (Fig. 198.3). Photophobia and epiphora result from corneal edema (often with associated breaks in Descemet's membrane, or Haab's striae). The baby may be noted to recoil from bright light and to bury his or her head in a parent's shoulder or crib bedding. Even indoors, the infant may show an apparent reluctance to face upward and may be mistakenly considered shy. Blepharospasm or excessive blinking may be yet another manifestation of photophobia, often accompanying epiphora but without the mucoid discharge so often seen in congenital nasolacrimal duct obstruction.[9,39]

Click to view full size figure  

 

FIGURE 198.2  (a and b) Corneal enlargement and opacification in both eyes of a newborn with severe primary infantile glaucoma. Glaucoma was stabilized with angle surgery and medical therapy (see Fig. 198.6).

 

 

Click to view full size figure  

 

FIGURE 198.3  This infant with primary infantile glaucoma first presented with tearing, photophobia, and corneal enlargement.
Courtesy of David Walton, M.D.

 

 

The severity of presenting signs and symptoms varies among infants with primary infantile glaucoma, likely because of differences in the magnitude and duration of the IOP elevation. For example, newborn infants presenting with enlarged, cloudy corneas presumably suffered elevated IOP in utero, whereas those with milder signs and symptoms may have experienced the IOP elevation beginning some time after birth. Parents and healthcare providers have occasionally failed to recognize glaucoma in infants with clear, but enlarged, corneas (Fig. 198.4).[40] Some bilateral cases may present with such asymmetric signs and symptoms that glaucoma is initially suspected in only the more severely affected eye. In children in whom glaucoma has its onset after 1 year of age, fewer overt signs and symptoms may occur because of the decreased expansibility of the eye.

Click to view full size figure  

 

FIGURE 198.4  This child showed an enlarged but clear right cornea in early infancy, which was not recognized as primary infantile glaucoma until he was 3 years old. The IOP in the right eye was 36 mmHg and responded to goniotomy. Extensive optic nerve cupping was present, with myopic anisometropia and hand-motion vision.

 

 

 

 

DIFFERENTIAL DIAGNOSIS

When many classic findings (such as corneal enlargement and opacification, epiphora, photophobia, and blepharospasm) coexist with elevated IOP and optic nerve cupping, the diagnosis of primary infantile glaucoma poses little challenge. At other times, with one or more of these features absent, other diagnoses must be considered and excluded before a definitive diagnosis of primary infantile glaucoma can be reached (Table 198.2).[2,41]


TABLE 198.2   -- Differential Diagnosis of Classic Findings in Primary Infantile Glaucoma

Conditions sharing epiphora and 'red eye'

  

 

Conjunctivitis

  

 

Congenital nasolacrimal duct obstruction

  

 

Corneal epithelial defect, abrasion

  

 

Keratitis (especially herpes simplex)

  

 

Anterior segment inflammation (uveitis, trauma)

Conditions sharing corneal edema or opacification

  

 

Birth trauma (with Descemet's tears)

  

 

Congenital malformation, anomaly

  

 

Sclerocornea

  

 

Peters anomaly

  

 

Corneal dystrophy

  

 

Congenital hereditary endothelial dystrophy

  

 

Posterior polymorphous dystrophy

  

 

Keratitis

  

 

Herpetic

  

 

Rubella

  

 

Phlectenular

  

 

Storage (metabolic) disease

  

 

Mucopolysaccharidoses

  

 

Mucolipidoses

  

 

Cystinosis

  

 

Oculocerebrorenal (Lowe) syndrome

  

 

Idiopathic (diagnosis of exclusion only)

Conditions sharing corneal enlargement

  

 

Axial myopia

  

 

Megalocornea

Conditions sharing actual or 'pseudo' optic nerve cupping

  

 

Physiologically large optic nerve cup

  

 

Coloboma of the optic nerve

  

 

Atrophic optic nerve

  

 

Hypoplastic optic nerve

  

 

Malformation of the optic nerve

Glaucomas of other types (not primary infantile)

  

 

Other primary developmental glaucomas

  

 

Secondary glaucomas in infancy

Modified from Raab EL: Congenital glaucoma. Perspect Ophthalmol 1978; 2:135 and DeLuise VP, Anderson DR: Primary infantile glaucoma (congenital glaucoma). Surv Ophthalmol 1983; 28:1.

 

 

The isolated occurrence of epiphora in the infant, often accompanied by mucopurulent discharge, suggests nasolacrimal duct obstruction. Any of the various types of conjunctivitis in the infant may present with epiphora and a 'red eye', but with photophobia usually absent. When epiphora, photophobia, or blepharospasm, or a combination, accompanies a red eye, ocular inflammation (uveitis) and corneal injury or keratitis (e.g., abrasion, herpetic dendrite) should be considered.

Isolated corneal enlargement occurs in megalocornea and high axial myopia. Infants with megalocornea often present with symmetrically enlarged, clear corneas of diameter greater than 14 mm, with deep anterior chambers, iridodonesis, and without elevated IOP or optic nerve cupping. Megalocornea is a rare, X-linked recessive disorder; families have been described in which some individuals have megalocornea alone, whereas others present with primary infantile glaucoma.[42,43] Eyes with axial myopia often show enlargement of the globe and cornea but without elevated IOP; posterior segment examination usually demonstrates an oblique optic nerve head insertion and scleral crescent, often with suggestive chorioretinal findings. Any infant with corneal enlargement should be followed up over time for the development of elevated IOP.

Corneal edema or opacification may occur in the setting of birth trauma (with resultant Descemet's tears), congenital anomalies (e.g., sclerocornea, Peters anomaly), corneal dystrophies (e.g., congenital hereditary endothelial dystrophy or posterior polymorphous dystrophy), infection (e.g., maternal rubella), and storage diseases (e.g., mucopolysaccharidoses, mucolipidoses, cystinosis). Birth trauma may result in tears of Descemet's membrane that mimic Haab's striae of primary infantile glaucoma. Accompanying facial trauma, the unilateral presence and often vertical orientation of the traumatic Descemet's tears, and the absence of elevated IOP, corneal enlargement, or optic nerve changes help distinguish birth trauma from glaucoma.[44] The corneal and associated anterior segment abnormalities found in sclerocornea and Peters anomaly usually help distinguish these conditions from primary infantile glaucoma.[45] Glaucoma may coexist with these congenital anomalies.[46]

Posterior polymorphous dystrophy, an autosomal dominant condition, may present in an infant with photophobia and temporary IOP elevation; glaucoma may also accompany this condition.[47] Infants with congenital hereditary endothelial dystrophy, autosomal recessive in inheritance, present with bilateral corneal edema and stromal thickening, but usually without corneal enlargement or IOP elevation.[48,49]This disorder may rarely also be complicated by coexisting congenital glaucoma.[50]

Maternal rubella syndrome can cause glaucoma that is similar to primary infantile glaucoma in its presentation and response to therapy. Associated cataracts, keratitis, and systemic findings (deafness, mental retardation, cardiac anomalies) help distinguish this disorder, which is now becoming rare in modern societies; a tribute to rubella immunization programs that prevent later maternal infection.[49]

In the case of metabolic (storage) diseases, numerous systemic abnormalities usually help in excluding primary infantile glaucoma. In oculocerebrorenal (Lowe) syndrome, an X-linked recessive condition, accompanying cataracts, microphthalmia, and systemic findings (aminoaciduria among others) help distinguish this disease from primary infantile glaucoma. Glaucoma coexists in the majority of these cases.[51]

Although other nonglaucomatous eye conditions may share one or more findings with primary infantile glaucoma, care must be taken to rule out other types of childhood glaucoma in each of these cases. For example, glaucoma may complicate uveitis and has been reported in the setting of storage disease, corneal dystrophy, congenital anomalies such as Peters anomaly, and megalocornea. Glaucoma may even occur coincidentally with congenital nasolacrimal duct obstruction.[52]

 

 

OCULAR EXPANSION

The neonatal globe is distensible and often enlarges greatly with exposure to elevated IOP. Stretching of the infant eye is not limited to the cornea and may also involve the anterior chamber angle structures, sclera, optic nerve, scleral canal, and lamina cribrosa.[2] The normal newborn's cornea has a horizontal diameter ranging from 9.5 to 10.5 mm, which enlarges ~0.5-1.0 mm in the first year of life (Table 198.3).[48,53,54] Before 1 year of age, corneal diameters of 12-12.5 mm are suggestive of glaucoma. Asymmetry in diameter between the two corneas, or a corneal diameter of 13 mm or more at any age, strongly suggests an abnormality. From ~3 until 10 years of age, although the cornea no longer enlarges with elevated IOP, continued stretching of the sclera may lead to progressive myopia and astigmatism.[2]


TABLE 198.3   -- Corneal Diameter in Children: Normal and Glaucomatous Eyes

 

Corneal Diameter (horizontal, in mm)

Age

Normal

Suggestive of Glaucoma

Term (newborn)

9.5-10.5

11.5

1 year

10-11.5

>12-12.5

2 years

11-12

>12.5

Older child

?12

>13

Data from Becker B, Shaffer RN: Diagnosis and therapy of the glaucomas. St Louis: CV Mosby; 1965; and Kiskis AA, Markowitz SN, Morin JD: Corneal diameter and axial length in congenital glaucoma. Can J Ophthalmol 1985; 20:96.

 

Breaks in Descemet's membrane may occur as the infant's cornea stretches, resulting in acute localized corneal edema, followed by deposition of new basement membrane into hyaline ridges (called Haab's striae). Haab's striae, often oriented horizontally or curvilinearly, are found in ~25% of eyes diagnosed with primary infantile glaucoma at birth, and in more than 60% of those diagnosed at 6 months of age (Fig. 198.5).[55] By contrast, breaks in Descemet's membrane arising from obstetric trauma (usually involving the use of forceps) tend to have a more vertical orientation and to present at birth. Corneal edema may clear rapidly and completely after normalization of IOP in infants with glaucoma, but permanent scars result at sites of Descemet's breaks, and rarely does an enlarged cornea decrease notably in size (Fig. 198.6).

Click to view full size figure  

 

FIGURE 198.5  Haab's stria in infantile glaucoma, viewed through a Koeppe gonioscopy lens.
From Freedman SF, Walton DS: Approach to infants and children with glaucoma. In: Epstein DL, ed. Chandler and Grant's glaucoma. 4th edn. Baltimore: Williams & Wilkins; 1997.

 

 

Click to view full size figure  

 

FIGURE 198.6  Enlarged but clear corneas (14 mm diameter) persist in this child after control of primary infantile glaucoma. Corrected vision is 20/40 OU. (Same patient as shown in Fig. 198.2.)

 

 

The sclera also expands gradually when exposed to elevated IOP, with increasing axial length and resultant myopia and astigmatism.[43] Myopia, astigmatism, and anisometropia were all common findings in eyes of children with primary infantile glaucoma (the latter almost always present in unilateral cases).[43,56] Ultrasonography has been used to record axial length changes in infant eyes with elevated IOP, but it seems less helpful than corneal diameter in the evaluation of these glaucomatous infant eyes.[53]

 

 

OPTIC NERVE CUPPING

Optic nerve cupping occurs as a result of elevated IOP in children with primary infantile glaucoma, but its course is often different from that seen in adult glaucoma patients. In eyes of young glaucoma patients, there is often generalized enlargement of the optic cup with preservation of an intact neuroretinal rim. This symmetric optic nerve cupping has been attributed to stretching of the optic canal and backward bowing of the lamina cribrosa.[57] Although this pattern of optic nerve cupping can develop early and rapidly in infants with glaucoma, striking reversal of cupping may result with IOP reduction.[2] By contrast, both adults and children (especially older ones) with advanced glaucoma suffer loss of neuroretinal rim tissue, especially at the vertical disk poles, with extension of the optic cup to the disk margins.[2]

Significant optic nerve cup size, and asymmetry of cupping between fellow eyes, suggests but does not confirm glaucoma in an infant. Illustratively, the cup:disk ratio exceeded 0.3 in 68% of 126 eyes with primary infantile glaucoma examined by Shaffer and Hetherington,[58] but in only 2.6% of 936 normal newborn eyes examined by Richardson.[57] Marked optic cup asymmetry was noted in only 0.6% of normal eyes in this study, contrasted with 89% for infants with monocular glaucoma.[57]

 

 

IOP ELEVATION

IOP levels and measurement in children with glaucoma is discussed in the section on Diagnostic Examination.

