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

Macular Edema Clinical Trial

— P3F2  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02688309
• Other study ID #: IRB00045274
• Status: Terminated
• Start date: January 13, 2015
• Est. completion date: October 28, 2021

Study information

• Verified date: July 2022
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: October 28, 2021
• Est. primary completion date: October 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Fibrosis of the Retina
• Macular Edema
• Retinal Diseases

Intervention

Drug:
• Ozurdex
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.

Procedure:
• Surgery
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.
• Anterior Chamber (AC) Tap
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.

Locations

Country	Name	City	State
United States	Wilmer Eye Institute	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (8)

Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7. — View Citation

Campochiaro PA, Hafiz G, Channa R, Shah SM, Nguyen QD, Ying H, Do DV, Zimmer-Galler I, Solomon SD, Sung JU, Syed B. Antagonism of vascular endothelial growth factor for macular edema caused by retinal vein occlusions: two-year outcomes. Ophthalmology. 2010 Dec;117(12):2387-2394.e1-5. doi: 10.1016/j.ophtha.2010.03.060. Epub 2010 Jul 13. — View Citation

Lima e Silva R, Shen J, Hackett SF, Kachi S, Akiyama H, Kiuchi K, Yokoi K, Hatara MC, Lauer T, Aslam S, Gong YY, Xiao WH, Khu NH, Thut C, Campochiaro PA. The SDF-1/CXCR4 ligand/receptor pair is an important contributor to several types of ocular neovascularization. FASEB J. 2007 Oct;21(12):3219-30. Epub 2007 May 23. — View Citation

Marmor MF. Mechanisms of fluid accumulation in retinal edema. Doc Ophthalmol. 1999;97(3-4):239-49. Review. — View Citation

Oshima Y, Deering T, Oshima S, Nambu H, Reddy PS, Kaleko M, Connelly S, Hackett SF, Campochiaro PA. Angiopoietin-2 enhances retinal vessel sensitivity to vascular endothelial growth factor. J Cell Physiol. 2004 Jun;199(3):412-7. — View Citation

Scholl S, Kirchhof J, Augustin AJ. Pathophysiology of macular edema. Ophthalmologica. 2010;224 Suppl 1:8-15. doi: 10.1159/000315155. Epub 2010 Aug 18. Review. — View Citation

Tranos PG, Wickremasinghe SS, Stangos NT, Topouzis F, Tsinopoulos I, Pavesio CE. Macular edema. Surv Ophthalmol. 2004 Sep-Oct;49(5):470-90. Review. — View Citation

Vinores SA, Youssri AI, Luna JD, Chen YS, Bhargave S, Vinores MA, Schoenfeld CL, Peng B, Chan CC, LaRochelle W, Green WR, Campochiaro PA. Upregulation of vascular endothelial growth factor in ischemic and non-ischemic human and experimental retinal disease. Histol Histopathol. 1997 Jan;12(1):99-109. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of pro-permeability and pro-fibrosis factor levels and receptor/signaling molecule activation with disease activity.		Baseline
Secondary	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.
Secondary	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.