Combination therapy

1. A compound of formula (III):

wherein:

R 1 and R 2 are, independently, hydrogen or C 1 -C 4 alkyl, or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a ring of 3, 4, 5, 6, 7, or 8 member atoms;

A is —CH 2 CH(R 10 )—;

R 10 is aryl substituted with —CH 2 —OC(O)—NH—R b , wherein R b is phenyl, 2-chlorophenyl, 4-chlorophenyl, 4-methoxyphenyl, or C 1-4 alkyl; and

X 1 and X 2 are, independently, hydrogen, hydroxy, halogen, alkyl, amino, nitro, cyano, carbonyl, carbonylamino, alkoxy, aryloxy, sulfonyl, sulfonamido, thioalkyl, or carboxyl;

or the

is (rac)-2-(dimethylamino)-N-(1-hydroxyisoquinolin-6-yl)-2-(thiophen-3-yl)acetamide⊕, (R)-2-(dimethylamino)-N-(1-hydroxyisoquinolin-6-yl)-2-(thiophen-3-yl)acetamide⊕, or (S)-2-(dimethylamino)-N-(1-hydroxyisoquinolin-6-yl)-2-(thiophen-3-yl)acetamide⊕;

PG⊖ is a deprotonated free acid of a prostaglandin or a prostaglandin analog; and

wherein the prostaglandin or a prostaglandin analog is a compound of formula (IV):

or an optical isomer, diastereomer, or enantiomer thereof, wherein:

the dashed lines independently indicate the presence or absence of a bond;

A and B are, independently, —(CR a R b ) n —, wherein each R a and R b is, independently, hydrogen or C 1 -C 6 alkyl, and n is 0, 1, 2, 3, or 4;

R 1 is —C(O)O⊖;

R 2 is hydrogen or C 1 -C 6 alkyl;

R 3 , R 4 and R 5 are, independently, hydrogen or an alcohol protecting group;

Y is a bond, —O—, —S—, —S(O)—, —SO 2 —, —C(R g ) 2 —, —CR h ═CR i —, —NR j —, or —C═C—;

Z is hydrogen, cycloalkyl, heterocyclyl, aryl or heteroaryl;

R g , R h and R i are, independently, hydrogen, C 1 -C 6 alkyl, alkoxy or hydroxy; and

R j is hydrogen or C 1 -C 6 alkyl.

2. The compound of claim 1 , wherein X 1 is hydrogen and X 2 is hydrogen.

3. The compound of claim 1 , wherein the PG⊖ is a deprotonated free acid of latanoprost, bimatoprost, travoprost, tafluprost, AR-102, cloprostenol, 13,14-dihydrocloprostenol, latanoprostene bunod, unoprostone, PGE 1 , PGF 1α , PGF 2α , PGF 3α , or fluprostenol.

4. The compound of claim 1 , wherein for

R 1 and R 2 are, independently, hydrogen or C 1 -C 4 alkyl, or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form a ring of 3, 4, 5, 6, 7 or 8 member atoms;

A is —CH 2 CH(R 10 )—;

R 10 is aryl substituted with —CH 2 —OC(O)—NH—R b , wherein R b is phenyl, 2-chlorophenyl, 4-chlorophenyl, 4-methoxyphenyl, or C 1-4 alkyl; and

X 1 and X 2 are, independently, hydrogen, hydroxy, halogen, alkyl, amino, nitro, cyano, carbonyl, carbonylamino, alkoxy, aryloxy, sulfonyl, sulfonamido, thioalkyl, or carboxyl.

5. The compound of claim 1 , wherein R 10 is or phenyl substituted with —CH 2 —OC(O)—NH—R b , wherein R b is phenyl, 2-chlorophenyl, 4-chlorophenyl, 4-methoxyphenyl, or C 1-4 alkyl.

6. The compound of claim 1 , wherein the PG⊖ is

7. The compound of claim 1 , wherein the

is (rac)-2-(dimethylamino)-N-(1-hydroxyisoquinolin-6-yl)-2-(thiophen-3-yl)acetamide⊕, (R)-2-(dimethylamino)-N-(1-hydroxyisoquinolin-6-yl)-2-(thiophen-3-yl)acetamide⊕, or (S)-2-(dimethylamino)-N-(1-hydroxyisoquinolin-6-yl)-2-(thiophen-3-yl)acetamide⊕.

8. A composition, comprising the compound of claim 1 and at least one component selected from a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar, a sugar alcohol, or a surfactant.

9. A composition, comprising the compound of claim 2 and at least one component selected from a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar, a sugar alcohol, or a surfactant.

10. A composition, comprising the compound of claim 3 and at least one component selected from a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar, a sugar alcohol, or a surfactant.

11. A composition, comprising the compound of claim 4 and at least one component selected from a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar, a sugar alcohol, or a surfactant.

12. A composition, comprising the compound of claim 5 and at least one component selected from a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar, a sugar alcohol, or a surfactant.

13. A composition, comprising the compound of claim 6 and at least one component selected from a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar, a sugar alcohol, or a surfactant.

14. A composition, comprising the compound of claim 7 and at least one component selected from a buffer, a chelating agent, a tonicity agent, a preservative, a viscosity enhancer, a sugar, a sugar alcohol, or a surfactant.

15. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 1 .

16. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 2 .

17. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 3 .

18. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 4 .

19. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 5 .

20. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 6 .

21. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 7 .

22. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the composition of claim 8 .

23. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the composition of claim 9 .

24. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the composition of claim 10 .

25. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the composition of claim 11 .

26. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the composition of claim 12 .

27. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the composition of claim 13 .

28. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the composition of claim 14 .