Home Print this page Email this page Users Online: 148
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2018  |  Volume : 6  |  Issue : 2  |  Page : 45-48

A comparative evaluation of two commercially available formulations of brilliant blue G in idiopathic macular hole surgery

Shroff Eye Centre, New Delhi, India

Date of Web Publication20-Jun-2018

Correspondence Address:
Shubha Mehta
House No. 573, Sector-8, Faridabad - 121 006, Haryana
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcor.jcor_29_16

Rights and Permissions

Aim: The aim of this study is to comparatively evaluate “internal limiting membrane (ILM) blue (0.025% brilliant blue G (BBG) +4% polyethylene glycol” and “Brilliant Peel (0.025% BBG + heavy water)” in idiopathic full-thickness macular hole (FTMH) surgery with respect to anatomical and functional outcome and surgical ease of ILM peeling. Materials and Methods: It was a prospective comparative study. Thirty patients with idiopathic FTMH selected for pars-plana vitrectomy with ILM peeling were included in the study. Cataract extraction was combined with vitrectomy if cataract was significant. Fifteen eyes underwent ILM peeling with ILM blue – Group 1 and fifteen eyes with Brilliant Peel – Group 2. The adequacy of ILM staining was noted intraoperatively. All patients followed up next day, at 1 week, 6 weeks, and 3 months. Macular hole closure rate and gain in visual acuity (VA) and contrast sensitivity (CS) were noted. Statistical Analysis: Student's t-test was used to assess the baseline numeric differences among groups. Repeated measures ANOVA was used to assess VA improvement over time in each group. Chi-square test was used to compare two groups in terms of stage of macular hole. Means test was used to check the effect of lens status in visual recovery. Results: Both groups were well matched in demographic data, baseline VA, stage of macular hole, and percentage of eyes undergoing simultaneous cataract extraction. Macular hole closed in 100% of eyes. Mean pre- and postoperative logMAR best-corrected VA was 0.80 and 0.40 in ILM blue group and 0.993 and 0.527 in the Brilliant Peel group. VA improvement was clinically and statistically significant in both ILM blue (P = 0.004) and Brilliant Peel (P = 0.003) groups. The groups did not differ from each other at 3 months in terms of gain in VA (P = 0.291) and CS. Intraoperatively, both the dyes stained the ILM well. Conclusion: ILM peeling with ILM blue and Brilliant Peel dyes showed comparable intraoperative staining and good postoperative anatomic and functional outcome.

Keywords: Brilliant blue G, idiopathic macular hole, internal limiting membrane peeling

How to cite this article:
Gupta C, Agarwal P, Mehta S, Gupta A K, Shroff CM. A comparative evaluation of two commercially available formulations of brilliant blue G in idiopathic macular hole surgery. J Clin Ophthalmol Res 2018;6:45-8

How to cite this URL:
Gupta C, Agarwal P, Mehta S, Gupta A K, Shroff CM. A comparative evaluation of two commercially available formulations of brilliant blue G in idiopathic macular hole surgery. J Clin Ophthalmol Res [serial online] 2018 [cited 2019 Dec 16];6:45-8. Available from: http://www.jcor.in/text.asp?2018/6/2/45/234822

There is a consensus that the application of vital dyes facilitates the delicate removal of intraocular membranes during vitreoretinal surgery.[1] Brilliant blue has gained popularity as one such dye due to its properties of adequate of internal limiting membrane (ILM) staining and no reported toxicity. Recently, commercial preparations of “heavy” brilliant blue dye have been made available to prolong the macular contact time as well as reduce the volume and concentration of dye used intraocularly. These dyes on introduction into the vitreous cavity tend to gravitate to the macula instead of dispersing in the vitreous. Two such formulations are Brilliant Peel ® (Fluoron/Geuder, Heidelberg, Germany)[2] and ILM-BLUE® (DORC, Zuidland, The Netherlands).[3] Brilliant Peel is a modification of BBG (0.25 mg/ml) with addition of 0.065 ml or 13% deuterium oxide to its hydration shell. ILM blue, on the other hand, is a preparation containing 4% polyethylene glycol (PEG) which is a cohesive molecule and also renders the solution denser.

