The Use of Triamcinolone for Visualization During Vitreoretinal Surgery
Surgeons now have available the first FDA-approved chromovitrectomy agent.
RICHARD H. ROE, MD, MHS · DAVID S. BOYER, MD
Chromovitrectomy is the use of chemicals to aid in the visualization of semi-transparent preretinal membranes during vitrectomy surgery. Commonly used agents include indocyanine green (ICG), trypan blue and triamcinolone acetonide. Preservative-free triamcinolone acetonide (TRIESENCE® suspension, Alcon Laboratories Inc., Fort Worth, TX) is the first such agent approved by the FDA specifically for use in visualization.
Peyman and colleagues were the first to report on the use of triamcinolone as an aid to visualize the vitreous and posterior hyaloid during vitrectomy surgery.1 Since that time, the use of triamcinolone as a surgical adjunct has become commonplace, not only to visualize the vitreous and its removal, but also to aid visualization and peeling of epiretinal membranes (ERMs) and internal limiting membranes (ILMs) for various vitreoretinal diseases. In this article, we discuss findings from various researchers that support triamcinolone-assisted vitreoretinal surgery.
AIDING A FUNDAMENTAL MANEUVER
Pars plana vitrectomy is commonly performed for the treatment of retinal detachment, macular hole, ERM, vitreomacular traction syndrome and proliferative diabetic retinopathy. One of the fundamental maneuvers performed during vitrectomy surgery is the removal of the posterior hyaloid. The posterior hyaloid can exert tractional forces on the surface of the retina and also acts as a scaffold for proliferative membrane growth in diseases, such as proliferative diabetic retinopathy and proliferative vitreoretinopathy. Failure to remove the posterior hyaloid during repair of these vitreoretinal diseases can result in poorer anatomical and visual outcomes.2,3 Because of the transparent nature of the vitreous, visual confirmation that the posterior hyaloid has been completely removed can be difficult for the surgeon. Numerous studies have shown that triamcinolone aids in the removal of the posterior hyaloid.1,4
|Richard H. Roe, MD, MHS, practices at Retina-Vitreous Associates Medical Group, with offices in Southern California.|
David S. Boyer, MD, practices at Retina-Vitreous Associates Medical Group in Southern California. He is Clinical Professor of Ophthalmology, Doheny Eye Institute at USC/Keck School of Medicine. He is a consultant for Alcon, Genentech, Novartis, Allergan and Pfizer.
Peyman and colleagues and Enaida and colleagues noted that during surgery, water-insoluble triamcinolone particles could easily integrate into the collagen matrices of the vitreous gel (Figure 1).1,4 Moreover, triamcinolone particles were much more freely mobile in the fluid-filled posterior hyaloid space compared to the vitreous gel body, further aiding removal of the posterior hyaloid.
Figure 1. Water-insoluble triamcinolone particles integrated into the collagen matrices of the vitreous gel.
Matsumoto and colleagues definitively proved that posterior hyaloid removal was more successful in triamcinolone-assisted vitrectomy versus standard vitrectomy.5 Using transmission and scanning electron microscopy, they examined ILM specimens taken from eyes that underwent vitrectomy with or without triamcinolone. They found the ratio of residual posterior hyaloid on ILMs was significantly lower in specimens taken from eyes that underwent triamcinolone-assisted vitrectomy.
Enaida and colleagues examined 177 eyes from 158 patients who underwent vitrectomy for retinal detachment, macular hole and proliferative diabetic retinopathy with or without the aid of triamcinolone.4 At 6 months, researchers found no difference in vision or IOP between the two groups. However, there was a lower incidence of reoperation secondary to preretinal fibrosis in patients who had vitrectomy with the aid of triamcinolone. In particular, the greatest difference in the incidence of postoperative preretinal fibrosis was seen in cases of proliferative diabetic retinopathy.
FACILITATING ERM AND ILM PEELING
In addition to aiding removal of the vitreous and the posterior hyaloid, triamcinolone is also an effective aid in visualization and peeling of ERMs and ILMs (Figure 2). Removal of the ILM is thought to improve anatomic and visual outcomes of macular hole repair.6-9 Electron microscopy studies have shown that a small layer of residual cortical vitreous cells and collagen fibers remains on the surface of the retina, allowing triamcinolone particles to coat ERMs and ILMs.10,11 In contrast, other agents used in vitreoretinal surgery, such as ICG and trypan blue, stain and integrate into the membranes.
Figure 2. Triamcinolone can aid visualization and peeling of epiretinal and internal limiting membranes.
Indocyanine green and trypan blue are water-soluble agents that bind to type IV collagen, allowing visualization of ILMs. Residual staining of the ILM that is not peeled can remain for months.12 Conversely, because triamcinolone coats rather than stains the surface of ERMs and ILMs, any remaining triamcinolone particles can be removed from the eye with continuous aspiration or irrigation. Although controversial, ICG also has been reported to cause retinal toxicity. While some researchers have reported no adverse anatomical or functional outcomes,13,14 others have reported retinal pigment epithelial damage, optic nerve atrophy, decreased multifocal electroretinographic responses and visual field defects.15-18 Trypan blue has not had the same reported toxicities as ICG, but the quality of staining may not be as good.19,20 Vitrectomy with trypan blue also requires air-fluid exchange before application, which is not required when using triamcinolone. Additionally, unlike triamcinolone, ICG must be diluted before its use in vitreoretinal surgery. TRIESENCE® suspension, specifically, comes in a terminally prepackaged 1 mL vial at a concentration of 40 mg/mL and is ready for immediate injection.
