Ординатура / Офтальмология / Английские материалы / Pediatric Ophthalmology for Primary Care 3rd edition_Wright, Farzavandi_2008

Lens Implantation

Intraocular lenses have now become an accepted method for treating apha kia (absence of a natural lens) in children. One must be selective, however, when considering lens implantation in the pediatric age group. During the first year of life, there is a dramatic increase in eye length and consequent change in the lens power (approximately 10–14 diopters) needed to focus. Because of the significant change in eye size during the first year of life and severe inflammation in neonates, implantation of intraocular lenses in infants is controversial. By 2 years of age, however, the eye is close to adult size. Use of intraocular lenses after 1 year of age is now commonplace and for the most part, they are standard after 2 years of age. Because the poste rior capsule invariably opacifies after a lens implantation, a secondary YAG capsulotomy or secondary procedure is usually necessary. Some types of cataracts do not lend themselves to use of intraocular lenses, so these cases would require use of aphakic contact lens.

Spectacles and Contact Lenses

Spectacles

Spectacles are an option to correct bilateral aphakia in children. However, they are unsightly, do not provide constant correction, and are not used for monocular aphakia because of the unilateral magnification of the aphakic lens.

Contact Lenses

In newborns, contact lenses are the standard treatment for unilateral or bilateral aphakia. Aphakic spectacles can be used as a backup for contact lenses in bilaterally aphakic children.

Occlusion Therapy

Monocular pediatric cataracts require occlusion therapy to treat ambly opia. There is some controversy about the amount of patching for patients with monocular cataracts. The amount of patching should be based on the severity of amblyopia. Critical to the management of monocular congenital cataracts is educating the parents about amblyopia, the importance of a clear retinal image, and the need for occlusion therapy.

Visual Prognosis of Pediatric Cataracts

Monocular Cataracts

If surgery and optical correction are provided early, by 2 months of age, visual acuity outcomes are relatively good even for monocular congenital cataracts. Birch and Stager reported that a mean visual acuity of 20/60 (range 20/800–20/30) was achieved if surgery was performed before 2 months of age, whereas surgery after 2 months of age resulted in poor visual acuity (ranging from hand motion to 20/160). Historically, patients with monocular cataracts have a very poor prognosis for obtaining fusion, and virtually all studies report that almost 100% of patients will develop stra bismus. Taylor and Wright et al and Gregg and Parks reported that good visual acuity and good binocularity with stereopsis are possible in patients with monocular cataracts. The key points to these cases were that very early surgery (earlier than 2 months of age and as early as the first week of life) was performed with immediate contact lens fitting, and part time mono cular occlusion (<50%) for amblyopia was initiated during the first few months of life.

Cataracts in children do not always present during the first few months of life. Often, the clinician is faced with the child who has a unilateral or bilateral cataract and the question is, “Should the cataract be operated on or is there irreversible amblyopia?” Reports by Kushner and Wright et al indicate that many older children with presumed congenital cataracts can show significant visual acuity improvement after surgical treatment. Lack of strabismus (straight eyes) is also a good prognostic sign for patients with unilateral cataracts.

Binocular Cataracts

It is sometimes said that binocular cataracts are less amblyogenic than monocular cataracts. This is misleading because even though a monocular cataract causes a very dense amblyopia, binocular cataracts can also cause significant amblyopia. It is important that binocular cataracts are treated with urgency and are operated during the first few weeks of life. If a visually significant, bilateral, congenital cataract is not cleared by 2 months of age, patients will develop sensory nystagmus and very poor visual acuity (usu ally <20/200) in the majority of cases. Patients with non operated bilateral

cataracts and sensory nystagmus can show improvement in visual acuity and improvement of the nystagmus, even if surgery is performed late, after the critical period of visual development. This author has reported that visual acuity as good as 20/50 to 20/70 can be achieved even when late sur gery is performed. Surgery by 2 months of age is definitely the treatment of choice; however, older children who present late should be considered for cataract surgery even though they present with bilateral cataracts and nys tagmus. The exception to this are those patients with an abnormality of the retina or optic nerve, and aniridia. In patients with aniridia, cataract surgery usually does not improve vision because macular hypoplasia limits the visual acuity potential.

