Intravitreal Triamcinolone for Diabetic Macular Edema: Conflicting Reports
HEMA K. KARAMCHANDANI, MD · ATHANASIOS I. KOTSOLIS, MD
Macular edema caused by diabetic retinopathy has increased considerably as a public health problem. The prevalence of diabetic retinopathy is expected to rise and cause significant vision loss as the US population ages and the age-specific prevalence of diabetes increases over time.1 Therapeutic options for diabetic macular edema (DME) are also greater than before as new treatment modalities are being evaluated. This article serves to review recent publications delineating the role of intravitreal triamcinolone acetonide in the treatment of DME, focusing on conflicting reports on the efficacy of repeated injections. We will also provide a brief overview of current and future therapies for this disorder.
Laser photocoagulation is the only therapy that has been proven effective in reducing DME and improving or stabilizing visual acuity (VA). In a large-scale randomized controlled trial, incidence of severe visual loss at 5 years (VA less than 5/200 at 2 consecutive visits) was low in early and deferred treatment groups (2.6% and 3.7%, respectively).2 Although photocoagulation is the gold standard for treatment of DME, insight into the pathophysiology of DME has led to corticosteroid-based treatment strategies and alternative therapeutic options.
|Hema K. Karamchandani, MD, and Athanasios I. Kotsolis, MD are in practice with Vitreous, Retina, Macula Consultants of New York. Neither author reports any financial interests.|
Off-label intravitreal triamcinolone acetonide (IVTA) has become a common treatment for refractory DME. Although there has been a general consensus that IVTA effectively reduces macular thickness and improves visual acuity in the short term, there are conflicting reports on the outcome of repeated injections.3-5 The effectiveness of triamcinolone against DME is based on its ability to reduce inflammation and the expression of vascular endothelial growth factor (VEGF) and to stabilize the inner blood-retinal barrier.6,7 IVTA has well-documented risks for both early, ocular hypertension, and late, cataract. The side effects of repeated injections of triamcinolone are related to the procedure of injections or the drug itself.
|"Photocoagulation is the only therapy proven effectve in reducing DME."|
EFFICACY OF REPEATED INJECTIONS OF IVTA
There have been several studies reporting conflicting results on the efficacy of repeated injections of triamcinolone. One study reported on 75 eyes of 75 diabetic patients with clinically significant macular edema refractory to previous laser photocoagulation, who were treated with IVTA and followed for 2 years.3 During this period, 38% of eyes required reinjection. VA improved significantly from baseline at 3 months. After 3 months, there was no significant change from baseline VA. Foveal thickness was significantly reduced by three days post-injection. The reduction remained during follow-up, but it did not correlate with improvement in VA. Twenty-eight percent of eyes developed ocular hypertension which required therapy and 24% developed cataract.
Chan and colleagues presented 10 eyes with DME treated with 2 injections of IVTA at least 26 weeks apart.4 Transient improvements in VA and central foveal thickness occurred after each injection, but VA and central foveal thickness were significantly worse after the second injection compared with the first injection. There was no difference in post-injection adverse effects (elevated intraocular pressure or increase in cataract incidence) between the two injections.
Gillies and colleagues reported 33 eyes with DME and previous laser treatment, which were treated with IVTA and followed for 2 years.5 During this period, 82% of eyes were reinjected. VA improved significantly and to a similar extent after each successive injection. There was no correlation between the number of injections received and final improvement in VA, the central macular thickness, or requirement for glaucoma therapy. On the other hand, there was a significant correlation between number of injections received and the need for cataract surgery.
COMPLICATIONS OF INTRAVITREAL TRIAMCINOLONE
In a study concerning IVTA injections in 929 eyes, steroid-related ocular hypertension (intraocular pressure ≥ 21 mmHg) occurred in 21% of eyes, ocular inflammation in 0.6%, and corneal epithelial defects in 0.3% within three months after the procedure.8 In another study of 272 patients treated with IVTA for DME, at least 1 intraocular pressure measurement higher than 21 mm Hg during a mean follow-up of 10.4 months was measured in 41.2% of patients.9 In an elderly population of patients, clinically significant cataract with eventual surgery was observed in 15% to 20% of eyes within one year after the intravitreal injection.10
ALTERNATIVE TREATMENTS FOR DME
Ongoing clinical trials are evaluating the efficacy and safety of alternative corticosteroids and methods of delivery in the future. Several phase 3 studies are currently evaluating TA implants and intravitreal injections, a sustained-release formulation for delivery of dexamethasone to the posterior segment (Posurdex, Allergan, Inc.), and a sustained-release fluocinolone acetonide implant (Retisert, Bausch and Lomb Pharmaceuticals).
Off-label use of VEGF inhibitors is an emergent therapeutic option for DME. A study of 51 patients with DME not responding to previous treatments such as laser photocoagulation or IVTA were treated with intravitreal bevacizumab and followed for at least 6 weeks.11 Improvement of VA was observed at 6 weeks after injection. Decrease of retinal thickness was observed at 2, 6, and 12 weeks after injection. Paccola and colleagues reported 26 patients with DME treated with either IVTA or bevacizumab and followed for 24 weeks.12 Central macular thickness was reduced at 4, 8, 12, and 24 weeks and best corrected VA was higher at 8 and 12 weeks in the IVTA group compared with the bevacizumab group. Mean intraocular pressure was increased at week four only in the IVTA group. There was no increase in cataract incidence in either group.
A positive effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on chronic cystoid macular edema has been noted in a systematic review by Sivaprasad and colleagues.13 However, further studies are necessary to delineate the exact role of topical NSAIDs in the treatment of DME.
In summary, IVTA is effective in the short-term treatment of DME but has the well-documented risks of ocular hypertension and cataract. There are conflicting reports on the efficacy of repeated injections of triamcinolone. Novel agents and methods of delivery are being evaluated in several trials and may change the treatment of DME in the near future. RP
- Kempen JH, O'Colmain BK, Leske MC, et al. Eye Diseases Prevalence Research Group. Arch Ophthalmol. 2004;122:522-563.
- Early photocoagulation for diabetic neuropathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98(Suppl 5):766-785.
- Batio lu F, Ozmert E, Parmak N, et al. Two-year results of intravitreal triamcinolone acetonide injection for the treatment of diabetic macular edema. Int Ophthalmol. 2007;27:299-306.
- Chan CK, Mohamed S, Shanmugam MP, et al. Decreasing efficacy of repeated intravitreal triamcinolone injections in diabetic macular oedema. Br J Ophthalmol. 2006;90:1137-1141.
- Gillies MC, Islam FM, Zhu M, et al. Efficacy and safety of multiple intravitreal triamcinolone injections for refractory diabetic macular oedema. Br J Ophthalmol. 2007;91:1323-1236.
- Felinski EA, Antonetti DA. Glucocorticoid regulation of endothelial cell tight junction gene expression: novel treatments for diabetic retinopathy. Curr Eye Res. 2005;30:949-957.
- Brooks HL Jr, Caballero S Jr, Newell CK, et al. Vitreous levels of vascular endothelial growth factor and stromal-derived factor 1 in patients with diabetic retinopathy and cystoid macular edema before and after intraocular injection of triamcinolone. Arch Ophthalmol. 2004;122:1801-1807.
- Roth DB, Realini T, Feuer WJ, et al. Short-term complications of intravitreal injection of triamcinolone acetonide. Retina. 2008;28:66-70.
- Jonas JB, Degenring RF, Kreissig I, et al. Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology. 2005;112:593-598.
- Jonas JB, Degenring R, Vossmerbauemer U, et al. Frequency of cataract surgery after intravitreal injection of high-dosage triamcinolone acetonide. Eur J Ophthalmol. 2005;15:462-464.
- Haritoglou C, Kook D, Neubauer A, et al. Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina. 2006;26:999-1005.
- Paccola L, Costa RA, Folgosa MS, et al. Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study). Br J Ophthalmol. 2008;92:76-80.
- Sivaprasad S, Bunce C, Wormald R. Non-steroidal anti-inflammatory agents for cystoid macular oedema following cataract surgery: a systematic review. Br J Ophthalmol. 2005;89:1420-1422.