A 10-Day Course of Nerve Growth Factor Eye Drops Was Followed for Four Years. It Did Not Prove a Lasting Effect.

A 10-day course of experimental eye drops, followed by four years of stable vision and stable brain scans, sounds like the kind of result that invites a breakthrough headline. The actual finding is more useful and more restrained.

Fifteen young people with optic pathway glioma returned for long-term monitoring after taking part in a small randomized trial of murine nerve growth factor eye drops. Across 48 months, the researchers found no significant deterioration in the visual measures they tracked. Every participant also had stable disease on MRI.

But stability was seen across the cohort, including children who had originally received placebo. The extension was observational, not a second randomized efficacy trial. Its authors therefore made an important distinction: the results support long-term safety and tolerability, while sustained treatment efficacy remains unproven.

That distinction matters because optic pathway glioma is a slow-moving tumor in which a stable scan and protected sight are related, but not interchangeable, outcomes.

What the four-year study actually followed

The new paper, published in the Journal of Neuro-Oncology on September 1, 2026, returned to a cohort first studied a decade earlier. The original phase II trial enrolled 18 patients, ages 2 to 23, with stable optic pathway glioma and severe visual loss. Ten were assigned to receive a total of 0.5 mg of murine nerve growth factor as eye drops over 10 days. Eight received placebo.

Fifteen of those 18 participants agreed to the extended follow-up. Nine had originally received nerve growth factor and six had received placebo. None received another course of nerve growth factor, chemotherapy, or radiotherapy during the four-year observation period.

The monitoring was unusually broad for such a small study. Every six months, the team performed general and neuro-ophthalmic examinations. They measured visual evoked potentials, or VEPs, which capture the brain's electrical response to visual stimulation. They also recorded the photopic negative response, an electroretinogram signal associated with retinal ganglion-cell function. MRI was repeated annually.

When the investigators compared the beginning and end of follow-up, visual acuity, visual-field radius, VEP amplitude, and photopic negative response amplitude had not changed significantly. Brain MRI showed stable disease in all 15 participants.

Those are reassuring observations. They do not tell us that the eye drops caused the stability.

Why the original trial attracted attention

Nerve growth factor is a signaling protein that supports the development, maintenance, and survival of certain neurons. In this context, the goal was not to shrink the tumor directly. It was to test whether topical NGF could protect or improve the retinal and visual pathways damaged by the tumor.

The original randomized, double-blind trial, published in Brain in 2016, produced several encouraging signals over six months. The treated group showed statistically significant improvement in the photopic negative response at day 180 and in visual evoked potentials at day 30. Those changes were not seen in the placebo group.

Visual fields could be reliably measured in only a subset. Among those participants, three of four in the NGF group had significant visual-field enlargement. Worsening was observed only in placebo-treated cases. Patients or caregivers also reported better visually guided behavior, and the investigators reported no treatment-related adverse effects.

That was a plausible proof-of-concept result, not a definitive treatment trial. Eighteen participants is a very small sample. Different tests were performed at several time points, and the patients began with severe visual impairment. A handful of individual outcomes can have a large influence in a trial that size.

The four-year extension now answers one narrow question reasonably well: no delayed safety problem or obvious long-term deterioration emerged in the 15 people who returned. It does not answer the harder question of whether one brief NGF course preserved vision for years.

Stable tumor does not automatically mean stable vision

Optic pathway gliomas grow along structures that carry visual information from the eye toward the brain. They are often low-grade and slow-growing, yet their location makes even modest damage consequential. They are also associated with neurofibromatosis type 1, although not every case occurs in that setting.

The central clinical problem is that controlling tumor size does not guarantee recovery of visual function. Vision may already be damaged at diagnosis. It can also worsen without a dramatic radiologic change. That is why a neuroprotective treatment, aimed at vulnerable retinal ganglion cells rather than the tumor itself, is an appealing idea.

A separate 2026 study shows how high the stakes can be. Researchers reviewed 81 children diagnosed with optic pathway low-grade glioma before age three. After a median follow-up of 11 years, 45.7% were visually impaired and 26% were bilaterally blind. Most deterioration occurred within two years of diagnosis, but late events were recorded as far as 16 years later.

That cohort was retrospective and involved a different patient population. It cannot be used to estimate what NGF eye drops would do. It does, however, explain why “stable vision” is a meaningful endpoint rather than a disappointing substitute for tumor shrinkage.

The comparison that the extension cannot make

A strong long-term efficacy test would preserve the original randomized comparison and be large enough to detect clinically important differences between groups. This study could not do that.

Three of the original 18 participants did not join the extension. Only nine previously treated participants and six previous placebo recipients remained. The paper reports no significant change from the original baseline in any measured parameter, but it does not establish a durable advantage for the NGF arm over placebo.

The absence of chemotherapy or radiotherapy during follow-up removes one possible source of confusion. It also tells us that this was a selected group with sufficiently stable disease to remain untreated. Their course may not resemble that of a child with a newly diagnosed or actively progressing tumor.

Stable MRI in all participants is similarly double-edged. It is reassuring, but it gives the study little leverage to show that NGF altered tumor behavior. The intervention was designed as neuroprotection anyway, so the key proof would need to be a reproducible visual benefit against a control group.

