Int J Clin Pharm (2014) 36:438–442 DOI 10.1007/s11096-014-9918-9
Results of intravitreal triamcinolone acetonide in patients with macular edema secondary to branch retinal vein occlusion Mehmet Demir • Ersin Oba • Dilek Guven Zeynep Acar • Sonmez Cinar
Received: 22 June 2013 / Accepted: 21 January 2014 / Published online: 9 February 2014 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014
Abstract Background Macular edema is one of the most common causes of visual loss in patients with retinal vein oclusions. Intravitreal corticosteroids and intravitreal antivascular endothelial growth factors are modalities of treatment for macular edema secondary to branch retinal vein occlusion (BRVO). Objective To present the results of intravitreal triamcinolone acetonide therapy in patients with macular edema secondary to BRVO. Setting A retrospective clinical interventional study included 32 patients with macular edema secondary to BRVO. Method The records of 32 eyes of 32 patients who received 4 mg/0.1 mL injection of intravitreal triamcinlone for macular edema secondary to BRVO were evaluated. Patients with visual acuity \0.40 logMAR (logarithm of the minimum angle of resolution), central macular thickness (CMT) [260 lm and no neovascularization at baseline were included. Patients with diabetes mellitus, a history of intravitreal anti vascular endothelial growth factor injection, grid laser photocoagulation and ischemic BRVO were excluded. The re-injections were performed in cases with increased CMT [100 lm or vision loss of five or more letters. Results The mean follow-up was 12 ± 1.9 months. The visual acuity increased from 0.58 ± 0.16 at baseline to 0.25 ± 0.11 logMAR (P \ 0.001). The CMT decreased from 490 ± 107 lm at baseline to 266 ± 90 lm at 12 months
M. Demir (&) D. Guven Z. Acar S. Cinar Department of Ophthalmology, Sisli Etfal Training and Research Hospital, Halaskargazi caddesi Etfal sokak, Etfal Hastanesi, 34400 Istanbul, Turkey e-mail: [email protected]
E. Oba Department of Ophthalmology, Kafkas University, 36000 Kars, Turkey
(P \ 0.001). Both cataract and glaucoma developed in 18.75 % patients. Conclusion Intravitreal triamcinolone, due to absence of systemic side effects, can be used with confidence for treatment macular edema secondary to BRVO. However the main disadvantages of intravitreal triamcinolone injection are elevation of intraocular pressure and formation of cataract. Keywords Branch retinal vein occlusion Intravitreal triamcinolone Macular edema
Impact of findings on practice •
Intravitreal triamcinolone acetonide (IVTA) is effective for treatment macular edema secondary to branch retinal vein occlusion (BRVO). IVTA is a good alternative to intravitreal anti-VEGF for ME, because of thromboembolic side events of antiVEGF.
Introduction Retinal vein occlusion (RVO) is the most common retinal vascular disease after diabetic retinopathy. Although the pathogenesis is still not fully clear, several risk factors have been associated with RVO, including age, diabetes mellitus, atherosclerotic retinal vessel changes, hypertension, and open-angle glaucoma [1–4]. The most common cause of decreased vision in patients with BRVO is the accumulation of fluid within the macula . We designed a retrospective clinical study to present the 12th month results of intravitreal triamcinolone injection for macular
Int J Clin Pharm (2014) 36:438–442
edema secondary to BRVO. Intravitreal corticosteroids or anti-VEGF injections are commonly used for macular edema in patients with macular edema secondary to BRVO [6, 7]. The major stimulus for the formation of macular edema and neovascularization is the release of inflammatory cytokines, such as interleukin 6 (IL-6), IL-8 and IL-23 that increase vascular permeability  in patients with RVO [9–11]. The only proven treatment method for eyes with macular edema secondary to BRVO was macular grid laser photocoagulation, according to the Branch Vein Occlusion Study, only patients with macular edema associated with BRVO and a visual acuity of 0.40 logMAR (logarithm of the minimum angle of resolution) or less showed a significant visual benefit compared with the untreated control group . However, paracentral scotomas and scaring are irreversible complications of grid laser photocoagulation . Recently IVTA and anti–vascular endothelial growth factor injection are two modalities of therapy for patients with macular edema secondary to BRVO .
Aim of study To study the effects of intravitreal triamcinolone in patients with macular edema secondary to BRVO.
Ethical approval This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Local Ethics Committee. All patients gave written informed consent.
Methods This study included 32 patients (18 female, 14 male) with macular edema secondary to BRVO. Data of patients were evaluted from their charts. All patients were questioned for history of hypertension, smoking and hyperlipidemia. The inclusion criteria included the following: Macular edema secondary to BRVO, initial therapy started in the first month with IVTA a baseline visual acuity \0.40 logMAR, central macular thickness (CMT) [260 lm, and no neovascularization. Patients with diabetes mellitus, uveitis, a history of intravitreal anti-VEGF injection/s, grid laser photocoagulation and ischemic BRVO were excluded from this study. All patients had a complete ophthalmological examination at baseline, on 1st, 7th and 30th days after injection and one monthly intervals during follow-up.
