involvement, orbital invasion, central nervous system involvement, and distant metastasis. Treatment of extraocular retinoblastoma includes intensive multimodality chemotherapy, autologous hematopoietic stem cell rescue, and external-beam radiation. Long-term disease-free survival is possible if the central nervous system is not involved; otherwise, the prognosis is usually poor.
Patients with trilateral retinoblastoma have a primitive neuroectodermal tumor of the pineal gland or parasellar region, in addition to retinoblastoma. The risk of trilateral retinoblastoma has been less than 0.5% and 5%–15% in patients with unilateral and bilateral retinoblastoma, respectively. However, the rate of trilateral retinoblastoma appears to be lower in patients treated with chemoreduction. Treatment usually involves a multimodal approach, and the prognosis is poor.
Abramson DH, Dunkel IJ, Brodie SE, Marr B, Gobin YP. Superselective ophthalmic artery chemotherapy as primary treatment for retinoblastoma (chemosurgery). Ophthalmology. 2010;117(8):1623–1629.
Shields CL, Bianciotto CG, Jabbour P, et al. Intra-arterial chemotherapy for retinoblastoma: report no. 2, treatment complications. Arch Ophthalmol. 2011;129(11):1407–1415.
Monitoring Identification of RB1 mutations is very useful in determining how frequently to monitor patients. Patients with unilateral tumors who have somatic mutations are not at risk for development of additional tumors (ocular or systemic). Patients with bilateral tumors and patients with unilateral tumors who carry germline RB1 mutations are at high risk, and frequent monitoring is crucial. The risk of additional eye tumors decreases with age and is low after age 24 months. Genetic testing can also help determine the need to monitor siblings. If genetic testing is not available, siblings should be monitored routinely during the first 2 years of life.
Nonocular tumors are common in patients with germinal mutations; the estimated incidence rate is 1% per year of life (eg, 10% prevalence by age 10, 30% by age 30). The incidence is higher among patients treated with external-beam radiation before 1 year of age. The most common secondary tumors (and the mean age at diagnosis) are pinealoma (2.7 years), sarcoma (13 years), melanoma (27 years), and carcinomas (29 years). Patients in whom second, nonocular tumors develop are at even greater risk for additional malignant tumors.
Woo KI, Harbour JW. Review of 676 second primary tumors in patients with retinoblastoma: association between age at onset and tumor type. Arch Ophthalmol. 2010;128(7):865–870.
Acquired Disorders
Coats Disease
The classic findings in Coats disease are yellow subretinal and intraretinal lipid exudates associated with retinal vascular abnormalities—most often telangiectasia, tortuosity, aneurysmal dilatations, and retinal capillary nonperfusion. The clinical presentation varies, ranging from mild changes to total retinal detachment (Fig 25-23).
Figure 25-23 Coats disease. Affected right eye. Note extensive subretinal exudate and exudative retinal detachment.
Males are affected more frequently than females, and the condition is usually, but not always, unilateral. The average age at diagnosis is 6–8 years, but the disease has also been observed in infants. The etiology of Coats disease is unknown. Associations with various gene deletions have been reported, but the disease is isolated in most cases.
Diagnosis
The diagnosis of Coats disease requires the presence of abnormal retinal vessels, which occasionally are small and difficult to find. The subretinal exudate is thought to come from the leaking anomalous vessels. Fluorescein angiography may be helpful in identifying leakage from the telangiectatic vessels and in assessing the effectiveness of therapy.
The differential diagnosis includes PFV, ROP, toxocariasis, familial exudative vitreoretinopathy, Norrie disease, retinal dysplasia, endophthalmitis, leukemia, and retinoblastoma. Calcium is frequently detected by ultrasonography in retinoblastoma but is distinctly rare in Coats disease. Coats disease often presents with xanthocoria (yellow pupil reflex), whereas retinoblastoma presents with leukocoria (white pupil reflex).
Treatment
Treatment is directed at obliterating the abnormal leaking vessels and includes cryotherapy or laser photocoagulation. Exudative retinal detachments and subretinal fibrosis develop in eyes with progressive disease. Once the fovea is detached and the subretinal exudate becomes organized, the prognosis for restoration of central vision is poor. Use of intravitreal bevacizumab in addition to laser treatment has been reported, but one study found that this approach was associated with a higher
incidence of vitreoretinal fibrosis and tractional retinal detachment.
Mulvihill A, Morris B. A population-based study of Coats disease in the United Kingdom II: investigation, treatment, and outcomes. Eye (Lond). 2010;24(12):1802–1807.
Ramasubramanian A, Shields CL. Bevacizumab for Coats disease with exudative retinal detachment and risk of vitreoretinal traction. Br J Ophthalmol. 2012;96(3):356–359.