The use of triamcinolone to aid in peeling ERMs and ILMs has been well documented. Horio and colleagues reported on 12 patients with idiopathic macular holes who underwent triamcinolone-assisted vitrectomy with ILM peeling.21 Postoperatively, the macular hole was closed in all eyes and vision improved from 20/200 to 20/40. There were no reported complications. Others have reported similar results.22-24
One of the main observations that has concerned surgeons using triamcinolone during ILM peeling for macular hole repair has been residual triamcinolone crystals in or around the macular hole postoperatively. Although alarming when initially seen, this has not been reported to affect anatomical or final visual outcomes, and usually disappears after 1 or 2 weeks.23,25,26
Triamcinolone also aids in the visualization of ERMs and posterior hyaloid in retinal detachment complicated by proliferative vitreoretinopathy as well as myopic foveoschisis. Furino and colleagues reported on using triamcinolone to stain ERMs in 10 cases of retinal detachment complicated by proliferative vitreoretinopathy.27 In all cases, they felt that triamcinolone consistently aided in direct visualization and delineation of the posterior hyaloid and ERMs and facilitated their removal. Ikuno and colleagues also reported on 6 eyes in 5 patients who underwent triamcinolone-assisted vitrectomy for myopic foveoschisis.28 They observed the posterior cortical vitreous as a thin, transparent membrane that could be visualized only with triamcinolone. After careful removal of this layer and the ILM followed by gas tamponade, all patients had 2 lines of visual improvement at 6 months with no complications.
LOWER COMPLICATION RATES IN VITRECTOMY CASES
Potential adverse effects of intravitreal corticosteroid use include elevated IOP, endophthalmitis and cataract formation.29,30 While these have proven to be the case when treating macular edema and uveitis, they have not been reported when used during vitrectomy. Yamakiri and colleagues performed a prospective multicenter, controlled clinical trial looking at patients who underwent vitrectomy with or without triamcinolone.31 In 774 eyes, they found no difference in final vision, incidence of elevated IOP, endophthalmitis or cataract formation after 1 year.
Kampougeris and colleagues also reported on complication rates of using triamcinolone for macular hole repair.32 They found no difference in anatomical macular hole closure rates, final vision or IOP rise between patients who had received triamcinolone and those who had not. Sakamoto and colleagues retrospectively reviewed 1889 cases of triamcinolone-assisted vitrectomy taken from 7 different hospitals and found only 1 case (0.053%) of postoperative endophthalmitis.33 This was considerably lower than the incidence of endophthalmitis (0.87%) reported after intravitreal injection of triamcinolone as reported by Moshfeghi and colleagues.34 The reason for lower complication rates in triamcinolone-assisted vitrectomy is not known. It is possible, however, that because less corticosteroid is injected into the eye during vitrectomy and most if not all of the remaining steroid is removed from the eye during the surgery, any potential adverse effects from the steroid may be considerably decreased.
SAFE AND EFFECTIVE CHROMOVITRECTOMY AGENT
Corticosteroids have long been a mainstay in the treatment and management of ocular diseases. Triamcinolone acetonide, a synthetic corticosteroid, is widely used to treat macular edema and uveitis as well as to aid visualization during vitrectomy surgery. Recently, preservative-free triamcinolone acetonide (TRIESENCE®) became the first preservative free and FDA-approved agent for ophthalmic use. Its popularity as an agent for chromovitrectomy should continue to increase due to its known efficacy, ease of use and relatively low risk safety profile. RP
- Peyman GA, Cheema R, Conway MD, Fang T. Triamcinolone acetonide as an aid to visualization of the vitreous and the posterior hyaloid during pars plana vitrectomy. Retina. 2000;20:554-5.
- Han DP, Abrams GW, Aaberg TM. Surgical excision of the attached posterior hyaloid. Arch Ophthalmol. 1988;106:998-1000.
- Mein CE, Flynn HW, Jr. Recognition and removal of the posterior cortical vitreous during vitreoretinal surgery for impending macular hole. Am J Ophthalmol. 1991;111:611-3.
- Enaida H, Hata Y, Ueno A, et al. Possible benefits of triamcinolone-assisted pars plana vitrectomy for retinal diseases. Retina. 2003;23:764-70.
- Matsumoto H, Yamanaka I, Hisatomi T, et al. Triamcinolone acetonide-assisted pars plana vitrectomy improves residual posterior vitreous hyaloid removal: ultrastructural analysis of the inner limiting membrane. Retina. 2007;27:174-9.
- Yoshida M, Kishi S. Pathogenesis of macular hole recurrence and its prevention by internal limiting membrane peeling. Retina. 2007;27:169-73.