Diagnostic Examination

Every infant and child suspected of possible primary infantile glaucoma (or any other type of glaucoma) should have a full ophthalmic office evaluation. The goals of this examination include (1) confirming or excluding the diagnosis of glaucoma, (2) determining whether the glaucoma (if present) is primary infantile glaucoma or a different type, and (3) obtaining additional medical information needed to plan for subsequent anesthesia (for further examination and surgery, if needed). This initial office examination may conclude the diagnostic process if glaucoma can be confidently excluded.

 

 

OFFICE EXAMINATION

History and Equipment

Parents and caretakers can often provide valuable information regarding the presence or absence of characteristic signs and symptoms of primary infantile glaucoma. Additionally, relevant family history can be useful, as can any information about systemic abnormalities, possible ocular trauma, or drug or medication exposure. The office examination can be optimized by including the use of a portable slit lamp, millimeter ruler, Tono-Pen or Perkins tonometer (or both), and Koeppe diagnostic gonioscopic lenses.

Assessment of Vision, Ocular Adnexa, and Corneas

After one has evaluated the infant's visual function and overall general appearance, the penlight and direct ophthalmoscope may be helpful for inspecting the adnexa and corneas (leaving the infant unruffled for attempts at tonometry). During the external examination, one looks for abnormalities (e.g., lid malformations) to suggest congenital syndromes that may exclude glaucoma of the primary infantile type and for signs of lacrimal system obstruction that may explain epiphora. Corneal edema, opacification, and enlargement can usually be detected easily; recent Haab's striae often present as localized areas of corneal edema and opacification. One can estimate corneal diameter by holding a millimeter ruler just in front of each cornea.[43] Occasionally, one may notice subtle differences in overall size between the two corneas that are not obvious when corneal diameter measurements are made. Since the area of a circle varies as the square of its radius, it seems reasonable that the observer's eye may detect differences in area more easily than differences in diameter of a patient's two corneas.

Tonometry and IOP

The best IOP measurements are those achieved in a cooperative patient using only topical anesthesia, since IOP may be falsely elevated in a struggling patient and is often unpredictably altered by systemic sedatives and anesthetics (Table 198.4). A sleepy or hungry infant will often permit tonometry while taking a bottle in her or his parent's arms (Fig. 198.7). Although various instruments have been used for IOP measurement in children, the Perkins applanation tonometer and the Tono-Pen (a hand-held Mackay-Marg-type tonometer) rank highly in terms of accuracy and ease of use in these patients (Fig. 198.8).[59-62] Children as young as 3 or 4 years of age can often cooperate with Goldmann applanation tonometry.


TABLE 198.4   -- Intraocular Pressure and Sedatives and Anesthetics

Sedative-Anesthetic Agent

Route of Administration

Usual Effect on Intraocular Pressure

Chloral hydrate

Oral or rectal

?

Methohexital (Brevital)

Rectal, IM, IV

±?

Midazolam

Same as above

±?

Ketamine

IM

±?

Halothane (and similar agents)

Inhalation

?-???

Oxygen

Inhalation

?

Nitrous oxide-oxygen

Inhalation

?

Succinylcholine

IV

???

Endotracheal Intubation

-

???

From Freedman SF, Walton DS: Approach to infants and children with glaucoma. In: Epstein DL, ed. Chandler and Grant's glaucoma. 4th edn. Baltimore: Williams & Wilkins; 1997. IV, intravenous; IM, intramuscular.

 

 

Click to view full size figure  

 

FIGURE 198.7  Office tonometry using the Perkins applanation tonometer.
Courtesy of David Walton, M.D.

 

 

Click to view full size figure  

 

FIGURE 198.8  Office tonometry using the Tono-Pen.

 

 

Infants and young children with normal eyes appear to have IOP values lower than those expected in adults.[63-65] Using a Pulsair noncontact tonometer, Pensiero and colleagues reported a mean IOP of 9.59 ± 2.3 mmHg in premature and newborn infants, which rose gradually with increasing subject age, reaching 13.95 ± 2.49 mmHg by 7-8 years, and remaining essentially constant through the middle teenage years (Fig. 198.9).[64] Radtke and Cohen similarly found the mean IOP of unanesthetized newborns to be 11.24 ± 2.4 mmHg, using a Perkins applanation tonometer.[65] Infants with primary infantile glaucoma commonly present with unanesthetized IOPs in the range of 30-40 mmHg, although occasionally values greater or less than this range occur.[66] Useful tonometry cannot be achieved in a struggling infant because the IOP will be falsely and unpredictably elevated by the child's Valsalva maneuvers.

Click to view full size figure  

 

FIGURE 198.9  Normal IOP in children: Variation with age.

 

 

Anterior Segment Examination

The portable slit lamp provides details about the anterior segment after tonometry has been performed (or attempted). The typical corneal findings and abnormalities associated with primary infantile glaucoma have been described above. Nonetheless, the magnification of the portable slit lamp provides opportunity to further evaluate the cornea for the presence, location and severity of edema and Haab's striae, as well as stroma scarring in more chronic or severe cases. An unusually deep anterior chamber is commonly found in eyes with primary infantile glaucoma. Iris or lens abnormalities may provide clues to other diagnoses (such as aniridia or Axenfeld-Rieger syndrome). Gonioscopy, which can sometimes be performed in the office using a Koeppe contact lens and a portable slit lamp, helps identify the glaucoma type and severity, rather than its presence or absence. Gonioscopy can be more easily performed with the patient under anesthesia (unless glaucoma can be excluded by the office examination and findings). Gonioscopic findings are discussed at greater length further on.

Fundus Examination

The presence and extent of optic nerve cupping may be evaluated with direct or indirect ophthalmoscopy, or both; use of a 14-D lens with the latter provides additional magnification. As with gonioscopy, disk examination should be repeated with the patient under anesthesia, unless normal findings and IOP have obviated this next step.

Refraction and Perimetry

Myopia (and astigmatism) is often present in eyes of infants with primary infantile glaucoma. In unilateral cases, the affected eye is almost invariably more myopic. Astigmatism often results when Haab's striae cross the visual axis.

Children can often begin performing useful visual field testing at ~7-8 years of age, in the absence of nystagmus or cognitive delay. When glaucomatous loss can be documented in children with glaucoma, the visual fields are reportedly similar to those in adult-onset glaucoma, with an initial predilection for the arcuate areas[67,68]. Newer, faster testing algorithms (such as SITA, discussed in Chapter 196 on Visual Field Testing) may allow younger children to perform automated (Humphrey) visual field testing more reliably.[69] Frequency doubling perimetry (discussed in Chapter 196) may also hold promise for screening and following visual fields in children with known or suspected glaucoma.[70,71]

Other Office Testing Techniques

Central corneal thickness Measurement: Central corneal thickness (CCT, discussed in Chapter 200), measured by ultrasound pachymetry, has been important in the evaluation of adults with suspected and proven open-angle glaucoma,[72-76] and may play a role in the evaluation of children with glaucoma as well. In normal adult eyes there is a positive association between CCT and measured IOP (by both Goldmann applanation and Tono-Pen tonometry), and several 'correction factors' have been proposed for adjusting the measured IOP upward or downward in eyes with CCT higher or lower than the average value of ~540-550 ?m.[75,77-79] In a recent study of adult eyes, it has further been demonstrated that at several fixed known IOPs, measured IOP is higher when the CCT is thicker.[80]

Various authors have reported CCT values in infants and children; CCT of normal eyes ranges from ~540 ?m (6-23 months) to ~550-560 ?m for older children, with one report showing thinner CCT in black than white children.[81-87] CCT has been shown to be thinner in children with congenital glaucoma, and is probably a function of the larger, stretched corneas of many of these children.[86] One published study has confirmed a positive association between CCT and measured IOP in normal eyes of children, with a slope of ~2-3 mmHg in measured IOP per 100 mm increase in CCT.[84]

While measurement of CCT has become a standard part of the examination for adults with suspected or established glaucoma, its importance in the evaluation of children with glaucoma has yet to be well delineated. Measurement of CCT in children with congenital glaucoma may be reasonable once corneal edema has cleared, as one additional data input to assist in establishing a target IOP for each given eye.

Imaging Techniques: Fundus photography, Optical Coherence Tomography

Fundus photography of the optic disks has long been a mainstay in the evaluation of adults with glaucoma over time, and is useful in cooperative children with clear visual axes and without substantial nystagmus.

Optical coherence tomography (OCT) is a noninvasive imaging technique which can measure the thickness of the peripapillary nerve fiber layer, as well as the macular area and volume (discussed in Chapter 197). Several recent publications have reported OCT values for the peripapillary nerve fiber layer and macular region of normal eyes in children.[88-90] OCT demonstrates that adult eyes with primary open-angle glaucoma have a reduction in the peripapillary nerve fiber layer as well as the macular thickness and volume compared to those same parameters measured in normal adult eyes.[91-97] Two recent publications have shown that children with glaucoma have thinner peripapillary nerve fiber layer and lower macular volumes than those with normal eyes.[90,98] OCT and similar noninvasive imaging technologies may prove useful in assessing nerve fiber layer loss in children, and may be especially helpful for those children too young to perform reliable visual field testing. Currently, OCT is limited to those eyes with clear visual axes and without significant nystagmus; these sames eyes pose challenges to other evaluation techniques such as visual fields and fundus photography.

Unless the office examination adequately excludes the diagnosis of primary infantile (or other) glaucoma, an examination with the patient under anesthesia (or sedation; see further ahead) is usually warranted for further diagnosis and probably for surgical intervention (see section on Treatment).

 

 

EXAMINATION UNDER ANESTHESIA

General Anesthesia versus Sedation

General anesthesia in the operating room is usually preferable to conscious sedation because it allows surgical intervention without further delay once the diagnosis of primary infantile glaucoma is confirmed. By contrast, conscious sedation with chloral hydrate may be particularly useful when IOP determination is critical to the actual diagnosis of glaucoma because this agent appears to affect measured IOP in children minimally.[99] Jaafar and Ghulamqadir have reported no serious systemic side effects with oral doses of chloral hydrate as high as 100 mg/kg for the first 10 kg, then 50 mg/kg for each additional kg.[99] Basic guidelines for performing sedation with chloral hydrate (and other 'conscious sedation') within many medical centers currently include (1) patient evaluation by a physician before administration of medication, (2) informed consent to include risks of conscious sedation, (3) minimum of two available personnel (the operator, or physician performing the examination, as well as the monitor, or assistant trained to monitor the patient), (4) patient monitoring (and documentation) to include continuous pulse oximetry, as well as other vital signs and level of consciousness (recorded at least every 10 min), (5) minimal equipment available to include emergency airway equipment (e.g., oxygen, suction), pulse oximeter, blood pressure monitor, and cardiac arrest cart. Currently this policy at our institution limits oral chloral hydrate administration to 100 mg/kg, up to a maximal dose of 1 g. Children weighing much more that 10 kg often do not fall asleep with this regimen.

General Anesthesia and the Ophthalmic Examination

Tonometry should be performed during the earliest possible moments after anesthesia induction and before endotracheal intubation. Unfortunately, most sedatives, narcotics, and inhaled anesthetic agents variably alter IOP measurements in children, as does endotracheal intubation and even inhalation of 100% oxygen (see Table 198.4).[100-108] The truly elevated IOP fortunately often remains in an abnormal range, even with the patient under anesthesia. Asymmetric IOP measurements between fellow eyes more strongly suggest abnormality than do bilateral borderline IOP readings taken under anesthesia. The IOP recorded under anesthesia should never dictate the diagnosis of glaucoma; in the absence of other evidence, eyes with elevated IOP under anesthesia should be followed-up closely but conservatively. Conversely, when glaucoma is suggested by corneal and optic nerve findings, low IOP readings under anesthesia should not provide false reassurance.[66] After tonometry and brief external examination, one may proceed with corneal diameter measurements, followed by slit-lamp examination of the anterior segment, and Koeppe gonioscopy (Table 198.5).


