Ординатура / Офтальмология / Английские материалы / Clinical Pathways in Glaucoma_Zimmerman, Kooner_2001

10 Childhood Glaucoma

an accurate diagnosis include obtaining a complete history, paying careful attention to the clinical presentation, and doing a thorough examination.

How Does Primary Infantile (Congenital) Glaucoma

Present?

Primary infantile glaucoma typically presents with epiphora, photophobia, and blepharospasm. The presentation of congenital glaucoma is seen in children 3 years of age or younger. The parents will often report that the child is constantly tearing, is extremely light sensitive, and squints his or her eyes to avoid the light. These symptoms occur from corneal irritation secondary to epithelial edema caused by increased IOP.40 Buphthalmos, or “bull’s-eye”–like enlargement of the eye also can occur from the increased IOP and is recognized by an increased corneal diameter and progressive myopia. Buphthalmos occurs in children under 3 years of age because of elasticity and stretching of the ocular tissue. Additional findings include a cloudy cornea with breaks in Descemet’s membrane (Haab’s striae), anisometropic amblyopia, and strabismus.

How Does Juvenile Open-Angle Glaucoma Present?

In contrast to primary infantile glaucoma, juvenile open-angle glaucoma may have no external signs or symptoms. It presents after the age of 3 years and often goes undetected until advanced visual loss has occurred, with decreased central vision or extensive visual field loss. It can be detected early by screening exams if the IOP is measured and the optic nerve is evaluated.

What Is the Best Way to Examine a Child If Glaucoma

Is Suspected?

Examination of the pediatric patient is often difficult and depends largely on the patient’s age and ability to cooperate. Children older than 4 years of age are usually able to cooperate with slit-lamp evaluation, tonometry, and optic nerve evaluation. Gonioscopy and visual field examination are more difficult to perform on young children, but some are able to cooperate by the age of 5 to 6. By the age of 8 to 10, most children are able to perform automated visual fields and a complete ophthalmologic examination. In the younger pediatric age group (4 years and less), a mild sedative such as chloral hydrate syrup (25 to 50 mg/kg body weight) can be used in the office to perform a slit-lamp examination, applanation, gonioscopy, and fundus examination. This is not always successful, and often general anesthesia is needed to properly evaluate the child. It is important to remember that most general anesthetics lower the IOP, so this measurement should be obtained as soon as possible once the child is asleep.41 Ketamine has been known to raise the IOP.42

What Are the Clinical Signs to Look for During the Examination?

It is important to know that not all childhood glaucomas have presenting symptoms, but one can make the diagnosis by clinical signs and evaluation. Increased IOP, corneal edema, increased corneal diameter, iris and corneal anomalies, gonioscopic anomalies, refractive errors, and optic disc cupping are

12 Childhood Glaucoma

increased cup-to-disc ratio. The first three are common in children less than 3 years of age, and the last two are found in all ages. There are many other pediatric disease processes that can present with similar symptoms. It is important for the ophthalmologist to be knowledgeable of these conditions so that the child can receive proper diagnosis and treatment.

What Are Other Causes of Excessive Tearing?

The most common cause of tearing in the infant is obstruction of the lacrimal drainage system. It can be unilateral or bilateral and may be accompanied by purulent discharge. Photophobia is not commonly associated with this problem. Another cause of tearing is conjunctivitis, either viral or bacterial, which is usually associated with purulent discharge and injection of the conjunctiva. Trauma with resultant corneal abrasions can cause excessive tearing in the infant and can easily be diagnosed by examination. A corneal dystrophy can cause ocular pain and tearing as seen in Meesman’s corneal dystrophy secondary to epithelial vesicles. Other causes may be recurrent epithelial erosions as seen in Reis-Buckler’s dystrophy.

What Are Other Causes of a Cloudy Cornea?

There are many causes of congenital cloudy cornea. Table 1–3 lists the causes of congenital clouding of the cornea. It is important for the physician to keep in mind the differential diagnosis for a cloudy cornea in the infant and not always to assume it is secondary to increased IOP.

