CHAPTER 48  RETINAL DETACHMENT  385

Figure 48-9.  Postoperative appearance of patient shown in Fig. 48-8 after repair of traction RD.

Bibliography

Benson WE: Retinal detachment: diagnosis and management, ed 2, Philadelphia, 1988, J.B. Lippincott. Davis MD: Natural history of retinal breaks without detachment, Arch Ophthalmol 92:183–194, 1974.

Hilton GF, McLean EB, Chuang EL: Retinal detachment: ophthalmology monograph series, San Francisco, 1989, American Academy of Ophthalmology.

Kramer SG, Benson WE: Prophylactic therapy of retinal breaks, Surv Ophthalmol 22:41–47, 1977.

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1.What is retinoblastoma?

Retinoblastoma is the most common eye cancer in children. It arises from primitive cells destined to be retinal tissue. Generally, it is found in babies from birth to approximately 3 years of age.

2.How common is retinoblastoma?

Retinoblastoma occurs with a frequency of about 1 in 14,000 live births. Approximately 250 to 300 children in the United States each year are diagnosed with retinoblastoma. Worldwide, it is estimated that there are approximately 7000 children with this cancer yearly.

3.What causes retinoblastoma?

Retinoblastoma is the result of a genetic mutation on chromosome 13. If the mutation is somatic, then the child can develop one tumor in one eye. If the mutation is in the germ line, the child is at risk for multifocal tumors in both eyes, with an average total of five retinoblastomas. There are no specific exposures that lead to this mutation, but research has identified advanced paternal age and possible paternal radiotherapy exposure as risks.

4.On what chromosome is the genetic mutation associated with retinoblastoma?

The genetic mutation associated with retinoblastoma is found on chromosome 13 in the region 13q14. It is believed that this single locus exists for most forms of retinoblastoma. The esterase D gene is closely linked to this site.

5.What syndrome is associated with retinoblastoma?

Retinoblastoma is a manifestation of the 13q deletion syndrome. The characteristic findings include:

•microcephaly

•broad prominent nasal bridge

•hypertelorism

•microphthalmos

•epicanthus

•ptosis

•protruding upper incisors

•micrognathia

•short neck with lateral folds

•large low-set ears

•facial asymmetry

•imperforate anus

•genital malformations

•perineal fistula

•hypoplastic or absent thumbs

•toe abnormalities

•psychomotor delay

•mental delay

6.What is the laterality of retinoblastoma?

Retinoblastoma is unilateral in approximately 67% of cases and bilateral in 33% of cases. All bilateral cases have germ-line mutation. Approximately 15% of unilateral cases have germ-line mutation, whereas 85% have somatic mutation.

7.What is germ-line mutation retinoblastoma?

Germ-line mutation retinoblastoma is the occurrence of the retinoblastoma (Rb) mutation on all cells in the body, including the retina and systemic sites. These patients typically develop bilateral retinoblastoma and are at risk for pinealoblastoma and second cancers.

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CHAPTER 49  RETINOBLASTOMA  387

8.Who manifests germ-line mutation retinoblastoma?

All bilateral and all familial retinoblastomas by definition have germ-line mutation. About 10% to 15% of unilateral sporadic retinoblastomas have germ-line mutation.

9.What is somatic mutation retinoblastoma?

Somatic mutation retinoblastoma is the occurrence of the Rb mutation only in the retina in one clone of cells. Hence these patients typically develop unilateral sporadic retinoblastoma. These patients are generally not at increased risk for pinealoblastoma or second cancers.

10.Who manifests somatic mutation retinoblastoma?

Only unilateral sporadic retinoblastomas carry a somatic mutation.

11.What are the most common presenting findings of retinoblastoma (Fig. 49-1)?

In the United States, leukocoria is the presenting feature in nearly 50% of cases and strabismus in 20%. Other less common presenting features include poor vision, red eye, glaucoma, and orbital cellulitis. In less developed nations, these children often present with proptosis from tumor extension into the orbit.

12.What are the most common lesions simulating retinoblastoma?

Of all patients referred to an experienced ocular oncology center with the diagnosis of possible retinoblastoma, about 80% prove to have retinoblastoma and 20% have pseudoretinoblastoma. The most common pseudoretinoblastomas include Coats disease (40%), persistent hyperplastic primary vitreous (28%), and vitreous hemorrhage of infancy (16%).

13.At what age does retinoblastoma typically present?

Retinoblastoma is diagnosed typically in the first 1 to 2 years of life. Bilateral cases are recognized at an earlier average age of 1 year, whereas unilateral cases are typically older, at 2 years. In 5% of cases, the tumor is first diagnosed over age 5 years.

14.What is trilateral retinoblastoma?

