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ORIGINAL ARTICLE
Year : 2017  |  Volume : 4  |  Issue : 2  |  Page : 54-60

Intravitreal versus posterior subtenon injection of triamcinolone acetonide in treatment of diabetic macular edema


Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, Egypt

Date of Web Publication17-Nov-2017

Correspondence Address:
Dina Hossameldin Hassanein
9 Elcanal Street, Maadi, Cairo 11431
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/erj.erj_4_17

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  Abstract 


Purpose: The aim of the study was to compare the efficacy and safety of intravitreal triamcinolone acetonide (IVTA) versus posterior subtenon injection of triamcinolone acetonide (PSBTA) for diabetic macular edema (DME). Materials and Methods: The study design was a prospective, interventional, randomized controlled study. Participants: The study participants were 26 patients (Thirty eyes) with DME and central subfield thickness (CST) >250 μm. Intervention: Eyes were randomly assigned to two equal groups; Group A received a single 4 mg IVTA and Group B received a 40 mg PSBTA. Four patients had bilateral DME; they received IVTA in one eye and PSBTA in another eye. Main Outcome Measures: Changes in visual acuity (VA) and CST obtained using optical coherence tomography were measured during a 3-month follow-up. Potential treatment complications were monitored including change in intraocular pressure (IOP). Results: The mean preoperative CST was 393.7 ± 93.0 μm and 351.5 ± 56.4 μm in Group A and B, respectively. Both groups showed comparable significant improvement in CST and VA at 1 and 3 months postinjection compared to preoperative values. The mean CST in Group A was 282.2 ± 65.0 μm compared to 284.0 ± 59.0 μm in Group B at 1 month (P = 0.910) and 276.3 μm ± 71.1 compared to 260.2 μm ± 63.3 at 3 months (P = 0.519). The mean VA in LogMAR in both groups at 3 months was 0.47 ± 0.23 and 0.32 ± 0.29, respectively (P = 0.142), compared to preoperative VA of 0.80 ± 0.19 and 0.68 ± 0.23, respectively. The preoperative IOP was 13.80 ± 2.07 in the IVTA group and 13.07 ± 1.83 in the PSBTA group. IOP showed significantly higher elevation in the IVTA group at 1 and 3 months (19.4 mmHg ± 1.35 and 19.0 mmHg ± 1.36) compared to the PSBTA (16.5 mmHg ± 1.40 and 16.2 mmHg ± 1.50) (P = 0.000). No eyes had IOPs >21 mmHg. Conclusions: Posterior subtenon injection of TA is a safe and valid alternative to the intravitreal injection for the treatment of DME having a comparable effect on VA and CST, yet a lower risk of IOP elevation.

Keywords: Diabetic macular edema, posterior subtenon, triamcinolone acetonide


How to cite this article:
Elfassi SA, Hassanein DH, Riad RF, Hamza HS. Intravitreal versus posterior subtenon injection of triamcinolone acetonide in treatment of diabetic macular edema. Egypt Retina J 2017;4:54-60

How to cite this URL:
Elfassi SA, Hassanein DH, Riad RF, Hamza HS. Intravitreal versus posterior subtenon injection of triamcinolone acetonide in treatment of diabetic macular edema. Egypt Retina J [serial online] 2017 [cited 2020 Apr 5];4:54-60. Available from: http://www.egyptretinaj.com/text.asp?2017/4/2/54/218587




  Introduction Top


The number of adults with diabetes in Africa has been estimated to expand by 98% from 12.1 million in 2010 to 23.9 million in 2030 by the International Diabetes Federation. The potential risk of epidemic rise in diabetic retinopathy, therefore, poses a significant challenge for the continent.[1]

Diabetic macular edema (DME) is a major cause of visual loss in patients with diabetic retinopathy.[2] Given the apparent role of inflammation in the pathogenesis of DME, corticosteroids have been widely utilized for its treatment.[3],[4],[5] Many reports have proven the efficacy of intravitreal triamcinolone acetonide (IVTA) injection in DME,[6],[7] but the risk of elevated intraocular pressure (IOP), cataract development, and infectious endophthalmitis has remained a significant concern.[8],[9] This prompted some authors to investigate the efficacy and adverse effects of the posterior subtenon route of injection as an alternative to the conventional intravitreal route.[10],[11],[12],[13]

In our study, we compared the effect of the posterior subtenon injection of TA (PSBTA) with the IVTA on DME and IOP elevation.


