Diabetic Macular Edema: Relevance of Staging Progression on Therapeutic Outcome

Retrospective multi-center observational study on functional and morphological outcome of initial therapy for DME according to ESASO Morphologic Classification.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: intravitreal administration of bevacizumab/ranibizumab/aflibercept/desamethazone

Detailed Description

The ESASO morphologic classification of diabetic macular edema defines four stages of progression of the disease: early, advanced, chronic and atrophic maculopathy.

This grading is generated by the analysis of seven biomarkers that fully describe the level of retinal damage. Aim of this classification is to be a valid method for a comprehensive description of DME in scientific studies or clinical practice.

Given the recent publication of ESASO Classification, there aren't observations on the real relevance of grading DME on therapeutic outcome.

This retrospective study wants to give a preliminary answer to this important issue.

As a corollary outcome, this study will also evaluate the concordance of grading among participants.

• Study Type: Observational
• Enrollment (Actual): 608

Contacts and Locations

• Study Contact: Name: Giacomo Panozzo, MD; Phone Number: 045502390; Email: g.panozzo@iol.it
• Study Contact Backup: Name: Giacomo Panozzo; Phone Number: 045502390; Email: g.panozzo@iol.it

Study Locations

• Switzerland
  • Lugano, Switzerland, CH-6901
    • ESASO Scientific Projects

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

B. Major Eligibility Criteria

1. Age ≥ 50 years
2. Type 1 or type 2 diabetes
3. No history/presence of any other ocular/macular pathology
4. No history of IV/laser treatment in the past 8 months
5. No history of cataract or other ocular surgery in the past 6 months

Description

Inclusion Criteria. Eligible eyes at the retrospective review

1. Any stage of DME treated with a loading dose of 3 anti-VEGF (any type) or 1 IV dexamethasone (STEP 1).
2. OCT scans and retinal maps (radial/raster lines) at baseline (max 1 month before injection) and at one month (max 6 weeks) after the third anti-VEGF or at 3 months (max 16 weeks) after IV steroid injection (STEP 2).
3. VA at the time of both OCT examinations.

Exclusion Criteria:

1. Past ocular surgery of any kind (except for cataract surgery) or ocular pathologies other than diabetic retinopathy.
2. Macular edema considered to be due to a cause other than diabetic macular edema.
3. OCT examination suggesting that vitreoretinal interface abnormalities (e.g., a taut posterior hyaloid or epiretinal membrane) are the primary cause of the macular edema. In the case of ERM, an OCT scan must be sent to the Coordinating Center for approval.
4. Any ocular pathology or ocular condition other than diabetes that in the opinion of the investigator might affect macular edema.
5. History of any therapy (anti-VEGF treatment, focal/grid macular photocoagulation, intravitreous or peribulbar corticosteroids) for DME or diabetic retinopathy in the past 8 months.
6. History of YAG capsulotomy performed within two months before enrollment.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Early DME; Functional results after the loading therapeutic phase. The efficacy of different drugs (bevacizumab, ranibizumab, aflibercept, desamethazone) will be analyzed separately	Drug: intravitreal administration of bevacizumab/ranibizumab/aflibercept/desamethazone; intravitreal administration
Advanced DME; Functional results after the loading therapeutic phase. The efficacy of different drugs (bevacizumab, ranibizumab, aflibercept, desamethazone) will be analyzed separately	Drug: intravitreal administration of bevacizumab/ranibizumab/aflibercept/desamethazone; intravitreal administration
Severe DME; Functional results after the loading therapeutic phase. The efficacy of different drugs (bevacizumab, ranibizumab, aflibercept, desamethazone) will be analyzed separately	Drug: intravitreal administration of bevacizumab/ranibizumab/aflibercept/desamethazone; intravitreal administration
Atrophic diabetic maculopathy; Functional results after the loading therapeutic phase. The efficacy of different drugs (bevacizumab, ranibizumab, aflibercept, desamethazone) will be analyzed separately	Drug: intravitreal administration of bevacizumab/ranibizumab/aflibercept/desamethazone; intravitreal administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional and morphological improvement in DME after initial therapeutic loading phase, according to ESASO stage of progression of the disease.	Visual acuity and morphological (OCT) stage of the disease (as described in ESASO DME classification) will be evaluated at time 0 and four months after the first injection of intravitreal dexamethasone or one month after the loading phase (3 monthly injections) with anti-VEGF.	Four months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of ESASO DME staging classification	After preliminary instruction on ESASO Staging system of DME, participating centers will evaluate the stage of DME at time 0 of every eye retrospectically selected to participate to the study. This staging will be than validated by the Coordinating Center, and the total concordance of staging (K index) will be used to validate the Classification	3 months

Collaborators and Investigators

• Sponsor: European School of Advanced Studies in Ophthalmology

Publications and helpful links

General Publications

• Panozzo G, Cicinelli MV, Augustin AJ, Battaglia Parodi M, Cunha-Vaz J, Guarnaccia G, Kodjikian L, Jampol LM, Junemann A, Lanzetta P, Lowenstein A, Midena E, Navarro R, Querques G, Ricci F, Schmidt-Erfurth U, Silva RMD, Sivaprasad S, Varano M, Virgili G, Bandello F. An optical coherence tomography-based grading of diabetic maculopathy proposed by an international expert panel: The European School for Advanced Studies in Ophthalmology classification. Eur J Ophthalmol. 2020 Jan;30(1):8-18. doi: 10.1177/1120672119880394. Epub 2019 Nov 12.
• Panozzo G, Mura GD, Franzolin E, Giannarelli D, Albano V, Alessio G, Arrigo A, Casati S, Cassottana P, Contardi C, D'Aloisio R, Fasce F, Gusson E, Marchini G, Mastropasqua L, Niccolo M, Palmisano C, Pastore MR, Saviano S, Tognetto D, Bandello F. Early DMO: a predictor of poor outcomes following cataract surgery in diabetic patients. The DICAT-II study. Eye (Lond). 2022 Aug;36(8):1687-1693. doi: 10.1038/s41433-021-01718-4. Epub 2021 Aug 3.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): December 23, 2021
• Study Completion (Actual): July 26, 2022

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: October 4, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: diabetic macular edema; Therapy; ESASO Classification
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab; Bevacizumab; Aflibercept
• Other Study ID Numbers: ESASO

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: Yes
• Studies a U.S. FDA-regulated device product: No