Intra-Arterial Chemotherapy for Retinoblastoma and Other Chemotherapy Options

For decades, children with advanced retinoblastoma often lost the affected eye or received external radiotherapy, which raises the risk of other cancers later in life. Intra-arterial chemotherapy for retinoblastoma changed that picture: by delivering the drug straight into the artery that feeds the eye, it treats the tumor with a high concentration of chemotherapy while the rest of the body receives much less. Together with chemotherapy injected directly into the eye, it now allows many eyes to be saved that would once have been removed.

The disease itself, and how it is diagnosed and grouped, is described on our main retinoblastoma page.

What are the chemotherapy options for retinoblastoma?

Chemotherapy is often combined with focal consolidation: once tumors shrink, laser, thermotherapy or cryotherapy (freezing) destroys what remains.

Who is a candidate for intra-arterial chemotherapy for retinoblastoma?

Intra-arterial chemotherapy (IAC) is considered for:

• advanced retinoblastoma in one eye (Groups D and E), where it has become a main first treatment;
• less advanced eyes (Groups B and C), increasingly as the first treatment;
• tumors that did not respond or came back after systemic chemotherapy or radiotherapy;
• eyes with seeds, often combined with intravitreal injections;
• both eyes in selected children, treated in the same session ("tandem" therapy).

It is less suitable for very young babies in whom catheterization is not appropriate, for eyes with signs that the tumor may be escaping — such as tumor-related glaucoma or suspected optic nerve invasion, where removal of the eye is usually safer — and for cancer that has spread beyond the eye. The decision is made for each eye separately; the A–E groups are explained on our retinoblastoma page.

How was intra-arterial chemotherapy developed?

The idea was first put into practice in Japan. From the late 1980s, a team at the National Cancer Center in Tokyo — including Kaneko, Mohri, Suzuki and Yamane — developed selective ophthalmic arterial infusion (SOAI): a catheter passed from the groin into the internal carotid artery carries a tiny balloon, inflated briefly just beyond the origin of the ophthalmic artery so that melphalan flows preferentially into the eye's own artery. The technique was published in detail in 2004, and in 2011 Suzuki and colleagues reported long-term results in 343 children treated between 1988 and 2007.

In 2006, Abramson and Gobin in New York introduced direct catheterization of the ophthalmic artery with a microcatheter, often called super-selective intra-arterial chemotherapy or ophthalmic artery chemosurgery. Japanese centers continue to refine the balloon technique: a 2024 report of 125 children and 250 procedures described technical success in 99.2%.

How does each type of chemotherapy work?

Intra-arterial chemotherapy. The dose is small — typically 2.5–7.5 mg of melphalan per eye, adjusted for the child's age and the anatomy of the vessels — but it reaches the eye in high concentration. Treatment is usually given as a series of sessions a few weeks apart; the number depends on the response at each examination under anesthesia.

Intravitreal chemotherapy. Seeds floating in the vitreous gel have no blood supply of their own, so drugs carried in the blood reach them poorly. A tiny dose — for example 20–30 micrograms of melphalan or 20 micrograms of topotecan — is injected directly into the vitreous, usually every 7–10 days until the seeds regress. Injecting into an eye with retinoblastoma was long considered forbidden for fear of spreading tumor cells, until Munier and colleagues in Lausanne described a safety-enhanced technique in 2012: the injection is made through a tumor-free area, the eye pressure is lowered beforehand, and the entry site is frozen as the needle is withdrawn. With this approach, spread of tumor outside the eye has become exceedingly rare.

Intracameral chemotherapy. When seeds reach the fluid in the front chamber of the eye, melphalan can be injected into that space. Small case series from specialized centers report eyes saved in carefully selected cases; it remains an emerging technique.

Systemic chemotherapy (chemoreduction). Vincristine, etoposide and carboplatin through a vein — typically for up to 6 cycles, depending on the group — shrink tumors in both eyes at once. It is the usual choice for bilateral disease, very young babies, high-risk features in a removed eye (about 6 months of adjuvant chemotherapy lowers the risk of spread) and cancer outside the eye. It is prescribed and supervised by pediatric oncologists.

What happens during an intra-arterial chemotherapy session?