  Materials and Methods Top


The study was approved by Cairo University Hospital's Research Ethics Committee and followed the tenets of the Declaration of Helsinki. We conducted a prospective, comparative, randomized interventional study that was performed on thirty eyes of 26 type 2 diabetic patients with diabetic maculopathy causing DME and central subfield thickness (CST) >250 μm. A written informed consent was obtained from all patients. Patients with Stage 3 proliferative retinopathy, history of retinal vein or arterial occlusion, uveitis, any chorioretinal disease other than diabetic retinopathy, or epiretinal membranes were excluded from the study. Other exclusion criteria were any patients with vitreomacular interface abnormalities, moderate-to-severe macular ischemia, history of any previous focal, grid or panretinal laser treatment, or any previous intravitreal injection. Patients with glaucoma or significant cataract were also excluded from the study.

Eyes were randomly divided into two equal groups: Group A included 15 eyes which received IVTA injection and Group B included 15 eyes which received posterior subtenon TA (PSBTA) injection. Four included patients had bilateral DME; they received IVTA in one eye and PSBTA in another eye.

Evaluation of each patient's best-corrected distant visual acuity (BCDVA), IOP, and CST was done 1–3 days before injection and again at 1 and 3 months postinjection. BCDVA was assessed using a Snellen VA chart and converted to LogMAR, and IOP was measured using Goldmann applanation tonometry. Antiglaucoma medication was prescribed if IOP exceeded 21 mmHg at any point during follow-up. All patients were simultaneously being followed up in the University Hospital Diabetes clinic.

Spectral domain optical coherence tomography (OCT) was done within 1 week before injection and repeated at 1 and 3 months for follow-up. The CST, defined as the average retinal thickness in the central 1 mm diameter circle (C1) of the early treatment diabetic retinopathy study grid, was documented and analyzed.

All injections were performed by a single retina specialist all using the same protocol in the operating room under sterile conditions. In IVTA injection, after applying topical anesthesia, 0.1 ml solution containing 4 mg TA was injected through the pars plana using a 30-gauge needle in the superotemporal quadrant 3.5 mm from the limbus in aphakic/pseudophakic eyes and 4.0 mm from the limbus in phakic eyes. In PSBTA injection, 1 ml of 40 mg/ml of TA was injected. The patient was asked to look up and out exposing the inferonasal quadrant. A small tent of the conjunctiva and tenon capsule was raised with a pair of blunt, nontoothed forceps approximately 5–10 mm from the limbus. A small incision is made in the tissue using a pair of ophthalmic scissors, exposing the sclera below. The 27-gauge needle and an insulin syringe were inserted and passed posteriorly, following the curvature of the globe, until its tip is perceived to pass the equator, and the TA was injected into the posterior subtenon space. A topical fluoroquinolone antibiotic was then prescribed tid for 3 days.

Statistical analysis

Data were statistically described in terms of mean ± standard deviation, median and range or frequencies (number of cases), and percentages when appropriate. Comparison of numerical variables between the study groups was done using Student's t-test for independent samples when normally distributed and Mann–Whitney U-test for independent samples when not normally distributed. For comparing categorical data, Chi-square test was performed. Exact test was used when the expected frequency was <5. P < 0.05 were considered statistically significant. All statistical calculations were done using Statistical Package for the Social Sciences program (SPSS Inc., Chicago, IL, USA).


  Results Top


A total of 30 eyes of 26 patients were randomized into 15 eyes which received IVTA (Group A) and 15 eyes which received PSBTA injections (Group B). All of the patients completed the 3-month follow-up. Eleven patients (73%) in Group A and 11 patients (73%) in Group B received insulin, whereas 4 patients (27%) in Group A and 4 patients (27%) in Group B received oral hypoglycemic drugs with no statistical significance difference (P = 1.000).

