Methotrexate for proliferative vitreoretinopathy

Abstract

The use of methotrexate, e.g., repeated dosing or sustained-release formulations of methotrexate, for treating or reducing risk of proliferative vitreoretinopathy (PVR) or epiretinal membranes (ERM), e.g., after surgical vitrectomy to treat retinal detachment.

1 - 20 . (canceled) 
     
     
         21 . A method of treating or reducing the risk of proliferative vitreoretinopathy (PVR) or epiretinal membranes (ERM) in a subject, the method comprising administering a plurality of intravitreal injections of methotrexate over a period of at least one, two, three, or more months, given no more frequently than weekly. 
     
     
         22 . The method of  claim 21 , comprising administering ten or more intravitreal injections of methotrexate. 
     
     
         23 . The method of  claim 21 , wherein each injection provides a dose of 400 mcg in 0.1 ml methotrexate. 
     
     
         24 . The method of  claim 21 , wherein the methotrexate is administered posterior to the limbus. 
     
     
         25 . The method of  claim 21 , wherein the subject is undergoing an ocular surgical procedure that increases the subject's risk of developing ERM or PVR. 
     
     
         26 . The method of  claim 25 , 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. 
     
     
         27 . The method of  claim 26 , wherein the subject requires a PPV to treat a rhegmatagenous retinal detachment secondary to trauma; preexisting proliferative vitreoretinopathy; or for other indications associated with high risk condition for PVR development. 
     
     
         28 . The method of  claim 27 , 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. 
     
     
         29 . The method of  claim 25 , wherein:
 a first injection is given at conclusion of the surgical procedure;   eight weekly injections are given until postoperative month two; and   a final tenth injection is given at postoperative month three.   
     
     
         30 . The method of  claim 21 , comprising administering nine consecutive weekly injections, and a tenth injection three months after the first injection. 
     
     
         31 . The method of  claim 21 , comprising administering additional injections monthly after the tenth injection. 
     
     
         32 . The method of  claim 21 , comprising administering one, two, three, four, five, six, seven, eight, or nine additional injections after the tenth injection. 
     
     
         33 . The method of  claim 22 , wherein the additional injections are administered monthly. 
     
     
         34 . A method of treating or reducing the risk of PVR or ERM in a subject, the method comprising intravitreally administering a sustained release formulation of methotrexate or implanting into the eye of the subject a device that provides sustained release of methotrexate over at least a three-month period. 
     
     
         35 . The method of  claim 34 , wherein the sustained release formulation is or comprises a lipid-encapsulated formulation; multivesicular liposome (MVL) formulations of methotrexate (MTX); nano- or microparticles; polyion complex (PIC) micelles; or bioadhesive polymers. 
     
     
         36 . The method of  claim 34 , wherein the bioadhesive polymers comprise one or more of hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose (CMC), polyacrylic acid (PAA), or hyaluronic acid (HA). 
     
     
         37 . The method of  claim 34 , wherein the device is non-biodegradable. 
     
     
         38 . An implanted ocular device for sustained release of methotrexate for treating or reducing the risk of PVR or ERM in a subject, wherein the device releases methotrexate over at least a three-month period into the eye of the subject. 
     
     
         39 . The device of  claim 39 , wherein the device is non-biodegradable.