Table 1–3. Causes of Congenital Cloudy Cornea

I.Dystrophies

1.Congenital hereditary stromal dystrophy

2.Congenital hereditary endothelial dystrophy II. Dermoid

III. Sclerocornea

IV. Infection

1.Rubella

2.Herpes simplex virus

3.Syphilis

V. Metabolic (inborn errors rarely present at birth)

1.Mucopolysaccharidoses

2.Mucolipidoses

VI. Trauma

1. Forceps delivery with Descemet’s breaks

VII. Anterior chamber cleavage syndromes—can have glaucoma associated

1.Axenfeld-Rieger’s anomaly

2.Peter’s anomaly

3.Posterior keratoconus

VIII. Congenital glaucoma

IX. Congenital anterior staphyloma

What Dystrophies Can Cause a Cloudy Cornea

in the Infant?

Both stromal and endothelial dystrophies can cause a congenital cloudy cornea. Congenital hereditary stromal dystrophy presents at birth and is autosomal dominant. It has superficial corneal clouding with a flaky or feathery appearance of the anterior stroma.46 Congenital hereditary endothelial dystrophy may be autosomal recessive or autosomal dominant in nature. The autosomal-reces- sive form presents at birth with an edematous stroma, a thickened Descemet’s membrane, and nystagmus. The autosomal-dominant form is usually seen between ages 1 and 2 with photophobia and progressive corneal swelling.47

What Is the Difference Between a Dermoid

and Sclerocornea?

A corneal dermoid is a choristoma that is composed of epidermis and epidermal appendages within a fibrous stroma.48 Most dermoids are found on the inferior temporal limbus and span approximately 8 to 10 mm. Dermoids extend into the corneal stroma and adjacent sclera. Limbal dermoids are seen in association with Goldenhar’s syndrome. Dermoids can cover the visual axis or produce a large degree of astigmatism. Either of these situations can cause amblyopia and vision loss. If either case is present, excision may be warranted. Sclerocornea is a congenital condition in which the cornea is opaque, resembling the sclera, and the limbus cannot be identified.49

What Infections Can Cause a Cloudy Cornea in Children?

Rubella is caused by a single-stranded ribonucleic acid virus. Congenital rubella is the result of a maternal infection during the first trimester of pregnancy. The classic triad of infants born with rubella include heart defects, deafness, and cataracts. A variety of ocular abnormalities can be seen, including pigmentary retinopathy, anterior chamber anomalies, glaucoma, and microphthalmos. The central cornea is often cloudy at birth, which is caused by either an absence of or ruptures in Descemet’s membrane or by congenital glaucoma.50 Congenital syphilis is also a well-known infectious cause of childhood cloudy corneas. Congenital syphilis is caused by the spirochete Treponema pallidum and is passed to the fetus in utero. The classic triad of congenital syphilis consists of interstitial keratitis, Hutchinson’s teeth, and deafness. The interstitial keratitis of congenital syphilis usually is a late manifestation, presenting after the age of 2 years. The interstitial keratitis is secondary to an inflammatory response to previously present spirochetes and is not due to an active infection. Both corneas are usually involved within weeks of each other. The child can present with similar symptoms of childhood glaucoma including tearing, photophobia, and blepharospasm. Perilimbal injection is also present, differing from congenital glaucoma. The inflammation is usually sectoral and involves the superior stroma. Keratic precipitates are typically present in the early stages. As the disease progresses, neovascularization develops in the deep stroma. As neovascularization becomes denser, the cornea appears pink and is referred to as a salmon patch. As the disease regresses, the cornea is often left scarred, and ghost vessels can be seen in the midto deep stroma.

14 Childhood Glaucoma

What Metabolic Diseases of Childhood Can Cause

Cloudy Corneas?

