|Year : 2014 | Volume
| Issue : 4 | Page : 636-642
Intravitreal versus subtenon injection of triamcinolone acetonide for diabetic macular edema
Saber Hamid El-Sayed1, Amin Faisal Amin Ellakwa1, Nermeen Mahmoud Badawi1, Aml Mohamed Hamdy Abd El-Razik MBBCh 2
1 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Ophthalmology, Shibin El-Kom Ophthalmology Hospital, Menoufia, Egypt
|Date of Submission||02-Jan-2014|
|Date of Acceptance||27-Apr-2014|
|Date of Web Publication||22-Jan-2015|
Aml Mohamed Hamdy Abd El-Razik
Shibin El-Kom Ophthalmology Hospital, Menoufia
Source of Support: None, Conflict of Interest: None
The aim of this study was to compare the results of intravitreal injection with subtenon injection of triamcinolone in diabetic macular edema (DME).
Triamcinolone injection for DME.
Patents and methods
The study is a prospective randomized clinical trial including 80 eyes of patients with DME. Patients were divided into two groups: group I and group II. Group I (73.1% men and 26.9% women; mean age 55.7 ± 7.2 years) included 40 eyes that received 4 mg of intravitreal triamcinolone acetonide injection. Group II (65.5% men and 34.5% women; mean age 55.8 ± 7.9 years) comprised 40 eyes that received 40 mg of subtenon triamcinolone acetonide injection. The patients were followed up after 1 week and 1, 3, and 6 months later to assess best-corrected visual acuity, intraocular pressure, and macular thickness. Fluorescein angiography and optical coherence tomography were used to evaluate the improvement.
There was a statistically significant difference between the studied groups at 1 week and 1 month (P < 0.05) and no significant difference at 3 and 6 months (P > 0.05) as regards their post-treatment outcome for visual acuity, and there was no statistically significant difference between the studied groups at 1 and 6 months (P > 0.05) as regards their post-treatment outcome for macular thickness.
Both intravitreal and subtenon triamcinolone injections cause a significant increase in visual acuity; the effect is early and more pronounced in the intravitreal group but subtenon injection is safer.
Keywords: Diabetic macular edema, intravitreal, subtenon, triamcinolone acetonide
|How to cite this article:|
El-Sayed SH, Ellakwa AF, Badawi NM, Abd El-Razik AM. Intravitreal versus subtenon injection of triamcinolone acetonide for diabetic macular edema. Menoufia Med J 2014;27:636-42
|How to cite this URL:|
El-Sayed SH, Ellakwa AF, Badawi NM, Abd El-Razik AM. Intravitreal versus subtenon injection of triamcinolone acetonide for diabetic macular edema. Menoufia Med J [serial online] 2014 [cited 2020 Feb 28];27:636-42. Available from: http://www.mmj.eg.net/text.asp?2014/27/4/636/149629
| Introduction|| |
Diabetic macular edema (DME) is the major cause of visual impairment in diabetic patients .
Based on the observations of the Early Treatment Diabetic Retinopathy Study (ETDRS) Group, it has been concluded that laser panretinal photocoagulation reduces the risk of visual loss or blindness by preventing subsequent neovascularization in the eyes of patients with high-risk proliferative diabetic retinopathy and nonproliferative diabetic retinopathy .
Moreover, a significant number of patients with DME, especially of the diffuse type, remain refractory to focal or grid laser treatments, and this has driven many investigators to seek alternative treatments for the management of DME ,.
Among alternative treatments, triamcinolone acetonide (TA) has been reported to be effective against cases of DME when administered either by the intravitreal route , or by the posterior subtenon route ,.
In the current study, we prospectively investigated the efficacy and safety of both treatment modalities, intravitreal TA treatment and posterior subtenon TA treatment, in the management of DME.
| Patients and methods|| |
This study is a prospective randomized clinical trial carried out on patients in the Ophthalmology Department of Menoufia University Hospital for treatment of DME and included 80 eyes.
Diabetic patients with clinically significant or cystoid macular edema detected by an ophthalmoscope in whom fluorescein angiography (FA) showed diffuse or cystoid macular edema and who had central macular thickness more than 300 mm on optical coherence tomography (OCT) were included in the study.
Glaucoma patients and patients who had undergone intraocular surgery within 3 months or laser treatment within 1 month were excluded from the study.
Every patient was subjected to the following: full history taking, assessment of best-corrected visual acuity (VA) and refraction, full ophthalmic examination, measurement of intraocular pressure (IOP), FA, and OCT.
Patients were divided into two groups, each composed of 40 eyes. The first group underwent a single intravitreal injection of 4 mg TA, whereas the second group underwent a single subtenon injection of 40 mg TA.