No such conclusion is available from 15 observed participants.

How this fits beside current treatment research

Standard management of optic pathway glioma depends on age, symptoms, tumor behavior, neurofibromatosis status, and the threat to vision or other neurologic functions. Observation can be appropriate for stable disease. Progressive or symptomatic cases may involve chemotherapy, targeted therapy, surgery in selected circumstances, or other specialist strategies.

A 2022 systematic review found that reported outcomes varied widely across chemotherapy, radiotherapy, and surgery. Its pooled “favorable” visual category combined patients who improved with those who did not change, which makes the headline rate difficult to translate into restored sight.

Bevacizumab-based treatment has also been studied. A 2025 meta-analysis covering 10 studies and 185 pediatric patients estimated that visual acuity improved in 31%, remained stable in 60%, and worsened in 15%. Those data came from heterogeneous studies rather than a direct comparison with topical NGF. They should not be read as a treatment leaderboard.

The useful idea behind the NGF experiment is that tumor control and neural protection may need separate strategies. One treatment might slow growth. Another might help preserve the cells and circuits responsible for sight. That combination remains a research direction, not an established protocol.

A protein eye drop is not a consumer peptide protocol

Nerve growth factor belongs in the wider conversation about therapeutic polypeptides and protein signaling, but it should not be confused with short “research peptides” sold online. The trial used a defined murine protein preparation under clinical supervision in a pediatric oncology setting. It was not an over-the-counter drop, and the study does not provide a recipe for compounding or self-treatment.

Topical delivery is scientifically interesting because it may expose ocular tissues while limiting systemic treatment. Yet successful delivery, dose consistency, immune effects, formulation stability, and manufacturing all matter for a protein drug. A result from one investigational preparation cannot be transferred to a product with a similar label or marketing claim.

Parents and patients should not seek unapproved NGF eye drops or delay tumor-directed care because of this paper. Optic pathway glioma requires coordinated pediatric neuro-oncology and ophthalmology follow-up.

The Oria take

The best reading of this study is neither “the eye drops worked for four years” nor “nothing happened.” A tiny randomized trial produced short-term electrophysiologic and visual-field signals. Its observational extension then found four years of stability and no evident delayed tolerability problem among 15 returning participants.

That is enough to justify a larger trial. It is not enough to establish a treatment.

The next study should enroll more patients, prespecify a small set of vision-centered endpoints, and maintain a concurrent control group. It should distinguish children with neurofibromatosis-associated disease from sporadic cases, stratify by baseline visual function and tumor activity, and report outcomes that matter in daily life alongside electrophysiology and MRI. Repeated dosing may deserve study, but only after formulation, immunogenicity, and safety questions are addressed.

For now, the most important sentence in the new paper is its restraint: four-year stability is evidence of favorable long-term safety and tolerability, rather than proof of persistent efficacy.

Sources

1. Ruggiero A, et al. “Long-term outcomes after a randomized phase II trial of nerve growth factor eye drops for optic pathway gliomas: four-year follow-up findings in children.” Journal of Neuro-Oncology, 2026. https://pubmed.ncbi.nlm.nih.gov/42681266/ 2. Falsini B, et al. “Nerve growth factor improves visual loss in childhood optic gliomas: a randomized, double-blind, phase II clinical trial.” Brain, 2016. https://pubmed.ncbi.nlm.nih.gov/26767384/ 3. Picariello S, et al. “Visual morbidity, long-term outcome and prognostic factors in infants and young children with optic pathway low-grade glioma.” Neuro-Oncology Practice, 2026. https://pubmed.ncbi.nlm.nih.gov/42312116/ 4. Amato A, Imbimbo BP, Falsini B. “Neurofibromatosis type 1-associated optic pathway gliomas: pathogenesis and emerging treatments.” European Review for Medical and Pharmacological Sciences, 2023. https://pubmed.ncbi.nlm.nih.gov/37401302/ 5. Yousefi O, et al. “Management of Optic Pathway Glioma: A Systematic Review and Meta-Analysis.” Cancers, 2022. https://pubmed.ncbi.nlm.nih.gov/36230704/ 6. Hajikarimloo B, et al. “The efficacy and safety of Bevacizumab-based treatments in Optic Pathway Glioma among pediatric population: a systematic review and meta-analysis.” Neurosurgical Review, 2025. https://pubmed.ncbi.nlm.nih.gov/39849189/

Evidence grade: C. The research begins with a randomized, double-blind phase II cohort and includes objective visual electrophysiology, MRI surveillance, and four-year observation. Confidence remains limited by the 15-person extension, loss of three original participants, the absence of rerandomization, and the lack of a demonstrated long-term efficacy difference between prior treatment groups.

Medical disclaimer: This article is for educational purposes and is not medical advice. Nerve growth factor eye drops remain investigational for optic pathway glioma. Do not obtain unapproved products, alter cancer care, or delay specialist evaluation based on this report. Pediatric optic pathway glioma requires individualized care from qualified neuro-oncology and ophthalmology teams. Oria exists to help readers understand emerging peptide and protein research, not to diagnose disease or replace treatment.