PF-04523655 Dose Escalation Study, and Evaluation of PF-04523655 With/Without Ranibizumab in Diabetic Macular Edema (DME)

Patients will be enrolled concurrently according to one of two sets of criteria designated
as Stratum I and Stratum II.

1. Stratum I will enroll up to 24 subjects with low vision, inclusive of possible
intermediate doses, in up to 4 cohorts of 3-6 evaluable subjects.

2. Stratum II will enroll approximately 240 subjects with DME 1:1:1:1 in up to 4 cohorts
of 60 evaluable subjects.

Key Stratum I Inclusion Criteria:

1. Visual acuity in the study eye ≤ 20/200.

2. Low vision is the result of an irreversible condition affecting the posterior segment
of the study eye.

Key Stratum I Exclusion Criteria:

1. History of vitrectomy.

2. History of IVT injection in study eye within last 6 months.

3. History of vitreous hemorrhage, retinal detachment, or invasive trauma in study eye.

4. History of uveitis or endophthalmitis in either eye.

5. Any active inflammatory condition in study eye.

6. Received any drugs known to cause optic nerve or retinal toxicity within 14 days
prior to dosing.

7. Any medical condition, concomitant therapy or previous incisional or laser surgery
that, in the opinion of the Investigator, would preclude IVT injection in the study
eye.

8. Intraocular pressure in either eye ≥25 mmHg on maximal medication.

9. Cataract surgery and laser corneal surgery within 3 months prior to dosing in the
study eye and all other intraocular surgeries at any time.

10. Participation in a concurrent interventional study within 30 days prior to dosing.

Key Stratum II Inclusion Criteria:

1. History of diabetes mellitus (Type 1 or Type 2).

2. Retinal thickening secondary to the edema caused by diabetes mellitus.

3. Best corrected visual acuity (BCVA) of 20/40 or worse and up to 20/320 or better in
the study eye at Screening.

4. Standard of care treatment for DME can be withheld for at least 90 days after the
subject has enrolled in the study.

Key Stratum II Exclusion Criteria:

1. History of panretinal photocoagulation within 6 months or macular laser
photocoagulation within 3 months of prior to dosing in the study eye.

2. Any IVT injection therapy performed in the study eye within 3 months prior to dosing.

3. Iris neovascularization, vitreous hemorrhage, tractional retinal detachment,
vitreomacular traction, epiretinal membrane or preretinal fibrosis involving the
macula in the study eye.

4. History of IVT surgery in the study eye.

5. Prior intraocular surgery or corneal laser surgery, performed within 3 months prior
to dosing in the study eye.

6. Received any drugs known to cause optic nerve or retinal toxicity within 14 days
prior to dosing.

7. High risk proliferative diabetic retinopathy (PDR) in the study eye.

8. Current infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either
eye.

9. Monocular subjects.

10. History of idiopathic or autoimmune uveitis in either eye.

11. Aphakia or absence of the posterior capsule in the study eye.

12. Structural damage to the center of the macula in the study eye likely to preclude
improvement in visual acuity following the resolution of macular edema.

13. Uncontrolled glaucoma in either eye.

14. Spherical equivalent of the refractive error in the study eye of more than -8
diopters myopia.

15. Chronic use of systemic steroids.