Ординатура / Офтальмология / Английские материалы / The Pediatric Glaucomas_Mandal, Netland_2006

Introduction

Clinical features

The diagnostic examination

Conditions with overlapping signs of epiphora and ‘red-eye’

Conditions with overlapping signs of corneal enlargement

Conditions with overlapping signs of corneal edema and opacity

Conditions with overlapping signs of optic nerve abnormalities

Conditions associated with increased intraocular pressure

Conclusion

Introduction

Primary congenital glaucoma refers to a specific form of developmental glaucoma, which has an isolated maldevelopment of the trabecular meshwork (isolated trabeculodysgenesis) not associated with other developmental ocular anomalies or ocular disease that can raise the intraocular pressure. The term primary infantile glaucoma has the same meaning as primary congenital glaucoma. It is the most common form of developmental glaucoma, occurring in about 1 in 10 000 live births. Primary congenital glaucoma is typically bilateral, although a significant intraocular pressure elevation may

occur in only one eye in 25 to 30% of the cases. In this chapter, we will discuss the clinical features, the diagnostic examination and the differential diagnosis of the disease.

Clinical features

Primary congenital glaucoma may present with a classic triad of symptoms (Fig. 6.1A-C).1 These symptoms include epiphora (excessive tearing), photophobia (hypersensitivity to light), and blepharospasm (squeezing of the eyelids). Any combination of these symptoms should arouse suspicion of glaucoma in an infant or child. These symptoms are secondary to the corneal irritation that accompanies corneal epithelial edema caused by elevated intraocular pressure.

Epiphora may at first be attributed to a non-patent tear drainage system, which is a common condition. Photophobia commonly occurs and may be of gradual or sudden onset. The parents may first notice that their baby keeps the eyes closed when exposed to sunlight, and their usual reaction is to provide some shade, in the belief that the baby is merely showing normal sensitivity to light. Moderate photophobia may be noticed indoors as well; the baby will often keep the eyes closed even while eating. Severe photophobia will cause the baby to keep the eyes closed constantly or to hide the face from bright lighting or even from ordinary lighting. During the period of apparent discomfort, the baby may also be seen to rub the eyes frequently.2

Primary infantile glaucoma may also present as a ‘red eye,’ mimicking conjunctivitis and delaying the correct diagnosis.1,3,4 Enlargement of the eye occurs under the influence

of the elevated intraocular pressure, with the major enlargement occurring at the corneoscleral junction. A hazy appearance of the cornea can be intermittent in the early stages and precede breaks in Descemet’s membrane.

Ocular enlargement

Ocular enlargement occurs because the neonatal globe is still distensible (Fig. 6.2). The corneal and scleral collagen have not hardened sufficiently to prevent their expansion with increased intraocular pressure. This change includes stretching in all parts of the infant eye, including the cornea, the anterior chamber angle, the sclera, the optic nerve, the scleral canal, and the lamina cribrosa.1,3

The normal neonatal horizontal corneal diameter is approximately 10 to 10.5 mm, increasing an additional 0.5 to 1.0 mm in the first year of life.5 Enlargement of the corneal diameter to greater than 12 mm in the first year of life is highly suspicious of developmental glaucoma.1 This enlargement is more obvious in asymmetric cases. Corneal enlargement from increased intraocular pressure predominantly occurs before the age of three years,6,7 but the sclera may be deformable until approximately age 10 years.8

The increased intraocular pressure stretches the corneal endothelium and Descemet’s membrane, resulting in breaks in these layers, first described by Haab in 1863 (Fig. 6.3).4,7 As the edge of the rupture in Descemet’s membrane contracts into scrolls and ridges,7 infiltration of the aqueous humor causes localized corneal edema, compounding any diffuse edema that may also be present simply because of the elevated intraocular pressure. Haab’s striae form as endothelial cells lay down new basement membrane (Descemet’s membrane) and hyaline ridges develop.4,7 Haab’s striae are typically horizontal and linear when they occur centrally in the cornea, but parallel or curvilinear to the limbus when they occur peripherally.4,6,7,9 They do not seem to occur in corneas smaller than 12.5 mm in diameter. Breaks in the Descemet’s membrane from increased intraocular pressure rarely occur after the age of three years.7 Haab’s striae occur in approximately 25% of patients who have primary infantile

Figure 6.2 Infant with megalocornea and corneal edema due to primary congenital glaucoma.

