|Year : 2017 | Volume
| Issue : 3 | Page : 154-159
Efficacy of intravitreal triamcinolone acetonide with thermal combination therapy versus intravitreal triamcinolone acetonide monotherapy on diffuse diabetic macular edema
Ashraf M Gad Elkareem
Department of Ophthalmology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
|Date of Submission||13-Mar-2017|
|Date of Acceptance||08-Jun-2017|
|Date of Web Publication||17-Oct-2017|
Ashraf M Gad Elkareem
Department of Ophthalmology, Al-Azhar University Hospital, Assiut, 71524
Source of Support: None, Conflict of Interest: None
Purpose The aim of this study was to compare the efficacy of intravitreal triamcinolone acetonide (IVTA) monotherapy with IVTA plus macular grid laser photocoagulation combination therapy on the treatment of diffuse diabetic macular edema.
Patients and methods Fifty eyes of 38 patients exhibiting diffuse diabetic macular edema were evaluated in this prospective comparative study. The patients were divided into two groups: IVTA monotherapy group and combination therapy group (IVTA plus grid laser). The main outcome measures of the study were best-corrected visual acuity (VA) scored in logMAR and the central macular thickness (CMT) as estimated at 3 and 6 months after treatment. The study further assessed the potential complications associated with IVTA injection.
Results The baseline logMAR VA and CMT were 0.46±0.22 and 445.2±123.91 µm for the IVTA monotherapy group and 0.57±0.27 and 456.91 ±134.32 µm for the combination therapy group, respectively. The post-treatment logMAR VA at 3 and 6 months were 0.24±0.12 and 0.28±0.09 for the IVTA monotherapy group and 0.22±0.13 and 0.18±0.16 for the combination therapy group, respectively. The CMT values at 3 and 6 months were 305.5±115.30 and 310.8±86.8 µm for the IVTA monotherapy group and 280.9±43.9 and 254.2±45.95 for the combination therapy group. Improvement in VA and CMT after treatment was statistically significant in both groups. Approximately 10% of patients developed cataract after 5 months of intravitreal injection. The mean pretreatment intraocular pressure and the mean post-treatment intraocular pressure were 15.49±2.47 and 14.56±2.26 and 14.92±2.80 and 13.55±2.02 mmHg in both the IVTA monotherapy and combination therapy groups, respectively.
Conclusion Macular grid laser photocoagulation after IVTA effectively maintains the VA and macular thickness of the patients included in this study during the first 6 months of treatment.
Keywords: diabetes mellitus, diabetic macular edema, diabetic retinopathy, grid laser, intraocular pressure, intravitreal triamcinolone acetonide, macular edema
|How to cite this article:|
Gad Elkareem AM. Efficacy of intravitreal triamcinolone acetonide with thermal combination therapy versus intravitreal triamcinolone acetonide monotherapy on diffuse diabetic macular edema. Delta J Ophthalmol 2017;18:154-9
|How to cite this URL:|
Gad Elkareem AM. Efficacy of intravitreal triamcinolone acetonide with thermal combination therapy versus intravitreal triamcinolone acetonide monotherapy on diffuse diabetic macular edema. Delta J Ophthalmol [serial online] 2017 [cited 2022 Jan 26];18:154-9. Available from: http://www.djo.eg.net/text.asp?2017/18/3/154/216922
| Introduction|| |
Diabetes mellitus (DM) is a worldwide disease . The WHO has estimated that by 2030 there will be 370 million people affected with DM in the world and that every one of them will be at risk of developing retinopathy .
DM is a significant cause of visual morbidity . It was estimated that 40.3% of diabetic patients (≥40 years) have some degree of diabetic retinopathy and that 8.2% have vision-threatening retinopathy . According to the Wisconsin Epidemiologic Study of Diabetic Retinopathy, the estimated incidence of macular edema (ME) was 20.1 and 25.4% among patients with type 1 and type 2 diabetes treated with insulin, respectively ,.