TABLE 198.5   -- Examination Under General Anesthesia: Suggested Sequence

Tonometry (as early as possible after induction and before intubation)

External examination (brief)

Anterior segment examination

Corneal diameter measurement

Koeppe gonioscopy

Fundus examination (optic disc)

Ultrasound pachymetry to measure central corneal thickness (omit if edema present)

Ultrasound (axial length measurement and/or B-scan if indicated)

Optic nerve photography, refraction (if pupil large or dilated)

Appropriate surgical procedure (if indicated by prior findings)

 

The anterior chamber angle has a characteristic, although slightly variable, appearance in primary infantile glaucoma (Fig. 198.10). Usually the iris has an insertion more anterior than that in the normal infant, with altered translucency of the angle face rendering rather indistinct the ciliary body band, trabecular mesh, and scleral spur. The scalloped border of the iris pig-|ment epithelium and the trabecular meshwork itself, which is often prominent in infantile glaucoma, may appear through the translucent peripheral iris stroma as if viewed through a 'morning mist.'[31,32]

Click to view full size figure  

 

FIGURE 198.10  Gonioscopic view (through a Koeppe gonioscopy lens) of an eye with infantile glaucoma. (Same eye as shown in Fig. 198.5.)

 

 

After gonioscopy, optic nerve examination can often be accomplished using the direct ophthalmoscope through a Koeppe lens (and undilated pupil). Ultrasound evaluation can be useful to measure both the axial length of the eye (for baseline and comparative purposes over time) as well as to evaluate the fundus if corneal opacity or a small pupil precludes an adequate view. In eyes after tube-shunt surgery, ultrasound can also help confirm the patency of the system by confirming a fluid-filled cavity in the quadrant(s) with the tube-shunt reservoir (see further ahead).

If primary infantile glaucoma has been previously, or by this time, confirmed, one may proceed directly to appropriate surgical intervention (see section on Treatment). The entire examination under anesthesia can often be accomplished using a mask only, reserving endotracheal intubation until the need for surgical intervention has been confirmed in the operating room.

 

 

TREATMENT

Surgical intervention constitutes the definitive treatment modality for primary infantile glaucoma, although medications play an adjunctive role. Angle surgery (goniotomy or trabeculotomy) should be attempted as the initial procedure in most cases (see further ahead). Although other treatment modalities exist for eyes that do not respond adequately to angle surgery and pharmacologic therapy, the optimal treatment regimen must be fashioned individually for each given case (Table 198.6).


TABLE 198.6   -- Treatment Sequence in Primary Infantile Glaucoma

  

 

Secure the diagnosis of primary infantile glaucoma

  

 

Classic features to confirm on examination

  

 

Elevated IOP

  

 

Corneal enlargement, edema, Haab's striae

  

 

Optic nerve cupping

  

 

No other ocular diseases

  

 

Proceed to treatment if primary infantile glaucoma confirmed (discussed under Angle surgery)

  

 

Proceed to appropriate treatment of other types of infantile glaucoma

  

 

Careful follow-up as indicated if glaucoma not confirmed

  

 

Angle surgery

  

 

Goniotomy (may repeat one or more times)

  

 

Primary congenital (infantile) open-angle glaucoma

  

 

Cornea clear enough to permit gonioscopic angle view

  

 

Trabeculotomy (may repeat one time)

  

 

Same as for goniotomy, but preferred in the presence of corneal opacification

  

 

Performed by some surgeons after two goniotomies have failed

  

 

May be combined with trabeculectomy (discussed under Filtration Surgery)

  

 

Medical therapy (see Table 198-7)

  

 

Preoperatively, to help clear cornea for angle surgery

  

 

To temporize when infant unstable for anesthesia, surgery

  

 

Adjunctive modality once angle surgery has been completed if IOP too high

  

 

Adjunctive modality after other incisional or cycloablation if IOP too high

  

 

Filtration surgery

  

 

Combined trabeculotomy-trabeculectomy

  

 

When trabeculotomy cannot be completed (failure to cannulate Schlemm's canal)

  

 

Failed previous angle surgery (?two goniotomies or trabeculotomies, or both)

  

 

Preferred to trabeculotomy as initial surgery by some surgeons in severe newborn cases

  

 

Trabeculectomy (almost always with intraoperative mitomycin C)

  

 

After angle surgery (and medication) have failed to control IOP

  

 

Relative contraindication if <1 yr of age at surgery, or poor compliance

  

 

Drainage implant (seton) surgery

  

 

Failed trabeculectomy with intraoperative mitomycin C and reasonable visual potential

  

 

High risk for complication or failure with trabeculectomy (<2 yr old, Sturge-Weber, aphakia)

  

 

High risk for infection with trabeculectomy (poor hygiene, poor compliance, aphakia)

  

 

Cyclodestructive procedures

  

 

Transscleral Laser cycloablation (diode laser preferred)

  

 

Failed angle surgery (and medications) and minimal visual potential

  

 

Failed trabeculectomy or seton, or both (and medications) with poor central vision

  

 

Failed all other surgical interventions and medications

  

 

Anatomy precludes intraocular glaucoma surgery (more common with anterior segment dysgenesis)

  

 

Endoscopic diode laser cycloablation

  

 

Failed angle surgery (and medications)

  

 

Failed trabeculectomy and/or drainage implant surgery

  

 

High risk for failing trabeculectomy and/or drainage implant surgery

  

 

May have already failed transscleral diode laser cycloablation (surgeon's preference)

  

 

Cyclocryotherapy

  

 

Failed other forms of cycloablation, or very distorted anterior segment anatomy

  

 

Repeat therapy in selected quadrants after previous cyclocryotherapy

  

 

Long-term follow-up

  

 

Lifetime, even if IOP controlled

  

 

Aggressive treatment of amblyopia to maximize vision once IOP controlled

 

IOP, intraocular pressure; Nd:YAG, neodymium:yttrium-aluminum garnet.

 

 


TABLE 198.7   -- Using Topical Glaucoma Medications in Congenital Glaucoma

Medication (Class, Name)

Indications

Contraindications/Side Effects

Beta-Blockers

  

 

Nonselective (timolol, etc.)

  

 

Selective (betaxolol, may be safer for reactive airways)

1st-line for many, 2nd-line for some older children

  

 

Systemic effects: bronchospasm, bradycardia;

  

 

Avoid in premature or tiny infants, children with reactive airways; begin with 0.25% in small, higher risk children

Carbonic Anhydrase Inhibitors (topical)

Dorzolamide, Brinzolamide

1st- or 2nd-line in young children, add well to other classes

Systemically safe; Probably best to avoid or use as later option in children with compromised corneas, especially with corneal transplant

Miotics

Echothiophate iodide, Pilocarpine

Echothiophate used rarely in aphakia; pilocarpine useful after angle surgery, not to lower IOP

  

 

Systemic effects (echothiophate):

  

 

Diarrhea (sometimes), interaction with succinylcholine for general anesthesia, possible pro-inflammatory effect; (both) headache; (both) myopic shift

Adrenergic Agonists

Epinephrine compounds

Not very useful

Systemic effects: hypertension, tachycardia

Alpha-2 agonists

 

 

-Apraclonidine (0.5%)

During/after angle surgery; short-term in infants & after corneal transplant

Systemically usually safe; effect may wear off; rarely local allergy or red eye

-Brimonidine

Only in older children!!! Usually 3rd-line, last resort before more surgery or oral CAI

DO NOT USE IN INFANTS/SMALL CHILDREN < ?40 lbs (may cause bradycardia, hypotension, hypothermia, hypotonia, apnea (especially if used with beta-blocker))

Prostaglandins and similar

Latanoprost; travoprost; bimatoprost

Usually 2nd- or 3rd-line after beta blockers and topical CAIs

Systemically safe; long, thick, eyelashes; redness common (especially with bimatoprost); use caution before surgery (?bleeding or inflammation risk)

 

JOAG (juvenile open-angle glaucoma)

CAI (carbonic anhydrase inhibitor)

 

 

MEDICAL TREATMENT

Medications play an adjunctive role to surgery in the therapy of primary infantile glaucoma (Table 198.6 and 198.7). Preoperatively, medications may help clear the cornea to facilitate goniotomy, and postoperatively, they may help control IOP until the adequacy of the surgical procedure has been verified. Medical therapy is also indicated in managing those difficult cases in which surgery poses life-threatening risks or has incompletely controlled the glaucoma.[2] Many obstacles conspire against the success of chronic medical therapy for primary infantile glaucoma; for example, inadequate IOP control, difficulties with long-term compliance, and potential adverse systemic effects of protracted therapy.

The child with glaucoma often adheres to his/her prescribed ocular medications quite well in the early years, especially when strong family support is present. However, complicated dosing regimens can profoundly affect the child's and the family's quality of life, as well as compliance. When needed to achieve the target IOP, additional medications should be added to one eye at a time (monocular trial) when possible, preferably without other changes in the medication schedule.

Most of the commercially available glaucoma drugs in the United States today were approved without any data on their safety in children. The FDA is currently encouraging pharmaceutical companies to test their newer drugs in children, and some have done so, as indicated on the package insert (such as with dorzolamide, for example).[109]

The glaucoma drugs can be divided into five main types, which will be discussed briefly as they relate to the treatment of children with primary infantile glaucoma.

Carbonic Anhydrase Inhibitors

Acetazolamide (Diamox) has effectively reduced elevated IOP in infants and children with primary infantile (and other types of) glaucoma for decades, and often lowers IOP in these patients ~20-35%. When administered orally with food or milk three or four times daily (total dose 10-20 mg kg?1 day?1), acetazolamide is often well tolerated.[2,110] Parents sometimes note diarrhea, diminished energy levels, and loss of appetite in children on this therapy, requiring dosage adjustment or discontinuation. The metabolic acidosis that has been reported in infants may be ameliorated with oral sodium citrate (Bicitra) (1 mEq kg?1 day?1).[66]

The topical carbonic anhydrase inhibitor dorzolamide (Trusopt) offers an excellent alternative to acetazolamide for some patients. In a small cross-over trial, 11 children whose glaucoma was controlled on topical ?-blockers and oral acetazolamide switched from the oral acetazolamide to topical dorzolamide tid in the study eye. Mean IOP reduction on the topical agent was ~25%, compared with ~35% on acetazolamide.[111] Although systemic side effects occurred commonly on acetazolamide in these patients, no adverse effects were noted on the topical dorzolamide. In a recent prospective, randomized study of dorzolamide versus timolol in children under age 6 with elevated IOP, dorzolamide was found to be effective (IOP reduction ~20% from baseline) and safe.[109] The addition of dorzolamide to oral acetazolamide has been reported to reduce IOP further than when dorzolamide is used alone (AlexLevin, personal communication).

A second topical carbonic anhydrase inhibitor, brinzolamide (Azopt), has also been well tolerated by children, with similar IOP reduction to dorzolamide, but no published studies are yet available to our knowledge.

The carbonic anhydrase inhibitors are very useful drugs for treating pediatric glaucoma patients, and may be appropriate first- and second-line agents, respectively, in cases where beta-blocker use is contraindicated, or inadequately effective (see further ahead).

Miotics

Miotic drugs have a limited role in treating patients with primary infantile glaucoma, perhaps in part because of the abnormally high insertion of the ciliary muscle into the trabecular meshwork.[36,48] Miotics have been useful in achieving miosis just before and after angle surgery (see further ahead).[66] Phospholine iodide therapy occasionally assists in IOP control but has sometimes been accompanied by diarrhea[48] and requires care in the concurrent use of succinylcholine for general anesthesia. Its use is often limited to treatment of aphakic eyes with glaucoma. Older (phakic) children often suffer substantial visual blur attributable to miotic-induced ciliary spasm and resultant myopia.