This study was conducted to assess and compare the intraoperative ease of use and staining intensity, anatomical closure, functional recovery, and safety profile after macular hole surgery with these two formulations using standard parameters such as Snellen's visual acuity (VA) and optical coherence tomography (OCT) and less studied parameters such as contrast sensitivity (CS), automated perimetry (macular threshold), and fundus autofluorescence (FAF). We wanted to study if the fundamental difference between the composition of these two dyes altered their staining characteristics and safety profile. There is no published literature comparing these formulations which prompted us to undertake this study.

  Materials and Methods Top

This prospective comparative study was conducted in accordance with the tenets of Helsinki and was commenced after a clearance from the institutional ethics committee and scientific committee. The study included a total of 30 patients with OCT documented idiopathic full-thickness macular holes from our outpatient department, selected to undergo pars-plana vitrectomy with ILM peeling. The patients were alternately selected to undergo ILM peeling with staining using ILM blue and Brilliant Peel, respectively, thereby allocating 15 patients to each group. Exclusion criteria were history of any previous vitreous or retinal surgery; associated retinal detachment; any other ocular disease such as glaucoma and corneal opacity; inability to maintain prone position for 1 week postoperatively; eyes with high myopia; and history of trauma.

All patients underwent a detailed clinical evaluation including best-corrected VA (BCVA) using Snellen's and ETDRS charts; intraocular pressure (IOP) measurement using noncontact tonometer (NIDEK NT 530P, NIDEK, Japan); anterior segment biomicroscopy with cataract evaluation using Haag Streit BQ 900 slit-lamp biomicroscope; CS using CSV-1000; visual field analysis-macular threshold program using Humphrey visual field analyzer (VFA) (VFA 745i, Carl Zeiss Meditec, Germany); macular and optic disc evaluation using 78 diopter (D) and 90D lens; peripheral retinal evaluation using indirect ophthalmoscopy, OCT using RTVue (Optovue, Fremont, California); and FAF captured by Fundus camera (TRC-50DX, Topcon, Netherlands).

The macular holes were clinically staged from Stages 1 to 4 using Gass classification, and the staging was confirmed with the help of OCT.[4]

The surgical procedure was done after obtaining a written informed consent from all patients. Cataract surgery was combined with the vitrectomy procedure if patient had a significant cataract assessed using modified age-related eye disease study grading method.[5] All macular hole surgeries were performed by a single surgeon. Standard three-port 23-gauge vitrectomy was done. Core vitrectomy was done followed by induction of posterior vitreous detachment. Injection of 0.1 ml of undiluted brilliant blue G (BBG) dye was done to stain the ILM. Infusion was kept on during the injection of the dye. The dye was noted to sink immediately to the macular area owing to its high-specific gravity. After 30 seconds, the dye was aspirated using flute needle till the vitreous cavity was clear. An area of two-disc diameter of stained ILM within the macular arcade centered at the fovea was peeled off in a circular fashion using Tano's scraper and end-gripping forceps. Peripheral retina was checked to look for any retinal breaks, and if present, photocoagulation with laser indirect ophthalmoscopy (LIO) was done. This was followed by fluid-air exchange and injection of 14% C3 F8 or 20% SF6. All patients were asked to maintain a face-down position for 1 week after surgery.

Intraoperatively, staining was assessed subjectively by the surgeon in terms of ease of injection of dye, staining intensity, and ease of ILM peeling following staining. All these three parameters were graded as poor, satisfactory, or good after each surgery by the operating surgeon.

All patients were followed up next day, at 1 week, 6 weeks, and at 3 months in accordance with the detailed proforma. BCVA, IOP measurement, slit-lamp examination, 78/90 D examination, and indirect ophthalmoscopy were repeated at each follow-up. OCT was done at 6-week and 3-month follow-up visits. CS and VFA were repeated at 3-month follow-up visit.

Shapiro–Wilk test was done to assess the normality of the data. Baseline numeric differences among groups were assessed with the Student's t-test. Statistical differences in CS and visual field sensitivity improvement within each group were analyzed using Student's t-test. Repeated measures ANOVA for mixed models was used to compare the two dyes in terms of VA improvement over time. Chi-square test was used to assess if the two groups were similar with respect to stage of macular hole. Means test was used to check the effect of lens status on visual recovery. SPSS version 20.0, Armonk, NY: IBM Corp was used for statistical analysis, and P < 0.05 was considered to be statistically significant.