A

B

Figure 6.3 Slit lamp biomicroscopy of Haab’s striae with diffuse illumination (A) and retroillumination (B).

glaucoma at birth and are evident in over 60% of infants presenting with primary infantile glaucoma at 6 months of

age.10,11

The initial corneal edema in primary infantile glaucoma is simple epithelial edema due to elevated intraocular pressure. In chronic primary infantile glaucoma, there is permanent stromal edema.14,15 Persistence and progression of primary infantile glaucoma may lead to permanent sequelae, such as stromal scarring, chronic stromal corneal edema, and irregular corneal astigmatism12,13 Younger children are more likely to present to the ophthalmologist with corneal edema and haze, while older children will more commonly present with frank corneal enlargement or buphthalmos.16

The sclera also expands slowly under the influence of elevated intraocular pressure. The associated scleral thinning causes an increased visibility of the underlying uveal tissue in the neonate and a ‘blue-sclera’ appearance (Fig. 6.4). With the gradual deposition of additional extracellular connective tissue that occurs during growth,17 no further expansion of sclera occurs. Once buphthalmos has developed, the globe usually does not return to normal size with normalization

Figure 6.4 Child with congenital glaucoma and ‘blue-sclera’ appearance due to buphthalmos and scleral thinning.

A

B

Figure 6.5 Glaucomatous optic nerve damage in congenital glaucoma with elevated intraocular pressure. Note the enlarged optic nerve cup with an intact neural rim (A). End-stage cupping (B).

of the intraocular pressure.17 As the axial length of the globe increases, myopia and astigmatism result.18,19 Myopic astigmatism and anisometropia are particularly common in cases of unilateral or asymmetric primary infantile glaucoma.

Optic nerve cupping

The optic nerve changes in primary congenital glaucoma are different from those occurring in adults with glaucoma. Optic nerve cupping may occur rapidly and early in infants (Fig. 6.5).17,20–23 Also, cupping of the optic nerve head may be reversible with normalization of intraocular pressure (Fig. 6.6),24,25 whereas this is uncommon in the adult with glaucomatous induced optic nerve head damage.17

Several hypotheses have been proposed to explain the optic nerve head cupping in infants. First, it has been suggested that astroglial cell loss may be induced by elevated intraocular pressure.21 Second, extracellular fluid shifts in the optic nerve head may contribute to changes in the cup at different levels of intraocular pressure.26 Third, posterior displacement of the lamina cribrosa and enlargement of the scleral canal may account for changes in the cup size with fluctuation of intraocular pressure during infancy.17,27 The third explanation

Figure 6.6 Appearance of the optic nerve of a child with congenital glaucoma after surgical treatment and normalization of the intraocular pressure. The cup shows mild concentric enlargement with increased vertical cup-to-disc ratio and an intact neural rim.

currently seems most reasonable, based on the fact that the connective tissue of the lamina cribrosa is not yet mature during early neonatal life.17

Reversibility of cupping in infantile glaucoma appears to be due to incomplete development of connective tissue in the lamina cribrosa, which allows posterior movement of the

The diagnostic examination

The history of blepharospasm, photophobia, and tearing is very useful in arousing the suspicion of glaucoma and in distinguishing it from other conditions. Other historical information of importance is the family history of glaucoma, associated congenital defects, maternal history of infection (rubella) during pregnancy, and birth history.13

Initial examination

During the initial office visit, the examiner may be able to observe the degree of photophobia, blepherospasm, and tearing. Ideally, the examiner captures the infant’s open-eyed attention with a slowly blinking flashlight or a gentle jingle of keys and then can observe the corneal size and clarity without touching the baby’s face. The effort may be unavoidably impossible, and often the inexperienced examiner aggravates the difficulty by moving too quickly or frightening the child with a loud clatter of keys, whistling and clicking sounds, and perhaps a futile effort to pry open the lids. Meanwhile, the anxious mother, realizing the importance of the examination and sensing the examiner’s desire for a close look, frantically pats and rocks the baby. As the baby cries, the mother and the examiner not only feel frustrated in their efforts, but become tense. The examiner with insight will avoid making the examination more difficult than it is already.

At this point, the examiner may have determined that there is an enlarged or cloudy cornea, and that the patient has photophobia, blepharospasm, and tearing. The diagnosis of primary infantile glaucoma may be sufficiently obvious or likely that it is almost certain that examination and possible surgery under general anesthesia is going to be required. In any event, it should be kept in mind that the goal of the office examination is to accomplish an examination sufficient to rule out glaucoma making examination under anesthesia unnecessary; or to gather enough information to establish the suspicion of primary infantile glaucoma, justifying administration of general anesthesia for a more complete ocular examination and probable surgery.

