More Than Meets the Eyes

However, when it comes to brain tumors, there is still a lot of progress to be made before we reach the same treatment stages as leukemia. With the aim of improving the outcomes for children in Denmark with brain tumors, we established the Danish Collaborative Comprehensive Childhood CNS tumor Consortium. The consortium is a multi-disciplinary collaboration between pediatric neuro-oncology teams aimed at coordinating childhood brain tumor research in the country, and together we have devised a comprehensive research program, with one major focus area being earlier diagnosis.

Children with brain tumors can often experience lengthy diagnostic delays in many countries, including Denmark. These prolonged delays can allow time for the tumor to grow, causing irreversible brain damage and, in some cases, making the tumor more difficult to treat. And although the actual impact that these delayed diagnostic times have on survival rates can be debated, the long-term neurological disabilities associated with them are an important factor in determining patients’ outcomes and their subsequent post-operative quality of life.

Initially inspired by the Headsmart campaign, a public awareness campaign conducted by the Brain Tumour Charity in the UK in 2011 that led to a marked decrease in time from onset of first symptoms to diagnosis (1), our team conducted a similar investigation into the status of diagnostic delays in Denmark, specifically in terms of ophthalmology. Ophthalmic manifestations of brain tumors are common; we wanted to know how involved ophthalmologists were in this diagnostic process. We found that ophthalmology has a significant role to play in timely diagnosis of pediatric brain tumors.

In the 2025 Eye study, we examined the symptoms and clinical findings in a nationwide cohort of 437 children diagnosed with brain tumors in Denmark over an 11-year period. We found that over half of these children had had some form of ophthalmological signs prior to their tumor diagnosis (2). In addition, in more than 10% of the patients, eye symptoms were in fact the very first manifestation of the tumor. This indicates that a rather large percentage of parents might take their children to an ophthalmologist as their first port of call.

The ophthalmological complaints most commonly reported in these cases were reduced visual acuity and strabismus – symptoms that are seen frequently in an ophthalmology clinic, and consequently may often be overlooked or dismissed. Our study found that the likelihood of being diagnosed within one month was especially low if reduced vision or strabismus were noted as the first presenting symptoms, especially if the child was under five years old.

We also noted that, in the majority of cases, once the child had had a thorough examination, the strabismus or reduced vision would be attributed to a more serious underlying cause, such as cranial nerve palsy, optic atrophy, or papilledema.

In addition to these ophthalmological signs, the children also displayed systemic symptoms. While the most common systemic complaints were headaches and nausea, some of the children displayed more subtle, harder-to-detect symptoms, such as behavioral changes and development delays. By the time a brain tumor diagnosis was made, on average at least four different symptoms or clinical findings were reported for each child.

When we took a closer look at those children whose ophthalmic manifestations were not the very first sign but instead developed over time, we found that reduced visual acuity and strabismus were again frequent. Some of these children were seen by an ophthalmologist as part of a broader clinical investigation based on systemic symptoms, and the ophthalmological findings  (most often papilledema, optic nerve atrophy, and abnormal pupils) were used to prompt further investigations leading to the brain tumor diagnosis.

Interestingly, we found that nystagmus, present in many of the cases, was a sign that had been missed by parents, the child, and even pediatricians assessing the child prior to the visit to the ophthalmologist (3). For most cases, this consisted of gaze-evoked nystagmus, but there were also cases of more subtle nystagmus in primary position. In cases where nystagmus was observed by the ophthalmologist, it was immediately recognized as an alarming sign and prompted earlier diagnosis. As checking for nystagmus is a relatively easy task, we recommend that non-ophthalmologists remember to check eye motility as part of their initial investigations in children with unspecific symptoms, as this could potentially be used to speed up tumor diagnoses. 

Taken together, what we have learned from our Danish children is that ophthalmologists hold great responsibility in getting children with brain tumors diagnosed. Even though the ophthalmic complaints we observed may be viewed as common, the co-existing clinical findings and presence of systemic – sometimes subtle – complaints can help us to distinguish those children that need immediate CNS imaging. 

Based on our study findings, we have devised an online clinical tool that can help to guide clinicians in all specialties when they are evaluating children. We hope that this tool will result in shorter diagnostic delays and better long-term outcomes for our children, as well as acting as inspiration for ophthalmologists in other countries.

We must never forget that children are more than their eyes, and that serious diseases can be hidden in common, seemingly innocuous ophthalmic complaints, ones that, if we search hard enough and bear in mind our past learning, we can hope to locate and diagnose early enough to ensure timely, effective intervention.