Vital dyes necessary for vitreomacular surgery but may have risks

Researchers are looking for alternatives that would minimize the toxicity risk to patients, maximize visualization for specialists and reduce overall costs.

Vital dyes are used by vitreoretinal specialists to visualize transparent preretinal tissues, to enhance identification and to remove transparent anatomical layers during vitreoretinal surgery, but the dyes can result in irreversible acute toxicity in some cases, according to a review article in Ophthalmic Surgery Lasers & Imaging Retina.

Vitreoretinal specialists most commonly use indocyanine green (ICG), triamcinolone acetonide, trypan blue and brilliant blue G (BBG) as chromovitrectomy dyes to help visualize transparent preretinal tissues such as the epiretinal membrane and vitreous cortex.

“The vital dyes play an important role by facilitating removal of the desired microscopic anatomical layers during vitreoretinal surgery,” OSLI RetinaEditorial Board Member Caroline R. Baumal, MD, told Ocular Surgery News.

Caroline R. Baumal, MD
Caroline R. Baumal

Dye preferences

Trypan blue and preservative-free triamcinolone acetonide are FDA-approved dyes for intraocular use. According to the 2017 American Society of Retina Specialists Preferences and Trends Survey, 69% of respondents used ICG as their internal limiting membrane (ILM) and epiretinal membrane (ERM) removal dye, with 14.8% preferring BBG and 9.5% preferring triamcinolone acetonide.

However, the use of dyes for ERM removal and ILM peeling could lead to an increased risk for adverse outcomes in some patients. Studies have suggested that ICG, especially if utilized at higher concentrations and for long periods of contact during surgery, may have some degree of toxicity to the retinal pigment epithelium (RPE).

“Safety is the main concern when using a surgical adjuvant. There are concerns regarding dye toxicity to the tissues of the retina and the retinal pigment epithelium. Potential issues may occur during mixing of the dye, be related to direct exposure to the dye or due to dye-potentiated phototoxicity,” Baumal said.

Vitreoretinal specialists can reduce or limit dye-related issues by taking a few steps during a procedure. Specialists should use the “smallest amount of dye possible” with limited retinal exposure time and may consider shielding the central fovea with viscoelastic material. Additionally, mixing a dye such as ICG with dextrose 5% in water and avoiding direct illumination on the fovea when the dye is in the vitreous cavity may limit issues, Baumal said.

Alternative dyes

There is an unmet need for safe, versatile dyes that effectively stain both the ILM and the ERM, especially given the transparent nature of the tissues, co-author Thomas A. Ciulla, MD, MBA, told OSN.

Several types of dye have been proposed as alternatives to those currently in use. Researchers have attempted to find new alternatives that would minimize the toxicity risk to patients, maximize visualization for specialists and reduce overall costs, according to the review.

Most of the researched alternatives since 2004 never advanced past preclinical testing. However, several have been investigated to a greater degree, such as bromophenol blue, which results in moderate staining of the ERM, ILM and vitreous. No evidence of toxicity has been found in patients despite in vitro suggestion of delayed toxicity. The dye is commercially available outside of the United States with BBG as Brilliant Peel Dual Dye (Fluoron) at a concentration of 1.3 mg/mL, according to the review.

Naturally occurring dyes have also been researched, with dyes from the acai fruit showing the most promise. The purple-colored anthocyanin dye successfully stains the ILM and recently underwent human trials, but results have yet to be released, according to the review.

Thomas A. Ciulla
Thomas A. Ciulla

Ideal dye

The ideal dye would distinguish surrounding tissues and maximally delineate the tissue of interest without inducing toxicity to the retina or RPE, Baumal said.

“One interesting concept is to use dye or a combination of dyes to image more than one tissue of interest with one injection. For example, Triesence (triamcinolone acetonide, Alcon) or Kenalog (triamcinolone acetonide, Bristol-Myers Squibb) highlight the hyaloid attachments with ERM, while ICG delineates the ILM. It would be more efficient if a single injection of one of two materials could delineate all of the structures of interest. MembraneBlue-Dual, from the Dutch Ophthalmic Research Center, is available outside of the United States and stains both ILM and ERM in one injection, and newer agents, some of which are available in Europe, may tackle this issue,” she said.

In addition to the development of new dyes, several other possible advances could help increase safety and precision of membrane peeling by vitreoretinal specialists, Ciulla said.

“In the future, advances in intraoperative lighting and imaging, including intraoperative OCT, may also enhance the safety and effectiveness of vitrectomy for a wide variety of retinal conditions,” he said. – by Robert Linnehan

Disclosures: Baumal reports she has served as a consultant for Stealth BioTherapeutics, on the advisory board for Genentech and as a speaker for Optovue and Zeiss outside the submitted work. Ciulla reports he has an employment relationship with Spark Therapeutics, but the manuscript was written during his work as a volunteer clinical professor of ophthalmology at Indiana University School of Medicine, and none of the work represents any official position or opinion of Spark Therapeutics or its management.