Usually, a complete ocular examination, including slit-lamp examination, applanation tonometry, gonioscopy, and optic

B

Figure 6.7 Distracting an awake child with a bottle or pacifier can permit accurate measurement of intraocular pressure and a thorough examination. Many children are cooperative with an office examination (A, B). In these photographs, the intraocular pressure is measured using an electronic (Tonopen) tonometer.

nerve evaluations can be performed in the office in children over the age of 5 years and, with some training, in children as young as 3 years. Timing the examination of an infant to occur when the child is placated by a bottle feeding can be helpful in allowing a complete examination (Fig. 6.7). If necessary, in an older child, a mild sedative such as chloral hydrate syrup (25 to 50 mg/kg body weight) can be given (Fig. 6.8). Chloral hydrate can mildly lower the intraocular pressure, and this approach is usually not necessary if patience and gentleness are exercised.

Visual field examination can be performed at 5 to 6 years of age, but the patient’s short attention span and poor fixation often prevent a detailed study. The older and more cooperative the child, the more detailed the examination. By the age of 8 to 10 years, most children can cooperate for a full quantitative visual field examination.

Figure 6.8 A mild sedative such as chloral hydrate can allow complete examination, and avoid deep anesthesia (examination under anesthesia) requiring respiratory support. This child’s anterior segment and anterior chamber angle is examined using Koeppe gonioscopy.

A reasonably good office examination can sometimes be performed in infants younger than 3 months of age using the infant diagnostic lens of Richardson–Shaffer or a small diameter Koeppe lens. The lens assists in examination of the anterior segment, and enables the physician to perform gonioscopy and visualize the optic disc. It is well tolerated when placed on the eye with topical anesthesia, and, with a direct ophthalmoscope set at approximately +10.0 diopters, a very good view of the posterior pole can be obtained even with small pupils and mild corneal haze.

Examination under anesthesia (EUA)

The examination under anesthesia, when necessary, provides an opportunity to thoroughly examine the eye. Anesthesia should be administered in the operating room by skilled individuals who have experience with pediatric patients. For a brief examination, oftentimes administration of intravenous and mask anesthesia is sufficient. For more prolonged examination and treatment, an endotracheal tube may be necessary. The basic equipment required to perform an adequate examination under anesthesia to ascertain the diagnosis of primary infantile glaucoma is shown in Table 6.1.

Corneal clarity and corneal diameter

The cornea is examined to document the presence or absence of corneal edema, breaks in Descemet’s membrane (Haab’s striae), and corneal enlargement in order to distinguish the glaucomatous signs from other corneal abnormalities.

The corneal diameter is measured along the horizontal and vertical meridian. The vertical meridian may be difficult to measure accurately due to encroachment of sclera at the superior limbus. Corneal diameter can be measured with calipers, but a problem with calipers is that it may be difficult to judge the actual diameter when the examiner is measuring meridian length. Kiskis and coworkers28 introduced a series of transparent plastic plates (templates) with holes of different diameters in quarter-millimeter increments to fit close to the eye so that the location of the limbus can accurately be

aligned. A corneal diameter greater than 12 mm in the first year of life is highly suggestive of infantile glaucoma.1 With an increase in the horizontal diameter above 13 mm, the limbus becomes indistinct, making measurement difficult. However, the measurement should be recorded accurately, even when it is clearly abnormal, to serve as a baseline to allow determination of further corneal enlargement at later examinations.

Refraction

Determination of refractive error, including the astigmatic change by streak retinoscopy, is used as a diagnostic method to recognize ocular enlargement and distortion. Assessment of the refractive error also establishes a baseline which can be helpful to judge future progression.

Intraocular pressure measurement

Tonometry can be performed with a Schiotz tonometer, Perkins hand-held applanation tonometer, or electronic (Tonopen) tonometer (Fig. 6.9). One method is usually sufficient, although, in cases where uncertainty exists, checks can be performed with other instruments.

All anesthetics alter the intraocular pressure of patients with primary infantile glaucoma,29 seemingly in relation to the level of anesthesia29 and as a direct function of their effect on cardiovascular tone.13 A rapid lowering occurs particularly with halothane (Fluothane) anesthesia,13,24,29 which may produce readings 15 to 20 mm below the ‘true’ measurement.29 The intraocular pressure may be at least transiently elevated by cyclopropane or succinylcholine.13 Anesthetic drugs that achieve only light anesthesia and those that induce deeper anesthesia only slowly, such as diethyl ether, cyclopropane,13 or ketamine, allow the intraocular pressure to be measured somewhere between the artificially elevated intraocular pressure of ‘excitement’ stage of anesthesia and the artificially

Table 6.1 Equipment for examination under anesthesia (EUA)

1.Pediatric lid speculum

2.Balanced salt solution

3.Tonometer (Perkins and/or Tonopen)

4.Direct ophthalmoscope

5.Retinoscope

6.Koeppe goniolens and light source

7.Calipers or templates with different sized holes (to measure corneal diameter)

