Intraocular Cytokines in Non-responders to Ranibizumab Treatment for Neovascular AMD

NCT ID: NCT02218177

Last Updated: 2018-10-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2016-12-31

Brief Summary

The purpose of this study is to evaluate the level of cytokines (which are small proteins important in cell signalling) in eye fluid (aqueous humour) in patients with wet age related macular degeneration patients who have been treated with an injection in the eye (intravitreal injection) with a drug called ranibizumab. The level of cytokines will be compared between patients who have a good response to ranibizumab treatment and patients who are non-responsive to ranibizumab and need other forms of therapy. This knowledge will help for the future treatment and to potentially develop new medication for wet age-related macular degeneration.

Detailed Description

In the treatment of CNV (Choroidal NeoVascularization) secondary from AMD (Age Related Macular Degeneration) by using ranibizumab, patients who are non-responders can be found in approximately 1-10% of treatments. Thus, failure of treatment can lead to loss of vision. Growth factors and cytokines, such as vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF), interleukin 6 (IL-6) and placenta growth factor (PLGF) are known to play an important role in the development of CNV angiogenesis.

The rationale for conducting this study to compare VEGF, PEDF, IL-6 and PLGF cytokine levels in the aqueous humor of wet AMD and Polypoidal Choroidal Vasculopathy (PCV) patients who are poor responders to anti VEGF treatment and age-matched "good" responders to anti VEGF. Ranibizumab poor responders in AMD and PCV, who are treated with a combination of PDT/ranibizumab or intravitreous injection of aflibercept (Eyelea®, Regeneron Pharmaceuticals Inc. Tarrytown, NY, USA and Bayer, Basel, Switzerland) will be enrolled to the study. An aqueous humor sample will be obtained when patient receives intravitreal injection treatment and also at 1, 2 months follow up period. VEGF, PEDF,IL-6 and PLGF in aqueous will be analyzed and used to compare between the poor response group and age matched patient with good response to ranibizumab. Age, gender, visual acuity, central macular thickness by OCT, lesion size and fundus autofluorescence data will be collected and used to compare between these groups. Subgroup analysis of different treatment comparison with ranibizumab good responder group will be evaluated. Factors associated with the non-responders of ranibizumab will be analyzed.

Non-responders to ranibizumab treatment in AMD may have different levels and responses of inflammatory cytokines compared to the responder group. Understanding the pathogenesis and characteristic of this specific group of patients can help narrow down a specific choice of treatment and prevent the reduction of visual acuity of the patient. This study also helps identify factors associated to poor responders from ranibizumab treatment for wAMD.

Conditions

Age Related Macular Degeneration

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Non-responders receiving aflibercept therapy

Non-responders to ranibizumab who are now receiving aflibercept therapy

Aflibercept

Intervention Type: DRUG

anti-VEGF treatment for wet age related macular degeneration

Non-responders receiving PDT combo therapy

patients who are non-responders to ranibizumab who have been switched to combination photodynamic therapy (PDT)

Combination Photodynamic Therapy

Intervention Type: PROCEDURE

Use of cold laser with an intravitreal injection of dexamethasone to treat wet age related macular degeneration

Responders to ranibizumab

Patients who are responders to ranibizumab and are continuing monthly injections.

Ranibizumab

Intervention Type: DRUG

anti-VEGF treatment for wet age related macular degeneration

Interventions

Aflibercept

anti-VEGF treatment for wet age related macular degeneration

Intervention Type: DRUG

Ranibizumab

anti-VEGF treatment for wet age related macular degeneration

Intervention Type: DRUG

Combination Photodynamic Therapy

Use of cold laser with an intravitreal injection of dexamethasone to treat wet age related macular degeneration

Intervention Type: PROCEDURE

Other Intervention Names

Eylea (R); Lucentis

Eligibility Criteria

Inclusion Criteria

• Age 50 years or more
• Ranibizumab resistance/poor responder patients in all AMD entities (typical AMD, PCV and RAP) who will be treated with intravitreous ranibizumab in combination with verteporfin photodynamic therapy
• Ranibizumab resistance/poor responder patients in all AMD entity (typical AMD, PCV and RAP) who will be treated with intravitreous aflibercept injection
• AMD patient who is good response to the treatment of ranibizumab (control group)

Exclusion Criteria

• Any evidence of good response in treatment of ranibizumab,
• Uncooperative patients to intravitreal treatment
• Patients who have clinically active ocular inflammation
• Patients who have previous PDT treatment within 6 months
• Patient who previously have ocular treatment of immunosuppressive agent within 3 months
• Patient who previously have ocular treatment of steroid with in 3 months
• Patients who are currently on systemic treatment of anti-VEGF medication or immunosuppressive agents.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Wai-Ching Lam

Professor University of Toronto, Residency Program Director Dept. of Ophthalmology, Continuing Medical Education Director Dept. of Ophthalmology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wai-Ching Lam, MD

Role: PRINCIPAL_INVESTIGATOR

Toronto Western Hospital, University Health Network, University of Toronto

Locations

Toronto Western Hospital

Toronto, Ontario, Canada

Countries

Canada

References

Pongsachareonnont P, Mak MYK, Hurst CP, Lam WC. Neovascular age-related macular degeneration: intraocular inflammatory cytokines in the poor responder to ranibizumab treatment. Clin Ophthalmol. 2018 Sep 26;12:1877-1885. doi: 10.2147/OPTH.S171636. eCollection 2018.

Reference Type: DERIVED

PMID: 30310267 (View on PubMed)

Other Identifiers

VEGF wAMD cytokine study

Identifier Type: -

Identifier Source: org_study_id