Systemic Diseases and Disorders With Retinal
Manifestations
Diabetes Mellitus
Type 1, or insulin-dependent, diabetes mellitus was formerly called juvenile-onset diabetes mellitus. The prevalence of retinopathy in this condition is directly proportional to the duration of diabetes after puberty. Retinopathy rarely occurs less than 5 years after the onset of diabetes mellitus. Proliferative diabetic retinopathy is rare in pediatric cases.
A variety of nonproliferative changes may occur in the pediatric age group. Microaneurysms are the first ophthalmoscopic sign; they may be followed by retinal hemorrhages, areas of retinal nonperfusion, cotton-wool spots, hard exudates, intraretinal microvascular abnormalities, and venous dilation.
A rapid rise of blood glucose may produce myopia, and sudden reduction of blood glucose can induce hyperopia, because of osmotic changes in the lens and alteration of its refractive status. Several weeks may be required before acuity returns to normal. True diabetic cataracts are uncommon, occurring most often in patients with poorly controlled disease. Such cataracts resemble a snowstorm that affects the anterior and posterior cortices of young patients.
Diabetes mellitus, especially in young children, may be part of DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). This condition, which is also known as Wolfram syndrome, is associated with congenital cataracts as well.
Diagnosis
To screen for diabetic retinopathy, the American Academy of Ophthalmology recommends annual ophthalmic examinations beginning 5 years after the onset of diabetes mellitus (www.aao.org/ppp). The American Academy of Pediatrics (AAP) recommends an initial ophthalmic examination 3–5 years after diagnosis if the patient is older than 9 years, with annual follow-up examinations thereafter (www.aap.org). Specifically, the AAP states that children younger than 9 years do not require screening examinations, because the incidence of diabetic retinopathy is negligible in this age group.
Lueder GT, Silverstein J; American Academy of Pediatrics Section on Ophthalmology and Section on Endocrinology. Screening for retinopathy in the pediatric patient with type 1 diabetes mellitus. Pediatrics. 2005;116(1):270–273.
Treatment
Treatment is discussed in BCSC Section 12, Retina and Vitreous.
Albinism
Albinism is a group of conditions that involve the synthesis of melanin in the skin and eye
(oculocutaneous albinism [OCA]) or the eye alone (ocular albinism [OA]).
Diagnosis
The major ophthalmic findings in all types of OCA and OA are iris transillumination from decreased pigmentation, foveal aplasia or hypoplasia, and a characteristic deficit of pigment in the retina, especially peripheral to the posterior pole (Fig 25-24A, B). Nystagmus, light sensitivity, high refractive errors, and reduced central visual acuity are often present, and visual acuity ranges from 20/25 to 20/200. If a child has significant foveal hypoplasia, nystagmus will begin at 2–3 months of age. The severity of the visual impairment tends to be proportional to the degree of nystagmus and foveal hypoplasia. Optical coherence tomography has demonstrated that the size of the photoreceptor outer segment is the strongest predictor of visual acuity. An abnormally large number of crossed fibers appear in the optic chiasm of patients and animals with albinism, precluding stereopsis and often inducing strabismus. Asymmetric visually evoked potentials are often seen in affected patients and may be helpful in diagnosis.
Figure 25-24 A, Transillumination of iris in albinism, right eye. B, Fundus in albinism, right eye, demonstrating complete lack of pigment and macular hypoplasia. C, Child with oculocutaneous albinism type 2 (OCA2). Note white hair, eyebrows, and lashes and light-colored irides and freckles. (Parts A and C courtesy of Edward L. Raab, MD.)
There are 4 major types of OCA, all of which exhibit various degrees of skin and hair pigmentation (Fig 25-24C). They are autosomal recessive and are caused by different genes (Table 25-10).
Table 25-10
Ocular albinism (OA1), also called Nettleship-Falls albinism, is usually caused by a mutation in the GPR143 gene on the X chromosome. This gene controls melanosome number and size; the mutation results in macromelanosomes, which may be revealed by skin biopsy. An autosomal recessive form of OA has also been reported. Affected individuals appear to have decreased pigment in the eyes but not the skin. Patches of decreased pigment in the fundus and iris transillumination are apparent in many female carriers.
Albinism can be part of a broader syndrome, such as Hermansky-Pudlak syndrome or ChédiakHigashi syndrome, both of which are autosomal recessive. Hermansky-Pudlak syndrome occurs with higher frequency in Puerto Rico and is characterized by pulmonary interstitial fibrosis and bleeding abnormalities. Chédiak-Higashi syndrome is a rare condition characterized by increased susceptibility to bacterial infections. Whenever a patient is diagnosed with albinism, the clinician should inquire about bleeding or bruising tendencies and frequent infections.
Treatment
Tinted glasses may be used for patients with photophobia. Patients with OCA are at risk for skin cancer and should be counseled.
Levin AV, Stroh E. Albinism for the busy clinician. J AAPOS. 2011;15(1):59–66.
Mohammad S, Gottlob I, Kumar A, et al. The functional significance of foveal abnormalities in albinism measured using spectral-domain optical coherence tomography. Ophthalmology. 2011;118(8):1645–1652.