Instruments and machines
The injections were administered in the operating room under complete aseptic conditions using a Zeiss surgical microscope. After sterilization and draping, the conjunctiva was anesthetized using benox drops; a lid speculum was used to keep eye lashes away from the conjunctiva, and betadine 5% eye drops was administered to the conjunctival sac. During the follow-up period, IOP was measured using a Goldman applanation tonometer, FA was performed, macular thickness was measured by means of OCT, refraction was assessed with a refractometer, and best-corrected VA for far and near vision was measured using a Landolt broken ring chart. VA measurements were converted to the logarithm of minimal angle of resolution (log MAR).
Intravitreal triamcinolone acetonide
Injection of 4 mg nonprecipitated TA (Kenacort A) was administered transconjunctivally into the vitreous cavity at a distance to the limbus of 3.5 mm in phakic and 3 mm in pseudophakic eyes; we used a 27-G needle for the nonprecipitated ampule, and the injection was performed in the lower temporal bulbar conjunctiva. The patients were asked to sit up immediately after the injection and continue to maintain an erect posture for the following 6 h to prevent the cortisone crystals from settling in the macular region causing transient visual loss. The patient was given antibiotic eye drops for 2 weeks.
Subtenon triamcinolone acetonide
A caliper was used to mark 8 mm from the limbus, a small button hole in the upper temporal bulbar conjunctiva, and a tenon capsule was created at the mark using a pair of Wesscot scissors to give access to the subtenon space, avoiding blood vessels. Injection of 40 mg nonprecipitated TA (Kenacort A) was administered by means of a 24-G curved blunt metallic subtenon canula into the retrobulbar space. The patient was given antibiotic eye drops for 2 weeks.
Data were statistically presented as range, mean, and SD. Comparison of quantitative variables between the study groups was made using the t-test for paired samples. A P value less than 0.05 was considered statistically significant. All statistical calculations were performed using statistical package for the social science (SPSS, version 12; SPSS Inc., Chicago, Illinois, USA) for Microsoft Windows.
| Results|| |
The intravitreal group included 40 eyes of 26 patients, including 19 male patients and seven female patients; the age of the patients ranged from 45 to 69 years with a mean of 57 years. The mean preoperative central macular thickness (CMT) was 478.10 mm, with a SD of ± 139.73 mm. At 1 week after injection, the mean CMT was 412.25 mm, with an SD of ± 141.65 mm, showing an improvement in 39 (97.5%) patients. At 1 month after injection, the mean CMT was 384.30 mm with an SD of ± 142.11 mm, showing an improvement in 38 (95%) patients from baseline. At 3 months, the mean CMT was 399.95 mm with an SD of ± 151.88 mm, showing an improvement in 39 (97.5%) patients from baseline. At 6 months, the mean CMT was 299.55 mm with an SD of ± 146.28 mm, showing an improvement in 38 (95%) patients from baseline.
The subtenon group included 40 eyes of 29 patients including 19 male patients and 10 female patients; the age of the patients ranged from 43 to 76 years with a mean of 59.5 years; the mean preoperative CMT was 391.82 mm with an SD of ± 58.89 mm. At 1 week, the mean CMT was 321.18 mm with an SD of ± 87.65 mm, showing an improvement of 97.5% from baseline. At 1 month after injection, the mean CMT was 284.9 mm with an SD of ± 86.65 mm, showing an improvement of 97.5% from baseline. At 3 months, the mean CMT was 249.08 mm with an SD of ± 89.67 mm, showing an improvement of 97.5% from baseline. At 6 months, the mean CMT was 227.78 mm with an SD of ± 92.45 mm, showing an improvement of 97.5% from baseline.
The VA of the intravitreal group before injection ranged from 0.017 (1/60) to 0.5 (6/12). The mean VA was 0.14. At 1 month after injection the mean VA was 0.25; at 3 months after injection the mean VA was 0.28; and at 6 months after injection the mean VA was 0.26.
The VA of the subtenon group before injection ranged from 0.033 (2/60) to 0.5 (6/12) with a mean VA of 0.17. At 1 month after injection the mean VA was 0.25; at 3 months after injection the mean VA was 0.33; and at 6 months after injection the mean VA was 0.42.
The mean IOP before injection in the intravitreal group was 15.12 mmHg with an SD of ± 2.37 mmHg. At 1 month after injection, the mean IOP was 18.17 mmHg with an SD of ± 5.93, with 11 eyes suffering from increasing IOP ranging from 22.3 to 31.6 mmHg; these patients received beta blocker twice daily. At 3 months after injection only six eyes suffered from increasing IOP; at 6 months after injection all eyes had baseline values.