Demographic and preoperative data

Females constituted 69% (18 females) and males 31% (8 males) of the total number of included patients. Demographic and preoperative data of the patients are shown in [Table 1].
Table 1: Demographics and Preoperative Data

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Best-corrected distant visual acuity

In both groups, the BCDVA significantly improved at 1st and 3rd month postinjection compared to the baseline values. However, there was no statistically significant difference in improvement between both groups [Table 2].
Table 2: Comparison between pre injection BCDVA (in LogMAR), 1 and 3months post injection BCDVA

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Initial mean BCDVA (LogMAR) and at 1st and 3rd months in both groups thereafter are shown in [Figure 1].
Figure 1: Best-corrected distant visual acuity in the intravitreal and subtenon injected eyes at baseline and at 1 and 3 months after injection

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Intraocular pressure

In both groups, the IOP showed a significant elevation at 1st and 3rd month postinjection compared to the baseline values. However, there was a statistically significant higher IOP values in the intravitreal group compared to the subtenon group at both 1st and 3rd month postinjection (P = 0.000) [Table 3] and [Figure 2].
Table 3: Comparison between pre injection IOP (in mmHg), 1, and 3months post injection in both groups

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Figure 2: Intraocular pressure in the intravitreal and subtenon injected eyes at baseline and at 1 and 3 months after injection

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None of the eyes required antiglaucoma medication in both groups.

Central subfield thickness

The mean CST showed statistically significant improvement at 1 and 3 months after injection in both groups compared to the baseline values. Meanwhile, between the two groups, there was no statistically significant difference at the 1st month (P = 0.910) nor at the 3rd month after injection (P = 0.519), as shown in [Table 4] and [Figure 3].
Table 4: Comparison between pre injection CST in μm, 1, and 3months post injection in both groups

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Figure 3: Central subfield thickness in micrometer in the intravitreal and subtenon injected eyes at baseline and at 1 and 3 months after injection

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Bilateral cases

Four patients out of 26 patients in this study had bilateral DME, in which one eye was randomized to one group and the second eye in another group. Pre- and post-injection OCT scans of both eyes of one of the bilateral patients are shown in [Figure 4] and [Figure 5].
Figure 4: Optical coherence tomography scans of the left eye which received subtenon injection showing (a) A horizontal optical coherence tomography scan obtained through the fovea revealed loss of the normal foveal contour, diffuse macular thickening, and areas of low intraretinal reflectivity consistent with fluid accumulation and a central subfield thickness of 315 μm. (b) One month after injection, an optical coherence tomography scan showed that the central subfield thickness has decreased to 253 μm. (c) Three months after injection, an optical coherence tomography scan showed that the central subfield thickness decreased to 232 μm

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Figure 5: Optical coherence tomography scans of the right eye of the same patient in Figure 4 which received intravitreal injection showing (a) A horizontal optical coherence tomography scan obtained through the fovea revealed loss of the normal foveal contour, diffuse macular thickness, and areas of low intraretinal reflectivity consistent with fluid accumulation and a central subfield thickness of 327 μm. (b) One month after injection, an optical coherence tomography scan showed that the central subfield thickness has decreased to 265 μm. (c) Three months after injection, an optical coherence tomography scan showed that the central subfield thickness is 239 μm

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One of the bilateral patients, who received right IVTA and left PSBTA injection, showed an unexpected response in both eyes where the CST showed a progressive increase in thickness at 1 and 3 months postinjection. OCT scans of both eyes are shown in [Figure 6] and [Figure 7].
Figure 6: Optical coherence tomography scans of right eye which received intravitreal injection showing (a) preinjection diffuse macular thickening with fluid accumulation and central subfield thickness of 296 μm. (b) One month after injection, an optical coherence tomography scan showed that the central subfield thickness had progressively increased to reach 328 μm. (c) Three months after injection, an optical coherence tomography scan showed that the central subfield thickness had progressed to 386 μm

