Intraoperative Utility of Brilliant Blue g (Bbg) and Indocyanine Green (Icg) Assisted Chromovitrectomy

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by University Hospital, Basel, Switzerland
Sponsor:
Collaborators:
Clinical Trial Unit, University Hospital Basel, Switzerland
University of Pittsburgh
Ludwig-Maximilians - University of Munich
General Hospital Linz
Medical University of Graz
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT01485575
First received: November 28, 2011
Last updated: February 18, 2013
Last verified: February 2013
  Purpose

Intravitreal dyes are intended to make the surgical extraction of the Internal limiting membrane (ILM) safer and more complete. However, the search for an adequate vitaly dye is ongoing. The most commonly used vital dye is Indocyanine green (ICG), although it is not approved for intravitreal use and has been associated with ocular toxicity. The reason for its continued popularity seems to be that it stains the ILM better than the approved and less toxic alternative substances Brilliant Blue G (BBG) and Trypan blue (TB). According to anecdotal reports from surgeons, another reason for ICGs popularity may be the fact that it seems to make ILM removal easier. Ultimately, the intention of the investigators research is to identify possible modifications to existing dyes to reach improved intraoperative dye utility combined with a favorable safety profile.


Condition Intervention
Macular Edema
Procedure: Use of intraoperative filters in vitrectomy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Intraoperative Utility of Brilliant Blue g (Bbg) and Indocyanine Green (Icg) Assisted Chromovitrectomy

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • ILM thickness, stiffness and roughness [ Time Frame: No further patient contact is requried after surgery. Analysis of the specimens may take up to one year ] [ Designated as safety issue: No ]
    Measurements under the Atomic force microscope will show wether the use of ICG or BBG influences material properties of the ILM (for example, an increased stiffness may explain a better "grip").


Secondary Outcome Measures:
  • Contrast between the stained ILM and the underlying tissue [ Time Frame: No further patient contact is requried after surgery. Analysis of the video frames may take up to one year ] [ Designated as safety issue: No ]
    Intraoperative videos will be analysed to understand under which circumstances vital dyes produce the best contrast visible to the human eye


Biospecimen Retention:   Samples Without DNA

Internal limiting membrane as removed during routine surgery.


Estimated Enrollment: 50
Study Start Date: November 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Filter use during vitrectomy Procedure: Use of intraoperative filters in vitrectomy
During vitrectomy with xenon endoillumination, an orange, green and a yellow filter are applied sequentially to determine which one produces the best contrast behavior of vital dyes
Other Name: Stellaris PC surgical (Bausch&Lomb surgical,Aliso Viejo,CA)

  Hide Detailed Description

Detailed Description:

The human retina is a light-sensitive tissue lining the inner surface of the posterior segment of the eye. It is a complex, layered structure containing the photoreceptors and several layers of neurons. Proper retinal function requires a smooth interface between the retina and the adjoining vitreous body (vitreous), a gelatinous and transparent substance occupying the cavity of the posterior ocular segment. The innermost of the retinal layers, a basement membrane called Inner limiting membrane (ILM), represents the boundary between the retina and the vitreous. Excessive contact between the ILM and the vitreous leads to vitreoretinal traction and represents a common cause of ocular pathology: The vitreous adheres to the ILM and shearing forces are conveyed to the retina. Vitreoretinal traction concentrates around the Macula lutea, the small area in the center of the retina which is responsible for central vision. It may be associated with significant visual disturbance as it creates retinal folds, provokes retinal edema and epiretinal metaplastic membranes through the liberation of inflammatory messenger substances and may ultimately result in the formation of macular holes. Macular holes tend to lead to sudden and often complete loss of central vision.

Removal of the vitreous (vitrectomy) may improve vitreoretinal traction, but a complete relief of traction is only achieved if the ILM is removed from the retina in the area around the macula: At the end of vitrectomy, the surgeon grasps the ILM with a fine forceps and carefully peels it off the underlying retinal layers. This procedure is extremely delicate, as the ILM is transparent, extremely thin and in direct contact with highly vulnerable retinal structures. Vital dyes have been employed to make the ILM more visible and because some dyes have been described to improve "grip" of the ILM during its extraction. The most commonly used dye, Indocyanine green (ICG) is not approved for intravitreal use and a discussion on possible toxic side effects is ongoing. The approved alternative substance Brilliant blue G is employed only by a minority of vitreoretinal surgeons. It is our hypothesis, that the popularity of ICG is due to superior staining capacity and a stiffening effect which may make ILM removal easier for the surgeon.