Retinoblastoma

Retinoblastoma is a malignant tumor of the sensory retina and is the most common primary ocular malignancy in childhood. Critical to the treatment of retinoblastoma is early identification, as cure rates are higher than 90% if the tumor is localized within the eye. A white reflex within the pupil (leu kocoria) is a serious sign that could suggest retinoblastoma and deserves immediate referral (Figure 22 7A).

Clinical Signs of Retinoblastoma

The most common presenting signs of retinoblastoma are leukocoria and strabismus. Retinoblastoma also may present with findings that mimic other ophthalmic disorders such as primary angle closure glaucoma, vitreous hemorrhage, retinal detachment, hyphema, hypopyon, and even preseptal cellulitis. Usually retinoblastoma presents with a quiet eye; however, tumor necrosis can lead to intraocular hemorrhage, inflammation, and a red, pain ful eye. Angle closure glaucoma occurs when the posterior pole fills with tumor, thus pushing the lens iris diaphragm anteriorly. Even though reti noblastoma is rare (estimated at 1:20,000 live births), the pediatrician must hold high suspicion for this disease in any child with leukocoria.

Retinoblastoma tumors have a yellow or slightly pink gelatinous appear ance (Figure 22 8). There may be white areas within the tumor that repre sent calcification. Calcification is a hallmark of retinoblastoma and can be detected by computed tomography scan (Figure 22 7B), although magnetic resonance imaging is now preferred. Calcification is associated with tumor

Figure 22 7.

A, Nineteen-month-old child with leukocoria in the left eye secondary to retinoblastoma. B, Computed tomography scan showing extensive intraocular calcification associated with retinoblastoma. Calcification represents area of tumor necrosis.

necrosis that occurs as the tumor outgrows its blood supply. The presence of calcium in a retinal mass is highly suggestive of retinoblastoma, although in rare cases, retinoblastoma tumors will not be calcified. Also, some ocular diseases such as Coats disease have tissue necrosis and can show calcifica tions as well.

Genetics of Retinoblastoma

Retinoblastoma is caused by a mutation in a growth suppressor gene. The site of the gene for retinoblastoma is chromosome 13q14, and the gene has been sequenced. The paternal and maternal alleles must be affected for the development of a retinoblastoma tumor because a single intact suppressor gene is all that is necessary to regulate retinal cell growth. Knudson was the first to suggest this “2 hit” hypothesis. Retinoblastoma can be inherited

Figure 22 8.

Fundus photograph of endophytic retinoblastoma. Note the yellow-white appearance of the domed mass. Normal attached retina is seen in the background to the right.

or secondary to a sporadic mutation. Inherited cases are often cited as an autosomal dominant disorder. It is the mutation of one allele (first hit) that is inherited as an autosomal dominant trait. The second allele mutation occurs after conception and is a somatic mutation. Retinoblastoma is actu ally an autosomal recessive trait because both alleles must be affected to express the disease. There are 2 recognized mechanisms that cause a muta tion of both alleles, resulting in hereditary retinoblastoma and sporadic retinoblastoma.

Hereditary Retinoblastoma

In the hereditary form of retinoblastoma, a mutation of both retinoblas toma genes occurs by inheriting an abnormal gene from one parent (ger minal mutation) and then acquiring a spontaneous mutation of the other allelic gene at the retinal cell level later in development (somatic mutation). Patients with hereditary retinoblastoma have a defective retinoblastoma gene in virtually all cells in their body. Because of this, patients with hereditary retinoblastoma are predisposed to acquiring secondary non ocular tumors, such as osteosarcoma, in late childhood and adulthood.