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Figure 7: Optical coherence tomography scans of the left eye of the same patient in Figure 6 which received subtenon injection showing (a) central subfield thickness of 312 μm and areas of low intraretinal reflectivity consistent with fluid accumulation. (b) One month after injection an optical coherence tomography scan showed that the central subfield thickness progressively increased to 320 μm. (c) Three months after injection an optical coherence tomography scan showed that the central subfield thickness progressed to 360 μm

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None of the eyes had any injection-related complications such as endophthalmitis or retinal detachment. The detailed data of all eyes in both groups are listed in [Table 5]. The highlighted rows include the eyes of bilateral cases.
Table 5: Detailed data of all eyes in both groups

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  Discussion Top


Our study was conducted to assess the efficacy and safety of the PSBTA injection as compared to IVTA injection for the treatment of DME. We considered the VA, which is an outcome of high importance to patients, the primary measure of efficacy and the change in the CST, the secondary prognostic measure. The main measure of harm was increase in IOP. Both groups enrolled showed a comparable improvement of VA as well as significant reduction of CST; however, the IOP in the IVTA group was significantly higher than in the PSBTA group at 1 and 3 months after injection.

We are aware that our study had several limitations; a short follow-up period which limited the assessment of chronic IOP changes as well as cataract progression. The small sample size and the lack of accurate data regarding the duration of the DME before entry to the study were another limiting factors.

Several studies comparing both routes of TA injection in DME reported similar results to our study regarding VA and CST improvement, and the follow-up period in all of these studies was 6 months.[13],[14],[15],[16],[17]

In contrast to our results, a study carried out by Cardillo et al. on 24 eyes of 12 patients with bilateral DME [18] and another by Takata et al. on the same number of eyes [19] with a 6-month follow-up concluded that the intravitreal injection was more favorable than the posterior subtenon injection and that the mean of CST in eyes that received intravitreal injection was significantly lower than in the subtenon injected eyes.

Another comparative contralateral study by Luo et al. included forty eyes of twenty patients with bilateral DME, in which one eye received the IVTA and another eye received the PSBTA injection and followed up for 6 months. It demonstrated better improvement in eyes receiving SBTA as compared to IVTA groups at 2nd month after injection as well as reversal of VA score and CST in eyes receiving IVTA injection after the 3rd month. On the other hand, eyes receiving PSBTA showed a stable VA and CST.[17]

One of the four patients included in our study with bilateral DME showed a bilateral progressive increase in Charcot-Marie-Tooth and reduction in VA at 1 and 3 months after injection. We could not attribute the cause of this paradoxical effect except to her uncontrolled hypertension, and she was considered for shifting to anti-vascular endothelial growth factor injections after referring her to the internal medicine specialist.

Regarding IOP, in comparison to Luo et al.,[17] who reported a rise in IOP after IVTA injection requiring antiglaucoma treatments, none of our patients required antiglaucoma eye drops. Oppositely, Cardillo et al. did not show any significant difference in the IOP between the two groups at any follow-up visit.[18]

Although most of the previously mentioned studies followed the same technique of injection and the same methodology and outcome measures as our study, some studies performed additional investigations as Cellini et al., who performed a B-scan before and after administration of PSBTA to ensure the deposition of injection material in the macular region,[15] whereas Cardillo et al.[18] and Bonini-Filho et al. evaluated the lens density status.[20]

We encountered no injection-related complications in both groups such as endophthalmitis, retinal detachment, or perforation other than the IOP elevation postinjection.

We conclude that PSBTA injection for the treatment of DME has a comparable effect to the IVTA injection and carries a lower risk of IOP elevation. It is considered an easy, safe, and valid alternative to the intravitreal injection. A larger number of patients with longer follow-up periods are necessary to confirm those findings.