?-Adrenergic Antagonists (?-Blockers)

Topical ?-blockers have played an important role in treating children with primary infantile glaucoma since timolol became available in 1978. Several studies have examined the role of timolol in treating uncontrolled childhood glaucomas, but none has addressed solely primary infantile glaucoma patients.[112-115] In these studies, mean IOP decreased between ~20 and 30%, with IOP controlled in a substantial fraction over several years of follow-up. Although uncommon, systemic side effects can occur in children treated with topical ?-blockers. The most severe of these have included acute asthma attacks, bradycardia,[113,115] and apneic spells (the latter in neonates).[116,117]

Passo and colleagues measured plasma timolol levels in children treated with topical 0.25% timolol and in adults treated with 0.5% timolol. Plasma drug levels recorded in the children ranged from 3.5 ng/mL in a 5-year-old up to 34 ng/mL in a 3-week-old infant and far exceeded those in the adults (range 0.34-2.45 ng/mL).[117] Topical timolol therapy may result in high plasma drug levels in infants and children, who have a small volume of distribution for the drug compared with their adult counterparts. Therefore, timolol treatment in small children should always begin with 0.25% drops and should exclude children with a history of asthma or bradycardia. Topical ?-blockers should be used with extreme caution in neonates, who may be especially susceptible to apnea. Punctal occlusion, when feasible, should be performed by parents or caretakers.[112]

Few data are available on the use of topical ?-blockers other than timolol in the treatment of primary infantile or other childhood glaucomas. As a relatively ?1-selective drug, betaxolol (Betoptic) may be less likely than the nonselective ?-blockers to precipitate acute asthma attacks in children (which may present as coughing). The remaining nonselective ?-blockers would be expected to display risks and efficacy similar to that of timolol. ?-Blockers have an additive effect to carbonic anhydrase inhibitors when used in children with glaucoma.[114]

Topical beta-blockers still have an important role in treating children with glaucoma, despite their contraindication in some cases. These drugs are appropriate first-line drugs for many children.

Adrenergic Agonists

Epinephrine compounds have been used in infants and children with glaucoma,[41,48] but there are few published data documenting the extent of IOP reduction to be expected from these drugs or their optimal dosing schedules. Epinephrine compounds pose risks of systemic side effects (e.g., tachyarrhythmias, hypertension) as well as many ocular ones (e.g., irritation, reactive hyperemia, adrenochrome deposits). Based on studies of adult patients, adding either dipivefrin (Propine) or epinephrine to a nonselective ?-blocker should produce minimal additional IOP reduction.[118]

There are no published data available involving the use of the alpha-2 agonist apraclonidine (Iopidine) to treat children with glaucoma. This drug has been found (as the 0.5% solution) to be valuable in the setting of goniotomy to minimize intraoperative bleeding (see section on Goniotomy). It may also have a short-term role for treating infants who cannot tolerate beta-blockers, or who have had recent corneal transplantation (in whom one therefore may wish to avoid topical carbonic anhydrase inhibitors). The occurrence of somnolence to topical 0.5% apraclonidine has been reported, but it is rare.[119]

Brimonidine (formulated as brimonidine 0.2%, as well as Alphagan P 0.15 and 0.10%) can be useful in reducing IOP in older children, but must be used with extreme caution in younger children. Its use should be avoided altogether in infants and in small and underweight children, due to its propensity to cause severe systemic side effects. Topical brimonidine administration has caused bradycardia, hypotension, hypothermia, hypotonia and apnea in infants, and severe somnolence in toddlers.[120-125]

Due to its propensity for central nervous system depression, brimonidine is rarely an appropriate first-line drug for children, except in selected older children with intolerance to beta-blockers and carbonic anhydrase inhibitors. Nonetheless, brimonidine may be a useful adjunct when other interventions and medications have inadequately controlled IOP in older children with glaucoma.

Prostaglandin Analogs

The prostaglandin derivative latanoprost (Xalatan), although effective at IOP reduction in adults with open-angle glaucoma,[126,127] failed to show significant IOP reduction in patients with primary infantile glaucoma in our experience.[128,129] While no serious systemic side effects related to latanoprost use have been reported in children on latanoprost, thickening and elongation of eyelashes in the treated eye(s) is well established. There is no published experience using the other drugs in this group to treat children; some eyes with inadequate IOP reduction to latanoprost may nonetheless respond to treatment with brimatoprost or travoprost, albeit with conjunctival hyperemia in some cases.

Prostaglandin-like agents do not yet seem appropriate first-line treatment for children, except perhaps for selected cases of juvenile open-angle glaucoma with special risk for beta-blocker use. They may play an important adjunctive role in cases where IOP control is inadequate despite use of other medications already discussed above.

 

 

SURGICAL TREATMENT

Surgical intervention is the most definitive therapy for most cases of primary infantile glaucoma (see Table 198.6), but this can be challenging in young children. Anesthesia itself poses significant risks in infants. Furthermore, the infant's eye behaves differently from that of an adult intraoperatively by virtue of its more flexible and sometimes thinned limbus and sclera. Postoperative care of the infant eye often challenges the parents and surgeon alike.

Angle Surgery

The introduction of angle surgery (first goniotomy and then trabeculotomy ab externo) has drastically improved the previously dismal prognosis for children with primary infantile glaucoma. Both goniotomy and trabeculotomy ab externo have their staunch advocates, but neither procedure has been definitively proved better than the other for treating primary infantile glaucoma. Reported success has been similarly high (from ~80 to <90%) with both procedures in favorable cases of glaucoma (e.g., previously unoperated eyes with primary congenital glaucoma, with onset postnatally but before 1 year of life), although goniotomy needs to be repeated more often than trabeculotomy in some reports.[2,130-132] Although goniotomy spares conjunctival tissues for possible later surgery, trabeculotomy can proceed even when corneal opacity precludes an angle view.

Goniotomy

Goniotomy, a procedure intended to incise the uveal trabecular meshwork under direct visualization, was introduced as an operation for primary congenital (infantile) glaucoma by Barkan in 1938.[4] Dubbing the procedure 'goniotomy' (from the Greek gonio, which means angle, and tomein, which means to cut), Barkan modified the technique earlier described by deVincentiis[133] to include direct gonioscopic visualization of the angle structures. The goniotomy procedure remains essentially as Barkan described it ~60 years ago, underscoring its importance and widespread use as the initial procedure for primary infantile glaucoma.[2] Proponents of goniotomy feel that this procedure incises the poorly functioning internal layers of the trabecular meshwork, allowing aqueous humor to exit the anterior chamber into Schlemm's canal more easily.[66,130] Although the exact mechanism of IOP reduction from successful goniotomy remains unknown, the procedure seems to improve the facility of aqueous outflow.[134] The success of goniotomy in controlling primary infantile glaucoma has been reported in the 80-90% range after one to two procedures, with best success when the glaucoma presents between 3 months and 1 year of age.[2]

If the diagnosis of glaucoma has been confirmed before anesthesia, and if goniotomy is the preferred surgical procedure, oral acetazolamide (or other medical) therapy for at least several days preoperatively may help maximize corneal clarity by lowering IOP. Preoperative topical antibiotics may also be used for 1-2 days preoperatively. Gonioscopy performed with the patient under anesthesia before surgery confirms whether the angle visualization is adequate for goniotomy. Pilocarpine 1% or 2% should be placed onto the eye or eyes to be operated after the IOP has been checked in the operating room to aid in protecting the crystalline lens from injury during surgery. Several drops of sodium chloride 5% can assist in reducing corneal haze from edema, to maximize the gonioscopic angle view. One drop of apraclonidine 0.5% helps to limit angle bleeding during and after the trabeculum has been incised (as noted above).

Goniotomy is performed using a surgical goniolens and a goniotomy knife. There are several goniolenses and goniotomy knives available. A Barkan goniotomy lens modified with an added handle, and placed onto a mound of healon on the central cornea works well. The nontapered Swan knife (or needle-knife) enters the anterior chamber easily and cuts in either direction.[134] Alternatively, a disposable 25-gauge needle attached to a syringe containing hyaluronic acid (Healon) may be used, obviating a separate incision. The needle is single-use, readily available, and always sharp; further its uniform shaft diameter maintains the deep anterior chamber as the instrument is withdrawn after incision.[135]

The surgeon may use a binocular operating loupe or operating microscope to view the angle for goniotomy (the latter method affords the assistant a view of the angle). When using the microscope with a Barkan goniotomy lens, the former should be tipped ~45° from the vertical to afford the best angle view. The surgeon positions opposite the portion of the angle to be operated on (i.e., to the temporal side of the patient undergoing nasal goniotomy), and stabilizes the globe with locking forceps, preferably placed onto the Tenon's insertion near the limbus at 6- and 12-o'clock for a nasal or temporal goniotomy. Next, the goniotomy lens is placed onto the cornea. The goniotomy knife or needle then enters through peripheral clear cornea 1 mm from the limbus, opposite the midpoint of the intended goniotomy. The knife or needle passes parallel to and over iris tissue (not pupil) to engage trabecular meshwork in its anterior third, just posterior to Schwalbe's line (Fig. 198.11a), and incises the angle for ~4-5 clock hours (Fig. 198.11b). A cleft of whitish tissue may be noted in the wake of the incision, with a widening of the angle. After careful removal of the knife or needle, blood often egresses from the angle incision, usually stopping when the chamber is refilled. A single suture of 10-0 Vicryl secures the corneal wound.

Click to view full size figure  

 

FIGURE 198.11  Goniotomy using a Barkan goniotomy lens and a Swan goniotomy knife. (a) Incision in anterior trabecular meshwork, shown beginning from right to left. (b) Correct placement and depth of the goniotomy incision.
(a and b) From Buckley EG, Freedman SF, Shields MB: Atlas of ophthalmic surgery, vol III. Strabismus and glaucoma surgery. St Louis: Mosby-Year Book; 1995.

 

 

Postoperative treatment includes a topical antibiotic and steroid, as well as pilocarpine drops. Bilateral goniotomies may be performed during one anesthesia provided all instruments are replaced or sterilized; all drapes, gowns, and gloves replaced; and the fellow eye reprepared and draped in sterile fashion after the first procedure.[136] Postoperative complications commonly include limited hyphema and rarely include irido- or cyclodialysis, peripheral anterior synechiae in the angle incision, cataract, and retinal detachment.[136,137] The results of goniotomy should be evaluated weekly in the immediate postoperative period and are often evident by 3-6 weeks.[134] Repeat goniotomy in another angle location is usually carried out if IOP control is not achieved after a single procedure.

Trabeculotomy Ab Externo

The trabeculotomy procedure seeks to create a direct communication between the anterior chamber and Schlemm's canal. Trabeculotomy ab externo is performed by cannulating Schlemm's canal from an external approach and then tearing through the trabecular meshwork into the anterior chamber. Burian and Smith independently described this procedure in 1960 as an alternative to goniotomy.[138,139]Modifications were later introduced by Harms, Dannheim, and McPherson.[2] The reported success with trabeculotomy ab externo for control of primary infantile glaucoma ranges from 73% to 100%.[2] In a series of 71 patients (most with primary infantile glaucoma), Akimoto and colleagues found a probability of success after one or more trabeculotomies of 92.5% and 76.5% at 5 and 10 years, respectively.[140]The salient disadvantage of trabeculotomy is conjunctival scarring. As noted earlier, however, trabeculotomy's signal advantage is that it is little affected by an edematous or scarred cornea. In addition, the procedure can easily be combined with trabeculectomy (see further ahead) when Schlemm's canal cannot be adequately identified or cannulated.

Trabeculotomy, performed with either a limbus- or a fornix-based flap, uses a partial-thickness triangular or rectangular scleral flap (as created for standard trabeculectomy), ideally placed temporally (to spare superior conjunctiva). Pilocarpine used preoperatively assists in achieving miosis.[136] After a paracentesis (and injection into the anterior chamber of a small amount of viscoelastic substance), Schlemm's canal is identified by making and gradually deepening a radial scratch incision across the sclerolimbal junction in the bed of the scleral flap. A small amount of blood or aqueous humor often refluxes through the cut ends of Schlemm's canal. Passage of a 5-0 or 6-0 nylon suture into the cut ends of Schlemm's canal helps to confirm the location of the canal; the internal arm of a trabeculotome is then advanced gently into one cut end of the canal and rotated into the anterior chamber (Fig. 198.12a and b). Rotation of the trabeculotome into the anterior chamber tears through the intervening trabecular meshwork and requires minimal force (Fig. 198.12c). The anterior chamber often shallows slightly, with egress of blood from the torn trabecular meshwork, as the trabeculotome is removed from the eye. In similar fashion, the trabeculotome should be placed into the other cut end of Schlemm's canal and the procedure repeated to the opposite side. The scleral flap is then secured with 10-0 nylon or Vicryl, whereas the Tenon and conjunctival layers may be closed with a running suture of 8-0 or 10-0 absorbable suture, as for standard trabeculectomy.[141,142] Postoperative care is similar to that for goniotomy.