Trilateral retinoblastoma is the association of bilateral retinoblastoma with midline brain tumors, especially pinealoblastoma. Trilateral disease represents 3% of all retinoblastoma cases and typically occurs before the age of 5 years.

A

B

Figure 49-1.  A, Leukocoria from retinoblastoma. B, Enucleated globe showing large white retinoblastoma within the eye.

388  OPHTHALMOLOGY SECRETS IN COLOR

15.When is pinealoblastoma diagnosed?

Pinealoblastoma is generally diagnosed within 1 year of retinoblastoma diagnosis. In fact, most cases are found before the age of 5 years. Keep in mind that benign pineal cyst can resemble malignant pinealoblastoma and magnetic resonance imaging is necessary to differentiate these two conditions.

16.What second cancers are associated with retinoblastoma?

The most common second cancers associated with retinoblastoma include osteosarcoma (especially of the femur), cutaneous melanoma, and other sarcomas. Second cancers are believed to be related to germ-line mutation of chromosome 13. Second cancers present in 20% of germ-line mutation patients by 20 years and 50% by 50 years.

17.How often do eyes with retinoblastoma present with glaucoma?

From a clinical standpoint, about 17% of eyes with retinoblastoma have glaucoma, most often neovascular or angle closure glaucoma. From a pathology standpoint, glaucoma is present in 40% of eyes that come to enucleation.

18.How often does retinoblastoma invade the optic nerve?

In the United States, optic nerve invasion by retinoblastoma occurs in 29% of eyes that come to enucleation. Usually it occurs in the prelaminar area. Risks for optic nerve invasion by retinoblastoma include a large exophytic tumor measuring greater than 15 mm and secondary glaucoma.

19.What is high-risk retinoblastoma?

High-risk retinoblastoma is retinoblastoma that has invaded:

•the optic nerve beyond the lamina cribrosa

•the uvea, with greatest dimension of at least 3 mm

•any combination of the optic nerve and uvea

High-risk retinoblastoma requires systemic chemotherapy.

20.What is the survival rate with retinoblastoma?

Currently in the United States, Europe, and Japan, nearly 98% of children with retinoblastoma survive this cancer. Less developed nations carry a relatively high risk for metastasis and death. The rate for death in South America is approximately 40% and in Africa it is 70%. Risks for metastatic disease include substantial optic nerve, choroidal, or orbital invasion by the tumor.

21.What are the clinical growth patterns of retinoblastoma?

The growth patterns are endophytic and exophytic. Endophytic retinoblastoma arises from the inner retina and seeds the vitreous. Exophytic retinoblastoma arises from outer retinal layers and causes a solid retinal detachment. A variant of endophytic retinoblastoma is the diffuse infiltrating retinoblastoma. These patterns impart no difference to the patient’s life prognosis.

22.What is the differential diagnosis of endophytic retinoblastoma?

The differential diagnosis of endophytic retinoblastoma includes various inflammatory or infectious processes of the eye in children, such as toxocariasis, endophthalmitis, or advanced uveitis.

23.What is the differential diagnosis of exophytic retinoblastoma?

The differential diagnosis of exophytic retinoblastoma includes Coats disease, retinal capillary hemangioma, familial exudative vitreoretinopathy, and other causes of rhegmatogenous or nonrhegmatogenous retinal detachment in children.

KEY POINTS: RETINOBLASTOMA

•Retinoblastoma is an ocular cancer of childhood, usually detected before age 3 years. However, about 5% of newly diagnosed cases are in children over 5 years of age.

•The diagnosis of retinoblastoma must be excluded in any child, even a teenager or young adult, who manifests atypical uveitis, vitreous hemorrhage, or nonrhegmatogenous retinal detachment.

•Do not perform a vitrectomy or intraocular needle aspiration biopsy on an eye with retinoblastoma. This could seed the tumor.

•Any child with spontaneous hyphema or vitreous hemorrhage should be evaluated for trauma, retinoblastoma, and other intraocular tumors and inflammations.

CHAPTER 49  RETINOBLASTOMA  389

KEY POINTS: RETINOBLASTOMA—CONT’D

•The best way to diagnose retinoblastoma is with indirect ophthalmoscopy by an experienced observer. If uncertain, ultrasonography, fluorescein angiography, and computed tomography can be useful tests. Magnetic resonance imaging is most useful for evaluation of tumor invasion into the optic nerve or orbit, as well as assessment of the brain for related intracranial neuroblastic malignancy (trilateral retinoblastoma; pinealoblastoma).

24.Can retinoblastoma spontaneously regress?

Yes, about 3% of all cases of retinoblastoma are classified as spontaneously regressed or arrested. They are also termed “retinoma” and “retinocytoma.” These tumors do carry a 5% risk of recurrence and becoming active, requiring therapy.

