Treatment of Macular Edema After Cataract Surgery With Subconjunctival Aflibercept

Irvine-Gass Syndrome Clinical Trial

— ACME  

Official title:

Subconjunctival Aflibercept Injection for Pseudophakic Cystoid Macular Edema

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03396861
• Other study ID #: 12338
• Status: Terminated
• Phase: Phase 1
• Start date: February 22, 2019
• Est. completion date: January 2, 2020

Study information

• Verified date: August 2020
• Source: Tufts Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study is being conducted to determine the safety and tolerability of subconjunctival injections of aflibercept in the treatment of pseudophakic cystoid macular edema that has not responded well to first-line standard of care treatment (eye drops).

Pseudophakic cystoid macular edema (CME) is swelling of the retina that can occur weeks or years after cataract surgery and typically results in decreased vision. Subconjunctival injections are injections placed just beneath the clear membrane (conjunctiva) of the eye.

A recent report of one patient who received two subconjunctival injections of a similar medication to the one being studied here indicated that subconjunctival injections of this class of medication may be an effective and less invasive alternative to intravitreal injections for pseudophakic CME. Because of the similarity of the drugs and the patient's treatment success, we would like to see if subconjunctival injection(s) of aflibercept will work in treating pseudophakic CME. If successful, the risk of an intraocular infection and glaucoma that comes with standard of care treatments might be greatly reduced.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: January 2, 2020
• Est. primary completion date: August 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosed with pseudophakic CME defined as central retinal thickness (CRT)>300 microns, presence of intraretinal cysts on optical coherence tomography (OCT) and visual acuity <=20/32 with petaloid leakage on fluorescein angiogram and late leakage at the disc

2. Diagnosed with "recalcitrant" CME, defined as less than a 15% decrease in CRT after at least 6 weeks of topical non-steroidal anti-inflammatory drug

3. Has had cataract surgery in the study eye with posterior chamber or anterior chamber intraocular lens implantation

4. Willing and able to comply with clinic visits and study-related procedures

5. Provide signed informed consent

Exclusion Criteria:

1. Retinal diseases (including diabetic retinopathy, retinal vein or artery occlusion, neovascular age-related macular degeneration, radiation retinopathy, vitreomacular traction, epiretinal membrane).

2. Active intraocular inflammation (grade trace or above) in the study eye, or history of idiopathic or autoimmune-associated uveitis in either eye.

3. Active infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.

4. Prior treatment with sub-Tenon's or intravitreal steroids.

5. Prior treatment with an intravitreal anti-vascular endothelial growth factor (VEGF) agent in the study eye or systemic administration of anti-VEGF.

6. Use of topical prostaglandin analogues or pilocarpine.

7. Uncontrolled glaucoma in the study eye (defined as intraocular pressure =30 mmHg despite treatment with glaucoma medications.

8. Previous subfoveal focal laser photocoagulation involving the foveal center in the study eye.

9. Vision loss in the study eye, determined by the investigator to be from a cause other than CME, e.g. optic neuropathy, end-stage glaucoma.

10. Any significant media opacity including vitreous hemorrhage or corneal scarring.

11. Fluorescein dye allergy or intolerance

12. Allergy to aflibercept or any of the components

13. Cerebrovascular accident or myocardial infarction within 1 year of the screening visit.

14. Pregnant or breast-feeding women

15. Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception starting at least 2 menstrual cycles prior to the baseline visit, during the study and in the 3 months immediately following the last dose of study drug.

Related Conditions & MeSH terms

• Irvine-Gass Syndrome
• Macular Edema

Intervention

Drug:
• Aflibercept
Subconjunctival aflibercept

Locations

Country	Name	City	State
United States	Tufts Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Tufts Medical Center	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (9)

Arevalo JF, Garcia-Amaris RA, Roca JA, Sanchez JG, Wu L, Berrocal MH, Maia M; Pan-American Collaborative Retina Study Group. Primary intravitreal bevacizumab for the management of pseudophakic cystoid macular edema: pilot study of the Pan-American Collaborative Retina Study Group. J Cataract Refract Surg. 2007 Dec;33(12):2098-105. — View Citation

Bahar I, Yeung SN, Sella R, Slomovic A. Anterior segment uses of bevacizumab. Curr Opin Ophthalmol. 2012 Jul;23(4):303-16. doi: 10.1097/ICU.0b013e3283548459. Review. — View Citation

Guo S, Patel S, Baumrind B, Johnson K, Levinsohn D, Marcus E, Tannen B, Roy M, Bhagat N, Zarbin M. Management of pseudophakic cystoid macular edema. Surv Ophthalmol. 2015 Mar-Apr;60(2):123-37. doi: 10.1016/j.survophthal.2014.08.005. Epub 2014 Sep 2. Review. — View Citation

Kitchens JW, Do DV, Boyer DS, Thompson D, Gibson A, Saroj N, Vitti R, Berliner AJ, Kaiser PK. Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials. Ophthalmology. 2016 Jul;123(7):1511-20. doi: 10.1016/j.ophtha.2016.02.046. Epub 2016 Apr 12. Review. — View Citation

Lin CJ, Tsai YY. USE OF AFLIBERCEPT FOR THE MANAGEMENT OF REFRACTORY PSEUDOPHAKIC MACULAR EDEMA IN IRVINE-GASS SYNDROME AND LITERATURE REVIEW. Retin Cases Brief Rep. 2018 Winter;12(1):59-62. doi: 10.1097/ICB.0000000000000414. Review. — View Citation

Muakkassa NW, Klein KA, Hamrah P, Reichel E. Subconjunctival Bevacizumab for the Treatment of Keratoprosthesis-Associated Cystoid Macular Edema. Ophthalmic Surg Lasers Imaging Retina. 2016 Mar;47(3):276-9. doi: 10.3928/23258160-20160229-11. — View Citation

Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, Pyles EA, Yancopoulos GD, Stahl N, Wiegand SJ. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012 Jun;15(2):171-85. doi: 10.1007/s10456-011-9249-6. — View Citation

Raghava S, Hammond M, Kompella UB. Periocular routes for retinal drug delivery. Expert Opin Drug Deliv. 2004 Nov;1(1):99-114. Review. — View Citation

Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol. 2008 May;92(5):667-8. doi: 10.1136/bjo.2007.134874. Epub 2008 Mar 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Systemic and ocular adverse events of subconjunctivally administered aflibercept injection in the treatment of pseudophakic cystoid macular edema at Month 2	Month 2
Secondary	Change in visual acuity	Change in best-corrected visual acuity at Months 2 and 6	Month 2 and Month 6
Secondary	Change in central retinal thickness	Change in central retinal thickness as measured by optical coherence tomography at Months 2 and 6	Month 2 and Month 6
Secondary	Proportion of patients needing re-treatment	Proportion of patients needing subconjunctival aflibercept injection treatment at Month 1	Month 1
Secondary	Proportion of patients needing additional non-study treatment though Month 6	Proportion of patients receiving additional non-study treatment (e.g. periocular or intravitreal steroid) through Month 6	Month 6
Secondary	Adverse Events - end of study period	Incidence and severity of systemic and ocular events at Month 6	Month 6