ME reduces a person’s central vision . It occurs because of the accumulation of fluid in the inner retinal layers, which is caused by breakdown of the inner blood–retinal barrier with increased vascular permeability. These retinal changes lead to the structural and functional damage of the macular cells ,,. Although the diagnosis of diabetic macular edema (DME) is mainly a clinical entity in which slit-lamp biomicroscopy with the +90 D lens is used, optical coherence tomography (OCT) is used for the quantification of edema and for follow-up purposes. Fluorescein angiography is further used to exclude ischemic maculopathy and to differentiate focal from diffuse retinal thickening ,,,.
Macular laser photocoagulation remains the gold standard in the treatment of DME, although its precise mechanism is still unknown . Some previous studies have shown that macular laser photocoagulation is not effective in diffuse DME. Because of this limited efficacy of macular laser photocoagulation, several pharmacotherapy agents have evolved over the past few years as an alternative effective treatment. Most of these agents are currently used as an adjuvant or alternative therapy for ME patients who are refractory to thermal laser treatment ,.
The intravitreal triamcinolone acetonide (IVTA) injection is one of these pharmacotherapy agents ,,. It prevents the breakdown of the inner blood–retinal barrier and reduces the release of the vascular permeability factors such as vascular endothelial growth factor, interleukins 6, and prostaglandins ,,.
The aim of this study was to compare the clinical outcomes of intravitreal triamcinolone injection monotherapy with the combination therapy of intravitreal steroid injection followed by thermal laser photocoagulation in patients with diffuse DME.
| Patients and methods|| |
This prospective, randomized comparative study included 50 eyes of 38 diabetic patients diagnosed with diffuse DME according to the ETDRS definition from July 2016 to December 2016. The procedures were performed at Al-Azhar University Hospital, Assiut Ophthalmology Department. The Research and Ethical Committee of the School of Medical Sciences, Al-Azhar University, Egypt, approved the study.
Diffuse DME is an area of retinal elevation of 1 or more disc diameter, any part of which is within 1 disc diameter of the center of the macula on biomicroscopic examination .
These 38 patients were divided into two groups: the IVTA monotherapy group and the combination therapy group. Each group consisted of 25 eyes.
The IVTA monotherapy group comprised 25 eyes in 18 diabetic patients (10 male and eight female). This group was injected with 4 mg of IVTA. The combination therapy group comprised 25 eyes of 20 diabetic patients (12 male and eight female). Patients in this group were injected with 4 mg of IVTA followed by laser treatment after 3 weeks.
Patients with media opacity impairing intravitreal injection or those having previous laser photocoagulation procedure, as well as those with ischemic diabetic maculopathy, were excluded from this study. In addition, patients with recent ocular surgery or having YAG procedure, glaucoma patients, patients exhibiting central macular thickness (CMT) less than 250 µm by OCT, patients with vitreomacular traction, and patients having previous intravitreal injections were also excluded from the study.
All patients underwent complete ophthalmic examination. This included best-corrected visual acuity that was converted to logMAR, slit-lamp examination, measurement of intraocular pressure (IOP) by applanation tonometry, fundus examination by the indirect ophthalmoscope, and slit-lamp biomicroscopy with noncontact +90 D lens. The diagnosis of diffuse DME was made on a clinical basis and by reduction in the reflectivity of the outer layers and/or subfoveal fluid collection on OCT and by diffuse fluorescein leakage on fluorescein angiography.
Having obtained an informed consent from all patients, those in the IVTA monotherapy group were injected with 4 mg of triamcinolone acetonide (Kenacort-A; Bristol-Myers Squibb, Cairo, Egypt) in 0.1 ml at 4 mm from the limbus. The injection was conducted in the operating theater under complete aseptic conditions, using a 27-G needle.