440 b Fig. 1 A 48-year-old male had left superior temporal branch retinal
vein occlusion. The baseline visual acuity was 1/10 (Snellen) and central macular thickness (CMT) of 566 lm. After 4 mg/0.1 mL IVTA injection visual acuity increased to 20/28.5 and CMT decreased to 255 lm
The examinations included; visual acuity, slit-lamp examinations for anterior and posterior segments, intraocular pressure, macular thickness, and color fundus photography (Fig. 1). Fluorescein angiography was performed at baseline and 10th months to identify the presence of BRVO, active extravasation and areas of retinal nonperfusion. All patients received an initial injection of triamcinolone acetonide 4 mg/0.1 mL. The re-injections were performed at 3-monthly intervals when there was an increase in CMT [100 lm or a vision loss of five or more letters. All intravitreal injections were performed in the operating room under sterile conditions. Triamcinolone acetonide was injected into the vitreous body via pars plana using a 27-Gauge (G) needle at the inferior temporal area at a 3.5-mm distance from the limbus. The mean visual acuity, CMT and intraocular pressure are expressed as mean ± standard deviation (SD). The data at baseline and at the end of follow up time were compared. Visual acuity was converted into the logMAR for statistical calculation . The statistical analysis of this study was carried out by the paired samples t test (SPSS for Windows 16.0, Chicago, IL). A P value of less than 0.05 was considered to be statistically significant.
Results This retrospective study included 32 eyes of 32 (mean age 61.8 ± 7.4, range 48–78 years) patients. Hypertension rate was 62.5 %, smoking rate was 50 % and hyperlidemia rate was 28.1 % in patients. The follow-up period was 12 ± 1.9 months (range 10–16), (Table 1). At baseline, the mean visual acuity was 0.58 ± 0.16 logMAR, and the mean CMT was 490 ± 107 lm (range 267–685 lm). At the end of follow-up time, the mean values of visual acuity had increased to 0.25 ± 0.11 logMAR) (P \ 0.001) whereas the mean CMT had decreased to 266 ± 90 lm (P \ 0.001), (Table 2). The frequency of intravitreal triamcinolone injection (mean 1.4 ± 0.9, range 1–4) is presented in (Table 3). Eight (25 %) of 32 eyes needed reinjection. Pseudo-endophthalmitis was observed in one (3.12 %) patient, who was treated with topical dexamethasone 0.1 %; 8 9 1/day for 3 weeks. Epiretinal membrane was observed in two (9.1 %) patients, who did not require surgery. Cataract developed in 6 (18.75 %) patients and
Int J Clin Pharm (2014) 36:438–442 Table 1 The demographic characteristics of patients Parameters
Mean age ± SD (years)
61.8 ± 7.4
SD standard deviation
Table 2 The values of baseline and after therapy Parameters (mean ± SD)
12.4 ± 1.9
0.58 ± 0.16
0.25 ± 0.11
490 ± 107
266 ± 90
17.7 ± 1.6
20.3 ± 3.3
SD standard deviation, VA visual acuity, CMT central macular thickness, IOP intraocular pressure, SCH subconjunctival hemorrahge Table 3 The numbers of IVTA injection Number of injection (s)
1.4 ± 0.9
IVTA intravitreal triamcinolone acetonide
cataract surgery was performed at between 10 and 11 months during follow up. Glaucoma developed in 6 (18.75 %) patients, among whom five needed antiglaucoma drug and one needed trabeculectomy. Retinal detachment or intravitreal hemorrhage were not recorded. Subconjunctival hemorrhage was recorded in 8 (25 %) patients. No neovascularization was recorded on the retina, optic nerve head or iris.