Vital dyes are used by vitreoretinal specialists to visualize transparent preretinal tissues, to enhance identification and to remove transparent anatomical layers during vitreoretinal surgery, but the dyes can result in irreversible acute toxicity in some cases, according to a review article in Ophthalmic Surgery Lasers & Imaging Retina.

Vitreoretinal specialists most commonly use indocyanine green (ICG), triamcinolone acetonide, trypan blue and brilliant blue G (BBG) as chromovitrectomy dyes to help visualize transparent preretinal tissues such as the epiretinal membrane and vitreous cortex.

“The vital dyes play an important role by facilitating removal of the desired microscopic anatomical layers during vitreoretinal surgery,” OSLI RetinaEditorial Board Member Caroline R. Baumal, MD, told Ocular Surgery News.

Caroline R. Baumal, MD
Caroline R. Baumal

Dye preferences

Trypan blue and preservative-free triamcinolone acetonide are FDA-approved dyes for intraocular use. According to the 2017 American Society of Retina Specialists Preferences and Trends Survey, 69% of respondents used ICG as their internal limiting membrane (ILM) and epiretinal membrane (ERM) removal dye, with 14.8% preferring BBG and 9.5% preferring triamcinolone acetonide.

However, the use of dyes for ERM removal and ILM peeling could lead to an increased risk for adverse outcomes in some patients. Studies have suggested that ICG, especially if utilized at higher concentrations and for long periods of contact during surgery, may have some degree of toxicity to the retinal pigment epithelium (RPE).

“Safety is the main concern when using a surgical adjuvant. There are concerns regarding dye toxicity to the tissues of the retina and the retinal pigment epithelium. Potential issues may occur during mixing of the dye, be related to direct exposure to the dye or due to dye-potentiated phototoxicity,” Baumal said.

Vitreoretinal specialists can reduce or limit dye-related issues by taking a few steps during a procedure. Specialists should use the “smallest amount of dye possible” with limited retinal exposure time and may consider shielding the central fovea with viscoelastic material. Additionally, mixing a dye such as ICG with dextrose 5% in water and avoiding direct illumination on the fovea when the dye is in the vitreous cavity may limit issues, Baumal said.

Alternative dyes

There is an unmet need for safe, versatile dyes that effectively stain both the ILM and the ERM, especially given the transparent nature of the tissues, co-author Thomas A. Ciulla, MD, MBA, told OSN.

Several types of dye have been proposed as alternatives to those currently in use. Researchers have attempted to find new alternatives that would minimize the toxicity risk to patients, maximize visualization for specialists and reduce overall costs, according to the review.

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Most of the researched alternatives since 2004 never advanced past preclinical testing. However, several have been investigated to a greater degree, such as bromophenol blue, which results in moderate staining of the ERM, ILM and vitreous. No evidence of toxicity has been found in patients despite in vitro suggestion of delayed toxicity. The dye is commercially available outside of the United States with BBG as Brilliant Peel Dual Dye (Fluoron) at a concentration of 1.3 mg/mL, according to the review.

Naturally occurring dyes have also been researched, with dyes from the acai fruit showing the most promise. The purple-colored anthocyanin dye successfully stains the ILM and recently underwent human trials, but results have yet to be released, according to the review.

Thomas A. Ciulla
Thomas A. Ciulla

Ideal dye

The ideal dye would distinguish surrounding tissues and maximally delineate the tissue of interest without inducing toxicity to the retina or RPE, Baumal said.

“One interesting concept is to use dye or a combination of dyes to image more than one tissue of interest with one injection. For example, Triesence (triamcinolone acetonide, Alcon) or Kenalog (triamcinolone acetonide, Bristol-Myers Squibb) highlight the hyaloid attachments with ERM, while ICG delineates the ILM. It would be more efficient if a single injection of one of two materials could delineate all of the structures of interest. MembraneBlue-Dual, from the Dutch Ophthalmic Research Center, is available outside of the United States and stains both ILM and ERM in one injection, and newer agents, some of which are available in Europe, may tackle this issue,” she said.

In addition to the development of new dyes, several other possible advances could help increase safety and precision of membrane peeling by vitreoretinal specialists, Ciulla said.

“In the future, advances in intraoperative lighting and imaging, including intraoperative OCT, may also enhance the safety and effectiveness of vitrectomy for a wide variety of retinal conditions,” he said. – by Robert Linnehan

Disclosures: Baumal reports she has served as a consultant for Stealth BioTherapeutics, on the advisory board for Genentech and as a speaker for Optovue and Zeiss outside the submitted work. Ciulla reports he has an employment relationship with Spark Therapeutics, but the manuscript was written during his work as a volunteer clinical professor of ophthalmology at Indiana University School of Medicine, and none of the work represents any official position or opinion of Spark Therapeutics or its management.

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