Click to view full size figure  

 

FIGURE 198.12  Trabeculotomy, under a limbus-based conjunctival and partial-thickness scleral flap. Superior approach is shown, using a traction suture to hold back the conjunctival and Tenon's layers. (a) Placement of trabeculotome into the cut end of Schlemm's canal to the right. (b) Rotation of the trabeculotome into the anterior chamber, tearing through the intervening trabecular meshwork. (c) View of internal arm of trabeculotome tearing through trabecular meshwork as the instrument is rotated into the anterior chamber.
(a-c) From Buckley EG, Freedman SF, Shields MB: Atlas of ophthalmic surgery, vol III. Strabismus and glaucoma surgery. St Louis: Mosby-Year Book; 1995.

 

 

Beck and Lynch have proposed a modification of trabeculotomy involving the use of a 6-0 Prolene suture to perform a 360° trabeculotomy at one surgery, using one or two external incisions into Schlemm's canal.[143] Angle surgery can thereby be completed in one surgical session, and use of a flexible suture in place of a rigid metal probe diminishes the risk of a false passage; the early results of this procedure are similar to those reported for more conventional trabeculotomy procedures (which usually affect 100-120° of the angle described previously).[143]

Although hyphema occurs commonly after trabeculotomy, rarer complications include inadvertent filtering blebs, choroidal detachment, iridotomy, damage to the lens, creation of a false passage into the anterior chamber or suprachoroidal space, and infection.[2,141] The effects of trabeculotomy should be determined 3-4 weeks after surgery. Although the procedure may be repeated in a different portion of the angle, it may be reasonable to combine a second trabeculotomy with trabeculectomy (see further ahead) if no effect was noted after the first trabeculotomy.

Combined Trabeculotomy and Trabeculectomy

If Schlemm's canal has not been successfully cannulated, or if previous similar trabeculotomy procedures have failed to control IOP, the trabeculotomy can be combined with a trabeculectomy by removal of a block of limbal tissue in the bed of the scleral flap, followed by peripheral iridectomy as in standard trabeculectomy.[136] If conversion to trabeculectomy seems likely, one may apply an antimetabolite such as mitomycin C to the sclera at the site of intended scleral flap formation before dissection of the scleral flap (as described for adult trabeculectomy, Chapter 219, Incisional Surgery Techniques for Angle-Closure Glaucoma). If mitomycin C has been applied, the use of a rectangular partial-thickness scleral flap and a subsequent separate running closure of both the Tenon and the conjunctival layers with 10-0 absorbable suture is favored. Postoperative care should be as for pediatric trabeculectomy in this case (see section on Trabeculectomy). Although angle surgery alone is considered standard initial surgical management for primary congenital glaucoma by many surgeons, some do advocate combined trabeculotomy and trabeculectomy instead, with excellent surgical success (66% at 5 years).[144]

Procedures for Refractory Primary Infantile Glaucoma

Filtering surgery

When one or more angle procedures (and medications) have failed to achieve IOP control in refractory primary infantile glaucoma cases, filtering surgery is often undertaken. Success rates of the various filtration procedures used for pediatric glaucoma in years past - iridencleisis, cyclodiathermy, thermal sclerostomy (Scheie's procedure), and standard trabeculectomy - have been modest (37-54%), at best, with significant rates of complication.[2,145-147] Many factors conspire against successful filtration surgery in children, including lower scleral rigidity, more rapid healing and exuberant scarring processes, and enlargement of glaucomatous eyes with thinning and distortion of intraocular anatomy. Additional challenges to success include difficulties in the postoperative care of children, as well as visual loss from amblyopia even if glaucoma has been controlled.

Although most glaucoma filtration surgery in children was standardly performed using a limbus-based conjunctival incision, many surgeons performing trabeculectomy in both adults and children now advocate fornix-based incisions.[148]

Postoperative wound modulation has been attempted with trabeculectomy in children. Intraoperative beta irradiation, used in Britain, increased success of trabeculectomy from ~40% to greater than 65%.[149]Subconjunctival 5-fluorouracil has been administered after trabeculectomy in children, but its administration often requires multiple sequential anesthesias and is limited by corneal epithelial toxicity, as in adults.[150]

The use of intraoperative mitomycin C with trabeculectomy, which is so helpful for refractory adult glaucoma cases, has somewhat enhanced the success of this procedure in the pediatric glaucoma patient, although not without significant and, as yet, unquantifiable risk. Early series by Susanna and colleagues reported successful IOP control (IOP 21 mmHg) in 67% of 79 eyes (mean age 76 months, with a mean follow-up 17 months). Mitomycin C, 0.2 mg/mL, was applied beneath the partial-thickness scleral flap for 5 min. Severe complications (phthisis, endophthalmitis) occurred in two eyes.[151] Mandal and associates reported success of 66% at 30 months in a series of 38 eyes, most of which had refractory primary congenital glaucoma.[152] Other authors have also reported varying rates of success over relatively short follow-up times, using mitomycin doses ranging from 0.2 to 0.5 mg/mL, applied for from 2 to 5 min; bleb-related infections have been reported in most of these series.[153-156] Infants younger than 1-2 years old, and those eyes which are aphakic, fare poorly with trabeculectomy, even when mitomycin is employed.[151,153,155]

The response of young children to mitomycin C-augmented trabeculectomy is extremely variable, with some patients scarring rapidly despite antifibrotic therapy, whereas others experience hypotony with large avascular filtration blebs. Postoperative care and complications of this procedure in children are similar to those in adults, except that periodic examinations under anesthesia are usually required in young children. The presence of thin-walled avascular filtering blebs in pediatric patients after mitomycin C-augmented trabeculectomy raises serious concern about the lifetime risk of the development of endophthalmitis, bleb leaks, and wound rupture with minor trauma in these eyes (all of which have already occurred). Furthermore, the application of even small amounts of this potent alkylating agent to a child's eye raises the theoretical concern of long-term carcinogenicity (seen in rodents after systemic mitomycin C application).[157,158]

At least one published series noted no difference in surgical success in a retrospective comparison of trabeculectomy with and without mitomycin use in primary congenital glaucoma.[159]

Drainage implant (seton) surgery

When trabeculectomy fails or is not the best option (see Table 198.6) for refractory cases of primary infantile glaucoma, remaining options include glaucoma implant (seton or drainage) or cyclodestructive procedures. Published series have used the Molteno, Baerveldt, and Ahmed implants in refractory pediatric glaucomas of various types; reported success and complications vary widely.[160-175]

The Molteno implant has achieved success rates of 56-95%, with success rates lower in series including exclusively younger children, and slightly higher success rates (and higher complication rates) noted with the two-plate implant than with the one-plate implant.[160-164]

Success with the Ahmed glaucoma implant in refractory pediatric glaucoma (not specifically primary congenital) has been reported in several series, and has been modest ~60% by 3 years.[168-170] Several published series have reported on use of the Baerveldt glaucoma implant for refractory pediatric glaucoma, with success varying from ~60-80% at 2-3 years, but declining over time in all series.[171-175]

Complications seen with glaucoma drainage implants in children are numerous, including not only those encountered after trabeculectomy in children (discussed earlier) but also those specific to seton implantation. Most common among the latter in many series were contact between the tube and the corneal endothelium (tube-cornea touch), erosion of the tube externally through the conjunctiva, migration of the tube, and cataract formation or progression. Although infection has been reported after glaucoma drainage implant surgery in children, this complication fortunately seems fairly rare. Pupil abnormalities and motility disturbance are not uncommon in children after glaucoma drainage implant surgery.[175-177]

Seton implantation can successfully control glaucoma in children, although many patients need postoperative glaucoma medications. Most published series include refractory pediatric glaucoma of various types, rather than solely refractory primary infantile glaucoma. Postoperative care of these patients must be meticulous because many complications may occur, and long-term effects of drainage implants in the eyes of children are not yet known. Eid and co-workers suggest caution with implants in children because they noted a 28% rate of loss of light perception in a series of 18 eyes with long-term follow-up.[167] In children with eyes scarred from previous surgeries, we prefer a fornix-based approach, securing the tube of the implant under a full-thickness donor scleral graft. Tube ligation or two-stage implantation is recommended in buphthalmic eyes that are aphakic or have undergone previous cyclodestruction, even when using the valved Ahmed implant.

In one reported series, drainage implant surgery appeared more successful at IOP control than did trabeculectomy, for children below the age of 2 years.[178]

Cyclodestructive procedures

In contrast to trabeculectomy and glaucoma implant procedures, cyclodestructive procedures reduce the rate of aqueous production by injuring the ciliary processes; results are often unpredictable and complications frequent. Cyclodestruction nonetheless constitutes a valid means of attempting control of especially refractory cases of primary infantile glaucoma, once medical and other surgical means have been exhausted or have proved inadequate to the task. Cyclocryotherapy (freezing the ciliary processes from an external approach) has been used as therapy for difficult childhood glaucomas for many years. Unfortunately, overall success (pressure control without severe visual loss or phthisis) has been fairly poor (30% in a large series of children with advanced congenital glaucoma), with retreatment the rule.[179] In children, cryotherapy should be applied to a maximum of 180° of the circumference of the eye at one session, using six or seven freezes (60 s each at ?80°C) with a 2.5-mm-diameter cryoprobe centered ~2.5 mm from the limbus, or over the ciliary body as located by transillumination in buphthalmic eyes.[118] Retreatments generally include one quadrant or slightly more, with care taken to leave at least one quadrant untouched. Aside from the risks of hypotony or phthisis (~10-15%), uveitis, cataract formation, and attendant visual loss are the major problems with cyclocryotherapy in children.[180-181]

Transscleral cyclophotocoagulation with both the contact neodymium:yttrium-aluminum garnet and diode lasers has been shown to reduce IOP in a fashion comparable with that of cyclocryotherapy in children with refractory glaucomas.[182,183] Each study reported a similar 50% success rate, with retreatment in 70% of cases. Phthisis was reported in one of 10 eyes treated with the neodymium:yttrium-aluminum garnet laser and in none of 26 eyes treated with the diode laser, but follow-up times were limited for both studies.[182,183] Further experience with transscleral cyclophotocoagulation in children suggests that this technique is of limited efficacy (success ~50% at 1 year), but seems to have a lower incidence of phthisis than cyclocryotherapy.[184,185] As with transscleral laser cycloablation in adults, this 'blind' procedure sometimes misses the intended ciliary processes in pediatric eyes, many of which have enlarged eyes with distorted anterior segment anatomy.[186,187]

Endoscopic application of laser energy to the ciliary processes has also been used to treat refractory pediatric glaucoma, with most reported cases having aphakic glaucoma.[188,189] Endoscopic cyclophotocoagulation was performed in these two studies using the microendoscopic system incorporating fiber optics for a video monitor, diode laser endophotocoagulation, and illumination in a 20-gauge probe (Microprobe (Endo Optiks, Little Silver, NJ). Although endoscopic diode laser cycloablation improves the accuracy of delivered laser energy, therefore requiring less energy than the transscleral diode laser cycloablation technique, this modality nonetheless has modest success in treating pediatric glaucoma, and often requires retreatment. Cumulative success of all procedures at last follow-up was 43% in this series of 36 eyes, after a mean cumulative arc of treatment of 260°, with mean follow-up time 19 months; retinal detachment, hypotony, and visual loss were all reported.[188]

In spite of its limited efficacy and significant complications, cycloablation remains a reasonable treatment option for selected eyes with particularly refractory congenital glaucoma that has failed other medical and surgical interventions.

