Methods and compositions for daily ophthalmic administration of phentolamine to improve visual performance
The invention provides methods, compositions, and kits containing phentolamine for improving visual performance. In particular, the invention provides improvement in visual performance, such as improvement in visual acuity, by daily ophthalmic administration of a phentolamine solution to an eye of a patient at or near the bedtime of the patient for an extended duration while minimizing the occurrence of adverse side effects, such as eye redness during the patient's waking hours.
1. A method of improving visual performance in a patient while minimizing eye redness during the patient's waking hours, comprising administering to an eye of a patient once per day within 1 hour of the patient's bedtime for at least five consecutive days a daily dosage of phentolamine or a pharmaceutically acceptable salt thereof sufficient to provide improved visual performance for at least twenty hours, wherein the patient experiences an increase in eye redness of no more than two grades measured using the CCLRU Redness Grading Scale during the patient's waking hours compared to the patient's level of eye redness without receiving said dosage; wherein the daily dosage is an ophthalmic solution comprising water, a polyol, and phentolamine or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the improvement in visual performance is improved contrast sensitivity.
3. A method of reducing pupil diameter in a patient while minimizing eye redness during the patient's waking hours, comprising administering to an eye of a patient once per day at or near the bedtime of the patient for at least five consecutive days a daily dosage of phentolamine or a pharmaceutically acceptable salt thereof sufficient to reduce pupil diameter for at least twenty hours, wherein the patient experiences an increase in eye redness of no more than two grades measured using the CCLRU Redness Grading Scale during the patient's waking hours compared to the patient's level of eye redness without receiving said dosage; wherein the daily dosage is an ophthalmic solution comprising water, a polyol, and phentolamine or a pharmaceutically acceptable salt thereof.
4. The method of claim 3 , wherein the reduction in pupil diameter under mesopic conditions is at least 5% compared to the pupil diameter of the patient under the same mesopic conditions but not having received said dosage.
5. The method of claim 3 , wherein the reduction in pupil diameter under mesopic conditions is at least 10% compared to the pupil diameter of the patient under the same mesopic conditions but not having received said dosage.
6. The method of claim 3 , wherein the patient experiences a reduction in pupil diameter of at least 0.5 mm when measured under mesopic conditions relative to the diameter of the patient's pupil under the same mesopic conditions but not having received said dosage.
7. A method of reducing an aberrant focus of scattered light rays in a patient's eye while minimizing eye redness during the patient's waking hours, comprising administering to an eye of a patient once per day at or near the bedtime of the patient for at least five consecutive days a daily dosage of phentolamine or a pharmaceutically acceptable salt thereof sufficient to reduce aberrant focus of scattered light rays in a patient's eye for at least twenty hours, wherein the patient experiences an increase in eye redness of no more than two grades measured using the CCLRU Redness Grading Scale during the patient's waking hours compared to the patient's level of eye redness without receiving said dosage; wherein the daily dosage is an ophthalmic solution comprising water, a polyol, and phentolamine or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 , wherein the method results in an improvement in visual acuity characterized by at least a one-line improvement in the patient's vision measured using a Snellen chart.
9. The method of claim 2 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 2% (w/v) of phentolamine mesylate;
(b) about 1% (w/v) to about 6% (w/v) of at least one polyol compound selected from the group consisting of is mannitol, glycerol, and propylene glycol;
(c) about 1 mM to about 6 mM of an alkali metal acetate; and
(d) water;
wherein the solution has a pH in the range of 4.5 to 5.5 and does not contain a chelating agent.
10. The method of claim 2 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 2% (w/v) of phentolamine mesylate;
(b) about 3% (w/v) to about 5% (w/v) of mannitol;
(c) about 2 mM to about 4 mM of sodium acetate; and
(d) water;
wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain a chelating agent.
11. The method of claim 2 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 1% (w/v) of phentolamine mesylate;
(b) about 4% mannitol;
(c) about 3 mM sodium acetate; and
(d) water;
wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain a chelating agent.
12. The method of claim 3 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 2% (w/v) of phentolamine mesylate;
(b) about 1% (w/v) to about 6% (w/v) of at least one polyol compound selected from the group consisting of is mannitol, glycerol, and propylene glycol;
(c) about 1 mM to about 6 mM of an alkali metal acetate; and
(d) water;
wherein the solution has a pH in the range of 4.5 to 5.5 and does not contain a chelating agent.
13. The method of claim 3 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 2% (w/v) of phentolamine mesylate;
(b) about 3% (w/v) to about 5% (w/v) of mannitol;
(c) about 2 mM to about 4 mM of sodium acetate; and
(d) water;
wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain a chelating agent.
14. The method of claim 3 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 1% (w/v) of phentolamine mesylate;
(b) about 4% mannitol;
(c) about 3 mM sodium acetate; and
(d) water;
wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain a chelating agent.
15. The method of claim 4 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 1% (w/v) of phentolamine mesylate;
(b) about 4% mannitol;
(c) about 3 mM sodium acetate; and
(d) water;
wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain a chelating agent.
16. The method of claim 3 , wherein the daily dosage is administered within 1 hour of the patient's bedtime.
17. The method of claim 12 , wherein the daily dosage is administered within 1 hour of the patient's bedtime.
18. The method of claim 14 , wherein the daily dosage is administered within 1 hour of the patient's bedtime.
19. The method of claim 15 , wherein the daily dosage is administered within 1 hour of the patient's bedtime.
20. The method of claim 7 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 2% (w/v) of phentolamine mesylate;
(b) about 1% (w/v) to about 6% (w/v) of at least one polyol compound selected from the group consisting of is mannitol, glycerol, and propylene glycol;
(c) about 1 mM to about 6 mM of an alkali metal acetate; and
(d) water;
wherein the solution has a pH in the range of 4.5 to 5.5 and does not contain a chelating agent.
21. The method of claim 7 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 2% (w/v) of phentolamine mesylate;
(b) about 3% (w/v) to about 5% (w/v) of mannitol;
(c) about 2 mM to about 4 mM of sodium acetate; and
(d) water;
wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain a chelating agent.
22. The method of claim 7 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 1% (w/v) of phentolamine mesylate;
(b) about 4% mannitol;
(c) about 3 mM sodium acetate; and
(d) water;
wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain a chelating agent.
23. The method of claim 8 , wherein the daily dosage is an aqueous ophthalmic solution free of a chelating agent, comprising:
(a) about 0.5% (w/v) to about 1% (w/v) of phentolamine mesylate;
(b) about 4% mannitol;
(c) about 3 mM sodium acetate; and
(d) water;
wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain a chelating agent.
24. The method of claim 7 , wherein the daily dosage is administered within 1 hour of the patient's bedtime.
25. The method of claim 20 , wherein the daily dosage is administered within 1 hour of the patient's bedtime.
26. The method of claim 23 , wherein the daily dosage is administered within 1 hour of the patient's bedtime.