Indirect ophthalmoscopy was performed to confirm proper intravitreal localization of the suspension and perfusion of the optic nerve head. Patients in the combination therapy group underwent macular argon laser photocoagulation 3 weeks after the injection. A 50–100-μm spot size, 0.1-s exposure time, and a laser power were used to just have light whitening of the treated areas in a grid pattern.
Visual acuity, IOP, slit-lamp, and fundus examination were performed on the second day after injection to evaluate serious adverse effects such as endophthalmitis and elevated IOP. They were further evaluated after 1, 3, and 6 months after the treatment. The CMT was also analyzed by comparing pretreatment OCT with post-treatment OCT using Stratus-OCT (Carl Zeiss Meditec, Jena, Germany) at the third and sixth months, postoperatively.
Statistical analyses were performed by a commercially available statistical software package (SPSS for Windows, version 16, SPSS Inc., Chicago, Illinois, USA). Wilcoxon signed-rank test was conducted to determine the statistical significance of the differences of visual acuity, IOP, and macular thickness at different visits compared with the baseline level within the same group. The Mann–Whitney U-test was conducted to determine the differences between the two groups.
| Results|| |
Twenty-five eyes of 18 diabetic patients were enrolled in the IVTA monotherapy group. In addition, 25 eyes of 20 diabetic patients were enrolled in the combination therapy group. The demographic and clinical data of the patients enrolled in both groups are presented in [Table 1].
The mean pretreatment logMAR visual acuity was 0.46±0.22 and 0.57±0.27 in the IVTA monotherapy and combination therapy groups, respectively.
The mean logMAR visual acuity after 1 month of treatment was 0.24±0.13 and 0.29±0.16; 0.24±0.12 and 0.22±0.13 after 3 months; and 0.28±0.09 and 0.18±0.16 after 6 months in the IVTA monotherapy and combination therapy groups, respectively ([Table 2] and [Figure 1]).
|Table 2 Comparison between pretreatment, 1-, 3-, and 6-month logMAR visual acuity in the study groups|
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|Figure 1 Comparison of pretreatment, 1-, 3-, and 6-month logMAR visual acuity in the study groups.|
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In the IVTA monotherapy group, the visual acuity showed an improvement in nearly all patients of approximately two lines at the end of the 6-month follow-up period. The P-value for the logMAR visual acuity improvement was 0.001, which was statistically significant.
Similarly, there was a statistically significant difference in the combination therapy group between the pretreatment visual acuity and the 6-month visual acuity. Six-month visual acuity showed an improvement of approximately four lines (P<0.001).
In both groups, there was an improvement in the visual acuity at the end of the follow-up period. However, more significant improvement was noticed in the combination therapy group than in the IVTA monotherapy group (P=0.001). In the combination therapy group, the improvement in visual acuity continued until the end of the follow-up period. However, in the IVTA monotherapy group, there was a decline in the visual acuity of approximately one line between the 3- and 6-month visits.
The mean pretreatment IOP was 15.49±2.47 (11.2–22.50) and 14.56±2.26 (12.25–19.10) mmHg in the IVTA monotherapy and combination therapy groups, respectively ([Table 3]).
After treatment, however, the IOP was higher in the IVTA monotherapy group than in the combination therapy group. The P values after 1, 3, and 6 months of treatment were 0.001, 0.00002, and 0.0006, respectively, which were highly statistically significant.
It was also observed that the IOP returned to its normal pretreatment levels within 3 months in both groups without the need for any operative interference. At the end of the follow-up period, the IOP was 14.9 mmHg in the IVTA monotherapy group and 13.50 mmHg in the combination therapy group (P=0.0006).