*8. Portable hand-held slit-lamp

*9. Ultrasound (A- or B-mode; ultrasound biomicroscope, [UBM])

*10. Hand-held Kowa camera or a specially adapted fundus camera (for optic disc and possibly fundus photographs)

*Optional

Figure 6.9 An examination under anesthesia (administered by mask). The intraocular pressure is measured using the Perkins hand-held applanation tonometer.

lowered intraocular pressure of deep anesthesia observed with halothane. Standardization of anesthesia for intraocular pressure measurement for diagnosis and follow-up of primary infantile glaucoma is obviously highly desirable, and inconsistent readings should always be interpreted with consideration of the patient’s general state of anesthesia and the specific anesthetic used.13

The normal intraocular pressure in an infant under halothane anesthesia is said to be approximately 9 to 10 mmHg30 and a pressure of 20 mmHg or more should arouse suspicion.30 The most reliable method of measuring the intraocular pressure is probably with the child awake, if cooperation permits, and the Perkins tonometer has been found to be particularly suitable in this situation.31 In one study, the mean intraocular pressure in unanesthetized newborns was 11.4 ± 2.4 mmHg.32

Another potential source of error is the method of tonometry itself. Schiotz tonometry, a commonly used method for measurement of the intraocular pressure in the operating room, is affected by corneal edema and swelling, corneal surface distortion and irregularities, and by changes in corneal curvature and ocular rigidity, conditions that all exist in primary infantile glaucoma.33,34 In cases of scarred or edematous corneas, the Mackay–Marg tonometer is considered to be more accurate.35–37 The electronic (Tonopen) tonometer is useful, but the mires observed using the Perkins applanation tonometer may be helpful in assessing the accuracy of the measurement. The normal intraocular pressure in an infant is slightly lower than in an adult, but 21 mmHg remains a useful upper limit.

There is no one way of measuring intraocular pressure that is ideal. Our preference is the hand-held Perkins applanation tonometer used at that earliest stage of inhalation anesthesia before intubation to reduce errors related to anesthesia, relying on the rest of the examination to interpret the importance of the intraocular pressure reading.

Slit lamp examination

This portion of the examination is best performed with a portable hand-held slit lamp. The corneal findings are judged with magnification and stereopsis. The anterior chamber in primary congenital glaucoma is characteristically deep, especially when distention of the globe is present. The iris is typically normal, although it may have stromal hypoplasia with loss of the crypts.

Gonioscopy

Evaluation of the anterior chamber angle is essential for the accurate diagnosis of the developmental glaucomas. The Koeppe 14 to 16 mm lens with a Barkan light and hand-held binocular microscope provides the surgeon with the appropriate view of the angle (Fig. 6.10). Alternatively, the handheld slit lamp, if available, may be used to visualize the angle through the Koeppe lens. The Goldmann lens may also be used for viewing the angle through the operating microscope. If corneal clouding is marked, the view may be improved

Figure 6.10 The Koeppe lens is useful for assessing the anterior segment and the anterior chamber angle, especially during an examination under anesthesia. An excellent view of the disc and macula, also, may be obtained using the Koeppe lens and a direct ophthalmoscope.

by instilling topical glycerine solution or, if necessary, by removing the epithelium with a surgical blade38 or applying a 70% alcohol solution with a cotton applicator.

The anterior chamber angle in childhood differs significantly from that of adults. In the normal newborn eye, the iris usually inserts posterior to the scleral spur. The anterior extension of the ciliary body is seen as a distinct band anterior to the iris insertion. The iris insertion into the angle is flat, because the angle recess has not yet formed. The trabecular meshwork appears thicker and more translucent than that of the adult. Absence of acquired pigmentation of the trabecular meshwork is normal in the infant eye. Illuminating the angle from the side with a slit beam may help determine the location of the trabecular meshwork posterior to the area where the light beam narrows at the end of the cornea. The formation of the angle recess, characteristic of the adult angle, in which the iris turns slightly posteriorly before inserting into the ciliary body, develops in the first 6 to 12 months of life. The normal infant eye may have some thinning of the peripheral iris.2

Gonioscopy of the eye with primary congenital glaucoma reveals an anterior insertion of the iris directly into the trabecular meshwork (Fig. 6.11).39,40 This iris insertion is most commonly flat, although a concave insertion may also be seen. In a concave insertion, the plane of the iris is posterior to the level of the scleral spur, but the anterior stroma of the iris sweeps upward to insert into the trabecular meshwork. The level of the iris insertion may vary at different areas of the angle, with some portions of the iris inserting anterior and other areas posterior to the scleral spur. The surface of the trabecular meshwork may have a stippled appearance and the meshwork may appear thicker than normal. There is no pigmented band present, but a thin section of the ciliary body may be visible through the thickened trabeculum. The peripheral iris may show a thinning of the anterior stroma.

