Functional Assessment of the Possible Toxicity of Indocyanine Green Dye in Macular Hole Surgery

doi:10.1016/j.ajo.2006.05.054

American Journal of Ophthalmology

Volume 142, Issue 5, November 2006, Pages 765-770.e1

https://doi.org/10.1016/j.ajo.2006.05.054 Get rights and content

Purpose

To evaluate the possible toxicity of indocyanine green (ICG) dye in macular hole surgery by comparing functional results after successful surgeries performed with and without staining.

Design

Prospective observational case series.

Methods

In a study conducted at our department, 30 eyes of 29 patients with idiopathic macular hole underwent pars plana vitrectomy, with peeling of the internal limiting membrane (ILM). In 21 eyes (group A), ICG staining was used to visualize the membrane; in nine eyes (group B), no dye was applied. Pre- and postoperative examinations (at three, six, 12, and 20 months) included visual acuity (VA) (Snellen chart), slit-lamp biomicroscopy, multifocal electroretinography (mfERG), and optical coherence tomography (OCT). For statistical analysis, the Mann-Whitney U test and Newman-Keuls post hoc analysis were used.

Results

The macular hole was closed in all patients. At 20 months, VA improvement (logarithm of minimal angle of resolution units) compared with baseline was more pronounced in group B (P < .001) than in group A (P = .022); VA was also better for group B compared directly with group A (P = .048). For mfERG, preoperative responses were subnormal. Postoperatively, responses initially decreased, but at 20 months significant improvement was seen in both groups (P < .001). When data from the groups are compared at 20 months, significantly greater mfERG improvement was found in group B in both central and perimacular areas (P < .001).

Conclusions

The significantly better outcomes without staining may suggest dye toxicity. Alternative internal limiting membrane visualization substances with fewer adverse effects (trypan blue, triamcinolone) may be preferable.

Section snippets

Methods

In a prospective observational case series, 30 eyes of 29 patients (nine men and 21 women) underwent macular hole surgery at our department between May 2001 and April 2003. The ages of the patients ranged from 65 to 72 years (mean ± SD, 66.9 ± 5.7 years). Nine of the eyes had stage 2, 12 stage 3, and nine stage 4 macular holes; the median duration of the macular hole was six months (range, one to 12 months). Postoperative follow-up time was a minimum of 20 months. Patients with macular

Results

Preoperatively, there was no significant difference in VA, stage of macular hole, duration of the symptoms, and age of the patients (Table). In all eyes, a closure of the macular hole was noted on clinical examination, and the anatomical success was confirmed by OCT.

In both the C1 and C2 areas, retinal response densities decreased at three and six months after the operation; an increase was noted at 12 months. At the 20-month follow-up examination, the b-waves in the central retinal area showed

Discussion

We performed vitrectomy combined with removal of the ILM in patients with macular hole. The patient diagnosis was confirmed by OCT examination; a central defect was observed in all examined patients, regardless of the stage of the disease. The decrease of retinal response densities measured by mfERG in the foveal area (area C1) may reflect the loss of photoreceptors.¹⁰ The decrease of the retinal response densities is not limited to the foveal area, but also involves the perifoveal area (area

Mária Ferencz, MD, graduated from Semmelweis University of Medicine, Faculty of Medicine in 1991. In the same year, Dr Ferencz joined the 2^nd Department of Ophthalmology, which is today the Maria Street Department of Ophthalmology. As a leader of the Vitreoretinal Team, her major clinical and research interest is surgical retina, with emphasis on the pathology of the vitreoretinal interface.

References (14)

A.K. Kwok et al.
Indocyanine green staining and removal of internal limiting membrane in macular hole surgery: histology and outcome
Am J Ophthalmol
(2001)
A.P. Da Mata et al.
Indocyanine green–assisted peeling of the retinal internal limiting membrane during vitrectomy surgery for macular hole repair
Ophthalmology
(2001)
V. Mester et al.
Internal limiting membrane removal in the management of full-thickness macular holes
Am J Ophthalmol
(2000)
T.G. Sheidow et al.
Outcome results in macular hole surgery
Ophthalmology
(2003)
R. Tadayoni et al.
Persistence of fundus fluorescence after use of indocyanine green for macular surgery
Ophthalmology
(2003)
C. Haritoglou et al.
Light-absorbing properties and osmolarity of indocyanine green depending on concentration and solvent medium
Invest Ophthalmol Vis Sci
(2003)
F.A. Teba et al.
Trypan blue staining in vitreoretinal surgery
Ophthalmology
(2003)

There are more references available in the full text version of this article.

