OCT and OCT-Angiography Biomarkers of Treatment Response to Dexamethasone Implant in Macular Edema Due to Retinal Vascular Diseases - DME and RVO

March 22, 2024 updated by: IRCCS Multimedica

Imaging Biomarkers of Treatment Response to Dexamethasone Implant in Macular Edema Due to Retinal Vascular Diseases - Diabetic Macular Edema and Retinal Vein Occlusion.

The purpose of this pilot study is to evaluate different imaging parameters in patients with previously treatment-naive DME and ME due to RVO before and after treatment with dexamethasone implant, in order to find specific retinal inflammatory and microvascular biomarkers that may be predictive of treatment outcome.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Diabetic retinopathy (DR) and retinal vein occlusion (RVO) are complex multifactorial diseases and the leading causes of visual impairment worldwide. The exact mechanisms leading to Macular Edema (ME) in DR and RVO are not fully understood, actual evidence focuses on the role of inflammation as critical contributing factor in ME pathogenesis and several studies described the association between high levels of systemic and local inflammatory molecules and the development of ME. Even if vascular endothelial growth factor (VEGF) is the most studied factor involved in ME pathogenesis in retinal vascular diseases and the main target of available therapeutic strategies, its role cannot explain alone all the events taking place in the onset and progression of these diseases. VEGF selective inhibition is not sufficient to stop the inflammatory cascade in DR and RVO and anti-VEGF therapies are frequently of transient benefit, especially in DME treatment, needing repeated injections over time and suggesting the involvement of other molecular pathways. Intravitreal corticosteroids block the production of inflammatory mediators (including VEGF) and inhibit leukostasis. In particular, dexamethasone has the highest relative clinical efficacy of any corticosteroid applied to ophthalmology practice. Intravitreal dexamethasone implant (Dex) slowly releases steroids into the vitreous over a period of up to 6 months. Dex 0.7 mg (Ozurdex™; Allergan, Irvine, CA, USA) has been used to reduce ME in patients with DR and RVO and its efficacy in terms of best corrected visual acuity (BCVA) improvement and central macular thickness (CMT) reduction has been demonstrated in many different studies. Thanks to the great advances in retinal imaging technologies of the last years, a new concept of non-invasive "imaging biomarker" of retinal inflammation has emerged and has made its way in the study of patients with DR and RVO. Clinical research has consequently developed great interest in finding specific retinal inflammatory parameters in DR and RVO and there is a growing body of scientific evidence on the importance of this topic. Moreover, the evaluation of these inflammatory biomarkers might be helpful in the prediction of treatment response. Nowadays, main proposed imaging biomarkers of inflammation include subfoveal neuroretinal detachment (SND) and hyperreflective retinal spots (HRS), visible on optical coherence tomography (OCT). SND consists in extracellular fluid accumulation between the outer segments of photoreceptors and the retinal pigment epithelium and is present in approximately 15-30% of eyes with DME and in an even greater number of patients with ME secondary to RVO. The presence of SND has been associated with higher levels of local inflammatory molecules, in particular IL-6. HRS are increased in number in patients with diabetes (with or without DR) and RVO; they have specific characteristics and are thought to represent aggregates of activated microglial cells that progressively migrate from the inner to the outer retina, confirming their role as inflammatory biomarkers. The purpose of this pilot study is to evaluate different imaging parameters in patients with previously treatment-naive DME and ME due to RVO before and after treatment with dexamethasone implant, in order to find specific retinal inflammatory and microvascular biomarkers that may be predictive of treatment outcome. The novelty of this study is a detailed evaluation of multimodal imaging modifications in DME and ME due to RVO after treatment with Dex in order to document its anti-inflammatory effect.

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

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

No

Sampling Method

Probability Sample

Study Population

Patients indicated for intravitreal Dexamethasone implantation for diabetic macular edema and retinal vein occlusion.

Description

Inclusion Criteria:

  • previously untreated centre-involving DME or ME secondary to RVO with CMT ≥ 300 μm;
  • pseudophakic eyes or eyes with a transparent lens or only initial sclerosis of the lens, in order to obtain good quality retinal imaging
  • patient agreement to participate in the study.

Exclusion Criteria:

  • any retinal disease other than DR or RVO;

    • a positive history of retinal surgery and/or any other macular/retinal treatment (laser, intravitreal injections of anti-VEGF and/or steroids);
    • cataract surgery within 6 months in the study eye;
    • refractive error > +/- 4D;
    • Advanced glaucoma
    • neurodegenerative diseases (e.g. multiple sclerosis, Alzheimer disease, Parkinson disease, etc.)
    • poor quality of OCT and/or OCT-A images due to significant media opacity or poor patient cooperation.
    • Ocular or periocular infections (including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases
    • Non-intact posterior lens capsule
    • Hypersensitivity to any component of the product

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modification of inflammatory biomarkers on OCT and perfusion density parameters on OCT-A at 4 months after surgery (Change measure)
Time Frame: pre-surgery and at 4 months after each surgery (if applicable)

Evaluate different inflammatory and microvascular parameters on imaging exams (OCT-A, OCT, and FAF) in patients with DME and ME secondary to RVO before and after treatment with intravitreal Dexamethasone implant, in order to identify specific predictive (imaging) biomarkers of treatment.

If a new surgery is required at 4 months, an additional follow-up will be scheduled 4 months after the second surgery
pre-surgery and at 4 months after each surgery (if applicable)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Initial clinical characteristics in patients with a gain in BCVA (Best Corrected Visual Acuity) of ≥ 5, ≥ 10, and ≥ 15 ETDRS (Early Treatment Diabetic Retinopathy Study) letters.
Time Frame: pre-surgery and up to every 2 months
Evaluate different inflammatory and microvascular parameters on imaging exams (OCT, OCT-A, and FAF) in patients with improvement in BCVA (≥ 5, ≥ 10, and ≥ 15 ETDRS letters) at the final visit; and in patients showing recurrence during the follow-up period.
pre-surgery and up to every 2 months

Collaborators and Investigators

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

Sponsor

IRCCS Multimedica

Collaborators

AbbVie

Investigators

  • Principal Investigator: Stela Vujosevic, MD, MultiMedica - IRCCS MultiMedica

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

October 17, 2023

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

March 17, 2024

First Submitted That Met QC Criteria

March 22, 2024

First Posted (Actual)

March 27, 2024

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 22, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 514.2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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