The Safety and Efficacy of Intravitreal Topotecan for the Treatment of Proliferative Vitreoretinopathy

Rhegmatogenous retinal detachment (RRD) is an acute, sight-threatening condition that occurs after separation of the neurosensory retina from the underlying retinal pigment epithelium (RPE) due to the presence of a retinal break. Proliferative vitreoretinopathy (PVR) represents growth of ectopic fibrocellular growth on the surface of, within and underneath the retina. PVR is hypothesized to occur secondary to the migration of RPE cells to the peri-retina, leading to a mesenchymal transition into contractile myofibroblasts. PVR affects 5-10% of RRDs and is the most common cause of surgical failure in RRD.

Given that PVR involves a pro-inflammatory and pro-fibrotic cellular response, adjuvants such as corticosteroids and antimetabolites such as 5-fluorouracil have been attempted in the treatment of this condition. Overall, the efficacy results of these treatments have been mixed, and no standard of care adjuvant therapy has emerged.

Topotecan is a chemotherapeutic agent that acts as a topoisomerase inhibitor. It is most commonly administered intravitreally for patients with refractory or recurrent vitreous seeds from retinoblastoma, and shows high efficacy in this setting. At the same time, intravitreal topotecan administered at doses of 5-30µg has been associated with no ocular or systemic complications or adverse electroretinogram changes. To the best of available knowledge, topotecan has not been administered for the treatment of proliferative vitreoretinopathy. Topotecan has anti-inflammatory, anti-proliferative and anti-fibrotic activity that is hypothesized to exhibit high efficacy for the treatment of PVR. In this study, the efficacy and safety of intravitreal topotecan for the treatment of PVR will be investigated.

Inclusion criteria

• Patients > 18 years old
• Patients presenting with retinal detachment due with PVR (grade C or higher) or retinal detachment associated with open globe trauma
• Patients undergoing vitrectomy or vitrectomy with scleral buckle as part of standard care.

Exclusion criteria

• Patient unable to give consent
• Patient unable to follow-up
• Females of childbearing age who are pregnant at the time of recruitment. A pregnancy test will be done to all women of ages 18-55 prior to surgery to ensure they are not pregnant at the time of recruitment.
• Patients with a history of tractional or exudative retinal detachment.
• Patients with other planned ocular surgery following PPV
• Active or chronic or recurrent uncontrolled ocular or systemic disease
• Active or history of chronic or recurrent inflammatory eye disease
• Diagnosis of severe nonproliferative or proliferative diabetic retinopathy or vasoproliferative disease in the operative eye
• Signs of ocular infection at presentation in either eye
• Known or suspected sensitivity or allergy to any of the medications used in the operation or postoperatively
• No Light Perception vision in the operative eye
• Failure to achieve intraoperative reattachment
• Patient with silicone oil instilled in the operative eye at time of presentation