  Results Top

The age of patients ranged from 48 to 75 years, mean age being 66.17 years (standard deviation (SD) =6.25). Majority of the patients (50%) belonged to 60-70 years age group. The mean age was 65.27 (SD = 7.36) and 67.07 years (SD = 5.01) in ILM blue and Brilliant Peel groups, respectively. The two groups were similar in terms of age (P = 0.440). ILM blue group had ten male patients (67%) and five female patients (33%). In Brilliant Peel group, four patients (27%) were males and eleven (73%) were females. The two groups were dissimilar in terms of gender distribution (P = 0.028).

The two groups were similar with respect to the stage of macular holes (P = 0.547). Brilliant Peel group had three patients with Stage 2 macular hole, six patients with Stage 3 macular hole, and six patients with Stage 4 macular hole. ILM blue group had two patients with Stage 2 macular hole, nine patients with Stage 3 macular hole, and four patients with Stage 4 macular hole.

Preoperative lens status was phakic, pseudophakic, or cataract. A patient who had cataract underwent combined cataract surgery with macular hole surgery. Overall, the number of phakic, pseudophakic, and combined surgery was 4 (13.3%), 8 (26.7%), and 18 (60%), respectively. In ILM blue group, three, five, and seven patients belonged to phakic, pseudophakic, and combined surgery subgroup, respectively. In Brilliant Peel group, one, three, and eleven patients belonged to phakic, pseudophakic, and combined surgery subgroup, respectively. The distribution of lens status in the two groups was found to be similar (P = 0.303).

ILM blue and Brilliant Peel were compared on the basis of ease of injection, staining intensity, and ease of ILM peeling. ILM blue dye is available as a prefilled syringe whereas Brilliant Peel dye needs to be loaded into a syringe before injection. It was found in the initial few cases that injecting ILM blue was difficult as the piston of the prefilled syringe was hard. The surgeon in later cases decided to transfer the contents of the prefilled syringe of ILM blue in an alternate syringe and then inject the dye. Staining intensity was graded as good and ease of ILM peeling was graded as satisfactory in all patients in the two groups. Hence, there was no difference between the two dyes in the staining intensity and ease of ILM peeling and both the dyes scored equally well.

Postoperatively, 3-month follow-up showed hole closure in all 30 patients (100%) as documented by OCT and FAF. Repeated measures ANOVA using mixed models was used to assess the VA improvement between the two groups from baseline over the 6-week and 3-month follow-up. Mauchly's test indicated that the assumption of sphericity had been violated, χ2 (2) = 15.49, P < 0.001; therefore, degrees of freedom were corrected using Greenhouse-Geisser estimates of sphericities (ε = 0.69). There was a significant difference in logMAR VA in all patients across the three time points, F (1.39, 38.98) = 29.40, P < 0.001. However, there were no significant differences in logMAR VA between groups, F (1, 28) = 1.35, P = 0.255. There was no significant interaction between time and group, F (1.39, 38.98) =0.41, P = 0.595. The mean baseline vision in ILM blue group was 0.800 logMAR (mean SD = 0.409) and in the Brilliant Peel group was 0.993 logMAR (mean SD = 0.442). The mean 6-week vision in ILM blue group was 0.627 logMAR and in Brilliant Peel group was 0.720. The mean 3-month vision in ILM blue group was 0.400 logMAR (mean SD = 0.295) and in the Brilliant Peel group was 0.527 logMAR (mean SD = 0.347). The change in logMAR VA from baseline to 3 months and from 6 weeks to 3 months was statistically significant in both ILM blue group (P< 0.001) and Brilliant Peel group (P< 0.001). However, the change in VA from baseline to 6 weeks was significant for Brilliant Peel (P = 0.016) but not significant for ILM blue (P = 0.195).

We also compared the visual recovery with lens status (combined and noncombined), and it was found to be statistically insignificant (P = 0.495), inferring that combining the two procedures is safe.

Difference in the mean values of CS at 3 months and at baseline was 0.584 for low frequency, 0.447 for mid-frequency, and 0.503 for high frequency in ILM blue group. Difference in the mean values of CS at 3 months and at baseline was 0.586 for low frequency, 0.561 for mid-frequency, and 0.647 for high frequency in Brilliant Peel group. CS improved in all patients for all frequencies (low, mid, and high range). The difference in CS improvement between ILM blue and Brilliant Peel groups was studied using independent t-test. The difference between the two groups was statistically not significant for low (P = 0.986), mid (P = 0.294), or high frequencies (P = 0.198).

