Serum Cholinesterases, Paraoxonase, and Cardiovascular Risk After Intravitreal Bevacizumab

April 22, 2026 updated by: Büşra Çalışkan, Ataturk University

Serum Acetylcholinesterase, Butyrylcholinesterase, Paraoxonase Activity, and Cardiovascular Risk Factors in Patients Treated With Intravitreal Bevacizumab

Bevacizumab, an anti-VEGF (vascular endothelial growth factor) agent used in the treatment of diabetic retinopathy and macular edema associated with retinal vein occlusion, is commonly administered in ophthalmology clinics through intravitreal injection. The systemic use of bevacizumab has been associated with serious conditions such as thromboembolism and bleeding. Although intravitreal bevacizumab is administered in smaller amounts and has limited systemic circulation, it requires repeated injections over a long period. These long-term intravitreal anti-VEGF therapies may lead to adverse outcomes, particularly thromboembolism, due to systemic inhibition of VEGF. However, limited information is available regarding the potential effects of this treatment on the systemic and cardiovascular systems. To evaluate this risk, the study aims to assess changes in the activities of paraoxonase 1 (PON1), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), which are closely associated with lipid metabolism, coronary artery disease, and atherosclerosis. These enzymes are known biomarkers of cardiovascular health and play significant roles in protection against oxidative stress and inflammation. For this purpose, a case-control study is planned. Serum BChE and PON1 activities, as well as triglyceride (TG)/high-density lipoprotein (HDL) and TG/glucose ratios, will be determined in patients receiving repeated intravitreal bevacizumab injections and in control groups, and cardiovascular disease risk will be assessed. This study may help us better understand the safety profile of this treatment by revealing the effects of bevacizumab on serum enzyme activities and cardiovascular risk factors. These findings could contribute to optimizing treatment strategies in clinical practice.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

180

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey (Türkiye)
    • Erzurum
      • Erzurum, Erzurum, Turkey (Türkiye), 25240
        • Recruiting
        • Ataturk University Research Hospital, Department of Ophthalmology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

The patient group consists of individuals receiving repeated doses of intravitreal bevacizumab treatment for diabetic macular edema, retinal vein occlusion, and age-related macular degeneration-related macular edema, along with a control group (the control group will also be divided into two subgroups: individuals with diabetes but without macular edema or diabetic retinopathy, and completely healthy individuals).

Description

Inclusion Criteria:

  • Age ≥ 55 years.
  • Ability to provide written informed consent.
  • Patient group: Diagnosis of macular edema secondary to diabetic retinopathy, retinal vein occlusion, or age-related macular degeneration, and having received repeated intravitreal bevacizumab injections (≥2 doses).
  • Control group: Healthy volunteers with no ocular pathology other than cataracts and not receiving intravitreal anti-VEGF treatment.

Exclusion Criteria:

  • Chronic inflammatory disease.
  • Chronic infectious disease.
  • History of cardiovascular disease (e.g., coronary artery disease, heart failure, arrhythmia requiring treatment).
  • History of cerebrovascular disease (e.g., stroke, transient ischemic attack).
  • Any additional ocular pathology that may affect the study outcomes (other than the index retinal condition in the patient group and cataract in the control group), such as:

glaucoma

uveitis

retinal dystrophies

significant media opacity preventing adequate ocular evaluation

- Use of systemic medications or conditions known to affect cholinesterase activity markedly

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
control
Procedure: blood test
Serum samples will be collected from the patient group included in the study starting from at least the second dose of intravitreal bevacizumab treatment. Serum samples will be collected within one week after the last injection.
diabetic macular edema
Procedure: blood test
Serum samples will be collected from the patient group included in the study starting from at least the second dose of intravitreal bevacizumab treatment. Serum samples will be collected within one week after the last injection.
retinal vascular occ
Procedure: blood test
Serum samples will be collected from the patient group included in the study starting from at least the second dose of intravitreal bevacizumab treatment. Serum samples will be collected within one week after the last injection.
age macular degeneration
Procedure: blood test
Serum samples will be collected from the patient group included in the study starting from at least the second dose of intravitreal bevacizumab treatment. Serum samples will be collected within one week after the last injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum butyrylcholinesterase (BChE) activity
Time Frame: Within 7 days after the most recent intravitreal bevacizumab injection

Description:

Measurement of serum butyrylcholinesterase (BChE) activity in participants who received at least 2 consecutive intravitreal bevacizumab injections. Serum samples will be collected after the most recent injection, and BChE activity will be compared among subgroups defined by the number of previous consecutive injections (early: 2-3 doses; mid: 4-6 doses; long: >6 doses).
Within 7 days after the most recent intravitreal bevacizumab injection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum acetylcholinesterase (AChE) activity
Time Frame: Within 7 days after the most recent intravitreal bevacizumab injection
Measurement of serum acetylcholinesterase (AChE) activity in participants who received at least 2 consecutive intravitreal bevacizumab injections. Serum samples will be collected after the most recent injection, and AChE activity will be compared among subgroups defined by the number of previous consecutive injections (early: 2-3 doses; mid: 4-6 doses; long: >6 doses).
Within 7 days after the most recent intravitreal bevacizumab injection

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum paraoxonase-1 (PON1) activity
Time Frame: Within 7 days after the most recent intravitreal bevacizumab injection
Measurement of serum paraoxonase-1 (PON1) activity in participants who received at least 2 consecutive intravitreal bevacizumab injections. Serum samples will be collected after the most recent injection, and PON1 activity will be compared among subgroups defined by the number of previous consecutive injections (early: 2-3 doses; mid: 4-6 doses; long: >6 doses).
Within 7 days after the most recent intravitreal bevacizumab injection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ataturk University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 3, 2025

Primary Completion (Estimated)

June 10, 2026

Study Completion (Estimated)

July 10, 2026

Study Registration Dates

First Submitted

February 19, 2026

First Submitted That Met QC Criteria

April 22, 2026

First Posted (Actual)

April 24, 2026

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B.30.2.ATA.0.01.00/346

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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