All the retinal cells in the inherited form have an abnormal gene

(1 hit) at conception, and the second mutation occurs after conception in

approximately 80% of cases. Thus, almost all patients who have inherited the abnormal allele will develop the second mutation and develop retino blastoma. Most inherited retinoblastomas are bilateral, with only 15% being unilateral. Hereditary retinoblastoma is often multifocal, with multiple tumors developing in each eye. Patients with the hereditary form present early, around 12 months of age on the average. The inherited form can come from a parent with known retinoblastoma, from a germinal mutation in the egg or sperm, or from a mutation at the time of conception. In these latter cases, the family history is negative for retinoblastoma. In fact, the major ity of new cases of bilateral hereditary retinoblastoma are caused by a new germinal mutation, as only 10% have a positive family history. If a parent has retinoblastoma, there is a 50% chance of passing the predisposition (a retinoblastoma gene) to the child. Because not all children with one mutated allele develop a mutation in the second allele, the chance of a child develop ing retinoblastoma from a parent with retinoblastoma is 40%, rather than 50%. If there is no family history of retinoblastoma and a child is born with bilateral retinoblastoma, the chance that another sibling will develop retino blastoma is approximately 8%. Remember that most germinal mutations are not present in the germinal stem cells of the parents, so subsequent children are at low risk. With DNA testing, carriers of a germinal mutation of the retinoblastoma gene can be identified in most cases.

A large deletion in the area of the retinoblastoma gene will delete other local genes and cause an identifiable defect in the karyotype at chromosome 13q14. Patients with this deletion may have the clinical characteristics of facial dysmorphism, developmental delay, mental retardation, and low set ears. This phenotype only occurs in 3% of retinoblastoma cases where mul tiple genes are deleted in addition to the retinoblastoma gene.

Sporadic Retinoblastoma

The sporadic form of retinoblastoma is caused by a spontaneous mutation of both alleles at the retinal cell level (2 somatic mutations). This requires 2 independent mutational events that are not inherited. Sporadic retinoblas toma presents as a unilateral unifocal tumor. It must be noted, however, that 15% of hereditary retinoblastomas occur as a unilateral tumor, albeit usually multifocal. Approximately 60% of all retinoblastoma cases are the nonhe reditary form.

Staging of Retinoblastoma

Retinoblastoma has been classified by Reese Ellsworth by determining the prognosis of the eye. This classification has been mistakenly extrapolated to estimate the prognosis for patient survival. The extrapolation states that

small tumors located posterior to the equator have a favorable outcome. Any tumor at or anterior to the equator, or a tumor larger than 10 disc diameters in size, has an unfavorable prognosis. Massive tumors involving more than half the retina or the presence of vitreous seeding indicate a very unfavorable prognosis for salvaging the eye.

The classic histologic findings of retinoblastoma are Flexner Winter Steiner rosettes. Less commonly seen are fleurettes. Pathologic signs of poor systemic prognosis may include choroidal involvement, but most often seen is extrascleral extension and extension of the tumor into the optic nerve posterior to the lamina cribrosa. Local extension into the orbit and metas tasis through the subarachnoid space into the brain are the most common routes of tumor spread. Bone marrow, liver, and lungs are also distant sites for metastasis.

Pinealoblastoma (trilateral retinoblastoma)

Pinealoma associated with bilateral retinoblastoma has been termed trilat eral retinoblastoma and is a rare occurrence with an extremely poor prog nosis. The pineal body is considered a third eye because it has embryologic links to the retinal tissue.

Treatment of Retinoblastoma

Large unilateral tumors involving the macula are associated with a poor visual prognosis and generally are treated by enucleation. Smaller tumors can be treated with external beam radiation (approximately 4,000 rad) or chemo reduction. If the tumor is bilateral, every attempt should be made to save at least one eye. External beam radiation is most useful for posteriorly located tumors. Radioactive plaque treatment, which involves attaching a radioactive “button” directly over the site of the tumor, has also been used and has the advantage of minimizing radiation to normal tissue. External beam radiation may have the disadvantage of inducing or speeding up the development of secondary tumors in patients with the hereditary form of retinoblastoma. The use of chemotherapy to decrease the size of the tumor, followed by laser or cryotherapy, has been effective in eyes with salvageable

vision. Small peripheral tumors can be treated with cryotherapy or laser photocoagulation.