  Conclusions Top


The findings from our study favor the use of posterior subtenon injection of TA for the treatment of DME, particularly when IOP elevation is a concern in the intravitreal route.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
IDF. Diabetes Atlas. 4th ed. Brussels: International Diabetes Federation; 2009.  Back to cited text no. 1
    
2.
Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthalmology 1995;102:7-16.  Back to cited text no. 2
    
3.
Ip MS, Bressler SB, Antoszyk AN, Flaxel CJ, Kim JE, Friedman SM, et al. A randomized trial comparing intravitreal triamcinolone and focal/grid photocoagulation for diabetic macular edema: Baseline features. Retina 2008;28:919-30.  Back to cited text no. 3
    
4.
Haller JA, Kuppermann BD, Blumenkranz MS, Williams GA, Weinberg DV, Chou C, et al. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol 2010;128:289-96.  Back to cited text no. 4
    
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Jonas JB, Kreissig I, Söfker A, Degenring RF. Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol 2003;121:57-61.  Back to cited text no. 5
    
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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.  Back to cited text no. 6
    
7.
Yilmaz T, Weaver CD, Gallagher MJ, Cordero-Coma M, Cervantes-Castaneda RA, Klisovic D, et al. Intravitreal triamcinolone acetonide injection for treatment of refractory diabetic macular edema: A systematic review. Ophthalmology 2009;116:902-11.  Back to cited text no. 7
    
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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, 1449.e1-10.  Back to cited text no. 8
    
9.
Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, et al. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2011;118:609-14.  Back to cited text no. 9
    
10.
Jennings T, Rusin MM, Tessler HH, Cunha-Vaz JG. Posterior sub-Tenon's injections of corticosteroids in uveitis patients with cystoid macular edema. Jpn J Ophthalmol 1988;32:385-91.  Back to cited text no. 10
    
11.
Bakri SJ, Kaiser PK. Posterior subtenon triamcinolone acetonide for refractory diabetic macular edema. Am J Ophthalmol 2005;139:290-4.  Back to cited text no. 11
    
12.
Toda J, Fukushima H, Kato S. Injection of triamcinolone acetonide into the posterior sub-tenon capsule for treatment of diabetic macular edema. Retina 2007;27:764-9.  Back to cited text no. 12
    
13.
Choi YJ, Oh IK, Oh JR, Huh K. Intravitreal versus posterior subtenon injection of triamcinolone acetonide for diabetic macular edema. Korean J Ophthalmol 2006;20:205-9.  Back to cited text no. 13
    
14.
Ozdek S, Bahçeci UA, Gürelik G, Hasanreisoglu B. Posterior subtenon and intravitreal triamcinolone acetonide for diabetic macular edema. J Diabetes Complications 2006;20:246-51.  Back to cited text no. 14
    
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Cellini M, Pazzaglia A, Zamparini E, Leonetti P, Campos EC. Intravitreal vs. subtenon triamcinolone acetonide for the treatment of diabetic cystoid macular edema. BMC Ophthalmol 2008;8:5.  Back to cited text no. 15
    
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Qi HP, Bi S, Wei SQ, Cui H, Zhao JB. Intravitreal versus subtenon triamcinolone acetonide injection for diabetic macular edema: A systematic review and meta-analysis. Curr Eye Res 2012;37:1136-47.  Back to cited text no. 16
    
17.
Luo D, Zhu B, Zheng Z, Zhou H, Sun X, Xu X. Subtenon vs. intravitreal triamcinolone injection in diabetic macular edema, A prospective study in Chinese population. Pak J Med Sci 2014;30:749-54.  Back to cited text no. 17
    
18.
Cardillo JA, Melo LA Jr., Costa RA, Skaf M, Belfort R Jr., Souza-Filho AA, et al. Comparison of intravitreal versus posterior sub-Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema. Ophthalmology 2005;112:1557-63.  Back to cited text no. 18
    
19.
Takata C, Messias A, Folgosa MS, Lucena LR, Lucena DR, Scott IU, et al. Intravitreal injection versus subtenon infusion of triamcinolone acetonide during cataract surgery in patients with refractory diabetic macular edema. Retina 2010;30:562-9.  Back to cited text no. 19
    
20.
Bonini-Filho MA, Jorge R, Barbosa JC, Calucci D, Cardillo JA, Costa RA. 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.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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