 

 

LONG-TERM FOLLOW-UP AND PROGNOSIS

Patients with primary infantile glaucoma compose a heterogeneous group, with overall IOP control achievable in more than 80% of cases. Although rare cases of primary infantile glaucoma seem to have spontaneously remitted,[189,190] most untreated cases result in buphthalmos and blindness.[3] The prognosis for control of primary infantile glaucoma varies with the patient's age at initial presentation and at surgery. Angle surgery is most favorable for IOP control when the patient presents after the first 2 months and within the first year of life (<90%). Children presenting with glaucoma at birth or after the first year of life face a poorer prognosis for IOP control with angle surgery (~50%).[2,110] Even children whose glaucoma is well controlled after surgical therapy (with or without adjunctive medical therapy) deserve lifelong follow-up. Loss of IOP control (reported in up to a third of cases)[2] may occur months or even decades after initial success with surgery and may be asymptomatic in the older child and young adult.

Visual loss in eyes with primary infantile glaucoma may be multifactorial (see Table 198.1). Children with this disease often face vision-threatening difficulties such as corneal scarring, anisometropia, and resultant amblyopia even when IOP control has been achieved with preservation of healthy optic nerve tissue. Reports of visual success vary, with visual acuity less than 20/50 in about half of eyes with primary congenital glaucoma, despite maximal glaucoma and amblyopia therapy.[40,112]

Children with primary infantile glaucoma that is controlled without medications should be followed up at least every 6 months, and young children, or those whose IOP has been controlled for less than 2 years, should probably be evaluated at least every 3 or 4 months. During these office examinations, correlates of adequate IOP control include (1) stable visual function, refractive error, and optic nerve appearance, (2) corneas that are free of edema and stable in size, and (3) children who are free of epiphora, excessive photophobia, and blepharospasm. By contrast, even if the IOP is less than 20 mmHg, deteriorating vision, progressive myopia, and optic nerve cupping, or increases in corneal size, edema, or ocular symptoms suggest that control of glaucoma may be inadequate for the long term. Visual field testing and imaging of the optic nerve (and perhaps also the macula) by OCT may also prove useful in cooperative, older children with glaucoma.

Aggressive and persistent attention to control of glaucoma, as well as to correction of refractive errors and amblyopia therapy, is vital to optimizing the visual outcome for children with primary infantile glaucoma. Children who suffer serious visual impairment despite diligent treatment can benefit from early referral to programs that offer visual assistance (especially for school-aged children). The ophthalmologist can be an important advocate for the family in securing these services.

Despite tremendous advances in genetics, and in medical, laser, and surgical technology, we are still humbled by our failure to preserve sight in many children with glaucoma.

 

 

REFERENCES

1. Walton DS: Primary congenital open angle glaucoma. A study of the anterior segment abnormalities.  Trans Am Ophthalmol Soc  1979; 77:746.

2. DeLuise VP, Anderson DR: Primary infantile glaucoma (congenital glaucoma).  Surv Ophthalmol  1983; 28:1.

3. Duke-Elder S: Congenital deformities. System of ophthalmology,  St Louis: CV Mosby; 1969:548.

4. Barkan O: Technique of goniotomy.  Arch Ophthalmol  1938; 19:217.

5. Miller SJH: Genetic aspects of glaucoma.  Trans Ophthalmol Soc UK  1962; 81:425.

6. Hoskins HD, Shaffer RN: Evaluation techniques for congenital glaucomas.  J Pediatr Ophthalmol Strabismus  1971; 8:81.

7. Bardelli AM, Hadjistilianou T, Frezzotti R: Etiology of congenital glaucoma. Genetic and extragenetic factors.  Ophthalmic Paediatr Genet  1985; 6:265.

8. Kolker AE, Hetherington J: Diagnosis and therapy of the glaucomas,  St Louis: CV Mosby; 1983:317-362.

9. Chandler PA, Grant WM: Lectures in glaucoma,  Philadelphia, Lea & Febiger, 1965.

10. Phelps DD, Podos SM: Glaucoma.   In: Goldberg MD, ed. Genetic and metabolic eye disease,  Boston: Little, Brown; 1974:252.

11. Waardenburg PJ, Franceschetti P, Klein D: Genetics and ophthalmology,  Springfield, IL, Charles C Thomas, 1961.

12. Sarfarazi M, Akarsu AN, Hossain A, et al: Assignment of a locus (GLC3A) for primary congenital glaucoma (buphthalmos) to 2p21 and evidence for genetic heterogeneity.  Genomics  1995; 30:171.

13. Sarfarazi M: Recent advances in molecular genetics of glaucomas.  Hum Mol Genet  1997; 6:1667-1677.

14. Akarsu AN, Turacli ME, Aktan SG, et al: A second locus (GLC3B) for primary congenital glaucoma (buphthalmos) maps to the 1p36 region.  Hum Mol Genet  1996; 5:1199-1203.

15. Sena DF, Finzi S, Rodgers K, et al: Founder mutations of CYP1B1 gene in patients with congenital glaucoma from the United States and Brazil.  J Med Genet  2004; 41:e6.

16. Kakiuchi-Matsumoto T, Isashiki Y, Ohba N, et al: Cytochrome P450 1B1 gene mutations in Japanese patients with primary congenital glaucoma(1).  Am J Ophthalmol  2001; 131:345-350.

17. Martin SN, Sutherland J, Levin AV, et al: Molecular characterisation of congenital glaucoma in a consanguineous Canadian community: a step towards preventing glaucoma related blindness.  J Med Genet  2000; 37:422-427.

18. Mashima Y, Suzuki Y, Sergeev Y, et al: Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma.  Invest Ophthalmol Vis Sci  2001; 42:2211-2216.

19. Ohtake Y, Kubota R, Tanino T, et al: Novel compound heterozygous mutations in the cytochrome P4501B1 gene (CYP1B1) in a Japanese patient with primary congenital glaucoma.  Ophthalmic Genet  2000; 21:191-193.

20. Panicker SG, Reddy AB, Mandal AK, et al: Identification of novel mutations causing familial primary congenital glaucoma in Indian pedigrees.  Invest Ophthalmol Vis Sci  2002; 43:1358-1366.

21. Stoilov IR, Costa VP, Vasconcellos JP, et al: Molecular genetics of primary congenital glaucoma in Brazil.  Invest Ophthalmol Vis Sci  2002; 43:1820-1827.

22. Vincent AL, Billingsley G, Buys Y, et al: Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene.  Am J Hum Genet  2002; 70:448-460.

23. Mukhopadhyay A, Acharya M, Mukherjee S, et al: Mutations in MYOC gene of Indian primary open angle glaucoma patients.  Mol Vis  2002; 8:442-448.

24. Soley GC, Bosse KA, Flikier D, et al: Primary congenital glaucoma: a novel single-nucleotide deletion and varying phenotypic expression for the 1,546-1,555dup mutation in the GLC3A (CYP1B1) gene in 2 families of different ethnic origin.  J Glaucoma  2003; 12:27-30.

25. Sitorus R, Ardjo SM, Lorenz B, Preising M: CYP1B1 gene analysis in primary congenital glaucoma in Indonesian and European patients.  J Med Genet  2003; 40:e9.

26. Reddy AB, Kaur K, Mandal AK, et al: Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma patients.  Mol Vis  2004; 10:696-702.

27. Alfadhli S, Behbehani A, Elshafey A, et al: Molecular and clinical evaluation of primary congenital glaucoma in Kuwait.  Am J Ophthalmol  2006; 141:512-516.

28. Panicker SG, Mandal AK, Reddy AB, et al: Correlations of genotype with phenotype in Indian patients with primary congenital glaucoma.  Invest Ophthalmol Vis Sci  2004; 45:1149-1156.

29. Leighton DA, Phillips CI: Infantile glaucoma. Steroid testing in parents of affected children.  Br J Ophthalmol  1970; 54:27.

30. Worst JGF: The pathogenesis of congenital glaucoma. An embryological and goniosurgical study,  Springfield, IL, Charles C Thomas, 1966.

31. Barkan O: Pathogenesis of congenital glaucoma: gonioscopic and anatomic observation of the angle of the anterior chamber in the normal eye and in congenital glaucoma.  Am J Ophthalmol  1955; 40:1.

32. Anderson DR: The development of the trabecular meshwork and its abnormality in primary infantile glaucoma.  Trans Am Ophthalmol Soc  1981; 79:458.

33. Maul E, Strozzi L, Munoz C, Reyes C: The outflow pathway in congenital glaucoma.  Am J Ophthalmol  1980; 89:667.

34. Allen L, Burian HM, Braley AA: A new concept of the development of the anterior chamber angle. Its relationship to developmental glaucoma and other structural anomalies.  Arch Ophthalmol  1955; 53:783.

35. Mann I: Developmental abnormalities of the eye,  Philadelphia, JB Lippincott, 1957.

36. Maumenee AE: Further observations on the pathogenesis of congenital glaucoma.  Am J Ophthalmol  1963; 55:1163.

37. Kupfer C, Kaiser-Kupfer MS: Observations on the development of the anterior chamber angle with reference to the pathogenesis of congenital glaucomas.  Am J Ophthalmol  1979; 88:424.

38. Smelser GK, Ozanics V: The development of the trabecular meshwork in premature eyes.  Am J Ophthalmol  1981; 71:366.

39. Chandler PA, Granta WM: Glaucoma,  Philadelphia, Lea & Febiger, 1980.

40. Seidman DJ, Nelson LB, Calhoun JH: Signs and symptoms in the presentation of primary infantile glaucoma.  Pediatrics  1986; 77:399.

41. Raab EL: Congenital glaucoma.  Perspect Ophthalmol  1978; 2:35.

42. Kolker AE, Hetherington J: Diagnosis and therapy of the glaucomas,  St Louis: CV Mosby; 1979:276.

43. Robin AL, Quigley HA, Pollack IP, et al: An analysis of visual acuity, visual fields, and disc cupping in childhood glaucoma.  Am J Ophthalmol  1979; 88:847.

44. Waring GO, Laibson PR, Rodriguez M: Clinical and pathologic alterations of Descemet's membrane.  Surv Ophthalmol  1974; 18:325.

45. Wilson FMI: Congenital anomalies.   In: Smolin G, Thoft RA, ed. The cornea. Scientific foundations and clinical practice,  Boston: Little, Brown; 1987:457-473.

46. Kupfer C, Kuwabara AT, Stark WJ: The histopathology of Peters' anomaly.  Am J Ophthalmol  1975; 80:653.

47. Rodrigues MM, Phelps CD, Krachmer JH, et al: Glaucoma due to endothelialization of the anterior chamber angle: a comparison of posterior polymorphous dystrophy of the cornea and Chandler's syndrome.  Arch Ophthalmol  1980; 98:688.

48. Becker B, Shaffer RN: Diagnosis and therapy of the glaucomas,  St Louis, CV Mosby, 1965.

49. Kwito ML: Glaucoma in infants and children,  New York, Appleton-Century-Crofts, 1973.

50. Mullaney PB, Risco JM, Teichmann K, Millar L: Congenital hereditary endothelial dystrophy associated with glaucoma.  Ophthalmology  1995; 102:186.

51. Wadelius C, Fagerholm P, Petersson U, Anneren G: Lowe oculocerebrorenal syndrome. DNA-based linkage of the gene to Xq24-q26, using tightly linked flanking markers and the correlation to lens examination in carrier diagnosis.  Am J Hum Genet  1989; 44:241.

52. Walton DS: Glaucoma in infants and children.   In: Nelson LB, Calhoun JH, Harley RD, ed. Pediatric ophthalmology,  Philadelphia: WB Saunders; 1991:258-270.

53. Kiskis AA, Markowitz SN, Morin JD: Corneal diameter and axial length in congenital glaucoma.  Can J Opththalmol  1985; 20:93.

54. Sampaolesi R, Caruso R: Ocular echometry in the diagnosis of congenital glaucoma.  Arch Ophthalmol  1982; 100:574.

55. Morin JD, Bryars JH: Causes of loss of vision in congenital glaucoma.  Arch Ophthalmol  1980; 98:1575.

56. Broughton WL, Parks MM: An analysis of treatment of congenital glaucoma by goniotomy.  Am J Ophthalmol  1981; 91:566.