Cited by (50)

The Effect of an Inverted Internal Limiting Membrane Flap on Retinal Function after Macular Hole Surgery
2017, Ophthalmology Retina
Citation Excerpt :
Additionally, we did not observe any scotoma in either the upper field or the lower field. Several possible adverse effects of vitreous surgery have been reported: indocyanine green toxicity,23 nerve fiber damage after ILM peeling,24 mechanical damage after fluid–air exchange,25 and intraretinal potassium toxicity induced by perfluorocarbon.15 The ILM is the basement membrane of the retinal glia and thus plays an important role in buffering the intraretinal potassium concentration.
To study the effect of an inverted internal limiting membrane (ILM) flap on the retina.
Prospective case series.
Twenty-nine patients with large (>400 μm) unilateral macular holes underwent surgery using a modified inverted ILM flap technique.
The macular ILM was peeled, and a large (2–3 disc diameter) ILM flap was made on the superior side of the hole, and then the flap was inverted on the inferior side.
In all patients, multifocal electroretinograms (mfERGs) were recorded from operated eyes and normal fellow eyes. The peak time and amplitude of N1, P1, and N2 in the focal ERG from the upper retina without the ILM flap and those from the lower retina with the ILM flap were evaluated. In 14 patients, microperimetry was also performed in both eyes, and the averaged sensitivity was measured from the upper and lower areas.
The peak times of P1 and N2 from the upper and lower retina were significantly longer in operated eyes than in the fellow eyes (P1 upper and lower: P < 0.04, N2 upper: P < 0.01, and N2 lower: P < 0.04), although we could not identify a significant difference in peak time and amplitude of N1, P1, and N2 between the upper retina and lower retina in both eyes (fellow eye—N1 amplitude: P > 0.2, N1 peak time: P > 0.5, P1 amplitude: P > 0.9, P1 peak time: P > 0.4, N2 amplitude: P > 0.9, N2 peak time: P > 0.9; operated eye—N1 amplitude: P > 0.8, N1 peak time: P > 0.4, P1 amplitude: P > 0.6, P1 peak time: P > 0.4, N2 amplitude: P > 0.9, N2 peak time: P > 0.9). We could not observe a significant difference in sensitivity between the upper and lower retinas in both eyes (fellow eye: P = 0.28, operated eye: P = 0.66).
The results of this study revealed no significant difference between the upper retina without the ILM flap and the lower retina with the ILM flap, suggesting that an inverted ILM flap has little effect on retinal function.
Retinal function assessment of trypan blue versus indocyanine green assisted internal limiting membrane peeling during macular hole surgery
2013, Canadian Journal of Ophthalmology
Citation Excerpt :
The P1 mfERG amplitude ratio (central fovea/parafovea) was significantly increased 1 year postoperatively, and a reduction in P1 implicit time was observed in both groups. In Ferencz et al.’s study, the retinal response densities of foveal and perifoveal areas also increased in both groups (with and without ICG staining) at 12 months, but the improvement was markedly better in eyes where ICG was not used.30 In our study, results suggest similar mfERG responses with the use of ICG and TB.
To compare multifocal electroretinography (mfERG) retinal function and the anatomical and visual outcomes of macular hole surgery performed with indocyanine green (ICG) or trypan blue (TB).
Prospective, randomized study.
Twenty-five eyes of 24 patients.
Patients underwent a pars plana vitrectomy with removal of the internal limiting membrane. In 14 eyes, internal limiting membrane visualization during macular hole repair was performed using TB, and ICG was used in 11 eyes. The examination protocol (performed before surgery and at 3 weeks, 3 months, 6 months, and 12 months after surgery) included optical coherence tomography, mfERG (mfERG-103 hexagons), and assessment of best corrected visual acuity (BCVA) and contrast sensitivity (CS).
Closure of macular hole was achieved in 100% of the cases. In the TB group, P1 amplitude and implicit time improved significantly at 12 months after surgery (P < 0.05), whereas in the ICG group, significant improvement occurred at both 6 (P < 0.05) and 12 months (P < 0.01). BCVA improved significantly in both groups at 6 and 12 months (P < 0.01). Both groups also showed a statistically significant CS improvement at spatial frequency of 6 cycles per degree (P = 0.01) 1 year postoperatively. At 12 months, improvement of P1 amplitude and implicit time, BCVA, and CS was not different between groups.
In this study, the use of TB or ICG appears to yield similar improvement in terms of BCVA, CS, and mfERG amplitude and implicit time changes at 12 months.
Comparaison entre la fonction rétinienne par ERG multifocale ERG et les résultats anatomiques et visuels de l'entière chirurgie du trou maculaire avec le vert d'indocyanine (VIC) ou le bleu Trypan (BT).
Étude prospective et randomisée.
25 yeux de 24 patients.
Les patients ont subi une vitrectomie par la pars plana avec retrait de la membrane limitative interne (MLI). La visualisation par la MLI pendant la réparation du trou maculaire a été effectuée en utilisant le BT dans 14 yeux et le VIC dans 11 yeux. Le protocole de l'examen (effectué avant l'opération ainsi que 3 semaines, 3, 6 et 12 mois après la chirurgie) comprenait la tomographie par cohérence optique (TCO), l'électrorétinographie multifocale (ERGmf-103 hexagones), l'évaluation de la meilleure acuité visuelle corrigée (MAVC) et la sensibilité au contraste (SC).