The mean baseline four-quadrant total sensitivity in macular threshold program of VFA in ILM blue group was 432.67 (mean SD = 46.70) and in the Brilliant Peel group was 425.87 (mean SD = 39.87). The mean 3-month four-quadrant total sensitivity in ILM blue group was 434.27 (mean SD = 50.95) and in the Brilliant Peel group was 459.1 (mean SD = 46.26). The difference in four-quadrant total sensitivity from baseline to postoperative 3 months was statistically significant for Brilliant Peel (P = 0.04) as compared to ILM blue group (P = 0.929).

Preoperatively, all cases in both groups showed a hyper-autofluorescent area corresponding to the macular hole. Postoperatively, all cases in both groups showed normal autofluorescence. No abnormal autofluorescence was seen suggesting that there was no drug toxicity with either of the two dyes.

  Discussion Top

BBG is an anionic dye with a molecular weight of 854 Da. Also known as Acid blue or Coomassie blue, it has been used in the textile, paint, and food industries. Since its approval in 2007 for marketing in Europe, its use has been described to stain the ILM as an alternative to ICG with no descriptions of any toxic effect on the retina.[6],[7],[8]

BBG is commercially available at a concentration of 0.025%. The dye should be injected into the fluid-filled globe and washed out immediately to prevent ocular damage. Recently, efforts have been made to achieve higher dye concentrations directly on the surface of the ILM and prevent uncontrolled distribution of the dye within the vitreous cavity by addition of deuterium atoms (heavy water) as in case of Brilliant Peel or 4% PEG as in case of ILM blue. However, addition of these substances (heavy water, 4% PEG) to BBG, which has been studied as a safe vital dye for intraocular use, could alter the safety profile of the dye.

The commercially available preparation of Brilliant Peel was modified in June 2010, with addition of deuterium atoms, thereby yielding a higher density to the formulation. There is limited published literature to attest the safety of brilliant blue with heavy water. Initial clinical report by Gerding et al. in 2011 in a small sample of three patients showed favorable outcomes with no dye-related toxicity.[9] Haritoglou et al. reported the use Brilliant Peel in a case series of eight patients with macular hole or epimacular membrane.[10] Shukla et al. in 2012 reported the use of heavy BBG for ILM staining in macular hole surgery of twenty eyes. They prepared the dye by mixing it with 10% dextrose normal saline in a ratio of 2:1. They found the staining with heavy BBG to be marginally superior to the standard 0.5 mg/ml BBG and reported good anatomic and functional outcomes.[11] Heinrich et al. in 2013 published their results comparing standard BBG with heavy BBG and reported no significant chromaticity difference between the two preparations. However, they reported slightly improved contrasts between the ILM and underlying retina with heavy BBG.[12]

Recently, ILM blue became available commercially where BBG is made denser and cohesive by addition of 4% PEG and the formulation similarly gravitates to the macula. There is no published literature assessing the safety of ILM blue in human models, in vivo. However,in vitro studies with preparations of BBG with 4% PEG in cultured human retinal pigment epithelial cells (animal retinal pigment epithelium-19) showed no change in the toxicity compared to BBG at 0.025% in phosphate-buffered saline solution.[13]

We attempted to study and compare, by means of clinical examination, CS, visual fields, OCT and FAF, the toxicity of these dyes and visual outcome following ILM peeling using these dyes. The results of this study show that both the commercially available preparations of heavy BBG stained the ILM well. Both groups showed similar ease of ILM peeling intraoperatively, good anatomical result, and postoperative improvement in VA. Brilliant Peel is available in a vial and has to be loaded before injection. ILM blue is available as a prefilled syringe, and initially, it was found that injecting ILM blue was difficult as the piston of the prefilled syringe was hard. This shortcoming was overcome by the surgeons by simply transferring the contents of ILM blue into a fresh syringe before injecting.

