Targeting refractory vitreous seeds in retinoblastoma

Reviewed by Raksha Rao, MD

Hyderabad, India-Tri-weekly injection of topotecan is safe and effective as monotherapy for management of refractory vitreous seeds in retinoblastoma. Such findings are according to a retrospective study conducted by ocular oncologists at the National Retinoblastoma Foundation, Centre for Sight Superspecialty Eye Hospital, Hyderabad, India.

The review included 17 eyes, all International Classification for Intraocular Retinoblastoma Group C or D, with persistent or recurrent vitreous seeds after standard intravenous chemotherapy ± local therapy. Tri-weekly topotecan 30 mcg/0.15 mL was administered until there was complete regression of the seeds and was followed by an additional injection for consolidation of probable microscopic residual seeds.

Complete regression of vitreous seeds was achieved in all eyes after a mean of three injections, and 7 eyes (41%) required just two injections. No ocular or systemic complications were noted during a mean follow-up of 12 months.

“To our knowledge, we are reporting the first case series of intravitreal topotecan as monotherapy in the management of refractory vitreous seeds in retinoblastoma, and our results indicate topotecan is a potent agent providing impressive control of refractory vitreous seeds,” said Raksha Rao, MD.

“Our results with regard to vitreous seed regression and eye salvage are comparable to those previously reported for intravitreal melphalan,” Dr. Rao said. “However, the mean number of injections required was lower using topotecan than with melphalan, and according to previous reports and our own experience, intravitreal melphalan also causes few ocular side effects, whereas topotecan does not.”

Treatment protocol

Treatment protocol

The treatment protocol for retinoblastoma at the center where the study took place, begins with triple drug intravenous chemotherapy or superselective intraarterial chemotherapy. Periocular carboplatin or topotecan are administered if viable diffuse vitreous seeds are present after three cycles. Intravitreal chemotherapy is administered in those eyes that have persistent or recurrent vitreous seeds after the completion of intravenous or intraarterial chemotherapy.

“Initially, we were using melphalan for intravitreal therapy, but we switched to topotecan because of the need for multiple injections with melphalan and the development of complications including iritis, posterior synechiae, and retinal pigment epithelial mottling,” Dr. Rao said.

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“Topotecan has known activity as a treatment for retinoblastoma when given by intra-arterial injection, periocular injection, or with melphalan in an intravitreal injection,” she said. “The latter combined treatment was also found to be associated with minimal ocular or systemic side effects.”

The patients in the series were predominantly female (76.5%) and had a mean age of 35 months. All patients had received at least 6 cycles of intravenous chemotherapy with a mean of 10 cycles.

Three eyes had persistent vitreous seeds and 14 had recurrent vitreous seeds. The vitreous seeds were diffuse in 13 eyes and focal in 4 eyes. The intravitreal topotecan was given through a tranconjunctival pars plana route using a 30-gauge needle at a site that was based on patient age.

A safety-enhanced technique was used wherein the needle was withdrawn through the first ice ball formation of cryotherapy, followed by two more cycles of freeze and thaw. Then, forceps assisted jiggling of the eye was done to disperse the drug evenly in the vitreous cavity.

One eye with a recurrent retinal tumor was enucleated at 5 months’ follow-up, and histopathology showed no tumor cells in the needle track. 

Extending its use

“We have extended the use of intravitreal topotecan to Group E eyes for refractory vitreous seeds following intravenous and intra-arterial chemotherapy,” said Santosh G. Honavar, MD, director, Ophthalmic and Facial Plastic Surgery and Ocular Oncology, Centre for Sight Superspeciality Eye Hospital.

“To date, 36 eyes have received intravitreal topotecan monotherapy at our center, and we have achieved 100% success in vitreous seed control, and 98% eye salvage in these advanced tumors,” Dr. Honavar said. “Intravitreal topotecan is a promising treatment, and ensures higher globe salvage rates.”

Raksha Rao, MD

E: raoraksha@gmail.com

This article was adapted from Dr. Rao’s presentation at the 2015 meeting of the American Academy of Ophthalmology. She and her co-investigators have no relevant financial interests to disclose.