Pro-permeability and Pro-fibrosis Factors in the Aqueous of Patients With Retinal Diseases

Study Overview
=================
Brief Summary
-----------------
This study will examine potential factors in the aqueous humor that may contribute to the development or progression of macular edema or fibrosis (due to any underlying disease) in patients suffering from these conditions.

Detailed Description
-----------------
The primary purpose of this study is to determine the correlation of pro-permeability and pro-fibrosis factor levels and downstream receptor/signaling molecule activation with disease activity in patients with macular edema or fibrosis secondary to any underlying disease. 120 patients will be enrolled from both the clinic and OR, with the latter patients undergoing surgery for proliferative diabetic retinopathy, rhegmatogenous retinal detachment with Proliferative vitreoretinopathy (PVR), rhegmatogenous retinal detachment without PVR, macular pucker, or macular hole. Clinic patients must be receiving an intraocular injection of a steroid as part of standard of care for macular edema or progressive fibrosis. Surgical patients will receive an anterior chamber (AC) tap at the beginning of surgery, while clinic patients will receive an AC tap prior to the intraocular injection of steroid with a second AC tap at a follow-up visit 6 +/- 2 weeks after the first injection. The aqueous sample will then be analyzed by measuring the levels of various pro-permeability and pro-fibrosis factors and/or their downstream receptor/signaling molecule activation. We will also determine the correlation between reductions in foveal thickness or improvements in visual acuity with changes in the aqueous levels of pro-permeability and pro-fibrosis factors from baseline to week 6 in the clinic group.

Official Title
-----------------
Pro-permeability and Pro-fibrosis Factors in the Aqueous of Patients With Retinal Diseases

Conditions
-----------------
Macular Edema, Fibrosis of the Retina

Intervention / Treatment
-----------------
* Drug: Ozurdex
* Procedure: Surgery
* Procedure: Anterior Chamber (AC) Tap


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent and authorization of use and disclosure of protected health information Age >= 18 years Undergoing surgery as part of standard care for one of the following conditions: (1) Proliferative Diabetic Retinopathy (PDR), (2) rhegmatogenous retinal detachment with PVR, (3) rhegmatogenous retinal detachment without PVR, (4) macular pucker, (5) macular hole OR receiving as part of standard care, an intraocular injection of a steroid for macular edema or progressive fibrosis. Exclusion Criteria: Previous use of an anti-Vascular Endothelial Growth Factor (VEGF) drug within 1 month of study entry Any condition that the investigator believes would pose a significant hazard to the subject if standard study procedures were conducted. Inability to comply with study or follow up procedures Patients with active or suspected ocular or periocular infection, including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases. Pregnant patients.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Clinic Patients<br>Patients from the clinic will be considered for enrollment if they are receiving an intraocular injection of a steroid as part of standard care for macular edema or progressive fibrosis. Clinic patients who are receiving an intraocular injection of steroid (Ozurdex) as part of standard care who agree to participate will have an anterior chamber (AC) tap just prior to the intraocular injection of steroid and a second AC tap at a follow up visit 6 ± 2 weeks after the steroid injection. | Drug: Ozurdex<br>* Patients from the clinic will be considered for enrollment if they are receiving an intraocular injection of a steroid as part of standard care for macular edema or progressive fibrosis. Clinic patients who are receiving an intraocular injection of steroid (Ozurdex) as part of standard care who agree to participate will have an AC tap just prior to the intraocular injection of steroid and a second AC tap at a follow up visit 6 ± 2 weeks after the steroid injection.<br>* Other names: Dexamethasone intravitreal implant 0.7 mg;Procedure: Anterior Chamber (AC) Tap<br>* A paracentesis removing about 0.1 ml of fluid from the front part of the eye (the aqueous chamber) will be performed in the operating room just prior to surgery or in the clinic. In the operating room, the AC tap is done after the eye is anesthetized and cleaned with 5% povidone iodine for the surgery. A 30-gauge needle attached to a tuberculin syringe is inserted into the AC and 0.1 ml of aqueous is removed. The wound is self-sealing and has no effect on the surgery. In the clinic, the AC tap is done after drops of proparacaine and 5% povidone iodine is placed in the eye and a lid speculum is inserted. The patient is seated at a slit lamp and a 30-gauge needle attached to a tuberculin syringe is inserted into the AC and 0.1 ml of aqueous is aspirated and then the needle is removed.<br>|
| OR Patients<br>Patients undergoing surgery for one of the following conditions: (1) Proliferative Diabetic Retinopathy, (2) rhegmatogenous retinal detachment with PVR, (3) rhegmatogenous retinal detachment without PVR, (4) macular pucker, (5) macular hole. Surgical patients who agree to participate will have an anterior chamber (AC) tap at the beginning of surgery. | Procedure: Surgery<br>* The 60 patients from the operating room will be patients undergoing surgery for one of the following conditions: (1) Proliferative Diabetic Retinopathy, (2) rhegmatogenous retinal detachment with PVR, (3) rhegmatogenous retinal detachment without PVR, (4) macular pucker, (5) macula hole. All patients will be administered an AC (Anterior Chamber) tap just prior to the surgical procedure while in the OR.<br>Procedure: Anterior Chamber (AC) Tap<br>* A paracentesis removing about 0.1 ml of fluid from the front part of the eye (the aqueous chamber) will be performed in the operating room just prior to surgery or in the clinic. In the operating room, the AC tap is done after the eye is anesthetized and cleaned with 5% povidone iodine for the surgery. A 30-gauge needle attached to a tuberculin syringe is inserted into the AC and 0.1 ml of aqueous is removed. The wound is self-sealing and has no effect on the surgery. In the clinic, the AC tap is done after drops of proparacaine and 5% povidone iodine is placed in the eye and a lid speculum is inserted. The patient is seated at a slit lamp and a 30-gauge needle attached to a tuberculin syringe is inserted into the AC and 0.1 ml of aqueous is aspirated and then the needle is removed.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of pro-permeability and pro-fibrosis factor levels and receptor/signaling molecule activation with disease activity. |  | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between reduction in foveal thickness and changes in aqueous levels of pro-permeability and pro-fibrosis factors from baseline to week 6 in the clinic cohort. |  | Baseline, week 6. | 
| Correlation between changes in visual acuity and changes in the aqueous levels of pro-permeability and pro-fibrosis factors from baseline to week 6 in the clinic cohort. |  | Baseline, week 6. |