VA improvement was delayed in ILM blue group compared to Brilliant Peel group, but it was comparable in both the groups at final follow-up. The CS improvement in both ILM blue and Brilliant Peel groups was comparable. The visual field macular threshold showed a statistically significant improvement in the Brilliant Peel group but no change in ILM blue group. This parameter must be evaluated in greater detail in future studies by employing techniques such as microperimetry. Anatomical closure of macular hole was achieved in all cases with ILM peeling in both ILM blue and brilliant Peel groups, and this was further confirmed and documented on OCT and FAF. Normal autofluorescence postoperatively suggests that neither of the dyes caused any retinal pigment epithelium toxicity. In future, such a study may be carried out with a larger sample drawn from population so that findings can be more generalized.

  Conclusion Top

Both Brilliant peel and ILM Blue dyes facilitate macular hole surgery by staining the ILM well. The intraoperative staining intensity, postoperative anatomic and functional outcomes and safety profile of both dyes are comparable in patients undergoing idiopathic macular hole surgery.


The authors would like to thank Dr. Ranjan Dutta for his help in the statistical analysis.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Farah ME, Maia M, Rodrigues EB. Dyes in ocular surgery: Principles for use in chromovitrectomy. Am J Ophthalmol 2009;148:332-40.  Back to cited text no. 1
Brilliant Peel: Composition. Available from: http://www.fluoron.de/index.php?myID=327&sprache=e. [Last accessed on 2015 Feb 03].  Back to cited text no. 2
DORC: ILM Blue Specifications. Available from: http://www.dorc.nl/products.php?group=18143,18208,18447. [Last accessed on 2014 Nov 02].  Back to cited text no. 3
Lowe RJ, Gentile RC. Application of Optical Coherence Tomography and Macular Holes in Ophthalmology. Kawasaki M, editor. Optical Coherence Tomography: InTech;2013. Available from: https://www.intechopen.com/books/optical-coherence-tomography/application-of-optical-coherence-tomography-and-macular-holes-in-ophthalmology. [Last accessed on 2015 Feb 03].  Back to cited text no. 4
Age-Related Eye Disease Study Research Group. The Age-Related Eye Disease Study (AREDS) system for classifying cataracts from photographs: AREDS report no 4. Am J Ophthalmol 2001;131:167-75.  Back to cited text no. 5
Martinez-Toldos JJ, Hueso JR, editors. Basic vitrectomy. Step by Step: Vitrectomy. 2nd ed. Jaypee Brothers Medical Publishers (P) Ltd., New Delhi; 2013. p. 138.  Back to cited text no. 6
Ooi YL, Khang TF, Naidu M, Fong KC. The structural effect of intravitreal Brilliant blue G and Indocyanine green in rats eyes. Eye (Lond) 2013;27:425-31.  Back to cited text no. 7
Shukla D, Kalliath J, Neelakantan N, Naresh KB, Ramasamy K. A comparison of brilliant blue G, trypan blue, and indocyanine green dyes to assist internal limiting membrane peeling during macular hole surgery. Retina 2011;31:2021-5.  Back to cited text no. 8
Gerding H, Timmermann M, Thelen U. Intravital staining of the internal limiting membrane with a novel heavy solution of brilliant blue G. Klin Monbl Augenheilkd 2011;228:298-301.  Back to cited text no. 9
Haritoglou C, Schumann RG, Kampik A, Gandorfer A. Heavy brilliant blue G for internal limiting membrane staining. Retina 2011;31:405-7.  Back to cited text no. 10
Shukla D, Kalliath J, Patwardhan A, Kannan NB, Thayyil SB. A preliminary study of heavy brilliant blue G for internal limiting membrane staining in macular hole surgery. Indian J Ophthalmol 2012;60:531-4.  Back to cited text no. 11
[PUBMED]  [Full text]  
Henrich PB, Valmaggia C, Lang C, Priglinger SG, Haritoglou C, Strauss RW, et al. Contrast recognizability during brilliant blue G-and heavier-than-water brilliant blue G - assisted chromovitrectomy: A quantitative analysis. Acta Ophthalmol 2013;91:e120-4.  Back to cited text no. 12
Awad D, Schrader I, Bartok M, Mohr A, Gabel D. Comparative toxicology of trypan blue, brilliant blue G, and their combination together with polyethylene glycol on human pigment epithelial cells. Invest Ophthalmol Vis Sci 2011;52:4085-90.  Back to cited text no. 13


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Materials and Me...

 Article Access Statistics
    PDF Downloaded156    
    Comments [Add]    

Recommend this journal