Discussion There are disadvantages of anti-VEGF compared to intravitreal triamcinolone injection such as the need for more frequent re-injections [16, 17], shorter effective time period
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and possible systemic adverse effects (arterial thromboembolic events etc.) [18–21]. In this study, we evaluated the effect of IVTA in patients with ME secondary to BRVO. We compared data at baseline and after intravitreal triamcinolone injection therapy at the end of follow up time. In patients with BRVO, the intravitreal triamcinolone injection treatment can effectively improve both functional and morphological changes by decreasing the macular edema [22–24]. All patients in this study showed a significant response to intravitreal triamcinolone injection treatment with an increase in visual acuity and a reduction in CMT. Intravitreal triamcinolone injection has a longer duration and no systemic adverse effects. Elevation of intraocular pressure and the development of cataract are disadvantages of intravitreal triamcinolone injection therapy [25–29]. Cataract, ocular hypertension or glaucoma are frequently encountered with intravitreal triamcinolone therapy [30– 33]. In this study, cataract formation was recorded in 6 (18.75 %) patients, glaucoma was recorded in 6 (18.75 %) patients, subconjunctival hemorrhage was recorded in 8 (25 %) patients, and epiretinal membrane was recorded in 2 (6.25 %) patients during 12 months of follow-up. The visual acuity was recorded after surgery in patients who developed cataract for statistical analysis. Previous studies have reported that intravitreal triamcinolone injection showed longer mean improvement duration, less macular edema recurrence and required fewer injections than the anti-VEGF [18, 20]. In a case series , that was treated with anti VEGF, re-injection rate was recorded to be 70 %, however, re-injection was required for only 25.0 % of patients in the present study. Additionally, this study did not report any systemic adverse effects for intravitreal triamcinolone injection. The limitations of this study are small sample size, lack of patients treated with anti-VEGF or/and laser, and retrospective design. The results of this retrospective study showed that intravitreal triamcinolone treatment in patients with macular edema secondary to BRVO was associated with a significant improvement in visual acuity and a marked decrease in CMT at 12 months.
Conclusion Intravitreal triamcinolone injection is safe and effective in patients with macular edema secondary to BRVO. Also reinjection rate of intravitreal triamcinolone is lower than that intravitreal anti-VEGF. Elevation of intraocular pressure and formation of cataract can be seen in some patients who receive intravitreal triamcinolone. To avoid development of
cataract, intravitreal anti-VEGF may be the alternative to intravitreal triamcinolone in phakic patients. Acknowledgments The authors would like to thank the clinical secretaries for their assistance. Funding
Conflicts of interest of interest.
The authors declare that they have no conflicts
References 1. Cugati S, Wang JJ, Rochtchine E, Mitchell P. Ten-year incidence of retinal vein occlusion in an older population: the Blue Mountain Eye study. Arch Ophthalmol. 2006;124(5):726–32. 2. Hayreh SS, Zimmerman B, Mc Carthy MJ, Podhajsky P. Systemic diseases associated with various types of retinal occlusion. Am J Ophthalmol. 2001;131(1):61–77. 3. Blond J, Glacet-Bernard A, Bayani N, Blacher J, Lelong F, Nordmann JP, et al. Retinal vein occlusion and hyperhomocysteinemia. J Fr Opthalmol. 2003;26(3):249–53. 4. Rath EZ, Frank RN, Shin DH, Kim C. Risk factors for retinal vein occlusion. A case–control study. Ophthalmology. 1992;99(4): 509–14. 5. Aref AA, Scott IU. Management of macular edema secondary to branch retinal vein occlusion: an evidence-based update. Adv Ther. 2011;28(1):28–39. 6. Cheng KC, Wu WC, Chen KJ. Intravitreal triamcinolone acetonide vs bevacizumab for treatment of macular oedema secondary to branch retinal vein occlusion. Eye (Lond). 2009;23(11): 2023–33. 7. Higashiyama T, Sawada O, Kakinoki M, Sawada T, Kawamura H, Ohji M. Prospective comparisons of intravitreal injections of triamcinolone acetonide and bevacizumab for macular oedema due to branch retinal vein occlusion. Acta Ophthalmol. 2013;91(4): 318–24. 8. Aiello LP, Avery RL, Arrig PG, Keyt BA, Jampel HD, Shah ST, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331(22):1480–7. 9. Funk M, Kriechbaum K, Prager F, Benesch T, Georgopoulos M, Zlabinger GJ, et al. Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab. Investig Ophthalmol Vis Sci. 2009;50(3): 1025–32. 10. Kaneda S, Miyazaki D, Sasaki S, Yakura K, Terasaka Y, Miyake K, et al. Multivariate analyses of inflammatory cytokines in eyes with branch retinal vein occlusion: relationships to bevacizumab treatment. Investig Ophthalmol Vis Sci. 2011;52(6):2982–8. 11. Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, et al. Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion. Eye (Lond). 2008;22(1):42–8. 12. Branch Retinal Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol. 1984;98(3):271–82. 13. Akduman L, Olk RJ. Subthreshold (invisible) modified grid diode laser photocoagulation in diffuse diabetic macular edema (DDME). Ophthal Surg Lasers. 1999;30(9):706–14. 14. Channa R, Smith M, Campochiaro PA. Treatment of macular edema due to retinal vein occlusions. Clin Ophthalmol. 2010;5: 705–13.
442 15. Holladay JT. Visual acuity measurements. J Cataract Refract Surg. 2004;30(2):287–90. 16. Demir M, Oba E, Gulkilik G, Odabasi M, Ozdal E. Intravitreal bevacizumab for macular edema due to branch retinal vein occlusion: 12-month results. Clin Ophthalmol. 2011;5:745–9. 17. Kriechbaum K, Michels S, Prager F, Georgopoulos M, Funk M, Geitzenauer W, et al. Intravitreal Avastin for macular oedema secondary to retinal vein occlusion: a prospective study. Br J Ophthalmol. 2008;92(4):518–22. 18. Byun YJ, Roh MI, Lee SC, Koh HJ. Intravitreal triamcinolone acetonide versus bevacizumab therapy for macular edema associated with branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. 2010;248(7):963–71. 19. Carneiro AM, Barthelmes D, Falcao MS, Mendonca LS, Fonseca SL, Goncalves RM, et al. Arterial thromboembolic events in patients with exudative age-related macular degeneration treated with intravitreal bevacizumab or ranibizumab. Ophthalmologica. 2011;225(4):211–21. 20. Ding X, Li J, Hu X, Yu S, Pan J, Tang S. Prospective study of intravitreal triamcinolone acetonide versus bevacizumab for macular edema secondary to central retinal vein occlusion. Retina. 2011;31(5):838–45. 21. Tao Y, Hou J, Jiang YR, Li XX, Jonas JB. Intravitreal bevacizumab vs triamcinolone acetonide for macular oedema due to central retinal vein occlusion. Eye (Lond). 2010;24(5):810–5. 22. Cekic O, Cakır M, Yazıcı AT, Alago¨z N, Bozkurt E, Faruk OF. A comparison of three different intravitreal treatment modalities of macular edema due to branch retinal vein occlusion. Curr Eye Res. 2010;35(10):925–9. 23. Cakir M, Dogan M, Bayraktar Z, Bayraktar S, Acar N, Altan T, et al. Efficacy of intravitreal triamcinolone for the treatment of macular edema secondary to branch retinal vein occlusion in eyes with or without grid laser photocoagulation. Retina. 2008;28(3): 465–72. 24. Noma H, Funatsu H, Mimura T, Shimada K. Functional-morphological changes after ıntravitreal ınjection of triamcinolone acetonide for macular edema with branch retinal vein occlusion. J Ocul Pharmacol Ther. 2012;28(3):231–6.
Int J Clin Pharm (2014) 36:438–442 25. Chen SD, Sundaram V, Lochhead J, Patel CK. Intravitreal triamcinolone for the treatment of ischemic macular edema associated with branch retinal vein occlusion. Am J Ophthalmol. 2006;141(5):876–83. 26. Vasconcelos-Santos DV, Nehemy PG, Schachat AP, Nehemy MB. Secondary ocular hypertension after intravitreal injection of 4 mg of triamcinolone acetonide: incidence and risk factors. Retina. 2008;28(4):573–80. 27. Prager F, Michels S, Kriechbaum K, Georgopoulos M, Funk M, Geitzenauer W, Polak K, et al. Intravitreal bevacizumab (Avastin) for macular oedema secondary to retinal vein occlusion: 12-month results of prospective clinical trial. Br J Ophthalmol. 2009;93(4):452–6. 28. Ahmadi AA, Chuo JY, Banashkevich A, Ma PE, Maberley DA. The effects of intravitreal bevacizumab on patients with macular edema secondary to branch retinal vein occlusion. Can J Ophthalmol. 2009;44(2):154–9. 29. Kim JY, Park SP. Comparison between intravitreal bevacizumab and triamcinolone for macular edema secondary to branch retinal vein occlusion. Korean J Ophthalmol. 2009;23(4):259–65. 30. Hou J, Tao Y, Jiang YR, Li XX, Gao L. Intravitreal bevacizumab versus triamcinolone acetonide for macular edema due to branch retinal vein occlusion: a matched study. Chin Med J (Engl). 2009;122(22):2695–9. 31. Rezende MP, Dias AF, Oshima A, Andrade EP, Serracarbassa PD. Study of visual acuity and intraocular pressure in the treatment of macular diabetic edema with intravitreous triamcinolone. Arq Bras Oftalmol. 2010;73(2):129–34. 32. Gillies MC, Islam FM, Larsson J, Pasadhika S, Gaston C, Zhu M, et al. Triamcinolone-induced cataract in eyes with diabetic macular oedema: 3-year prospective date from a randomised clinical trial. Clin Exp Ophthalmol. 2010;38(6):605–12. 33. Islam MS, Vernon SA, Negi A. Intravitreal triamcinolone will cause posterior subcapsular cataract in most eyes with diabetic maculopathy within 2 years. Eye (Lond). 2007;21(3):321–3. 34. Hanada N, Iijima H, Sakurada Y, Imasawa M. Recurrence of macular edema associated with branch retinal vein occlusion after intravitreal bevacizumab. Jpn J Ophthalmol. 2012;56(2):165–74.