There are a number of inborn errors of metabolism that can cause congenital cloudy corneas. Fortunately, these disorders are rare, but they warrant discussing as a differential diagnosis in childhood glaucoma. These disorders are caused by an abnormal metabolism of carbohydrates and lipids. The major classifications include the mucopolysaccharidoses, the sphingolipidoses, and the mucolipidoses. Three mucopolysaccharidoses (MPSs) that cause diffuse clouding of the cornea include Hurler (MPS I-H), Scheie (MPS I-S), and Morquio (MPS IV) syndromes. Both Hurler and Scheie syndrome present with a cloudy cornea at birth and progress over the first 6 months, whereas Morquio syndrome does not show clouding of the cornea until after the age of 10. Fabry’s disease, gangliosidosis type I, gangliosidosis type II (Sandhoff’s disease), and Niemann-Pick disease are all disorders of sphingolipids. The most notable corneal changes seen in the sphingolipidoses consist of cornea verticillata, whorl-like lines in the corneal epithelium. This is a characteristic finding in Fabry’s disease. The mucolipidoses that present at birth with a cloudy cornea include MLS II and MLS IV. Cystinosis is an amino acid metabolic disorder that has an infantile, adolescent, and adult form. The infantile form is most severe, and cystine crystals can be present in the cornea at birth. This form of the disease is associated with renal failure in early childhood.51

What Are the Characteristics of a Cloudy Cornea Due to Birth Trauma?

Tears in Descemet’s membrane can be seen as a result of birth trauma due to forceps delivery. Classically these have been described as vertical tears, whereas Haab’s striae found in congenital glaucoma have a horizontal orientation. These are only generalizations, and either horizontal or vertical tears can be found due to each of the above causes. Not all tears secondary to trauma will cause diffuse corneal edema. If edema is present from trauma, it will usually resolve over the ensuing weeks spontaneously. The edema from childhood glaucoma will resolve only after the IOP has been successfully lowered.

What Are Other Causes of a Large Cornea?

Megalocornea and high myopia are two conditions other than congenital glaucoma and childhood glaucoma associated with ocular and congenital anomalies that can cause a large cornea in children. Megalocornea is an enlarged cornea that is nonprogressive. The cornea is clear and has normal histology. The diameter of megalocornea is 13 mm or greater in horizontal diameter. Ninety percent of patients are male, and the condition is usually bilateral. A sex-linked inheritance pattern is evident. Megalocornea is usually an isolated finding but can be seen in addition with cataracts, and glaucoma secondary to angle anomalies. Large corneas can also be seen in patients with high degrees of axial myopia. These children do not display the other signs of congenital or juvenile glaucoma.

What Are Other Causes of an Abnormal Optic Nerve?

It is important to recognize congenital causes of an abnormal optic nerve and be able to differentiate these causes from the enlarged cup-to-disc ratio found in the childhood glaucomas. It is often difficult to examine the posterior pole in the pediatric population. Every effort must be made to get a good look at the nerves. At times, evaluation under anesthesia is needed if an adequate exam cannot be obtained in the office. Congenital abnormalities include an optic nerve coloboma, optic nerve pits, hypoplasia, and tilting secondary to myopia. Optic nerve pallor and atrophy can also be seen in children, and the appropriate workup must be performed to ascertain an underlying cause. Physiologic cupping must be distinguished from glaucomatous cupping. This is difficult in the pediatric population, as most children do not perform well with the traditional visual field testing. Examination of family members can often be helpful to rule out physiologic cupping, and the new nerve fiber analyzers may become quite useful in the pediatric population.

What Steps Should Be Taken When Evaluating and

Diagnosing a Child for Possible Childhood Glaucoma?

This section of the chapter has dealt with the initial presentation, signs and symptoms, physical examination, and differential diagnosis of childhood glaucoma. It can be a challenging diagnosis, and a flow chart has been developed to help aid the practitioner in making the correct diagnosis (Fig. 1–1).

Treatment and Management

How Is Congenital Glaucoma Managed?

