The Use of Amniotic Membrane or Internal Limiting Membrane for Large or Refractory Macular Holes: A Prospective Study

May 1, 2025 updated by: Anna Carolina Carvalho Araujo, Hospital Oftalmologico de Sorocaba

The Use of Amniotic Membrane or Inverted Internal Limiting Membrane Flap for Large or Refractory Macular Holes: a Prospective, Comparative Study Using Microperimetry

Prospective, randomized, unmasked interventional study. To evaluate anatomical and functional results through microperimetry in cases of refractory or large macular holes (MH), using amniotic membrane (AM) or internal limiting membrane ( ILM ).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This study will evaluate functional outcomes through microperimetry in patients undergoing macular hole surgery. It will focus on patients with macular holes ≥600 microns, as well as those with holes refractory to conventional surgical treatment. The study will assess the use of amniotic membrane or internal limiting membrane (ILM) as adjuncts in the macular hole closure process.

The gold-standard treatment for idiopathic macular holes is pars plana vitrectomy (PPV), which involves removal of the posterior hyaloid (when adhered) and the ILM using a vital dye, followed by placement of buffering gas (C3F8 or SF6) at a non-expandable concentration. However, approximately 44% of large macular holes remain unclosed after conventional surgery.

To improve closure rates in such cases, new techniques have been introduced, including the inverted ILM flap technique and the free ILM flap technique. While studies demonstrate the effectiveness of these techniques, they show no significant improvement in visual function.

The amniotic membrane (AM) has recently been explored as an adjunct for macular hole closure and as a substrate for cell growth and visual acuity improvement. Amniotic membranes are believed to promote epithelialization and possess anti-fibrotic, anti-inflammatory, anti-angiogenic, and antimicrobial properties.

In this study, eligible patients will be randomized into two groups:

  • Group 1: Undergoing PPV with ILM removal, followed by placement of an amniotic membrane plug inside the macular hole, with its chorionic face in contact with the retinal pigment epithelium (RPE).
  • Group 2: Undergoing PPV with ILM removal, followed by placement of either an inverted ILM flap or a free ILM fragment for refractory cases, positioned over (inverted flap) or inside (free flap) the macular hole.

Once the AM plug or ILM flap is confirmed in its correct location, a fluid-gas exchange will be performed with 12.5% C3F8 buffering gas, and patients will maintain a face-down position for 7 days postoperatively.

Patients included in the study will undergo:

  • Preoperative assessment, including best-corrected visual acuity (BCVA) measurement, optical coherence tomography (OCT) using the Zeiss Cirrus 5000, and microperimetry using the Macular Integrity Assessment (MAIA) device.
  • Postoperative evaluations at day 1 and day 7, followed by assessments at 1, 3, 6, and 12 months. During these visits:- A complete ophthalmic examination will be performed.
  • OCT imaging will be conducted at day 7, month 1, month 3, month 6, and month 12.
  • Microperimetry will be conducted at months 1, 3, 6, and 12 to evaluate anatomical and functional responses.

The use of the amniotic membrane, given its anti-inflammatory, anti-fibrotic, and cell growth-supporting properties, is expected to increase closure rates in refractory and large macular holes and contribute to better functional outcomes by supporting outer retinal layer regeneration.

The Sorocaba Eye Bank (BOS) will provide, prepare, and preserve the amniotic membrane used in this study.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Not Applicable

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

  • Brazil
    • SP
      • Sorocaba, SP, Brazil, 18031060
        • Hospital Oftalmologico de Sorocaba/ Banco de Olhos de Sorocaba
    • Sao Paulo
      • Sorocaba, Sao Paulo, Brazil, 18031060
        • Sorocaba Eye's Hospital

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

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with a macula hole that falls into the two categories below:
  • Patients with idiopathic macular hole (with no history of secondary macular hole) ≥ 600 microns (measured using optical coherence tomography)
  • Patients with an idiopathic macular hole submitted to conventional treatment without closing it (of any size).
  • History of the disease less than 18 months
  • Aged over 18 years old
  • Visual acuity less than 20/32

Exclusion Criteria:

  • History of any previous macular disease other than idiopathic macular hole
  • Macular hole of other causes (secondary)
  • Patients with diabetic retinopathy or other retinal vascular diseases
  • Eyes subjected to intravitreal injection of any medication
  • Visual acuity <20/400 of any retinal cause in the contralateral eye or absence of the globe *Aged under 50 years old
  • Cataract and anti-glaucoma surgery less than 3 months before the study
  • Glaucoma with optic nerve excavation > 0.7 in the studied eye
  • Intraocular pressure > 24 mmHg with the use of maximum medication in the studied eye
  • History of vitreoretinal surgery for a condition other than the idiopathic macular hole (retinal detachment, vitreous hemorrhage)
  • History of retinal detachment of any etiology
  • A patient who manifests himself not being able to perform the head position in the postoperative period
  • A patient with active anterior or posterior uveitis

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Amniotic Membrane group
Patients who will be treated with a amniotic membrane plug
Device: Pars plana Vitrectomy with internal limiting membrane peeling

The pars plana 23-gauge (23G) vitrectomy technique will be performed with removal of the internal limiting membrane (ILM) (when adhered to the macula) and placement of either an amniotic membrane plug or an ILM flap in the macular hole. This will be followed by a fluid-air exchange and buffering gas infusion (12.5% C3F8).

The amniotic membrane plug will be prepared using a dermatological punch with a diameter of 1 to 2 mm, depending on the size of the macular hole as measured by OCT. It will be positioned inside the macular hole using 23G forceps, with its chorionic side facing the retinal pigmented epithelium (RPE).

The ILM flap will be created at the time of peeling-with an inverted flap in primary cases and a free flap in refractory cases. It will be positioned over the hole (inverted flap) or inside the macular hole (free flap) using 23G ILM forceps.

These techniques will be assisted by the use of an extra lighting sclerotomy.

Other Names:
  • Use of Amniotic membrane plug
  • Use of a internal limiting membrane inverted flap
  • gas tamponade (C3F8 12,5%)
Active Comparator: Internal Limiting Membrane group
patients who will be treated with a internal limiting membrane flap
Device: Pars plana Vitrectomy with internal limiting membrane peeling

The pars plana 23-gauge (23G) vitrectomy technique will be performed with removal of the internal limiting membrane (ILM) (when adhered to the macula) and placement of either an amniotic membrane plug or an ILM flap in the macular hole. This will be followed by a fluid-air exchange and buffering gas infusion (12.5% C3F8).

The amniotic membrane plug will be prepared using a dermatological punch with a diameter of 1 to 2 mm, depending on the size of the macular hole as measured by OCT. It will be positioned inside the macular hole using 23G forceps, with its chorionic side facing the retinal pigmented epithelium (RPE).

The ILM flap will be created at the time of peeling-with an inverted flap in primary cases and a free flap in refractory cases. It will be positioned over the hole (inverted flap) or inside the macular hole (free flap) using 23G ILM forceps.

These techniques will be assisted by the use of an extra lighting sclerotomy.

Other Names:
  • Use of Amniotic membrane plug
  • Use of a internal limiting membrane inverted flap
  • gas tamponade (C3F8 12,5%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The fixation stability
Time Frame: through study completion, an average of 1 year
measured by the microperimetry
through study completion, an average of 1 year
The retinal sensitivity
Time Frame: through study completion, an average of 1 year
measured by the microperimetry
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the macula hole closure rate
Time Frame: through study completion, an average of 1 year
measured by OCT
through study completion, an average of 1 year

Collaborators and Investigators

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

Sponsor

Hospital Oftalmologico de Sorocaba

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)

June 26, 2020

Primary Completion (Actual)

September 30, 2023

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

May 17, 2021

First Submitted That Met QC Criteria

May 24, 2021

First Posted (Actual)

May 27, 2021

Study Record Updates

Last Update Posted (Actual)

May 6, 2025

Last Update Submitted That Met QC Criteria

May 1, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HAMprotocol

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Only the microperimetry graphs and OCT images will be published, without any IPD.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on Macular Holes

Clinical Trials on Pars plana Vitrectomy with internal limiting membrane peeling

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Azerbaijan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe