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Retinal Toxicity Associated with Retained Indocyanine Green

Toxicity was observed after phacoemulsification for a traumatic cataract. Avoiding the use of ICG in such cases is recommended.

By: JAKE BREAZEALE, BA, ASGHAR “ABBAS” HAIDER, MD, MBA
New Retinal Physician November 1, 2023 Vol Retinal Physician 20, Issue November/December 2023 Page(s): 8-10

Indocyanine green (ICG) is a versatile contrast dye used in retinal imaging modalities and ophthalmic surgery. When used in surgery, it functions to stain or counterstain, facilitating better visualization of tissue like the internal limiting membrane (ILM), epiretinal membrane (ERM), and the anterior lens capsule. However, multiple reports implicate ICG as toxic to the neurosensory retina.1-6 Though alternative dyes are available, ICG remains widely used due to its cost, availability, and the excellent visualization it provides.

The following discussion features a case of a middle-aged male who demonstrated retinal toxicity from retained ICG used during cataract surgery for a traumatic cataract. To our knowledge, there are only 2 other cases in the literature of retained ICG following cataract surgery causing retinal toxicity.

CASE PRESENTATION

A 54-year-old male presented to the retina clinic 1 day after undergoing cataract surgery for a traumatic cataract in his left eye (OS). Before surgery, his vision was 20/20 in his right eye (OD) and 20/40 OS without clinically evident phacodonesis. During surgery, ICG was used to stain the anterior lens capsule and partially migrated beyond the retro-lenticular segment. This caused a dull red reflex, but the surgeon successfully completed the procedure and implanted an intraocular lens (IOL) in the capsular bag as planned.

On his postoperative day (POD) 1 visit, the patient had counting fingers (CF) vision OS and normal intraocular pressure (IOP). There was a limited view of the fundus that affected the quality of optical coherence tomography (OCT) (Figure 1A), and B-scan ultrasonography demonstrated mild vitreous opacities without evidence of retinal detachments or masses. Anterior segment examination of the left eye was notable for 1+ corneal edema, an IOL in good position, and a green hue in the vitreous cavity, consistent with retained ICG. The anterior segment and fundus exam of the right eye were normal. Given the known risk of toxicity to the RPE, a pars plana vitrectomy (PPV) was recommended for the next day.

FIGURE 1: These optical coherence tomography (OCT) images, taken with a Heidelberg Spectralis, demonstrate the progressive improvement in the patient’s media clarity from postoperative day 1 (A) and postoperative day 11 (B) to successive follow-up visits (C-F). The striking retinal thinning and inner segment/outer segment (IS/OS) disruption that is most prominent in the temporal macula is noted in the first interpretable OCT on postoperative day 28 (C). There is small progressive improvement to the outer retinal layer integrity from postoperative day 42 (D) to day 70 (E), and finally to postoperative day 100 (F). The near infrared reflectance imaging, shown on the left panel of each subfigure, also illustrates the resolving ICG-staining of the internal limiting membrane, with staining almost completed resolved by postoperative day 100 (F). IMAGES COURTESY JAKE BREAZEALE AND ASGHAR HAIDER, MD
FIGURE 1: These optical coherence tomography (OCT) images, taken with a Heidelberg Spectralis, demonstrate the progressive improvement in the patient’s media clarity from postoperative day 1 (A) and postoperative day 11 (B) to successive follow-up visits (C-F). The striking retinal thinning and inner segment/outer segment (IS/OS) disruption that is most prominent in the temporal macula is noted in the first interpretable OCT on postoperative day 28 (C). There is small progressive improvement to the outer retinal layer integrity from postoperative day 42 (D) to day 70 (E), and finally to postoperative day 100 (F). The near infrared reflectance imaging, shown on the left panel of each subfigure, also illustrates the resolving ICG-staining of the internal limiting membrane, with staining almost completed resolved by postoperative day 100 (F). IMAGES COURTESY JAKE BREAZEALE AND ASGHAR HAIDER, MD

During the PPV, anterior chamber washout, posterior capsulotomy, and an extended core vitrectomy were needed for adequate fundus visualization. A posterior vitreous detachment was induced without complication. No evidence of holes or tears was noted on a thorough inspection.

The following day, the patient’s vision was hand motion (HM) OS with an IOP of 13 mmHg. There was persistent +1 corneal edema and the view to the fundus was still limited. The patient was instructed to use topical prednisolone acetate and a combination antibiotic/steroid/NSAID drop 4 times daily.

The patient returned on POD 7. He continued to have HM vision but now had worsening corneal edema and an elevated IOP of 44 mmHg. His topical prednisolone acetate was increased to 6 times per day, and he was started on dorzolamide/timolol twice daily and brimonidine 3 times daily. Four days later, on POD 11, his vision improved to 20/400 and IOP to 15 mmHg. His corneal edema resolved and a view to the fundus improved but still limited a good quality OCT (Figure 1B).

On POD 28, the patient’s blurred vision was improving. His best-corrected visual acuity (BCVA) was 20/100, and his IOP was within normal limits. There was no relative afferent pupillary defect (RAPD) noted, and the confrontation visual field demonstrated a persistent severe central blur. OCT of the left eye showed retinal thinning with outer retinal layer disruption, particularly in the temporal macula (Figure 1C). The fundus exam showed resolving ILM staining from the ICG, consistent with the fundus photography done that day (Figure 2). At this point, the patient was instructed to continue topical prednisolone acetate 4 times daily and brimonidine 3 times daily.