The treatment for congenital glaucoma is surgical. Medical therapy alone is not sufficient in lowering the IOP in children. A study performed at the University of Ankara, Turkey, showed that medical therapy alone in congenital glaucoma reduced the IOP to less than 21 mm Hg in 11.8% in short-term follow-up and 9.7% in the long-term.52

The main surgical procedures of choice remain goniotomy, trabeculotomy, or trabeculectomy, with or without antimetabolites. Goniotomy was initially described by Barkan in the 1940s. This technique requires direct visualization of the trabecular meshwork with a surgical goniolens. A goniotomy knife is then inserted 1 mm anterior to the limbus through clear cornea. The blade is passed through the anterior chamber 180 degrees from the initial entry site. The blade is then used to incise one-third of the chamber angle. The incision is aimed at the abnormal layer of tissue in front of the trabecular meshwork. If the initial goniotomy procedure fails, repeat goniotomy may be needed. The trabeculotomy creates a direct communication between the anterior chamber and Schlemm’s canal. The technique was modified by Harms and Dannheim.53

The surgery involves creating a conjunctival flap similar to that performed in a filtering procedure. A partial-thickness limbal based scleral flap approximately 3 3 mm is then dissected. A radial incision is then made at the sclerolimbal junction until Schlemm’s canal is entered. This can be identified by a

16 Childhood Glaucoma

Figure 1–1. Algorithm for Evaluation of Childhood Glaucoma.

gush of aqueous humor or blood. A trabeculotome is then inserted into Schlemm’s canal and rotated so the arm tears through the trabecular meshwork and enters the anterior chamber. The trabeculotome is then inserted in the other direction and the same procedure is performed. The angle is opened 180 degrees with this technique. An additional scleral flap can be made 180 degrees away from the initial site to perform the procedure, for a total of 360 degrees. The trabeculectomy procedure performed is the same in children and adults. It involves conjunctival flap either limbal or fornix based, and a partial-thickness limbal based scleral flap of approximately 3 3 mm. A fistulizing technique is then performed. A peripheral iridectomy is made to prevent blockage of the fis-

tula with iris incarceration. The scleral flap is then closed with 10-0 nylon sutures and the conjunctiva is reapproximated with a vascular needle. There has been recent discussion as to whether anti-metabolites should be use in the pediatric population in hopes of increasing the long-term patency of the filter. Other surgical procedures are performed in childhood glaucoma in situations where the above have failed or are not indicated. These procedures include tube-shunt surgery, with the use of valved and nonvalved implants; cyclocryoablation; cyclophotocoagulation; and ciliary-body endophotocoagulation.

What Is the Best Surgical Treatment for Childhood Glaucomas?

The three principal initial surgical procedures for childhood glaucoma are goniotomy, trabeculotomy and trabeculectomy. Goniotomy and trabeculotomy have been the traditional choice for congenital glaucoma, with both having similarly high success rates. A study done at Moorfields Eye Hospital treating congenital glaucoma with initial goniotomy showed 93% of eyes controlled at 5 years.54 Goniotomy has both an advantage and disadvantage. The advantage is that it preserves conjunctiva if future surgery is needed, but the disadvantage is the need for a clear cornea to visualize the trabecular meshwork. The advantage to the trabeculotomy is that direct visualization of the trabecular meshwork is not needed, and if Schlemm’s canal cannot be identified, the procedure can be converted into a trabeculectomy. There has been recent interest in a combined trabeculotomy and trabeculectomy as the initial procedure in uncomplicated congenital glaucoma. A recent study performed in Saudi Arabia showed a 78% operative success in eyes with no coexistent anterior segment anomalies.55 Further studies comparing trabeculotomy, combined trabeculotomy and trabeculectomy, and trabeculectomy found that the results did not differ significantly.56 The best surgical choice for the initial treatment of congenital glaucoma is the technique that is most comfortable for the surgeon. Goniotomy is usually reserved for children of age 3 and under. Goniotomy and trabeculotomy are the first-line procedures in congenital glaucoma at a large referral center where the surgeons are experienced with these techniques. To the general ophthalmologist who is not experienced with the former procedures, the most appropriate primary surgery is the trabeculectomy.

What Is the Role of Mitomycin C in Filtration Procedures in Children?