The mean IOP before injection in the subtenon group was 14.78 mmHg with an SD of ± 2.34 mmHg. At 1 month after injection, the mean IOP was 16.49 mmHg with an SD of ± 4.43 mmHg, with five eyes suffering from increasing IOP ranging from 22.3 to 29 mmHg also controlled by b-blocker twice daily. At 3 and 6 months after injection all eyes had baseline values.
In the intravitreal group, three eyes suffered a worsening of VA at 6 months after injection, the first eye from 0.25 (6/24) to 0.167 (6/36) after transient improvement to 0.333 (6/18) at 1 and 3 months after injection, the second eye from 0.25 (6/24) to 0.167 (6/36) after a plateau of 0.25 (6/24) at 1 and 3 months after injection, the last eye from 0.05 (3/60) to 0.017 (1/60) after transient improvement to 0.083 (5/60) and 0.1 (6/60) at 1 and 3 months after injection, respectively. This was attributed to the recurrence of DME. Although nine eyes showed no improvement in vision, in seven of them vision returned to baseline at 6 months after injection after transient improvement and two of them showed no improvement during the follow-up period.
In the subtenon group, three eyes suffered worsening of their VA by the end of 6 months after injection; two of them dropped from 0.1 (6/60) to 0.083 (5/60) and the third from 0.033 (2/60) to 0.017 (1/60). These eyes had persistent macular edema, which did not improve after the injection and progressed to form submacular hard exudates. However, two eyes showed no improvement in vision during the follow-up period.
In our study, significant increase in IOP (over 21 mmHg) after 1 week was seen in 22.5% (nine eyes) of patients in the intravitreal group and in 10% (four eyes) of the subtenon group. This complication was reported to occur less frequently after subtenon injection. It was nonrefractory and easily controlled with ocular hypotensive drops.
Two (5%) patients in the intravitreal group developed posterior subcapsular cataract 6 months after injection and were excluded from the results. They were treated with phacoemulsification; the first was performed at 7 months after injection and the second was performed at 8 months after injection.
No cases of endophthalmitis, inadvertent intraocular penetration, or orbital masses were seen during the follow-up [Figure 1],[Figure 2] and [Figure 3] and [Table 1],[Table 2] and [Table 3].
|Figure 1: Distribution of groups I and II with respect to their visual acuity.|
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|Figure 2: Distribution of groups I and II with respect to their intraocular pressure (IOP).|
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|Figure 3: Distribution of groups I and II with respect to their macular thickness.|
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|Table 1: Comparison between the studied groups regarding the basal characteristics|
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|Table 2: Comparison between the studied groups at different times of follow up|
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| Discussion|| |
Corticosteroids have been successful in the treatment of DME because of their known antiangiogenic, antiedematous, anti-inflammatory, and antiproliferative effects ,. Furthermore, it has been demonstrated that its antiapoptotic effects also have a role in the treatment of DME ,.
This study compared the clinical outcomes of intravitreal injection of triamcinolone acetonide (IVTA) with those of subtenon injection of triamcinolone acetonide (STTA) for the treatment of DME. Both STTA and IVTA caused a significant increase in VA and a decrease in CMT. The effect was more pronounced in the IVTA group, especially in the short term; however, STTA injection also seemed to be a more effective and safer technique for the treatment of DME, especially in the long term.
Our study included 80 eyes of 55 patients with clinically significant macular edema who were divided into two groups, each of 40 eyes.
The first group included 40 eyes of 26 patients [19 (73.1%) male patients and seven (26.9%) female patients with a mean age of 57 years]; this group was treated with a single injection of IVTA. The second group included 40 eyes of 29 patients [19 (65.5%) male patients and 10 (34.5%) female patients with a mean age of 59.5 years], and this group was treated with a single injection of STTA.
Best-corrected visual acuity
The condition of three (7.5%) eyes deteriorated at the end of the study, 28 (70%) eyes showed improvement, and nine (22.5%) eyes showed no response.
The intravitreal application of crystalline cortisone can improve VA in patients with diffuse macular edema due to diabetic retinopathy, confirming previous reports .
In our study, there was an initial improvement in VA until 3 months after intravitreal injection, which then showed a decline 3-6 months after intravitreal injection; these results are nearly similar to those of another study , which has revealed that the improvement in VA was not constant for the entire follow-up period of the study and that ~5 months after the intravitreal injection VA showed a tendency to decline.
The intravitreal group demonstrated a dramatic response to the treatment during the early period, which started to diminish after the third month. This is in agreement with previous studies , but we differ with them in that they reported that the response to the treatment after 3 months almost disappeared in the sixth month and the VA values returned to baseline, although the central foveal thickness values were still significantly less than the baseline.
Our study showed that there is no correlation between improvement in VA and reduction in macular thickness especially in the third and sixth month after intravitreal injection. It was noticed that the VA started to decrease, and the macular thickness showed significant reduction at the same time. This is in agreement with other studies  whose data showed that there is no strong correlation between reduction in macular thickness and improvement in VA after intravitreal injection of 4 mg TA.