On OCT, the pretreatment CMT ranged from 251 to 695 (445.2±123.91) and from 255 to 598 (456.91+134.32) µm in the IVTA monotherapy and combination therapy groups, respectively ([Table 4] and [Figure 2]). Both groups showed a statistically significant reduction in CMT after 3 months of treatment, which was more in the combination therapy group than in the IVTA monotherapy group. The mean CMT in both groups was 280.9±43.9 and 305.5±115.30 µm, respectively.
|Table 4 Comparison of the mean central macular thickness in the study groups during the follow-up period|
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|Figure 2 Comparison of the mean central macular thickness in the study groups during the follow-up period.|
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After 6 months of treatment, there was a marked reduction in the mean CMT in the combination therapy group than in the IVTA monotherapy group. The mean CMT was 254.2±45.95 and 310.8±86.8, respectively (P=0.0007). The reduction of the baseline CMT in both groups was ∼200 and 135 microns, respectively, at the end of the follow-up period.
Three (12%) eyes in the IVTA monotherapy group and two (8%) eyes in the combination therapy group developed cataract after 5 months of treatment. However, there were no cases of endophthalmitis or inflammatory pseudoendophthalmitis following any of the intravitreal injections.
| Discussion|| |
Diabetic retinopathy and DME are the leading causes of blindness in the working-age population of most developed countries .
Macular laser photocoagulation is the main standard treatment for DME. However, diffuse DME may persist or recur in spite of adequate laser therapy . Over the past few years, the IVTA injection has yielded promising results in the treatment of diffuse DME . The short duration of action is the main limitation of steroid, which requires repeated injections. Ultimately, these repeated injections may result in potential complications related to both the injection and the steroid .
The present study demonstrated that the mean visual acuity has significantly improved in the combination therapy group compared with the monotherapy IVTA group, 3 months post-treatment and afterward. In addition, the laser photocoagulation appears to be responsible for the maintenance of the improved visual acuity throughout the follow-up period. The exact mechanism of action of the laser photocoagulation is not fully understood. However, one of the hypotheses for understanding this mechanism is that the laser destruction of some photoreceptors, which consume a high amount of oxygen, will increase the oxygen supply to the inner retinal layers. Accordingly, this would reduce the release of the VEGF, which may prevent the recurrence of ME.
Some previous studies have demonstrated that macular laser photocoagulation alone resulted in the reduction of visual loss in patients with diffuse DME . Other studies, however, have shown that visual acuity decreased by three lines or more in 24.6% of eyes with diffuse DME after grid laser photocoagulation . Diffuse DME represents an advanced stage of diabetic retinopathy that is caused by generalized breakdown of the blood–retinal barrier. Thus, the effects of laser on the retinal vascular endothelium and photoreceptors could not to be expected under such circumstances. These outcomes advocate the development of new modalities of treatment combined with or without laser photocoagulation. In this study, the CMT was reduced after 3 and 6 months of treatments in the combination therapy group. However, it increased again in the IVTA monotherapy group 3 months after injection.
Some previous studies have also demonstrated that the combined therapy of diffuse DME is more effective than single treatment ,. This may be attributed to a synergism between the actions of IVTA and laser photocoagulation for DME.The mechanism of corticosteroids in the treatment of ME may be explained by the inhibition of prostaglandin release and downregulation of the production of vascular endothelial growth factor, which results in a reduction of vascular permeability. Accordingly, such a reduction improves the inflammatory and vascular components of ME ,.
Some previous reports have shown that anatomical and functional outcomes did not correlate and the visual gain was limited in spite of the reduction of the CMT, which was attributed to irreversible structural damage . However, both anatomical and functional outcomes were correlated in the present study and have continued during the follow-up period in the combination therapy group. This may be attributed to both the small number of patients included in this study and the recent onset of ME with less macular ischemia in our patients, and as such not much structural damage has occurred. Steroid-related cataract progression and IOP elevation were observed at a rate similar to those observed in previous studies ,.
In conclusion, the study found that IVTA therapy combined with macular laser photocoagulation has better functional and structural outcomes during the 6-month follow-up period than in the IVTA monotherapy. Further studies involving large numbers of patients and longer follow-up periods are needed to know the long-term outcomes of the combined therapy and the necessity of reinjection or repeated laser treatment.
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Conflicts of interest
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]