At times a trabeculectomy is the procedure of choice in children. The trabeculectomy can be performed as the primary procedure or after previous failed trabeculotomy/goniotomy. In either case the question of the use of an antimetabolite must be considered. It is well known that trabeculectomy can fail in the pediatric population and is contributed to a thick Tenon’s layer and aggressive healing in children. A recent study evaluating the role of mitomycin C in childhood trabeculectomy showed a 1-year success rate of 76.9% in phakic patients.57 Interestingly, the same study revealed 0% success in aphakic eyes. Success was considered to be an IOP of less than 21 mm Hg with no need for antiglaucoma medication 1 year after the surgery. A similar study performed at

18 Childhood Glaucoma

Emory University School of Medicine showed a success rate of 67% 13% at 12 months and 59% 15% at 24 months. This same study identified aphakia and age of less than 1 year as significant risk factors for failure.58 The long-term complications such as bleb leaks with hypotony and endophthalmitis must be considered when using an antimetabolite in children.

What Is the Role of Tube-Shunt Procedures

in the Pediatric Population?

Tube-shunt procedures are considered in the pediatric population in children with glaucoma refractory to medical and previous surgical intervention. A study of 18 patients performed at Wills Eye Hospital revealed a 72.2% success rate at 6 months.59 Success was considered to be an IOP between 6 and 21 mm Hg with or without glaucoma medication. At 2-year follow-up, the success rate was 44.4%, although five eyes (27.8%) had lost light perception and 12 of the 18 eyes underwent 28 additional surgical procedures to control IOP or manage tube-related complications. Tube-shunt procedures can be a surgical option for childhood glaucoma, but is usually reserved for refractory glaucoma and not as an initial therapy.

What Are the Follow-Up Considerations in Children with Childhood Glaucoma?

The child must be followed carefully to ensure that the glaucoma is stable and not progressing. Serial examinations are needed to ensure proper care. In congenital glaucoma the corneal edema is followed to ensure its resolution. A cloudy cornea can cause amblyopia and permanent vision loss. Once the corneal edema has resolved, the child is followed every 3 months to check the IOP, corneal diameter, and cup-to-disc ratio. Once the child is stable, examination can be performed every 6 months. It is important to keep in mind that amblyopia can result not only from an opaque cornea but also from anisometropia caused by a myopic shift. Careful attention must be paid to the refraction, and the child must be observed for any signs of a lazy eye. Many of these children require glaucoma medication, and the child must be watched to avoid systemic manifestation of the drugs. When using a beta-blocker, a complete history must be obtained, paying special attention to cardiac disease and a history of asthma. Pilocarpine can cause myopia and may be very difficult to tolerate, especially for children of school age.

Future Considerations

What Does the Future Hold for Early Detection of Glaucoma?

There have been recent discoveries concerning glaucoma and the field of genetics. Glaucoma loci have been grouped into three categories: primary openangle glaucoma, primary closed-angle glaucoma, and congenital glaucoma. The congenital glaucoma group use the prefix GLC3. Primary open-angle glaucoma and primary closed-angle glaucoma use the prefix GLC1 and GLC2, respectively. There currently are two genes or genetic regions associated with

congenital glaucoma. The congenital loci are GLC3A and GLC3B. The GLC3A region is on chromosome 2p21 and the gene is CYP1B.60 The GLC3B subtype has been located on chromosome 1p36, but no gene has been identified yet.61 Secondary glaucomas have been linked to the PAX-6 and PITX2 genes. Aniridia and Peter’s anomaly have been linked to the PAX-6 gene located on chromosome 11p13.62,63 Axenfeld-Rieger syndrome type 1 and iridogoniodysgenesis type 2 have been linked to the PITX2 gene located on chromosome 4q25.64,65 Although still in its infancy, mapping and cloning of glaucoma genes hold a promising future. Early detection and treatment through genetic identification could halt advanced vision loss seen in childhood glaucoma.6

What Are the Future Challenges of Glaucoma Genetics?

The mapping and cloning of glaucoma-related genes have been progressing. It is anticipated that the actual number of glaucoma-causing genes will be much greater than the number currently known. There is considerable phenotypic variability that will make it difficult for clinicians and geneticists to associate clinical findings with the genes involved. However, as more genes are identified, the molecular pathogenesis of glaucoma may be better understood. Early genetic screening would allow the best treatment to be used for each patient. A greater number of patients can take advantage of early detection strategies to slow the progress of this insidious disease.6

Acknowledgment

This work was supported in part by a grant from Research to Prevent Blindness, New York, NY.

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