All eyes showed a significant reduction in foveal thickness, and VA improved in 19 of 24 eyes, which is consistent with previous reports ,.
The condition of four (10%) eyes deteriorated at the end of the study; 34 (85%) eyes showed improvement, and two (5%) eyes showed no response.
In the present study, the effect of subtenon injection seemed to increase slowly for 1 month and then rapidly increased at 3 months up to 6 months after injection. This duration is longer than that reported by other studies , in which the effect of subtenon injection seemed to last only for about 3 months.
Subtenon injection of 40 mg triamcinolone is beneficial in improving or stabilizing VA in patients with DME.
This nearly correlates with the results of other previous studies ,.
Intraocular pressure and other complications
In our study, significant increase in IOP (over 21 mmHg) was seen in 22.5% (nine eyes) of patients in the intravitreal group and in 10% (four eyes) of the subtenon group after 1 week. This complication was reported to occur less frequently after subtenon injection. This is in agreement with another study  that revealed an increase in IOP over 21 mmHg seen in 24.3% of the intravitreal group and in 8.2% of the subtenon group.
Our results on the safety of subtenon injection are similar to those of another study  that evaluated the elevation of IOP in 159 eyes of 158 patients treated with 40 mg (1.0 ml) subtenon injection of triamcinolone.
In that study, there were 18 of 159 eyes that required glaucoma medication due to increased IOP after injection, but the IOP in all 18 eyes was well controlled with the use of glaucoma medication. Therefore, there was no patient with uncontrolled IOP in that study.
In our study, two (5%) cases of posterior subcapsular cataract developed in the intravitreal group and was treated with phacoemulsification. This differs from the results of another study , which recorded progression of cataract in 2.1% after subtenon injection; this value is lower than the published rate of cataract progression due to intravitreal injection, which ranges from 3.8 to 6.6% ,.
Our study is in agreement with another work , which recorded progression of cataract in 16% of cases in the intravitreal group and in 10% of patients in the subtenon group.
The cataract in our study developed 6 months after injection. This is similar to another study  in which posterior subcapsular cataract developed in two of six patients 6 months after intravitreal triamcinolone; both patients required surgery. Another study  found that, by the 24-month visit, eight (24.2%) of 33 triamcinolone-treated eyes showed progression of posterior subcapsular cataract.
However, it may not be a major contraindication against the use of intravitreal corticosteroids, because cataract surgery can be performed months to years after injection without increased complications. Patients receiving intravitreal steroid injections should be informed of this complication and the increased likelihood of requiring cataract surgery.
Our study is in agreement with another study  in suggesting that subtenon injection results in no severe complications such as endophthalmitis, retinal detachment, inadvertent intraocular penetration, and orbital masses and has a relatively lower risk of IOP complications and cataract progression compared with intravitreal injection.
We revealed that the rate of complications was higher in the intravitreal group, with cataract being seen in 5% of patients and glaucoma in 22.5%; no cases of endophthalmitis were reported; in the subtenon group only glaucoma was noticed in 10% of the patients.
This is similar to another study  in which the rate of complications was higher in the intravitreal group, with cataract being seen in 16% of patients and glaucoma in 21%; however no cases of endophthalmitis were observed. In the subtenon group, only cataract was noticed in 10% of the patients.
All authors claimed that the steroid-induced IOP increase may not be a major contraindication for the treatment of endovascular and edematous ocular diseases with intravitreal injection , because adverse effects need to be balanced against the potential beneficial effects of any treatment.
Central macular thickness
In our study, the decrease in macular thickness was more significant after intravitreal injection at the end of the follow-up period, although the decrease in macular thickness was higher in the subtenon group at 1 week, 1 month, and 3 months but was markedly higher in the sixth month in the intravitreal group compared with the subtenon group. This is in agreement with another study  that revealed that DME responded well anatomically and functionally both to intravitreal and subtenon injection during the first 3 months of the treatment, but the decrease in macular thickness was significantly more dramatic after intravitreal injection.
In our study, improvement in CMT at the end of the study was seen in 38 of 40 (95%) eyes in the intravitreal group and in 39 of 40 (97.5%) eyes in the subtenon group. This differs from the results of another study  in which the overall percentage of patients who showed an improvement in their CMT at the end of the study was 76.5% in the intravitreal group and 75% in the subtenon group.
| Conclusion|| |
STTA achieves clinical results comparable to IVTA with respect to the reduction in CMT and the improvement in VA. The effect was more pronounced in the IVTA group, especially in the short term. Moreover, STTA seemed to be a safe and effective technique for the treatment of DME, especially in the long term. It lowers the IOP, making it suitable for glaucomatous patients.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]