Figure 6.11 Gonioscopic appearance of the anterior chamber angle in an infant with primary congenital glaucoma. Note the high insertion of the iris. There is no definite visible scleral spur.

Although the angle is usually avascular, loops of vessels from the major arterial circle may be seen above the iris, which has been called the ‘Loch Ness Monster phenomenon.’41 In addition, the peripheral iris may be covered by a fine, fluffy tissue that has been referred to as ‘Lister’s morning mist.’41 Sometimes exposure of the radial iris vessels may exist in normal blue-eyed infants or in the eyes with hypoplasia of the anterior iris stroma. In such eyes there is no vascular anomaly even though the vessels are easily seen.42

Ophthalmoscopy

Evaluation of the optic disc is an essential part of the examination. Ophthalmoscopy under general anesthesia is most easily performed through a semi-dilated pupil (Fig. 6.12). Mydriasis can be obtained by using a drop of 2.5% phenyl-

ephrine and 1% cyclopentolate. This seldom influences intraocular pressure or systemic blood pressure.43 If surgery is contemplated, ophthalmoscopy should be done without dilatation. One can use the hand-held direct ophthalmoscope to obtain monocular clues of optic nerve head cupping or enlargement. A good view can be facilitated by the use of a Koeppe contact lens, which neutralizes irregular corneal reflexes and also improves the view of the optic disc through a small pupil.

The optic nerve head in normal newborns is typically pink, but may have slight pallor, and a small physiological cup is usually present.44 In most cases, the physiologic cupping is bilaterally symmetric, and asymmetry is suggestive evidence of glaucoma. Cup-to-disc ratios greater than 0.3 are rare in normal infants but common in infants with glaucoma and must be considered suspicious. Cupping of the optic nerve is an early sign of increased pressure. Optic nerve cupping occurs much more quickly and at lower pressures than in adults.

The infant glaucomatous cup usually has a configuration different from adult glaucomas. Although it can be oval, it is more commonly round, steep walled, and central, surrounded by a uniform pink rim. The cup tends to enlarge circumferentially with glaucomatous progression, which probably results from a stretching of the scleral canal. A decrease in cupping can occur within hours or days after intraocular pressure control in the very young. This is especially marked in infants below 1 year of age.17,29

If therapy is successful, the cup will either remain stable or decrease in size. Evidence of increased cup size is indicative of uncontrolled glaucoma in an individual of any age. To provide records for future comparison, it is best to make a careful drawing or to take photographs of the optic nerve head.

Robin and associates19 examined in detail the features of the optic nerve head in their 59 patients with primary infantile glaucoma by stereophotographs when possible and by careful drawings. They found that the average vertical cup/disc ratio was 0.68 ± 0.24 and the average horizontal cup/disc ratio was 0.65 ± 0.24.19 In addition, they found that 14 (25%) of involved eyes had loss of neuroretinal rim tissue at the superior and inferior poles, as in adult glaucomatous optic nerve heads, and 12 (21%) had slit defects in the arcuate area of the nerve fiber layer. Finally, they documented three prognostic factors regarding cupping. First, males tended to lose more of the neuroretinal rim tissue compared with females. Second, eyes of bilaterally involved primary infantile glaucoma patients had larger cups than unilaterally glaucomatous patients. Third, the older the patient at the time of the initial diagnosis, the greater the cupping (P < 0.001).19

Figure 6.12 Examination of the disc is an essential part of the examination under anesthesia. This is also the best opportunity for photographic documentation of the appearance of the optic nerve.

Ocular fundus photography

Ocular fundus photography is very useful in keeping a record of the appearance of the optic disc. This is best done when the infant is anesthetized, using a hand-held Kowa camera or a fundus camera placed vertically to obtain fundus pictures. Sometimes it is necessary to put a special contact lens on the eye to see through the small pupil, such as a Koeppe lens without a dimple, or use a Kowa hand-held camera and an indirect lens.

Ultrasonography

Ultrasonic ocular biometry has been recommended by some investigators for routine use in the diagnosis and follow-up of congenital glaucoma.45,46–48 A-scan measurements can determine axial length, depth of anterior chamber, and lens thickness. The normal axial length in an infant ranges from 17.5 to 20 mm and increases to 22 mm in length by 1 year of age.