- Schumann RG, Rohleder M, Schaumberger MM, et al. Idiopathic macular holes: ultrastructural aspects of surgical failure. Retina. 2008;28:340-9.
- Thompson JT. The effect of internal limiting membrane removal and indocyanine green on the success of macular hole surgery. Trans Am Ophthalmol Soc. 2007;105:198-205; discussion -6.
- Brooks HL, Jr. Macular hole surgery with and without internal limiting membrane peeling. Ophthalmology. 2000;107:1939-48; discussion 48-9.
- Messmer EM, Heidenkummer HP, Kampik A. Ultrastructure of epiretinal membranes associated with macular holes. Graefes Arch Clin Exp Ophthalmol. 1998;236:248-54.
- Smiddy WE, Michels RG, de Bustros S, et al. Histopathology of tissue removed during vitrectomy for impending idiopathic macular holes. Am J Ophthalmol. 1989;108:360-4.
- Nakamura H, Hayakawa K, Imaizumi A, et al. Persistence of retinal indocyanine green dye following vitreous surgery. Ophthalmic Surg Lasers Imaging. 2005;36:37-45.
- Da Mata AP, Burk SE, Riemann CD, et al. Indocyanine green-assisted peeling of the retinal internal limiting membrane during vitrectomy surgery for macular hole repair. Ophthalmology. 2001;108:1187-92.
- Kwok AK, Li WW, Pang CP, et al. Indocyanine green staining and removal of internal limiting membrane in macular hole surgery: histology and outcome. Am J Ophthalmol. 2001;132:178-83.
- Posselt D, Rahman R, Smith M, Simcock PR. Visual outcomes following ICG assisted ILM peel for Macular Hole. Eye. 2005;19:279-83.
- Cheng SN, Yang TC, Ho JD, et al. Ocular toxicity of intravitreal indocyanine green. J Ocul Pharmacol Ther. 2005;21:85-93.
- Engelbrecht NE, Freeman J, Sternberg P, Jr., et al. Retinal pigment epithelial changes after macular hole surgery with indocyanine green-assisted internal limiting membrane peeling. Am J Ophthalmol. 2002;133:89-94.
- Ferencz M, Somfai GM, Farkas A, et al. Functional assessment of the possible toxicity of indocyanine green dye in macular hole surgery. Am J Ophthalmol. 2006;142:765-70.
- Teba FA, Mohr A, Eckardt C, et al. Trypan blue staining in vitreoretinal surgery. Ophthalmology. 2003;110:2409-12.
- Vote BJ, Russell MK, Joondeph BC. Trypan blue-assisted vitrectomy. Retina. 2004;24:736-8.
- Horio N, Horiguchi M, Yamamoto N. Triamcinolone-assisted internal limiting membrane peeling during idiopathic macular hole surgery. Arch Ophthalmol. 2005;123:96-9.
- Fraser EA, Cheema RA, Roberts MA. Triamcinolone acetonide-assisted peeling of retinal internal limiting membrane for macular surgery. Retina. 2003;23:883-4.
- Kumagai K, Furukawa M, Ogino N, et al. Long-term outcomes of macular hole surgery with triamcinolone acetonide-assisted internal limiting membrane peeling. Retina. 2007;27:1249-54.
- Kimura H, Kuroda S, Nagata M. Triamcinolone acetonide-assisted peeling of the internal limiting membrane. Am J Ophthalmol. 2004;137:172-3.
- Karacorlu M, Ozdemir H, Arf Karacorlu S. Does intravitreal triamcinolone acetonide-assisted peeling of the internal limiting membrane effect the outcome of macular hole surgery? Graefes Arch Clin Exp Ophthalmol. 2005;243:754-7.
- Takeuchi M, Katagiri Y, Usui M. Residual triamcinolone acetonide in the macular hole after vitrectomy. Am J Ophthalmol. 2003;136:1174-6.
- Furino C, Micelli Ferrari T, Boscia F, et al. Triamcinolone-assisted pars plana vitrectomy for proliferative vitreoretinopathy. Retina. 2003;23:771-6.
- Ikuno Y, Sayanagi K, Ohji M, et al. Vitrectomy and internal limiting membrane peeling for myopic foveoschisis. Am J Ophthalmol. 2004;137:719-24.
- Jonas JB, Kreissig I, Degenring R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol. 2003;87:24-7.
- Gillies MC, Simpson JM, Billson FA, et al. Safety of an intravitreal injection of triamcinolone: results from a randomized clinical trial. Arch Ophthalmol. 2004;122:336-40.
- Yamakiri K, Sakamoto T, Noda Y, et al. One-year results of a multicenter controlled clinical trial of triamcinolone in pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol. 2008;246:959-66.
- Kampougeris G, Cheema R, McPherson R, Gorman C. Safety of Triamcinolone acetonide (TA)-assisted pars plana vitrectomy in macular hole surgery. Eye. 2007;21:591-4.
- Sakamoto T, Enaida H, Kubota T, et al. Incidence of acute endophthalmitis after triamcinolone-assisted pars plana vitrectomy. Am J Ophthalmol. 2004;138:137-8.
- Moshfeghi DM, Kaiser PK, Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol. 2003;136:791-6.