Neuroblastoma is a rare cancer originating from immature nerve cells (neuroblasts). This malignancy occurs predominantly in infants and young children, with most cases diagnosed before age five. Although the primary tumor frequently develops in the adrenal glands, abdomen, or chest, neuroblastoma often spreads, causing symptoms that directly involve the eyes. These distinct ocular manifestations result from either the cancer spreading to the eye socket or the immune system reacting to the tumor.
Distinct Eye Symptoms of Neuroblastoma
One striking ocular manifestation of neuroblastoma is periorbital ecchymosis, often termed “raccoon eyes.” This symptom appears as bruising or dark discoloration around the eyes, occurring even without a history of trauma. This characteristic appearance signals that the cancer has spread to the bones surrounding the eye socket, causing fragile blood vessels and subsequent hemorrhage into the soft tissue.
Another significant sign is proptosis, which describes the visible bulging or protrusion of the eyeball. This displacement occurs when a metastatic tumor mass grows behind the eye within the confined space of the orbit. The rapid growth of this mass exerts pressure on the eye’s structures, sometimes leading to restricted movement or vision compromise.
Horner Syndrome presents as a triad of symptoms affecting one side of the face and eye. The signs include miosis (constriction of the pupil) and ptosis (drooping of the upper eyelid). The third component is anhidrosis, or decreased sweating, on the affected side of the face. This syndrome results from damage to the sympathetic nerve pathway, often caused by a neuroblastoma tumor in the neck or chest compressing the sympathetic nerves.
A separate neurological presentation is Opsoclonus-Myoclonus Syndrome (OMS), sometimes referred to as “dancing eyes, dancing feet.” The eye component, opsoclonus, involves chaotic, rapid, and involuntary multidirectional eye movements. This is often accompanied by myoclonus, which is involuntary jerking or twitching of the limbs and body, leading to difficulties with balance and coordination.
How Neuroblastoma Causes Ocular Issues
The varied eye symptoms of neuroblastoma stem from two fundamentally different biological processes: direct physical invasion and an immune-mediated attack. The most common mechanism for localized eye involvement is direct orbital metastasis. Here, neuroblastoma cells travel through the bloodstream from the primary tumor site (typically the adrenal gland, abdomen, or chest) to colonize the bones and soft tissues of the eye socket.
The resulting mass growth within the tight orbital space causes physical displacement (proptosis) and bruising (periorbital ecchymosis). The tumor mass can obstruct small palpebral vessels around the eye, leading to blood leakage and dark discoloration. This orbital involvement signifies that the neuroblastoma has disseminated, indicating advanced-stage disease.
The second mechanism is responsible for the neurological symptoms of Horner Syndrome and Opsoclonus-Myoclonus Syndrome. Horner Syndrome is a mechanical effect, occurring when a tumor growing in the chest or neck presses directly on the sympathetic nerve chain. This compression interrupts the nerve signals controlling pupil size and eyelid elevation, causing the characteristic drooping and small pupil.
In contrast, OMS is a paraneoplastic syndrome, meaning the symptoms are caused by the body’s immune response to the cancer, not the tumor growing in the brain. Neuroblastoma cells possess antigens resembling proteins found on healthy nerve cells. The immune system, fighting the tumor, mistakenly produces antibodies that attack these healthy neurological tissues, resulting in chaotic eye movements and loss of coordination.
Eye Signs and Disease Detection
The presence of specific eye signs often serves as an initial clue for detecting neuroblastoma, particularly in young children who cannot articulate other symptoms. Unexplained periorbital ecchymosis or rapidly developing proptosis should immediately prompt a medical investigation, especially without trauma. These visible signs accelerate the diagnostic process, which is essential because early detection impacts prognosis.
The specific ocular symptom also provides information regarding the disease stage and risk profile. Proptosis or periorbital ecchymosis due to orbital metastasis signals that the cancer has spread to distant sites, classifying the neuroblastoma as high-risk, advanced-stage disease. Conversely, the presence of Horner Syndrome usually suggests a tumor locally confined to the neck or chest region, often associated with a more favorable prognosis.
The diagnosis of OMS, the “dancing eyes” syndrome, is a distinct marker with prognostic implications. Although OMS is a severe neurological condition requiring immediate treatment, neuroblastoma associated with this paraneoplastic syndrome tends to be less aggressive biologically. Children with OMS-associated neuroblastoma often have a better long-term survival rate compared to those with metastatic disease presenting with proptosis.
Managing Neuroblastoma with Ocular Involvement
The management of neuroblastoma is complex when the eyes are involved, requiring strategies tailored to the underlying cause. For symptoms arising from orbital metastasis, such as proptosis and raccoon eyes, the primary treatment involves high-intensity systemic chemotherapy. This regimen aims to shrink the tumor everywhere in the body, including orbital deposits.
Local therapies are also incorporated to protect the child’s vision and ocular health. Low-dose radiation therapy may be directed at the orbital tumor to rapidly reduce its size and relieve pressure on the optic nerve. This approach requires careful planning to balance tumor control with minimizing long-term damage to the developing eye.
Managing Opsoclonus-Myoclonus Syndrome demands a dual focus on the tumor and the immune system attack. The neuroblastoma is treated with standard protocols, including chemotherapy, but the neurological symptoms require immune-modulating drugs. Treatment often includes corticosteroids and intravenous immunoglobulin (IVIG) to suppress the autoimmune response attacking the central nervous system.
The involvement of the eyes necessitates a highly specialized, multidisciplinary approach to care. Pediatric oncologists manage systemic cancer treatment, while pediatric ophthalmologists monitor vision, orbital pressure, and ocular complications. Neurologists are involved in diagnosing and managing the complex neurological effects of OMS or Horner Syndrome.