FIGURE 2: Montage fundus photograph of the left eye showing indocyanine green–stained internal limiting membrane on postoperative day 28. Images taken with a Topcon TRC-50DC Mydriatic Camera. IMAGE COURTESY JAKE BREAZEALE AND ASGHAR HAIDER, MD
FIGURE 2: Montage fundus photograph of the left eye showing indocyanine green–stained internal limiting membrane on postoperative day 28. Images taken with a Topcon TRC-50DC Mydriatic Camera. IMAGE COURTESY JAKE BREAZEALE AND ASGHAR HAIDER, MD

At subsequent follow-up visits, the OCTs (Figure 1, D-E) showed progressive improvement in the outer retinal layer integrity. During the patient’s most recent follow-up, postoperative day 100, IOP was normal without any topical drops, and BCVA remained 20/100 (Figure 1F).

DISCUSSION

In our literature search, we found 2 relevant case reports regarding the effects of retained ICG after traumatic cataract surgery.7,8 The first case involved a patient who presented on POD 1 with retained ICG in the vitreous cavity, CF vision, and a new RAPD.7 On POD 5, the patient’s vision had deteriorated to light perception (LP) and IOP had increased to 38 mmHg, so the patient was referred for a PPV to remove the dye. Over 8 months following the original cataract surgery, the patient’s BCVA improved to 20/40 and IOP stabilized, although the RAPD persisted. Like our patient, this case also exhibited elevated IOP and corneal edema.

The second case report involved a patient with a similar presentation of decreased visual acuity, anterior segment inflammation, corneal edema, and ICG in the eye after traumatic cataract removal.8 However, in this case, the patient did not have a reported IOP spike and the dye was not surgically removed. Over 6 months following phacoemulsification, the patient experienced an overall improvement in visual acuity from 20/400 to 20/30, though the patient still had a persistent paracentral scotoma.

The migration of ICG in all these cases was likely facilitated by zonular loss related to the traumatic cataract. Thus, it may be advisable not to use ICG in traumatic cataract cases.

Multiple mechanisms of ICG-induced retinal toxicity have been reported, including activation of RPE apoptosis, light-induced injury, direct biochemical injury to the ganglion cells, and photoreceptor damage.1-6 Higher concentration and longer durations of exposure to ICG in these reports are linked to more severe injury. Thus, when ICG is used in retinal surgery, the dye is diluted and removed relatively quickly, limiting clinically evident damage in most cases.

In our case, it is unclear if the timing of the vitrectomy would have made a difference since the other cases either had a vitrectomy later (POD 5) or no vitrectomy at all, and both had more favorable VA outcomes than our patient. Nonetheless, it is advisable to remove any ICG dye as soon as possible and to consider an alternative contrast dye to stain the lens capsule in traumatic cataract cases. Early and more liberal use of topical steroids and hypotensive eye drops may be beneficial to treat corneal edema and IOP spikes in these cases. NRP

JAKE BREAZEALE, BA, is a full-time scribe at Southeastern Retina Associates in Chattanooga, Tennessee, who is currently applying to medical school. He reports no relevant disclosures.

ASGHAR “ABBAS” HAIDER, MD, MBA, is a vitreoretinal surgeon and ocular oncologist at Southeastern Retina Associates. He reports no relevant disclosures. He can be reached at ahaider@seretina.com.

REFERENCES

  1. Ferencz M, Somfai GM, Farkas Á, et al. Functional assessment of the possible toxicity of indocyanine green dye in macular hole surgery. Am J Ophthalmol. 2006;142(5):765-770. doi:10.1016/j.ajo.2006.05.054
  2. Kawahara S, Hata Y, Miura M, et al. Intracellular events in retinal glial cells exposed to ICG and BBG. Invest Ophthalmol Vis Sci. 2007;48(10):4426-4432. doi:10.1167/iovs.07-0358
  3. Narayanan R, Kenney MC, Kamjoo S, et al. Toxicity of indocyanine green (ICG) in combination with light on retinal pigment epithelial cells and neurosensory retinal cells. Curr Eye Res. 2005;30(6):471-478. doi:10.1080/02713680590959312
  4. Penha FM, Pons M, de Paula Fiod Costa E, et al. Effect of vital dyes on retinal pigmented epithelial cell viability and apoptosis: implications for chromovitrectomy. Ophthalmologica. 2013;230 Suppl 2(0 2):41-50. doi:10.1159/000354251
  5. Rodrigues EB, Meyer CH, Mennel S, Farah ME. Mechanisms of intravitreal toxicity of indocyanine green dye: implications for chromovitrectomy. Retina. 2007;27(7):958-970. doi:10.1097/01.iae.0000253051.01194.ab
  6. Takayama K, Sato T, Karasawa Y, Sato S, Ito M, Takeuchi M. Phototoxicity of indocyanine green and brilliant blue G under continuous fluorescent illumination on cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2012;53(11):7389-7394. doi:10.1167/iovs.12-10754
  7. Allen RC, Russell SR, Schluter ML, Oetting TA. Retained posterior segment indocyanine green dye after phacoemulsification. J Cataract Refract Surg. 2006;32(2):357-360. doi:10.1016/j.jcrs.2005.12.038
  8. Ksiazek S, Grover S, Mojica G, Fishman GA. Indocyanine green toxicity of the retina after cataract surgery: a case report. Retin Cases Brief Rep. 2009;3(2):115-117. doi:10.1097/ICB.0b013e318162b123

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