25.When is genetic testing appropriate?

All children with retinoblastoma have genetic testing to ascertain whether they carry germ-line or somatic mutation. This affects their follow-up, because germ-line mutation children are at risk for pinealoblastoma and second cancers, unlike somatic mutation children.

26.How do we classify retinoblastoma?

In the past, the Reese Ellsworth classification scheme was used, but it is now outdated. Currently, the International Classification of Retinoblastoma is used worldwide (Table 49-1). This classification is simple and practical and pertinent for current therapies.

27.How does retinoblastoma appear on ultrasound?

On ultrasound, retinoblastoma appears as a mass originating from the retina with acoustic solidity and high internal reflectivity. Foci of calcium can be seen as dense echoes.

28.How does retinoblastoma appear on computed tomography?

On computed tomography, retinoblastoma appears as a solid mass within the globe with foci of bone density, representing calcium. Often retinal detachment can be detected.

29.How does retinoblastoma appear on magnetic resonance imaging?

On magnetic resonance imaging, retinoblastoma shows a hyperintense signal to the vitreous on T1-weighted images and a hypointense signal on T2. Contrast enhancement of the tumor is bright. The foci of calcium remain hypointense on both T1 and T2 without enhancement. Areas of necrosis appear similar to calcium except that they can show enhancement.

Table 49-1.  International Classification of Retinoblastoma

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30.Should pars plana vitrectomy or biopsy be performed to obtain tissue to confirm the diagnosis of retinoblastoma?

No. Biopsy is not indicated and should not be performed in any eye with retinoblastoma because it can potentially seed the tumor into the orbit and may lead to metastasis.

31.What are the pathology features of a well-differentiated retinoblastoma (Fig. 49-2)?

Flexner-Wintersteiner rosettes and fleurettes represent well-differentiated retinoblastoma.

32.List the options for management of an eye with intraocular retinoblastoma.

The options for management include:

•enucleation

•intravenous chemotherapy (chemoreduction)

•intra-arterial chemotherapy

•intravitreal chemotherapy

•thermotherapy

•cryotherapy

•laser photocoagulation

•plaque radiotherapy

•external beam radiotherapy

33.What are the conservative options for management of a small retinoblastoma posterior to the equator of the eye?

Intravenous chemotherapy, intra-arterial chemotherapy, or plaque radiotherapy are the most appropriate therapies for this tumor. Cryotherapy is generally limited to small tumors anterior to the equator of the eye.

34.What are the conservative options for management of a small retinoblastoma (<3 mm) anterior to the equator of the eye?

Chemoreduction combined with thermotherapy, laser photocoagulation, cryotherapy, or plaque radiotherapy are the most conservative options.

KEY POINTS: MANAGEMENT OF RETINOBLASTOMA

•The goal in management of retinoblastoma is, first and most important, to save the patient’s life; then consideration for globe salvage and vision preservation is made.

•The most common method for management of unilateral advanced retinoblastoma (group D or E) is enucleation or intra-arterial chemotherapy.

•Most bilateral retinoblastomas can be treated with intravenous chemotherapy. However, enucleation of one eye or intra-arterial chemotherapy is often necessary.

•Intravitreal chemotherapy injected directly into the vitreous cavity is useful for active vitreous seeds.

•Fresh retinoblastoma tissue should be harvested for DNA analysis and family genetic counseling.

Figure 49-2.  Flexner-Wintersteiner rosettes in well-differentiated retinoblastoma.

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CHAPTER 49  RETINOBLASTOMA  391

35.When do we use intravenous chemotherapy (chemoreduction) (Fig. 49-3)?

Chemoreduction is generally used for patients with bilateral retinoblastoma to cure the eyes, protect the patient from pinealoblastoma, and minimize long-term second cancers.

36.When do we use intra-arterial chemotherapy (Fig. 49-4)?

Intra-arterial chemotherapy is usually used for unilateral advanced retinoblastoma or those that fail intravenous chemotherapy.

37.When do we use intravitreal chemotherapy?

Intravitreal chemotherapy is used for eyes with viable vitreous retinoblastoma seeding following failure of standard intravenous or intra-arterial chemotherapy.

38.When do we use external beam radiotherapy and what are the risks?

External beam radiotherapy is used for children with retinoblastoma that have failed all standard methods and could potentially lose both eyes. We try to avoid this therapy because of its risks for short-term and long-term effects. The short-term effects include:

•dry eye

•cilia loss

•cutaneous erythema.

The long-term effects include:

•persistent dry eye

•cataract

•retinopathy

•papillopathy

•orbital fat atrophy

•maldevelopment of the orbital bones

•second cancers

A

B

Figure 49-3.  Retinoblastoma. A, before and B, after intravenous chemotherapy.