Several studies have indicated that ultrasonic measurement of the axial length of the eye in infants and children is a highly valuable parameter in the diagnosis of congenital glaucoma. Results confirmed the clinical value of ultrasonic biometry for both the diagnosis of congenital glaucoma in cases with borderline intraocular pressures and to detect glaucoma in the fellow eye of patients with presumed unilateral disease.44,45 Also, the method was effective in the follow-up45–48 of patients with congenital glaucoma who had undergone surgery. It has been reported that the axial length may decrease up to 0.8 mm following surgical reduction of the intraocular pressure.48

The values of the measurements of the anterior chamber depth, the length of the vitreous body, and the axial length are significantly higher in glaucomatous eyes. An interesting finding is that the lens thickness of glaucomatous eyes is notably reduced.46 This is an important contributing factor in the emmetropization of the glaucomatous eye, the axial length of which, when considered as an isolated factor, would predict a higher myopia than observed in glaucomatous eyes.46

In congenital glaucoma, although myopia is a common finding, its magnitude does not usually reach the expected value based on the enlargement of the eyeball. The final refraction will also be influenced by other changes induced by the disease in other eye structures. The enlargement of the eye and the cornea is associated with flattening of the cornea, which reduces myopia. Also, the lens decreases in thickness, probably due to expansion of the scleral ring adjacent to the ciliary body and stretching of the zonular fibers thereby decreasing the lens thickness. Furthermore, the deepening of the anterior chamber due to posterior positioning of the lens as the eye and cornea enlarge can influence the refraction in eyes with congenital glaucoma. All of these factors contribute to the so-called emmetropization, which involves harmonization of the different and interdependent parameters that have an influence on ocular refraction.

B-scan ultrasonography can support A-scan measurements in buphthalmic eyes by depicting a generalized enlargement of the globe. When the media are opaque (corneal edema, cataract), B-scan examination can delineate structural abnormalities such as retinal or choroidal detachment, or unsuspected mass lesion.

High frequency ultrasound examination of the anterior segment (ultrasonic biomicroscopy or UBM) uses higher resolution imaging to depict the cornea, anterior chamber, iris and angle. UBM has been used to determine angle development values for various post-conceptual age and birth weights, including those of premature infants.49,50 In eyes with trabeculodysgenesis, elongated and anteriorly placed

ciliary processes may be noted.51 In congenital glaucoma patients with dense corneal opacities, this technique may be useful in delineating the extent of anterior segment abnormalities to aid in surgical planning.51

Interpretation of examination findings

In most cases, after completion of the examination under anesthesia, the findings of corneal enlargement, optic nerve head changes, and buphthalmos are so typical of primary congenital glaucoma that there is little doubt about the diagnosis and the need for surgery. If the intraocular pressure is normal and the other findings are present, one can assume the intraocular pressure is artifactually lowered under anesthesia, and still secure the diagnosis and proceed with surgery. If ocular enlargement and optic nerve cupping are not typical or are absent, then it is appropriate to postpone diagnosis and therapy for 3 to 4 weeks, repeating the examination under anesthesia at that time to see if any changes have occurred to allow a clinical diagnosis.

It is important to inform the parents of the possibility of a diagnosis of primary infantile glaucoma before the examination under anesthesia and obtain consent for a possible surgical procedure. If the diagnosis is confirmed, goniotomy or trabeculotomy (or combined trabeculotomy–trabeculectomy) can be performed immediately. This spares the patient another inhalation anesthesia, and allows the clinician to proceed with the definitive procedure for the disease as early as possible.

Differential diagnosis

Some of the clinical features of primary congenital glaucoma are also found in other conditions, and these must be considered in the differential diagnosis. Several clinical entities deserve mention, to differentiate them from primary infantile glaucoma. Most have one of the signs or symptoms of primary infantile glaucoma, but none are completely characterized by photophobia, tearing, blepharospasm, and generalized ocular enlargement (buphthalmos) with optic nerve cupping.33 A differential diagnosis for congenital glaucoma is provided in Table 6.2.

Conditions with overlapping signs of epiphora and ‘red-eye’

The most common cause of epiphora in the infant is obstruction of the nasolacrimal drainage system. Photophobia is not associated with this problem and other signs typical of congenital glaucoma are absent. The epiphora of nasolacrimal duct obstruction is distinguished from that of infantile onset glaucoma in that the former condition is usually associated with fullness of the lacrimal sac and often has chronic mucopurulent discharge.