57. Richardson KT: Optic cup symmetry in normal newborn infants.  Invest Ophthalmol  1968; 7:137.

58. Shaffer RN, Heatherington J: Glaucomatous disc in infants. A suggested hypothesis for disc cupping.  Trans Am Acad Ophthalmol Otolaryngol  1969; 73:929.

59. Minckler DS, Baerveldt G, Heuer DK, et al: Clinical evaluation of the Oculab Tono-Pen.  Am J Ophthalmol  1987; 104:168.

60. Van Buskirk EM, Palmer EA: Office assessment of young children for glaucoma.  Ann Ophthalmol  1979; 11:1749.

61. Mendelsohn AD, Forster RK, Mendelsohn SL, et al: Comparative tonometric measurements of eye bank eyes.  Cornea  1987; 6:219.

62. Armstrong TA: Evaluation of the Tono-Pen and the Pulsair tonometer.  Am J Ophthalmol  1990; 109:716.

63. Speirer A, Huna R, Hirsh A, Chetrit A: Normal intraocular pressure in premature infants.  Am J Ophthalmol  1994; 117:801.

64. Pensiero S, DaPozza S, Perissutti P, et al: Normal intraocular pressure in children.  J Pediatr Ophthalmol Strabismus  1992; 29:79.

65. Radtke ND, Cohen BF: Intraocular pressure measurement in the newborn.  Am J Ophthalmol  1974; 78:501.

66. Walton DS: Diagnosis and treatment of glaucoma in childhood.   In: Epstein DL, ed. Chandler and Grant's glaucoma,  Philadelphia: Lea & Febinger; 1986.

67. Robin AL, Quigley HA: Transient reversible cupping in juvenile-onset glaucoma.  Am J Ophthalmol  1979; 88:580.

68. Marraffa M, Pucci V, Marchini G, et al: HPR perimetry and Humphrey perimetry in glaucomatous children.  Doc Ophthalmol  1995; 89:383-386.

69. Donahue SP, Porter A: SITA visual field testing in children.  J AAPOS  2001; 5:114.

70. Becker K, Semes LR: The reliability of frequency-doubling technology (FDT) perimetry in a pediatric population.  Optometry  2003; 74:173.

71. Burnstein Y, Ellish NJ, Magbalon M, Higginbotham EJ: Comparison of frequency doubling perimetry with humphrey visual field analysis in a glaucoma practice.  Am J Ophthalmol  2000; 129:328-333.

72. Herndon LW, Choudhri SA, Cox T, et al: Central corneal thickness in normal, glaucomatous, and ocular hypertensive eyes.  Arch Ophthalmol  1997; 115:1137-1141.

73. Herndon LW, Weizer JS, Stinnett SS: Central corneal thickness as a risk factor for advanced glaucoma damage.  Arch Ophthalmol  2004; 122:17-21.

74. Brandt JD, Beiser JA, Gordon MO, Kass MA: Central corneal thickness and measured IOP response to topical ocular hypotensive medication in the Ocular Hypertension Treatment Study.  Am J Ophthalmol  2004; 138:717-722.

75. Doughty MJ, Zaman ML: Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach.  Surv Ophthalmol  2000; 44:367-408.

76. Jonas JB, Stroux A, Velten I, et al: Central corneal thickness correlated with glaucoma damage and rate of progression.  Invest Ophthalmol Vis Sci  2005; 46:1269-1274.

77. Bron AM, Creuzot-Garcher C, Goudeau-Boutillon S, d'Athis P: Falsely elevated intraocular pressure due to increased central corneal thickness.  Graefes Arch Clin Exp Ophthalmol  1999; 237:220-224.

78. Dohadwala AA, Munger R, Damji KF: Positive correlation between tono-pen intraocular pressure and central corneal thickness.  Ophthalmol  1998; 105:1849-1854.

79. Ehlers N, Bramsen T, Sperling S: Applanation tonometry and central corneal thickness.  Acta Ophthalmol (copenh)  1975; 53:34-43.

80. Simsek T, Mutluay AH, Elgin U, et al: Glaucoma and increased central corneal thickness in aphakic and pseudophakic patients after congenital cataract surgery.  Br J Ophthalmol  2006.

81. Herse P, Weiping Y: Variation in corneal thickness with age in young New Zealanders.  Acta Ophthalmol  1993; 71:360-364.

82. Ehlers N, Sorensen T, Bramsen T, H PE: Central corneal thickness in newborns and children.  Acta Ophthalmol (Copenh)  1976; 54:285.

83. Copt R-P, Thomas R, Mermoud A: Corneal thickness in ocular hypertension, primary open-angle glaucoma, and normal tension glaucoma.  Arch Ophthalmol  1999; 117:14-16.

84. Muir KW, Jin J, Freedman SF: Central corneal thickness and its relationship to intraocular pressure in children.  Ophthalmology  2004; 111:2220-2223.

85. Hussein MA, Paysee EA, Bell NP, et al: Corneal thickness in children.  Am J Ophthalmol  2004; 138:744-748.

86. Henriques MJ, Vessani RM, Reis FA, et al: Corneal thickness in congenital glaucoma.  J Glaucoma  2004; 13:185-188.

87. Dai E, Gunderson CA: Pediatric central corneal thickness variation among major ethnic populations.  J Aapos  2006; 10:22-25.

88. Salchow DJ, Oleynikov YS, Chiang MF, et al: Retinal nerve fiber layer thickness in normal children measured with optical coherence tomography.  Ophthalmology  2006; 113:786-791.

89. Ahn HC, Son HW, Kim JS, Lee JH: Quantitative analysis of retinal nerve fiber layer thickness of normal children and adolescents.  Korean J Ophthalmol  2005; 19:195-200.

90. Hess DB, Asrani SG, Bhide MG, et al: Macular and retinal nerve fiber layer analysis of normal and glaucomatous eyes in children using optical coherence tomography.  Am J Ophthalmol  2005; 139:509-517.

91. Liu X, Ling Y, Luo R, et al: Optical coherence tomography in measuring retinal nerve fiber layer thickness in normal subjects and patients with open-angle glaucoma.  Chin Med J (Engl)  2001; 114:524-529.

92. Kanamori A, Nakamura M, Escano M, et al: Evaluation of the glaucomatous damage on retinal nerve fiber layer thickness measured by optical coherence tomography.  Am J Ophthalmol  2003; 135:513-520.

93. Guedes V, Schuman J, Hertzmark E, et al: Optical coherence tomography measurement of macular and nerve fiber layer thickness in normal and glaucomatous human eyes.  Ophthalmology  2003; 110:177-189.

94. Carpineto P, Ciancaglini M, Zuppardi E, et al: Reliability of nerve fiber layer thickness measurements using optical coherence tomography in normal and glaucomatous eyes.  Ophthalmology  2003; 110:190-195.

95. Greenfield D, Bagga H, Knighton R: Macular thickness changes in glaucomatous optic neuropathy detected using optical coherence tomography.  Arch Ophthalmol  2003; 121:41-46.

96. Bowd C, Weinreb R, Williams J, Zangwill L: The retinal nerve fiber layer thickness in ocular hypertensive, normal, and glaucomatous eyes with optical coherence tomography.  Arch Ophthalmol  2000; 118:22-26.

97. Pons M, Ishikawa H, Gurses-Ozden R, et al: Assessment of retinal nerve fiber layer internal reflectivity in eyes with and without glaucoma using optical coherence tomography.  Arch Ophthalmol  2000; 118:1044-1047.

98. Mrugacz M, Bakunowicz-Lazarczyk A: Optical coherence tomography measurement of the retinal nerve fiber layer in normal and juvenile glaucomatous eyes.  Ophthalmologica  2005; 219:80-85.

99. Jaafar MS, Ghulamqadir AK: Effect of oral chloral hydrate sedation on the intraocular pressure measurement.  J Pediatr Ophthalmol Strabismus  1993; 30:372.

100. Ausinsch B, Rayburn RL, Munson ES, Levy NS: Ketamine and intraocular pressure in children.  Anesth Analg  1976; 55:773.

101. Yoshikawa K, Murai Y: The effect of ketamine on intraocular pressure in children.  Anesth Analg  1971; 50:199.

102. Watcha MF, Chu FC, Stevens JL, Forestner JE: Effects of halothane on intraocular pressure in anesthetized children.  Anesth Analg  1990; 71:181.

103. Watcha MF, White PF, Tychsen L, Stevens JL: Comparative effects of laryngeal mask airway and endotracheal tube insertion on intraocular pressure in children.  Anesth Analg  1992; 75:355.

104. Murphy DF: Anesthesia and intraocular pressure.  Anesth Analg  1985; 64:520.

105. Dominiguez A, Banos MS, Alvare MG, et al: Intraocular pressure measurement in infants under general anesthesia.  Am J Ophthalmol  1974; 78:110.

106. Joshi C, Bruce DL: Thiopental and succinylcholine: action on intraocular pressure.  Anesth Analg  1975; 54:471.

107. Gallin-Cohen PF, Podos SM, Yablonski ME: Oxygen lowers intraocular pressure.  Invest Ophthalmol Vis Sci  1980; 19:43.

108. Gunderson CA, Freedman SF, Lohavichan J, et al: Nitrous oxide-effects on intraocular pressure.  Invest Ophthalmol Vis Sci  1994; 35(Suppl):2178.

109. Ott EZ, Mills MD, Arango S, et al: A randomized trial assessing dorzolamide in patients with glaucoma who are younger than 6 years.  Arch Ophthalmol  2005; 123:1177-1186.

110. Haas J: Principles and problems of treatment in congenital glaucoma.  Invest Ophthalmol Vis Sci  1968; 7:140.

111. Portellos M, Freedman SF, Buckley EG: Topical vs. oral carbonic anhydrase inhibitor therapy for pediatric glaucoma.  J Am Assoc Pediatr Ophthalmol Strabismus  1998; 2:43-47.

112. Zimmerman TJ, Kooner KS, Morgan KS: Safety and efficacy of timolol in pediatric glaucoma.  Surv Ophthalmol  1983; 28:262.

113. Hoskins HDJ, Hetherington JJ, Magee SD, et al: Clinical experience with timolol in childhood glaucoma.  Arch Ophthalmol  1985; 103:1163.

114. Boger WPI, Walton DS: Timolol in uncontrolled childhood glaucomas.  Ophthalmology  1981; 88:253.

115. McMahon CD, Hetherington JJ, Hoskins HDJ, Shaffer RN: Timolol and pediatric glaucomas.  Ophthalmology  1981; 88:249.

116. Olson RJ, Bromberg BB, Zimmerman TJ: Apneic spells associated with timolol therapy in a neonate.  Am J Ophthalmol  1979; 88:120.

117. Passo MS, Palmer EA, Van Buskirk EM: Plasma timolol in glaucoma patients.  Ophthalmology  1984; 91:1361.

118. Shields MB: Textbook of glaucoma,  Baltimore, Williams & Wilkins, 1992.

119. Bacal DA, Levy SR: The use of apraclonidine in the diagnosis of horner syndrome in pediatric patients.  Arch Ophthalmol  2004; 122:276-279.

120. Berlin RJ, Lee UT, Samples JR, et al: Ophthalmic drops causing coma in an infant.  J Pediatr  2001; 138:441-443.

121. Enyedi LB, Freedman SF: Safety and efficacy of brimonidine in children with glaucoma.  J Aapos  2001; 5:281-284.

122. Korsch E, Grote A, et al: Systemic adverse effects of topical treatment with brimonidine in an infant with secondary glaucoma.  Eur J Pediatr  1999; 158:685.

123. Al-Shahwan S, Al-Torbak AA, Turkmani S, et al: Side-effect profile of brimonidine tartrate in children.  Ophthalmology  2005; 112:2143.

124. Bowman RJ, Cope J, Nischal KK: Ocular and systemic side effects of brimonidine 0.2% eye drops (Alphagan) in children.  Eye  2004; 18:24-26.

125. Carlsen J, Zabriskie N, et al: Apparent central nervous system depression in166 after the use of topical brimonidinhe.  Am J Ophthalmol  1999; 128:255.

