Diabetic Macular Oedema Conclusions
DMO remains the leading cause of visual impairment in the working-age population. Emerging pharmacological approaches are being evaluated to treat DMO unresponsive to laser therapy. Many retinal physicians have begun to routinely inject TA as a promising option for the treatment of refractory DMO, although in these cases the intravitreal administration of TA is not FDA approved and has been mostly used off-label. Intravitreal TA has been found to significantly increase the visual acuity and decrease central macular thickness in short-term follow-up. Despite a very favourable systemic safety profile, a significant proportion of patients experience a rise in IOP and cataract development following intravitreal TA injections. The incidence of severe ocular adverse events such as infectious endophthalmitis, pseudoendophthalmitis, retinal toxicity and rhegmatogenous retinal detachment remains on the low side. Recently, a combined strategy of intravitreal injection of TA and laser photocoagulation has been evaluated for the treatment of DMO.31
In this study laser
photocoagulation appeared safer and more effective than the combination of intravitreal injection of TA and laser treatment. However, when considering patients that were pseudophakic at baseline, TA in combination with laser resulted in better visual outcomes than laser alone. The results of the combination of TA and laser were comparable to those obtained with the combination of laser and ranibizumab in this subgroup of patients after two years of
1. Machemer R, Sugita G, Tano Y, Treatment of intraocular proliferations with intravitreal steroids, Trans Am Ophthalmol Soc, 1979;77:171–80.
2. Abelson MB, Butrus S, Corticosteroids in ophthalmic practice. In: Abelson MB, Neufeld AH, Topping TM (eds), Principles and Practice of Ophthalmology, Philadelphia, PA: WB Saunders, 1994;1014.
3. Scholes GN, O’Brien WJ, Abrams GW, et al., Clearance of triamcinolone from vitreous, Arch Ophthalmol, 1985;103:1567–9.
4. Beer PM, Bakri SJ, Singh RJ, et al., Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection, Ophthalmology, 2003;110:681–6.
5. Audren F, Tod M, Massin P, et al., Pharmacokinetic- pharmacodynamic modeling of the effect of triamcinolone acetonide on central macular thickness in patients with diabetic macular edema, Invest Ophthalmol Vis Sci, 2004;45:3435–41.
6. Inoue M, Takeda K, Morita K, et al., Vitreous concentrations of triamcinolone acetonide in human eyes after intravitreal or subtenon injection, Am J Ophthalmol, 2004;138:1046–8.
7. Yilmaz T, Weaver CD, Gallagher MJ, et al., Intravitreal triamcinolone acetonide injection for treatment of refractory diabetic macular edema: a systematic review, Ophthalmology, 2009;116:902–11.
8. Juergens UR, Jager F, Darlath W, et al., Comparison of in vitro-activity of commonly used topical glucocorticoids on cytokine- and phospholipase inhibition, Eur J Med Res, 2004;31:383–90.
9. Tong JP, Lam DS, Chan WM, et al., Effects of triamcinolone on the expression of VEGF and PEDF in human retinal pigment epithelial and human umbilical vein endothelial cells, Mol Vis, 2006;12:1490–5.
10. Smit-McBride Z, Modjtahedi SP, Cessna CT, et al., In vivo gene expression profiling of retina postintravitreal injections of dexamethasone and triamcinolone at clinically relevant time points for patient care, Ophthalmol Vis Sci, 2011;10:7084.
11. Tsaprouni LG, Ito K, Punchard N, et al., Triamcinolone acetonide and dexamethasome suppress TNF-alpha-induced histone H4 acetylation on lysine residues 8 and 12 in mononuclear cells, Ann N Y Acad Sci, 2002;973:481–3.
12. Mizuno S, Nishiwaki A, Morita H, et al., Effects of periocular administration of triamcinolone acetonide on leukocyte- endothelium interactions in the ischemic retina, Invest Ophthalmol Vis Sci, 2007;48:2831–6.
13. Tamura H, Miyamoto K, Kiryu J, et al., Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina, Invest Ophthalmol Vis Sci, 2005;46:1440–4.
14. Sutter FK, Simpson JM, Gillies MC, Intravitreal triamcinolone for diabetic macular edema that persists after laser treatment: three-month efficacy and safety results of a prospective, randomized, double-masked, placebo-controlled clinical trial, Ophthalmology, 2004;111:2044–9.
15. Ciardella AP, Klancnik J, Schiff W, et al., Intravitreal triamcinolone for the treatment of refractory diabetic macular oedema with hard exudates: an optical coherence tomography study, Br J Ophthalmol, 2004;88:1131–6.
The rationale for combining laser photocoagulation and intravitreal TA lies in their synergistic mechanism of action and may offer the chance to reduce the number of intravitreal injections required and so decrease the rate of drug- and injection-related adverse events. However, several vision-threatening side effects have been reported as a result of thermal damage caused by laser procedure.98–100
In recent years advances in laser therapy of retinal diseases have been directed at reducing the unnecessary disruptive effect that laser photocoagulation produces in retinal tissues. Several studies have shown the efficacy of sub-threshold laser photocoagulation in treating DMO, producing fewer side effects than conventional laser treatment.101–105
Combining intravitreal TA and
sub-threshold laser photocoagulation may be a promising option to obtain good and durable visual outcomes while reducing the side effects correlated to either the laser procedure or the drug.
Many questions still remain unanswered concerning the optimal dose of TA for intravitreal use and the side-effect profiles of various commercially available formulations of TA with and without preservatives. Thus, an optimal balance between efficacy and safety profile has yet to be completely determined. Novel steroid implants and anti-VEGF drugs are being evaluated alone or in combination as promising options in the emerging armamentarium for the treatment of DMO. n
16. Micelli Ferrari T, Sborgia L, Furino C, et al., Intravitreal triamcinolone acetonide: valuation of retinal thickness changes measured by optical coherence tomography in diffuse diabetic macular edema, Eur J Ophthalmol, 2004;14:321–4.
