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NCT Number: NCT07550777

Serum Cholinesterases, Paraoxonase, and Cardiovascular Risk After 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.

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Key information

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Blood test

Procedure

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.

Primary outcomes

  1. 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).

Secondary outcomes

  1. 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).

Other outcomes

  1. 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).

Sponsors and collaborators

Lead sponsor

Ataturk University

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Apr 24, 2026
Registry last updated
Apr 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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