麻豆传媒

CHICAGO -- Intravitreal chemotherapy injections for the treatment of retinoblastoma are highly effective on the endpoints of ocular survival and disease-free survival (DFS).

A greater number of intravitreal injections, however, significantly increases retinal toxicity. Additionally, altering the injection site results in more degradation in retinal function than maintaining the same injection site.

These were the insights obtained from a retrospective review of 560 intravitreal chemotherapy injections given at Memorial Sloan-Kettering Cancer Center (MSKCC)/Icahn School of Medicine at Mount Sinai, New York City, reported by at the 2016 meeting here.

The treatment of retinoblastoma with vitreous seeds has evolved from enucleation to intra-arterial chemotherapy to most recently intravitreal chemotherapy (most commonly intravitreal melphalan).

The ocular survival, DFS, and toxicity of intravitreal chemotherapy injections with or without periocular chemotherapy given at MSKCC/Mount Sinai for the treatment of retinoblastoma were examined. In the study, 104 eyes (97 patients) receiving a total of 560 injections of melphalan or topotecan were followed for a median of 15.8 months.

Clinical evaluation included fundus photography, indirect ophthalmoscopy, ultrasonography and ultrasonic biomicroscopy. Electroretinograms were obtained during scheduled examinations, and responses to 30-Hz photopic flicker stimulation were recorded. Also, the cumulative change in ERG recording pre-injection to post-injection was assessed.

"It's clear that intravitreal injections are efficacious, and they're saving eyes that once would have been enucleated because prior treatments just didn't control the tumor, whereas these injections do control tumor," Francis said in an interview with 麻豆传媒.

The 2-year estimate of ocular survival was 98.8%, and the 2-year DFS (no recurrence of intraocular tumors) was 87.3%.

By individual injection, regression analysis revealed that the number of injections was the only influence on retinal toxicity (P=0.03). Each intravitreal chemotherapy injection results, on average, in a decrease of about 5 mV in the ERG amplitude, corresponding to about a 4% loss of retinal function, said co-investigator from Mount Sinai. "Obviously, the fewer injections you do, the better chance you have of preserving vision," he told 麻豆传媒. "Of course, the first priority is curing the cancer but within that, the goal is to minimize the number of injections."

Eyes that receive injections develop a salt and pepper retinopathy, and the amount of salt and pepper retinopathy seen in the fundus corresponds with the degradation in the ERG response, said Francis, "which means that you can predict what your electroretinogram degradation would be based on how much of the salt and pepper retinopathy seen. Having said that, there were some eyes that did not have any salt and pepper retinopathy that still had a decrease in their ERG response. So salt and pepper retinopathy doesn't tell you everything."

Increasing the interval between injections may permit fewer injections while preserving effectiveness. "Overall, we think that we were probably overtreating initially, and we think we're getting the same results with fewer injections," Brodie said. "We're getting better at recognizing the appearance in the eye of nonviable residual tissue or debris that does not represent persistence of viable tumor. These days, I think we are typically doing it once a month."

The authors also found that most of the toxicity with intravitreal chemotherapy is local, as most of the retinal damage is in the vicinity of the injection. Injecting the eye repeatedly at the same site exposes the already damaged retinal tissue to additional drug with little further damage, explained Brodie, "whereas if you space them out all over the eye, you continue to damage the retina more with each injection." Each additional injection site results in an average ERG decrement of 12.5 mV, "or roughly twice as large an ERG decrease as would an additional injection at an injection site which had already been used at least once," he said.

Factors not related to intravitreal chemotherapy toxicity were patient age, weight, and color of the iris "so we feel comfortable giving the same dose of drug no matter the age of the patient at this point, based on what we know," Francis said.