Childhood Retinal Tumors

Retinoblastoma primarily disrupts the retinal architecture, leading to abnormal retinal function, including reduced visual acuity, visual field defects, faulty contrast sensitivity, vision loss, and death if untreated (Figure 1). It is the most common primary intraocular childhood cancer, occurring in 1 per 18,000 births and accounting for 3% of pediatric malignancies.^1-3 Here, we discuss how to diagnose and treat this condition.

DIAGNOSIS

Retinoblastoma primarily affects children younger than 5 years of age, with approximately 90% of cases identified before 3 years of age.^1,2 Occurrences in older children and adults are rare.

Common presentations may include leukocoria (white pupillary reflex), strabismus, eye pain, larger-than-normal globe, red eye, or decreased visual acuity.^1,2,4,5 Proptosis, orbital inflammation, and secondary glaucoma due to tumor extension beyond the globe may occur in advanced cases. That said, other retinal conditions may present as retinoblastoma masqueraders. The most common masqueraders include Coats disease, astrocytic hamartomas, combined hamartomas of the retina and retinal pigment epithelium (RPE), and retinocytoma (Figures 2-5).

Coats disease is characterized by unilateral, telangiectatic retinal vasculature that has massive lipid exudation and is typically found in young males.⁶ Like retinoblastoma, this condition may present with leukocoria. The conditions can be differentiated through fundus evaluation and B-scan ultrasonography. As retinoblastoma includes calcium deposition, we must look out for areas of high internal acoustic reflectivity on ultrasound. While Coats disease does not present with calcification, advanced cases that have large exudative retinal detachments may confound a definitive diagnosis because thick lipid exudation also displays with high acoustic reflectivity. Keep in mind that lipid exudation typically shifts freely on echography, while retinoblastoma with calcification usually presents as a solid mass.

Astrocytic hamartomas are benign, amelanotic retinal lesions that arise from astrocytes in the sensory retina.⁷ Like retinoblastoma and Coats disease, these lesions may present with leukocoria if they are adjacent to the macula. Clinical presentation ranges from flat, translucent, noncalcified intraretinal patches to nodular, opaque, white inner-retinal lesions to large, yellow-white, calcified, multinodular mulberry-like tumors. OCT typically shows a dome-shaped hyperreflective mass with a “moth-eaten” appearance and posterior shadowing. These benign tumors may be sporadic or present as ocular manifestations of tuberous sclerosis. Because of this, baseline imaging of the brain should be obtained to rule out any associated neurological lesions.

Like astrocytic hamartomas, combined hamartomas of the RPE are also composed of glial tissue; however, these benign lesions also contain vascular and pigmented cells. These hamartomas appear grayish, with twisting intraretinal vasculature and scalloped edges. Spectral-domain OCT shows retinal folding and a highly reflective disorganized retina. These lesions may cause significant traction to the surrounding retina, leading to metamorphopsia if they are near the macula. Additionally, both astrocytic hamartomas and combined hamartomas of the retina may present with retinal edema.^7,8 Photodynamic therapy, intravitreal anti-VEGF therapy, and intravitreal steroid injections are effective in treating the vascular leakage associated with these lesions.⁷

Retinocytoma is a rare, benign, fully differentiated retinal tumor that acts as a variant or precursor to retinoblastoma. While not generally aggressive, these tumors, also often found in children, carry the same genetic implications as retinoblastoma (linked to RB1 gene mutations) and require lifelong monitoring due to potential, though rare, transformation into malignancy.⁹ The definitive diagnosis of retinoblastoma relies on clinical examination, imaging, and molecular testing. Molecular testing of the RB1 gene reveals mutations from hereditary retinoblastoma; this is usually ordered by a genetic counselor or medical oncologist. Regarding clinical examination, the gold standard is an ophthalmic evaluation under anesthesia that allows detailed retinal assessment with indirect ophthalmoscopy. Ultrasound, MRI, CT, and OCT are the imaging modalities that help confirm the diagnosis, evaluate the extent of the disease process, and rule out extraocular or metastatic spread.^1,2 MRI testing is useful on initial or subsequent examinations to eliminate optic nerve involvement, a key prognostic factor, along with intracranial tumors.^1,2

TREATMENT

Treatment strategies and predictive outcomes are based on accurate tumor staging and classification. Retinoblastoma classification is based on the International Intraocular Retinoblastoma Classification (IIRC) for intraocular tumors and the Tumor, Node, Metastasis (TNM) system for extraocular disease. Using the IIRC, retinoblastoma is categorized into five groups (A-E) based on tumor size, location, and extent. The least severe cases are represented by Group A, whereas Group E comprises advanced disease that requires enucleation. Considering the possibility of systemic spread, the TNM system includes lymph node involvement and distant metastases.¹

The treatment goal for retinoblastoma is primarily focused on the patient’s survival; however, globe salvation and vision preservation are significant secondary goals that have become more obtainable with evolving treatment modalities.¹⁰ Treatment is individualized to the patient based on several factors, including IIRC group, tumor location, patient age, and prior treatment.¹¹ For small lesions (less than 3 mm in diameter), laser ablation alone has shown to be an effective treatment option, with regression seen in up to 86% of cases.¹² These ablative treatments can be repeated on a 4- to 6-week interval until complete tumor regression occurs. Larger lesions tend to require the addition of chemo-reductive agents in conjunction with ablative therapy. Chemotherapy may be administered in multiple cycles via several different routes.

Systemic chemotherapy is the traditional administration method, but it is shown to cause systemic toxicities. Local chemotherapy routes that decrease systemic toxicity include periocular chemotherapy, intra-arterial chemotherapy, and intravitreal chemotherapy. Intra-arterial chemotherapy, in particular, is shown to be effective at targeting retinoblastoma while avoiding severe side effects, such as ototoxicity or secondary malignancy.¹³ For lesions that do not respond to globe-salvaging therapy or for advanced retinoblastoma, enucleation remains the definitive treatment option. Patients who require enucleation should be comanaged with us (optometrists) for implementation of monocular precautions, such as protective eyewear.

Retinoblastoma survival rates can reach up to 95% in specialized care centers, and vision is preserved in most cases.¹

GETTING A DEFINITIVE DIAGNOSIS

Retinoblastoma is a vision- and life-threatening malignancy in early childhood, the diagnosis of which can be muddied by masquerading conditions. Therefore, a thorough clinical examination, imaging, and molecular testing are needed for a definitive diagnosis. Advances in multidisciplinary management have improved outcomes. Early recognition and prompt referral optimize ocular and systemic prognosis.