The first goal of this interdisciplinary and translational project, integrating Medical physics, Biomedical engineering, Nanosciences, Biochemistry, Neurobiology, Medical Image analysis and Clinical ophthalmology is to assess and quantify the helpfulness of existing dyes in terms of staining behavior and their influence on ILM "grip". In a second step, the project will analyze how new application protocols and the introduction of novel components to the molecular structure of vital dyes can improve staining as well as "ILM-grip" while guaranteeing favorable toxicity profiles Hypotheses

  1. A novel "Heavy BBG" (BBG D2O) stains the ILM better than conventional BBG. A replacement of part of the water molecules with Deuterium Oxide (D20) in the BBG solvent increases the dye's specific gravity. After injection into the vitreous, this new preparation (BBG D2O) would collect on the retinal surface, increasing local concentration and retinal exposure. We hypothesize that this alteration of the BBG molecular structure could improve staining properties without compromising its favorable toxicity profile. This new BBG has already been introduced by the manufacturer, but its intraoperative usefulness has not been objectively examined.
  2. The use of intraoperative light filters improves the recognizability of the contrasts generated by vital dyes. Most endoillumination lighting systems are equipped with light filters, originally intended to reduce intraoperative light toxicity. Anecdotal reports by numerous surgeons indicate, however, that the use of some filters improves the recognizability of the stained ILM. The green filter is regarded as particularly useful for this purpose. A systematic analysis of the effects of light filters on the usefulness of intravitreal dyes has not been undertaken to date.
  3. ICG and TB's photochemical properties improve "ILM grip" through an ILM cross-linking effect resulting in an alteration of ILM material properties. We expect increased intra-operative ILM compressive and tensile stiffness and reduced ILM thickness in Atomic force microscopy examinations, explaining why many surgeons describe facilitated intraoperative manipulation and extraction of the ILM. BBG is not known to dispose of photochemical properties and should not influence ILM material properties.
  4. Novel Modified ICG preparation stains equally well but is less toxic An alteration of the molecular structure in a way such that photochemical properties of the substance would be largely eliminated would strongly reduce oxidative stress and retinal toxicity. Synthetization of such a preparation is being prepared by our group. Staining properties are different from the original preparation in that the absorption maximum is shifted towards shorter wavelengths and the staining effect is bluish rather than green. The substance's affinity to the ILM its staining strength and its toxicity have not been studied, to date.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Consecutive patients treated with Chromovitrectomy at 3 tertiary care hospitals.

Criteria

Inclusion Criteria:

  • Over 18 Years of age
  • No other chromovitrectomy in previous 6 months
  • Only one of three vitaly dyes used intraoperatively (BBG, ICG or TB)

Exclusion Criteria:

  • Previous chromovitrectomy during last 6 months
  • Pregnant patients
  • Patients under 18 years of age
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485575

Contacts
Contact: Paul B. Henrich, MD +41 61 265 2525 henrichp@uhbs.ch

Locations
Austria
General Hospital Linz Recruiting
Linz, Austria, 4010
Contact: Rupert W Strauss, MD    +43 732 7806 - 73425    rupert.strauss@akh.linz.at   
Switzerland
Universtiy of Basel Recruiting
Basel, BS, Switzerland, 4056
Contact: Paul B Henrich, MD    +41 265 2525    henrichp@uhbs.ch   
St. Gallen Hospital Recruiting
St. Gallen, SG, Switzerland, 9007
Contact: Christophe Valmaggia, MD    +41 71 494 11 11    Christophe.Valmaggia@kssg.ch   
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Clinical Trial Unit, University Hospital Basel, Switzerland
University of Pittsburgh
Ludwig-Maximilians - University of Munich
General Hospital Linz
Medical University of Graz
Investigators
Principal Investigator: Paul B Henrich, MD University of Basel, Department of Ophthalmology, Basel Switzerland
  More Information

No publications provided

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT01485575     History of Changes
Other Study ID Numbers: ILM-AMF2
Study First Received: November 28, 2011
Last Updated: February 18, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
Chromovitrectomy
Indocyanine green
ICG
Brilliant Blue G
BBG
Trypan blue
TB
Internal limiting membrane
ILM

Additional relevant MeSH terms:
Edema
Macular Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on July 22, 2014