126. Camras CB, The United States Latanoprost Study Group: Comparison of latanoprost and timolol in patients with ocular hypertension and glaucoma.  Ophthalmology  1996; 103:138.

127. Watson P, Stjernschantz J, The Latanoprost Study Group: A six-month, randomized, double-masked study comparing latanoprost with timolol in open-angle glaucoma and ocular hypertension.  Ophthalmology  1996; 103:126.

128. Enyedi LB, Freedman SF: Latanoprost for the treatment of pediatric glaucoma.  Surv Ophthalmol  2002; 47:S129-S132.

129. Enyedi LB, Freedman SF, Buckley EG: The effectiveness of latanoprost for the treatment of pediatric glaucoma.  J Aapos  1999; 3:33-39.

130. Hoskins HD, Shaffer RN, Heatherington J: Goniotomy vs. trabeculotomy.  J Pediatr Ophthalmol Strabismus  1984; 21:153.

131. Luntz MH: The advantages of trabeculotomy over goniotomy.  J Pediatr Ophthalmol Strabismus  1984; 21:150.

132. Anderson DR: Trabeculotomy compared to goniotomy for glaucoma in children.  Ophthalmology  1983; 90:805.

133. deVincentiis C: Incisions dell angolo irideo nel glaucoma.  Ann Ottalmol  1893; 22:540.

134. Walton DS: Goniotomy.   In: Thomas JV, ed. Glaucoma surgery,  St Louis: CV Mosby; 1992.

135. Hodapp E, Heuer DK: A simple technique for goniotomy.  Am J Ophthalmol  1986; 102:537.

136. Buckley EG, Freedman SF, Shields MB: Atlas of ophthalmic surgery, vol 3. Strabismus and glaucoma surgery,  St Louis, Mosby-Year Book, 1995.

137. Litinsky SM, Shaffer RN, Heatherington J, Hoskins HD: Operative complications of goniotomy.  Trans Am Acad Ophthalmol Otolaryngol  1977; 83:78.

138. Smith R: A new technique for opening the canal of Schlemm.  Br J Ophthalmol  1960; 44:370.

139. Burian HM: A case of Marfan's syndrome with bilateral glaucoma with a description of a new type of operation for developmental glaucoma.  Am J Ophthalmol  1960; 50:1187.

140. Akimoto M, Tanihara H, Negi A, Nagato M: Surgical results of trabeculotomy ab externo for developmental glaucoma.  Arch Ophthalmol  1994; 112:1540.

141. Shrader CE, Cibis GW: External trabeculotomy.   In: Thomas JV, ed. Glaucoma surgery,  St Louis: CV Mosby; 1992.

142. McPherson SDJ: Results of external trabeculotomy.  Am J Ophthalmol  1973; 76:918.

143. Beck AD, Lynch MG: 360 degree trabeculotomy for primary congenital glaucoma.  Arch Ophthalmol  1995; 113:1200.

144. Mandal AK, Gothwal VK, Nutheti R: Surgical outcome of primary developmental glaucoma: a single surgeon's long-term experience from a tertiary eye care centre in India.  Eye  2006.

145. Cadera W, Pachtman MA, Cantor LB, et al: Filtering surgery in childhood glaucoma.  Ophthalmic Surg  1984; 15:319.

146. Sheie HG: Results of peripheral iridectomy with scleral cautery in congenital and juvenile glaucoma.  Trans Am Ophthalmol Soc  1962; 60:116.

147. Beauchamp GR, Parks MM: Filtering surgery in children: barriers to success.  Ophthalmology  1979; 86:170.

148. Wells AP, Cordeiro MF, Bunce C, Khaw PT: Cystic bleb formation and related complications in limbus-versus fornix-based conjunctival flaps in pediatric and young adult trabeculectomy with mitomycin C.  Ophthalmology  2003; 110:2192-2197.

149. Miller MH, Rice NSC: Beta-irradiation with trabeculectomy for congenital glaucoma.  Br J Ophthalmol  1991; 75:584.

150. Zalish M, Leiba H, Oliver M: Subconjunctival injection of 5-fluorouracil following trabeculectomy for congenital and infantile glaucoma.  Ophthalmic Surg  1992; 23:203.

151. Susanna RJ, Oltrogge EW, Carani JCE, Nicolela MT: Mitomycin as adjunct chemotherapy with trabeculectomy in congenital and developmental glaucomas.  J Glaucoma  1995; 4:151-157.

152. Mandal AK, Prasad K, Naduvilath TJ: Surgical results and complications of mitomycin C-augmented trabeculectomy in refractory developmental glaucoma.  Ophthalmic Surg Lasers  1999; 30:473-480.

153. Beck AD, Wilson WR, Lynch MG, et al: Trabeculectomy with adjunctive Mitomycin c in pediatric glaucoma.  Am J Ophthalmol  1998; 126:648-657.

154. Sidoti PA, Belmonte SJ, Liebmann JM, Ritch R: Trabeculectomy with Mitomycin c in the treatment of pediatric glaucomas.  Ophthalmol  2000; 107:422-429.

155. Freedman SF, McCormick K, Cox T: Mitomycin c-augmented trabeculectomy with postoperative wound modulation in pediatric glaucoma.  J AAPOS  1999; 3:117-124.

156. Waheed S, Ritterband DC, Greenfield DS, et al: Bleb-related ocular infection in children after trabeculectomy with mitomycin C.  Ophthalmology  1997; 104:2117-2120.

157. Crooke ST, Bradner WT: Mitomycin C: A review.  Cancer Treat Rev  1976; 3:121.

158. Glaubinger D, Ramu A: Antitumor antibiotics.   In: Chabner BA, ed. Pharmacologic principles of cancer treatment,  Philadelphia: WB Saunders; 1982:402-415.

159. Rodrigues AM, Junior AP, Montezano FT, et al: Comparison between results of trabeculectomy in primary congenitalglaucoma with and without the use of mitomycin C.  J Glaucoma  2004; 13:228-232.

160. Molteno ACB, Ancker E, Van Biljon G: Surgical technique for advanced juvenile glaucoma.  Arch Ophthalmol  1984; 102:51.

160a. Billson F, Thomas R, Aylward W: The use of two-stage Molteno implants in developmental glaucoma.  J Pediatr Ophthalmol Strabismus  1989; 26:3.

161. Lloyd MA, Sedlak T, Heuer DK, et al: Clinical experience with the single-plate Molteno implant in complicated glaucomas.  Ophthalmology  1992; 99:679.

162. Munoz M, Tomey KF, Traverso C, Day SH: Clinical experience with the Molteno implant in advanced infantile glaucoma.  J Pediatr Ophthalmol Strabismus  1991; 28:68.

163. Hill RA, Heuer DK, Baerveldt G, et al: Molteno implantation for glaucoma in young patients.  Ophthalmology  1991; 98:1042.

164. Netland PA, Walton DS: Glaucoma drainage implants in pediatric patients.  Ophthalmic Surg  1993; 24:723.

165. Coleman AL, Smyth RJ, Wilson MR, Tam M: Initial clinical experience with the Ahmed glaucoma valve implant in pediatric patients.  Arch Ophthalmol  1997; 115:186.

166. Eid TE, Katz LJ, Spaeth GL, Augsburger JJ: Long-term effects of tube-shunt procedures on management of refractory childhood glaucoma.  Ophthalmology  1997; 104:1011.

167. Englert JA, Freedman SF, Cox TA: The Ahmed valve in refractory pediatric glaucoma.  Am J Ophthalmol  1999; 127:34-42.

168. Djodeyre MR, Peralta Calvo J, Abelairas Gomez J: Clinical evaluation and risk factors of time to failure of Ahmed Glaucoma Valve implant in pediatric patients.  Ophthalmology  2001; 108:614-620.

169. Morad Y, Craig ED, Kim YM, et al: The Ahmed drainage implant in the treatment of pediatric glaucoma.  Am J Ophthalmol  2003; 135:821-829.

170. Chen TC, Bhatia LS, Walton DS: Ahmed valve surgery for refractory pediatric glaucoma: a report of 52 eyes.  J Pediatr Ophthalmol Strabismus  2005; 42:274-283.quiz 304-305.

171. Donahue SP, Keech RV, Munden P, Scott WE: Baerveldt implant surgery in the treatment of advanced childhood glaucoma.  J AAPOS  1997; 1:41-45.

172. Rolim de Moura C, Fraser-Bell S, Stout A, et al: Experience with the baerveldt glaucoma implant in the management of pediatric glaucoma.  Am J Ophthalmol  2005; 139:847-854.

173. Budenz DL, Gedde SJ, Brandt JD, et al: Baerveldt glaucoma implant in the management of refractory childhood glaucomas.  Ophthalmology  2004; 111:2204-2210.

174. van Overdam KA, de Faber JT, Lemij HG, de Waard PW: Baerveldt glaucoma implant in paediatric patients.  Br J Ophthalmol  2006; 90:328-332.

175. Al-Torbak AA, Al-Shahwan S, Al-Jadaan I, et al: Endophthalmitis associated with the Ahmed glaucoma valve implant.  Br J Ophthalmol  2005; 89:454-458.

176. Gutierrez-Diaz E, Montero-Rodriguez M, Mencia-Gutierrez E, et al: Propionibacterium acnes endophthalmitis in Ahmed glaucoma valve.  Eur J Ophthalmol  2001; 11:383-385.

177. Beck AD, Freedman S, Kammer J, Jin J: Aqueous shunt devices compared with trabeculectomy with mitomycin-C for children in the first two years of life.  Am J Ophthalmol  2003; 136:994-1000.

178. Al Faran MF, Tomey KF, Al Mutlag FA: Cyclocryotherapy in selected cases of congenital glaucoma.  Ophthalmic Surg  1990; 21:794-798.

179. Wagle NS, Freedman SF, Buckley EG, et al: Long-term outcome of cyclocryotherapy for refractory pediatric glaucoma.  Ophthalmology  1998; 105:1921-1926.discussion 1926-1927.

180. Kirwan JF, Shah P, Khaw PT: Diode laser cyclophotocoagulation: role in the management of refractory pediatric glaucomas.  Ophthalmology  2002; 109:316-323.

181. Phelan MJ, Higginbotham EJ: Contact transscleral Nd:YAG laser cyclophotocoagulation for the treatment of refractory pediatric glaucoma.  Ophthalmic Surg Lasers  1995; 26:401.

182. Bock CJ, Freedman FF, Buckley EG, Shields MB: Transscleral diode laser cyclophotocoagulation for refractory pediatric glaucomas.  J Pediatr Ophthalmol Strabismus  1997; 34:235.

183. Autrata R, Rehurek J: Long-term results of transscleral cyclophotocoagulation in refractory pediatric glaucoma patients.  Ophthalmologica  2003; 217:393-400.

184. Lehmann OJ, McHugh JD, Garner A, et al: Diode laser transscleral cyclophotocoagulation in buphthalmic eyes: histological and clinical results.  Invest Ophthalmol Vis Sci  1994; 35(Suppl):

185. Barkana Y, Morad Y, Ben-nun J: Endoscopic photocoagulation of the ciliary body after repeated failure of trans-scleral diode-laser cyclophotocoagulation.  Am J Ophthalmol  2002; 133:405-407.

186. Neely DE, Plager DA: Endocyclophotocoagulation for management of difficult pediatric glaucomas.  J Aapos  2001; 5:221-229.

187. Plager DA, Neely DE: Intermediate-term results of endoscopic diode laser cyclophotocoagulation for pediatric glaucoma.  J Aapos  1999; 3:131-137.

188. Barkan O: Goniotomy.  Trans Am Acad Ophthalmol  1955; 59:322.

189. Scheie HG: Symposium on congenital glaucoma: diagnosis, clinical course and treatment other than goniotomy.  Trans Am Acad Ophthalmol Otolaryngol  1955; 59:309.

190. Biglan AW, Hiles DA: The visual results following infantile glaucoma surgery.  J Pediatr Ophthalmol Strabismus  1979; 16:377.



If you find an error or have any questions, please email us at admin@doctorlib.info. Thank you!