Topotecan for proliferative vitreoretinopathy
The use of topotecan, e.g., repeated dosing or sustained-release formulations of topotecan, for treating or reducing risk of proliferative vitreoretinopathy (PVR) or epiretinal membranes (ERM), e.g., after surgical vitrectomy to treat retinal detachment, is described herein.
1 . A method of treating proliferative vitreoretinopathy (PVR) in a subject, the method comprising administering to the subject multiple intravitreal injections of topotecan over a period of at least one, two, three, four, or more months, given no more frequently than weekly.
2 . The method of claim 1 , comprising administering five or more intravitreal injections of topotecan.
3 . The method of claim 2 , comprising administering seven intravitreal injections of topotecan.
4 . The method of claim 1 , wherein each injection provides a dose of about 5 mcg, about 6 mcg, about 7 mcg, about 8 mcg, about 9 mcg, or about 10 mcg topotecan, preferably administered in a volume of 0.1 ml.
5 . The method of claim 4 , wherein each injection provides a dose of about 8 mcg topotecan, preferably administered in a volume of 0.1 ml.
6 . The method of claim 1 , wherein the subject is undergoing an ocular surgical procedure that increases the subject's risk of developing PVR.
7 . The method of claim 6 , wherein the ocular surgical procedure is a pars plana vitrectomy (PPV), Retinal Detachment (RD) surgery; ERM surgery; scleral buckle surgery; or a procedure in the other eye.
8 . The method of claim 6 , wherein the subject requires a PPV to treat a rhegmatagenous retinal detachment (RRD) secondary to trauma; preexisting proliferative vitreoretinopathy; or for other indications associated with high risk condition for PVR development.
9 . The method of claim 8 , wherein the indication associated with high risk condition for PVR development is a giant retinal tear, a retinal break larger than 3 disc areas, a long-standing retinal detachment, or a detachment associated with hemorrhage.
10 . The method of claim 6 , wherein the topotecan is administered preoperatively, intraoperatively during surgery, and/or postoperatively.
11 . The method of claim 10 , wherein:
a first injection is given preoperatively within one week from surgery;
a second injection is given intraoperatively during surgery; and
five or more injections are given postoperatively, preferably at 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks postoperatively.
12 . The method of claim 11 , comprising administering additional injections after the seventh injection.
13 . The method of claim 1 , wherein the topotecan is administered in combination with one or more additional therapeutic agents.
14 . The method of claim 13 , wherein the one or more additional therapeutic agents is selected from the group consisting of melphalan, daunorubicin, lenalidomide, daclatsvir, stavudine, resveratrol, marbofloxacin, bendamustine HCl, semagacestat, methotrexate, and a Runx1 inhibitor, or an analogue thereof.
15 . The method of claim 14 , wherein the one or more additional therapeutic agents is administered simultaneously with the topotecan.
16 . The method of claim 1 , wherein the topotecan is administered posterior to the limbus.
17 . A method of treating proliferative vitreoretinopathy (PVR) in a subject, the method comprising intravitreally administering to the subject a sustained release formulation of topotecan over at least a four-month period.
18 . The method of claim 17 , wherein the sustained release formulation is or comprises a lipid-encapsulated formulation; multivesicular liposome (MVL) formulations of topotecan; nano- or microparticles; polyion complex (PIC) micelles; or bioadhesive polymers.
19 . The method of claim 18 , wherein the bioadhesive polymers comprise one or more of hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose (CMC), polyacrylic acid (PAA), or hyaluronic acid (HA).
20 . A method of treating proliferative vitreoretinopathy (PVR) in a subject, the method comprising implanting into the eye of the subject a device that provides sustained release of topotecan, and optionally one or more additional therapeutic agents, over at least a four-month period, preferably wherein the device is implanted within a week before the subject undergoes an ocular surgical procedure that increases the subject's risk of developing PVR.