Any of several causes of conjunctivitis1,3,4 in the infant can present with redness and tearing. Chemical conjunctivitis secondary to silver nitrate prophylaxis is a common cause in

Table 6.2 Differential diagnosis of primary congenital glaucoma

Conditions with overlapping signs of epiphoria and ‘red eye’ Nasolacrimal duct obstruction

Conjunctivitis

Corneal epithelial defect, abrasion Meesman’s corneal dystrophy Reis–Buckler’s corneal dystrophy

Ocular inflammation (e.g., keratitis, iridocyclitis)

Conditions with overlapping signs of corneal enlargement Axial myopia

Megalocornea

Conditions with overlapping signs of corneal edema or opacity Sclerocornea

Tears in Descemet’s membrane (e.g., obstetric trauma)

Ulcers (e.g., congenital neonatal corneal herpes infection, congenital syphilis)

Metabolic diseases (e.g., oculocerebrorenal syndrome of Lowe, mucopolysaccharidoses, cystinosis, mucolipidoses, amyloidosis, Fabry’s disease, glucose-6-phosphatase deficiency)

Peters anomaly

Endothelial dystrophies (e.g. posterior polymorphous dystrophy, congenital heriditary endothelial dystrophy)

Congenital hereditary stromal dystrophy Dermoid (central corneal dermoid)

Conditions with overlapping signs of optic nerve abnormalities Congenital malformation of the disc (e.g., pits, colobomas,

hypoplasia) Tilted disc

Large physiologic cups

Conditions with overlapping signs of increased intraocular pressure Maternal rubella syndrome

Secondary infantile glaucoma due to anterior chamber cleavage syndromes, phakomatoses (e.g., Sturge–Weber syndrome, Von Recklinghausen’s disease, Von Hippel–Lindau syndrome, nevus of Ota), and other secondary glaucomas

Modified from Raab.33

the newborn. Bacterial, chlamydial, and viral infections are usually associated with a mucoid or mucopurulent discharge and must be ruled out. Corneal epithelial defects or abrasions are frequent causes of acute ocular irritation in children and are diagnosed by history and external examinations.

Meesman’s corneal dystrophy usually presents in the first several months of life with ocular irritation. Examination reveals multiple clear to gray-white, punctate opacities of the corneal epithelium, which are intra-epithelial cysts. The condition is bilateral, dominantly inherited, and is the probable equivalent of Stocker–Holt dystrophy. Reis–Buckler dystrophy can present in the first few years of life with ocular pain secondary to recurrent epithelial erosion. Examination reveals irregular patches of opacity in the region of Bowman’s layer, with progression to a diffuse reticular pattern associated with an anterior stromal haze.

Congenital hereditary endothelial dystrophy can also present with tearing and photophobia along with corneal edema. Inflammatory disease, such as keratitis and iridocyclitis, can cause corneal edema and clouding associated with pain, redness and watering. Rubella keratitis may occur in newborn patients.

Conditions with overlapping signs of corneal enlargement

High degrees of axial myopia can present with large eyes, including large corneas. The other symptoms and signs of glaucoma are not present. The posterior pole findings serve to distinguish this condition from primary congenital glaucoma. A tilted appearance of the optic nerve head, peripapillary scleral halo (‘myopic crescent’), and choroidal mottling are characteristic of axial myopia, and are rarely seen in primary congenital glaucoma.

Megalocornea1,5 is a condition of marked corneal enlargement, often to diameters of 14.0 to 16.0 mm. Other signs of congenital glaucoma, such as elevated intraocular pressure, abnormal cupping of the optic disc nerve head, or tears in Descemet’s membrane, are not present. These eyes have deep anterior chambers and may have iridodonesis secondary to stretched zonules and a loose lens. On gonioscopic examination, one may find a normal angle, prominent iris processes, or a broad dense area of pigmented trabecular meshwork.24 The inheritance appears to be sex-linked, with ninety percent of cases occurring in males. Families have been reported in which some members have megalocornea and others have primary infantile glaucoma.19,52 Indeed, some have considered megalocornea a forme fruste of primary infantile glaucoma.49 These patients, while not in need of treatment, must be followed carefully for possible intraocular pressure changes indicative of primary infantile glaucoma.4,5,52

Conditions with overlapping signs of corneal edema and opacity

In sclerocornea, opaque scleral tissue extends into the cornea. Vessels usually accompany the tissue in this typically bilateral (90%), non-hereditary disease.