1. Assessment. An examination under anesthesia, retinal imaging and MRI confirm that the eye is suitable; blood tests are done beforehand.
2. Preparation. Your child fasts for some hours before the general anesthetic, as instructed by the anesthesia team. A parent can usually stay with the child until the anesthetic begins.
3. Access. With the child asleep, the interventional neuroradiologist places a thin tube in the femoral artery at the top of the leg.
4. Navigation. Under X-ray guidance, a microcatheter is guided to the opening of the ophthalmic artery — or, with the balloon technique, a small balloon is inflated just beyond it.
5. Infusion. The chemotherapy is infused slowly; if both eyes are treated, the second eye follows in the same session.
6. Recovery. The catheter is removed, pressure is applied to the groin, and the child is monitored while waking.
7. Response check. A few weeks later, an examination under anesthesia shows the response and whether another session, intravitreal injections or focal treatment are needed.

What results can families expect?

Results depend on the group, on whether IAC is the first treatment and on the presence of seeds:

Many eyes in the Tokyo series also received radiotherapy. Saving the eye did not come at the cost of survival: there were no metastases or deaths in the 341-eye series, and in Lausanne all children were alive without spread after a median of 22 months.

A Cochrane systematic review published in 2026, combining six studies, concluded that for advanced retinoblastoma in one eye, IAC probably roughly doubles the chance of keeping the eye without tumor progression at 2 years compared with intravenous chemotherapy (risk ratio 1.97), with similar overall survival and possibly fewer side effects in the rest of the body.

Seeds remain the main reason eyes are lost: without external radiotherapy, about 78% of eyes with localized seeds were saved at 5 years versus 49% with widespread seeds. Intravitreal chemotherapy now controls vitreous seeds in most eyes.

What are the risks and side effects?

Intra-arterial chemotherapy. Eyelid swelling or drooping and forehead redness on the treated side are common and temporary. More serious are effects on the blood vessels of the eye — blockage of the ophthalmic or retinal arteries, or thinning of the choroid — and bleeding into the vitreous, which can reduce vision. White blood cell counts can fall, severely (grade 3 or higher) after about 11–16% of treatments. Airway narrowing (bronchospasm) has been reported during about 8% of procedures in one analysis and 0.8% in the Japanese balloon series, and is managed by the anesthesia team. Catheterization succeeds in about 97–98.5% of attempts, no deaths or strokes have been reported in the major series, and the X-ray guidance gives the lens about 0.16 Gy per session.

Intravitreal chemotherapy. A small "salt-and-pepper" pigment change in the retina at the injection site is common (43% of eyes in the Lausanne series). Retinal toxicity depends on the dose; low eye pressure or shrinkage of the eye is rare.

Systemic chemotherapy. Low blood counts with a risk of infection, hearing loss (carboplatin), nerve damage (vincristine), kidney effects and a small risk of later leukemia (etoposide), monitored by pediatric oncologists.

Recovery, follow-up and travel

Each session involves a short recovery, but the course as a whole takes months. Examinations under anesthesia are repeated every few weeks to measure the response and add laser, cryotherapy or injections. Blood counts are checked between sessions, and a fever during this period needs prompt medical attention. After treatment, examinations continue about every 6–8 weeks until around age 3, with lifelong follow-up in the heritable form (see retinoblastoma genetics).

Plan trips around the treatment schedule. Whether and when a child can fly between sessions is decided by the treating team, based on recovery and blood counts. Keep a record of every session — date, drug, dose and response — for your doctors at home.

What are the alternatives?

Laser, thermotherapy or cryotherapy alone can treat very small tumors; plaque brachytherapy treats a single medium-sized tumor or a recurrence; removal of the eye is often the safest cure for very advanced eyes (see enucleation and the artificial eye); and external beam radiotherapy is reserved for resistant disease or spread outside the eye because it raises the risk of later cancers. See the treatment overview on our retinoblastoma page.

Chemotherapy for retinoblastoma in Antalya: how care is organized

Prof. Türkoğlu evaluates your child's case, explains the options and plans treatment with you; where a method needs specialized facilities, it is delivered together with the relevant specialist teams. Intra-arterial chemotherapy is performed by interventional neuroradiologists, with general anesthesia given by pediatric anesthesiologists; systemic chemotherapy is prescribed and supervised by pediatric oncologists; and the examinations under anesthesia, imaging and eye-directed treatment are planned and followed by the ocular oncologist.

Families living abroad can start with a remote second opinion by sending RetCam images, MRI files and records of previous chemotherapy — drug names, doses and the number of cycles or sessions. See also our pages for international patients and eye cancer treatment costs.