Infants who present with unilateral retinoblastoma must be followed closely, since 20% will develop a new tumor in the good eye. This risk diminishes greatly after 2 years of age. In cases of hereditary retinoblastoma, siblings are at risk for developing the tumor. They should be followed with serial retinal examinations using scleral depression (use of a special instru ment to view the peripheral retina).

Prognosis of Retinoblastoma

Unilateral retinoblastoma without extrascleral extension and without exten sion past the lamina cribrosa, having been treated by enucleation, is associ ated with long term survival of more than 90%. If the tumor cells extend posterior to the lamina cribrosa, the survival rate lowers to approximately 85%, even if the cut end of the optic nerve is free of tumor. Extrascleral extension of tumor cells beyond the surgical transection site of the optic nerve is associated with a long term survival rate of less than 65%. The use of eye saving therapies such as external beam radiation, radioactive plaque, and chemotherapy reduction performed in patients without extrascleral extension results in a cure in approximately 95% of patients.

Patients with hereditary retinoblastoma are at risk for developing sec ondary malignant tumors later in life. These tumors are often in the area of the external beam radiation but can also occur in remote sites. Secondary tumors include malignant melanoma, fibrosarcoma, leiomyosarcoma, osteo sarcoma, and renal cell carcinoma. Patients who have had radiation therapy develop secondary tumors earlier than patients who have not had radiation. The incidence for developing a secondary tumor in patients with hereditary retinoblastoma is probably higher than 50% with a long term follow up of more than 30 years.

Medulloepithelioma

Medulloepithelioma is a tumor that arises from the ciliary body or iris. It occurs sporadically and at virtually any time during life, but most commonly presents in early childhood between 4 and 8 years of age. The tumor prob ably stems from non pigmented ciliary epithelium.

The tumor is slow growing and tends to stay localized within the eye. Survival rates are excellent if the tumor is localized to the eye. The tumor usually arises from the ciliary body; however, rare reports of optic nerve and retinal involvement have been described. Because the tumors arise from the ciliary body, they usually are not detected until they are quite large. Often, patients present with angle closure glaucoma, pain, poor vision, or an ante rior chamber cyst or mass. Cataract, rubeosis, and PHPV have also been associated with medulloepitheliomas. The treatment for medulloepithelio mas is usually enucleation; however, iridocyclectomy can be curative if the entire lesion is removed.

Uveal Melanoma

Uveal melanomas are extremely rare in children. Tumors may involve the iris, ciliary body, or choroid. The diagnosis of melanoma should be enter tained in patients with an enlarging pigmented mass. Other causes of a pigmented intraocular mass in children include melanocytoma, choroidal nevus, iris cysts, pigmented neurofibroma, juvenile xanthogranuloma, and a retinal pigment epithelial hamartoma. Uveal melanomas may arise from ocular and oculodermal melanocytosis. Ocular ultrasound is an important tool for establishing the proper diagnosis in children, just as it is in adults.

The prognosis of uveal melanomas in children parallels that of adults. A review by Barr, McLean, and Zimmermann of choroidal and ciliary body tumors in children showed that of 42 patients, 13 died of metastatic dis ease, an incidence similar to the adult population. Poor prognostic features include extraocular extension, large basal diameter (>10 mm), aggressive cell type, and red painful eye with tumor necrosis at the time of presentation. The treatment is usually enucleation.

Leukemia

Leukemia can involve all ocular structures; however, the retina is the most commonly involved site. Acute lymphoblastic leukemia is the most common leukemic cell type in children. Retinal involvement includes cotton wool spots, exudates, dilated veins, and most commonly, retinal hemorrhages. Hemorrhages may take on the appearance of a Roth spot, with white centers