Obstetric trauma can cause rupture of the Descemet’s membrane with resultant corneal edema and clouding. The tears in Descemet’s membrane may mimic the Haab’s striae of primary infantile glaucoma.7 There is no unequivocal way of determining whether breaks in the Descemet’s membrane are due to birth trauma or increased intraocular pressure. It has often been stated that Descemet’s membrane breaks from birth trauma are vertically oriented while those caused by increased intraocular pressure are horizontal.7,53 However, they are also frequently curvilinear and often can run diagonally across the cornea as well. Obstetric corneal trauma is usually unilateral and more commonly affects the left eye because of the higher incidence of left occiput anterior presentation of the infant’s head at birth. There are attendant signs of periorbital skin changes as a result of trauma (bruising), normal intraocular pressure, and no corneal enlargement.7

Congenital or neonatal ocular herpes infections are extremely rare. Ocular herpes in the newborn include one or all of the following: conjunctivitis, epithelial keratitis, epithelial ulcer, stromal immune reaction, cataracts, and necrotizing chorioretinitis.54,55 In congenital ocular herpes, the infection may be acquired in utero via the transplacental route. Neonatal ocular herpes is almost invariably secondary to direct

exposure to HSV-2 in the birth canal during the late prenatal period or during passage of the baby through an infected canal at birth itself. Corneal involvement in congenital syphilis may manifest as bilateral interstitial keratitis and ulceration.

Several metabolic diseases can produce corneal clouding mimicking the corneal edema of primary congenital glaucoma. Other disorders may be associated with glaucoma, although they can be distinguished from primary congenital glaucoma. For example, oculocerebrorenal syndrome of Lowe, an X-linked recessive condition of renal tubular acidosis and cataracts, may be associated with glaucoma.3,4 However, other stigmata of the disease, especially cataracts and nephropathy, differentiate Lowe syndrome from primary congenital

glaucoma.3

Mucopolysaccharidoses (MPS) are inborn errors of metabolism characterized by excessive storage of mucopolysaccharides and defective degradation due to deficiencies of lysosomal acid hydrolases. In these diseases, excessive keratan sulfate appear in the cornea. In MPS I-H (Hurler syndrome), corneal clouding is a prominent feature of the disease (Fig. 6.13), which helps to differentiate it from Hunter’s syndrome. The opacities are located first in the anterior stroma and consist of fine gray punctate opacities. Later the posterior stroma and endothelium become involved. Histologically, ballooned macrophages are found in the cornea. MPS I-S (Scheie syndrome) is a variant of Hurler syndrome. The corneal haze that is often present at birth is very slowly progressive. The cornea appears thickened and somewhat edematous. The cloudiness is more marked in the corneal periphery. MPS II (Hunter syndrome) has clinical and biochemical features similar to those of Hurler syndrome, except Hunter syndrome is less severe. Corneal clouding is generally considered to be absent in Hunter syndrome, although exceptions in some older patients have been recorded. Corneal cloudiness does not occur in MPS III (Sanfilippo syndrome); however, corneal clouding is observed in MPS IV (Morquio syndrome). Corneal opacities occur in MPS VI (Maroteax–Lamy syndrome), but slit-lamp examination may be necessary to see them. Corneal clouding is absent or mild in MPS VII (Sly syndrome), which is due to

β-glucuronidase deficiency.

Cystinosis (Lignae–Fanconi syndrome) is a rare autosomal recessive genetic disorder of cystine storage. The lysosomal cystine transport system is defective. In some cases, cystine crystals may be deposited in the cornea and conjunctiva as the only manifestation of cystinosis. However, in the nephropathic type, patients may also develop renal failure and a ‘salt and pepper’ retinopathy. In the cornea, the crystals are glistening, polychromatic, needlelike to rectangular, and distributed throughout the anterior stroma with a slight predilection for the periphery. They appear early as 6 months of age and can cause intense photophobia. Crystals may be found throughout the entire thickness of the cornea,56 if they are extensive, and visual acuity may be reduced. Intracellular crystals have been demonstrated within corneal stromal cells as well as in cells of the iris, ciliary body, choroid, and retinal pigment epithelium.

A

B

Figure 6.13 Hurler syndrome (MPS I-H). This condition is a mucopolysaccharidosis that may be associated with corneal clouding (A), which may lead to initial consideration of the diagnosis of congenital glaucoma. The habitus of the same patient with MPS I-H (B).

The mucolipidoses are inherited metabolic diseases caused by defects in glycoprotein oligosaccharide degradation or biosynthesis that result in abnormal accumulation of acid mucopolysaccharides, sphingolipids and glycolipids. Progressive corneal clouding is due to accumulation of abnormal storage material around stromal keratocytes. Other ophthalmic manifestations include retinal pigmentary degeneration, a cherry-red spot, and optic atrophy. Psychomotor retardation and other systemic abnormalities are associated with this

group of diseases.

Amyloid is an eosinophilic material that has an affinity for dyes such as Congo red. Amyloid can be deposited in various tissues of the body, including the eyes, as part of a localized

or systemic disease. A specialized form of amyloid deposition in the cornea is seen in lattice corneal dystrophy. Amyloid

may be deposited in the cornea as the result of chronic inflammation. The corneas in amyloidosis may show corneal

scarring and opacification. Familial amyloidosis of the cornea has also been described.