17. Lee WF, Yang CM, Intravitreal triamcinolone injection for macular edema secondary to increased retinal vascular permeability, J Formos Med Assoc, 2004;103:692–700.
18. Karacorlu M, Ozdemir H, Karacorlu S, et al., Intravitreal triamcinolone as a primary therapy in diabetic macular oedema, Eye, 2005;19:382–6.
19. Bhagat N, Ruben A, Tutela A, et al., Diabetic macular edema: pathogenesis and treatment, Surv Opthalmol, 2009;54:1–32.
20. Audren F, Erginay A, Haouchine B, et al., Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month results of a prospective controlled trial, Acta Ophthalmol Scand, 2006;84:624–30.
21. Avitabile T, Longo A, Reibaldi A, Intravitreal triamcinolone compared with macular laser grid photocoagulation for the treatment of cystoid macular edema, Am J Ophthalmol, 2005;140:695–702.
22. Gillies MC, Sutter FK, Simpson JM, et al., Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial, Ophthalmology, 2006;113:1533–8.
23. Jonas JB, Kamppeter BA, Harder B, et al., Intravitreal triamcinolone acetonide for diabetic macular edema: a prospective, randomized study, J Ocul Pharmacol Ther, 2006;22:200–7.
24. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group, Arch Ophthalmol, 1985;103:1796–806.
25. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Early Treatment Diabetic Retinopathy Study Research Group, Ophthalmology, 1987;94:761–74.
26. Lee CM, Olk RJ, Modified grid laser photocoagulation for diffuse diabetic macular edema. Long-term visual results, Ophthalmology, 1991;98:1594–602.
27. Veritti D, Perissin L, Zorzet S, et al., The effect of triamcinolone acetonide, sodium hyaluronate, and chondroitin sulfate on human endothelial cells: an in vitro study, Eur J Ophthalmol, 2010;21:75–9.
28. Chang LK, Gomes NL, Zhou J, et al, Physical properties of commercially available formulations of triamcinolone acetonide, Br J Ophthalmol, 2009;93:1265–6.
29. Kupperman DB, Differentiating steroid delivery systems for macular edema, John Hopkins Advanced Studies in Ophthalmology, 2010;2:35–41.
30. Diabetic Retinopathy Clinical Research Network, A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema, Ophthalmology, 2008;115:1447–9.
31. Diabetic Retinopathy Clinical Research Network, Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema,
32. Choi KS, Chung JK, Lim SH, Laser photocoagulation combined with intravitreal triamcinolone acetonide injection in proliferative diabetic retinopathy with macular edema, Korean J Ophthalmol, 2007;21:11–7.
33. Kaderli B, Avci R, Gelisken O, et al., Intravitreal triamcinolone as an adjunct in the treatment of concomitant proliferative diabetic retinopathy and diffuse diabetic macular oedema. Combined IVTA and laser treatment for PDR with CSMO, Int Ophthalmol, 2007;26:207–14.
34. Zacks DN, Johnson MW, Combined intravitreal injection of triamcinolone acetonide and panretinal photocoagulation for concomitant diabetic macular edema and proliferative diabetic retinopathy, Retina, 2005;25:135–40.
35. Zein WM, Noureddin BN, Jurdi FA, et al., Panretinal photocoagulation and intravitreal triamcinolone acetonide for the management of proliferative diabetic retinopathy with macular edema, Retina, 2006;26:137–42.
36. Bandello F, Polito A, Pognuz DR, et al., Triamcinolone as adjunctive treatment to laser panretinal photocoagulation for proliferative diabetic retinopathy, Arch Ophthalmol, 2006;124:643–50.
37. Maia OO, Takahashi BS, Costa RA, Combined laser and intravitreal triamcinolone for proliferative diabetic retinopathy and macular edema: one-year results of a randomized clinical trial, Am J Ophthalmol, 2009;147:291–7.
38. Kim JE, Pollack JS, Miller DG, et al., ISIS-DME: a prospective, randomized, dose-escalation intravitreal steroid injection study for refractory diabetic macular edema, Retina, 2008;28:735–40.
39. Gillies MC, Simpson JM, Gaston C, et al., Five-year results of a randomized trial with open-label extension of triamcinolone acetonide for refractory diabetic macular edema, Ophthalmology, 2009;116:2182–7.
40. Audren F, Erginay A, Haouchine B, et al., Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month results of a prospective controlled trial, Acta Ophthalmol Scand, 2006;84:624–30.
41. Hauser D, Bukelman A, Pokroy R, et al., Intravitreal triamcinolone for diabetic macular edema: comparison of 1, 2, and 4 mg, Retina, 2008;28:825–30.
42. Lam DS, Chan CK, Mohamed S, et al., A prospective randomised trial of different doses of intravitreal triamcinolone for diabetic macular oedema, Br J Ophthalmol, 2007;91:199–203.
43. Massin P, Audren F, Haouchine B, et al., Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial, Ophthalmology, 2004;111:218–24.
44. Geroski DH, Edelhauser HF, Transscleral drug delivery for posterior segment disease, Adv Drug Deliv Rev, 2001;52:37–48.
45. Bonini-Filho MA, Jorge R, Barbosa JC, et al., Intravitreal injection versus sub-Tenon’s infusion of triamcinolone acetonide for refractory diabetic macular edema: a randomized clinical trial, Invest Ophthalmol Vis Sci, 2005;46:3845–9.
46. Cardillo JA, Melo LA, Jr., Costa RA, et al., Comparison of intravitreal versus posterior sub-Tenon’s capsule injection of
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