Retinal pigment epithelial changes after trypan blue-assisted internal limiting membrane peeling for idiopathic macular hole.

The use of Trypan blue for internal limiting membrane (ILM) staining has been reported to be safe and effective.[12] However, there are emerging reports of its toxic effects on the retinal pigment epithelium (RPE) and neural retina,[34] especially with longer exposures of more than five minutes.[56] In the context of ILM peeling for macular holes, the exposed (ILM peeled) neural retina and direct contact of trypan blue with the RPE in the region of the macular hole provide a potential route for the dye to reach the vulnerable tissue. Persistence of residual dye in the vitreous cavity or macular hole may prolong the exposure of RPE to the dye and cause damage.[7] Long-acting gas tamponade would further accentuate the effect of any persistent dye. This case report exemplifies such a possibility, while describing it for the first time in an Indian subject.

A 61-year-old lady presented with decreased vision in her right eye (OD) since one month. The best corrected visual acuity (BCVA) in this eye was 20 / 200, N18. The anterior segment examination revealed dense nuclear sclerosis with posterior subcapsular cataract. The fundus examination revealed a stage IV macular hole [Figure 1a] with areas of diffuse (arrows) and focal (arrowheads) RPE atrophy and treated areas of lattice degeneration. Clinical findings were confirmed on optical coherence tomography (OCT) (Stratus Model 3000 Carl Zeiss Meditec AG, Germany) [Figure 1b]. The patient underwent phacoemulsification with intraocular lens implantation (IOL), and macular hole repair with vitrectomy, trypan blue-assisted ILM peeling and intraocular gas tamponade. After vitrectomy, fluid–air exchange was performed. Trypan blue was aspirated in a 1 cc tuberculin syringe and mounted with a tapered flute needle tip. About 0.1 ml of trypan blue (0.15% w / v) (Retiblue manufactured by AUROLAB, 1 Sivaganga Main Road, Veerapanjan, Madurai 625020, India) was injected drop by drop, aimed toward the optic disc, and placed just a few millimetres above it. This approach helped to prevent the inadvertent subretinal injection of a jet of dye in the event of a sudden give-away on the piston's resistance of the dye-loaded syringe. The collected dye was centred on the macular hole and moved around it by moving the globe accordingly. The dye was aspirated after one minute using a flute needle. After air-fluid re-exchange, the ILM was peeled with a radius of about two disc diameters centered around the macular hole. A standard illumination probe (Alcon Laboratories, Fort Worth, TX, USA) was used for illumination. Fourteen percent of C3F8 gas was used as the intraocular tamponade. The patient was advised 12-14 hours of prone positioning per day for two weeks. Six weeks after surgery, the macular hole had closed and the BCVA improved to 20 / 80, N10. Three months later, the BCVA further improved to 20 / 40, N8. The macular hole remained closed. However, areas of RPE atrophy were noted within the area of the pre-existing macular hole. Areas of pre-existing diffuse RPE atrophy around the macular hole had also progressed. Perimetry revealed scattered points of depressed sensitivity in the posterior pole; the multifocal ERG revealed decreased central responses. Two years post surgery, the BCVA in the right eye was stable at 20 / 40, N8. However, progressive focal (area of erstwhile macular hole) and diffuse RPE atrophy (around the macular hole) were noted [Figure 2].

Figure 1

(a) Preoperative color fundus photo reveals a focal area of RPE atrophy within the macular hole (arrowheads) and diffusely (arrows), above it (b): An OCT scan confirms the presence of a full thickness macular hole

Figure 2

Postoperative color fundus photo reveals progressive focal (within the erstwhile macular hole — arrowheads) and diffuse RPE atrophy (arrows) Top left: The multifocal ERG scan reveals depressed responses corresponding to the areas affected. Below: OCT scan confirms macular hole closure

In the reported case, closure of the macular hole was achieved without intraoperative complications, which could have accounted for the RPE changes. The patient had improvement in vision, but had the most marked RPE damage at the fovea, the site of the full thickness retinal defect, and also diffusely around it.

This has not been reported before in other macular surgeries with similar dye usage and an intact retina (e.g., epiretinal membrane removal). Our case suggests a possible adverse effect of trypan blue on RPE, both direct and diffuse. A recent report on the use of heavy Trypan blue suggests elimination of the need for an air-fluid exchange (AFX) and appears to have little retinal toxicity.[8] However, the reported method still does not ensure possible subretinal migration of the dye. Following macular hole surgery, clinical manifestations of phototoxicity have been described.[9] However, in our case, there was no evidence of outer retinal whitening immediately following surgery, outer retinal atrophy, or RPE hypertrophy that could be attributed to phototoxicity.

The pattern and evolution of RPE changes in our case would indicate a more indolent, subacute change, suggestive of dye toxicity, manifesting in the area of exposure. Also, visual acuity progressively improved over the years instead of deteriorating as would be expected with phototoxicity. Hence, we feel that a shorter duration of exposure and thorough removal of dye from the vitreous cavity could avoid this occurrence.