La fermeture du trou maculaire a été effectuée dans 100 % des cas. Chez le groupe BT, l'amplitude P1 et le temps implicite se sont améliorés de façon significative 12 mois après la chirurgie (P < 0,05) alors que, chez le groupe VIC, l'amélioration significative est arrivée après 6 mois (P < 0,05) et 12 mois (P < 0,01). Les deux groupes ont aussi montré une amélioration de la SC à une fréquence locale de 6 CPD (P = 0,01) un an après l'opération. À 12 mois, l'amélioration de l'amplitude P1 et du temps implicite de la MAVC et la SC ne différaient pas entre les groupes.
Dans cette étude, les utilisations du TB ou du VIC semblent donner une amélioration similaire après 12 mois quant à la MAVC, la SC, ainsi que l'amplitude et le temps implicite mesurés à l'ERGmf.
Comparison of triamcinolone and VisCoat in indocyanine-green-assisted internal-limiting-membrane peeling in macular hole surgery
2013, Taiwan Journal of Ophthalmology
Citation Excerpt :
In ICG staining of the ILM, the ICG readily binds to Type-4 collagen fibers, greatly facilitating the visualization and removal of the membrane. However, the toxicity to the retinal pigment epithelial cells and the ganglion cells and the potential aggravation of the phototoxicity from the fiber optic light precludes the universal acceptance of ICG staining in ILM removal.15–17 Alternative materials have been used, such as trypan blue (TB), brilliant blue G (BBG), and TA suspension.
The objective of our study was to compare the clinical outcomes of idiopathic full-thickness macular hole surgery using either triamcinolone (TA) or VisCoat treatment of the macular hole before indocyanine-green (ICG)-assisted internal-limiting-membrane (ILM) peeling.
During macular hole surgery, the hole and adjacent areas were treated with TA (Group 1, n = 15 eyes) or VisCoat (Group 2, n = 22 eyes) to minimize ICG-induced toxicity during ILM peeling. Changes in visual acuity and anatomical success rates were compared between the two groups.
At 6 months following surgery, the hole closure rate was 80% (12/15 eyes) in Group 1 and 100% (22/22 eyes) in Group 2. The mean ± standard deviation logarithm of the minimum angle of resolution decreased from 1.40 ± 0.41 to 1.08 ± 0.38 in Group 1 (p = 0.04) and from 1.25 ± 0.41 to 0.75 ± 0.44 in Group 2 (p < 0.001), indicating that a greater increase in the average best corrected visual acuity had occurred in Group 2 than in Group 1 (p = 0.02). At 1 month following surgery, small outer-retinal blebs were noted in 42% of the closures in Group 1 and 9% of the closures in Group 2. The blebs persisted in four Group-1 participants for >1 year, but no long-standing outer retinal bleb occurred in Group 2.
Participants who received the VisCoat treatment displayed a higher hole closure rate and a better final visual acuity than those who received the TA treatment. Participants who received the TA treatment also had more outer retinal blebs at 1 month and 1 year or more following the surgery.
The Use of Vital Dyes in Ocular Surgery
2009, Survey of Ophthalmology
Citation Excerpt :
Following the Kadonosono et al publication of ICG use macular hole surgery, many authors have reported easier and less traumatic ICG-guided peeling with good clinical results (Fig. 3).54,89,91–93,158,161,195,197,202,204,205,207,222,353,391 Clinical data showed that macular closure rate may be achieved in 74–100% of patients using ICG-guided ILM peeling.8,20,54,55,75,115,138,141,158,193–195,197,210,211,217,224,239,254,255,271,274,298,305,306,309,310,313,325,326,329,337,345,370,371,375,379,389,405 The potential for toxic effects of ICG on the retina has been suggested.73,96,114,115,228–230
Vital dyes have advanced diagnosis and surgical technique in various specialties, including oncology, gastroenterology, and ophthalmology. In ocular surgery vital dyes are widely used in cataract and vitreoretinal surgery. Worldwide, intra-operative use of trypan blue during cataract surgery has enhanced visualization of the anterior capsule during capsulorrhexis, and patent blue has been recently licensed in Europe for cataract surgery. For chromovitrectomy, the vital dyes indocyanine green, infracyanine green, and brilliant blue stain the internal limiting membrane, and trypan blue and triamcinolone acetonide help visualize epiretinal membranes and vitreous, respectively. Intra-operative vital dyes are finding uses in corneal, glaucoma, orbit, strabismus, and conjunctival surgery. We provide a summary of current knowledge of the use of vital dyes in ocular surgery. We review the properties of dyes, techniques of application, indications, and complications in ocular surgery. Vital dyes represent an expanding area of research, and novel dyes deserve further investigation.
Electroretinographic Assessments of Macular Function after Brilliant Blue G Staining for Inner Limiting Membrane Peeling
2022, Journal of Clinical Medicine
Outcomes of epiretinal membrane removal utilizing triamcinolone acetonide visualization and internal limiting membrane forceps
2020, Clinical Ophthalmology

View all citing articles on Scopus

View full text

Original articleFunctional Assessment of the Possible Toxicity of Indocyanine Green Dye in Macular Hole Surgery

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Light-absorbing properties and osmolarity of indocyanine green depending on concentration and solvent medium

Invest Ophthalmol Vis Sci

Trypan blue staining in vitreoretinal surgery

Ophthalmology

Original article
Functional Assessment of the Possible Toxicity of Indocyanine Green Dye in Macular Hole Surgery