|ORIGINAL RESEARCH ARTICLE
|Year : 2018 | Volume
| Issue : 2 | Page : 35-40
Intravitreal dexamethasone implant versus triamcinolone acetonide for macular edema due to central retinal vein occlusion: Quantifying efficacy and safety
Sanjay K Mishra1, Abhishek Gupta1, Sagarika Patyal2, Santosh Kumar2, K Raji2, Anirudh Singh2, Vijay Sharma2
1 Department of Ophthalmology, Military Hospital, Jabalpur, Madhya Pradesh, India
2 Army Hospital Research and Referral, Delhi Cantt, New Delhi, India
|Date of Submission||05-Feb-2018|
|Date of Acceptance||25-Feb-2018|
|Date of Web Publication||12-Jul-2020|
Dr. Sanjay K Mishra
Department of Ophthalmology, Military Hospital, Jabalpur - 482 001, Madhya Pradesh
Background: Central Retinal vein occlusion (CRVO) is one of the commonest retinal vascular disease in Diabetics. Intravitreal corticosteroids (IVS) implants and injection are gaining popularity in managing Macular Edema (ME) of RVO.
Objective: To assess Intravitreal Dexamethasone Implant versus Triamcinolone Acetonide for Macular Edema due to Central Retinal Vein Occlusion: regarding Efficacy and Safety.
Materials and Methods: In a hospital-based prospective, comparative study, a single 0.7 mg IVD Ozurdex Implant compared to single injection of 1.0 mg IVTA for ME due to CRVO: regarding Efficacy and Safety. 40 patients, were involved between September 2012 and May 2014. In 5 follows-up Results; up to 24 months; were evaluated clinically and by fundus fluorescein angiography (FFA) beside optical coherence tomography (OCT) with significant cystoid ME as defined by CRVO study.
Results: IVD implant and IVTA both were effective in restoring vision in patients of early CRVO, with a high proportion (40%) gaining ≥3 lines. In terms of safety, drug-induced IOP rise 35% lesser with IVD compared than IVTA. 67% requiring combination of anti-glaucoma medications up to at 6 months. Cataract progression and propensity for cataract surgery is 25% and 100% lesser with IVD implant at same period. The as was the gain in the BCVA and at the end of 6 months (P = 0.582), were similar in both groups. Central Macular Thickness (CMT) decreased significantly in both groups, from 551 ± 17.16 μm to 237 ± 20.71 μm in the IVD-group (P < 0.001) and from 547.5 ± 13.79 μm to 232.6 ± 18.54 μm in the IVTA-group (P = 0.001) at the end of 6 months; thus, at the final follow-up, CMT was similar in both groups (P = 0.4244).
Conclusion: Intravitreal steroids are effective in managing ME of RVO, while the newer formulation of sustained-release dexamethasone implant is significantly safer than IVTA.
Keywords: Central retinal vein occlusion, dexamethasone implant, intravitreal triamcinolone, nonischemic central retinal vein occlusion, ozurdex, triamcinolone acetonide
|How to cite this article:|
Mishra SK, Gupta A, Patyal S, Kumar S, Raji K, Singh A, Sharma V. Intravitreal dexamethasone implant versus triamcinolone acetonide for macular edema due to central retinal vein occlusion: Quantifying efficacy and safety. Albasar Int J Ophthalmol 2018;5:35-40
|How to cite this URL:|
Mishra SK, Gupta A, Patyal S, Kumar S, Raji K, Singh A, Sharma V. Intravitreal dexamethasone implant versus triamcinolone acetonide for macular edema due to central retinal vein occlusion: Quantifying efficacy and safety. Albasar Int J Ophthalmol [serial online] 2018 [cited 2021 Sep 19];5:35-40. Available from: https://www.bijojournal.org/text.asp?2018/5/2/35/289599
| Introduction and Purpose|| |
Retinal vein occlusion (RVO) is the second-most common retinal vascular disease following diabetic retinopathy. Central RVO (CRVO) impedes blood supply leading to retinal ischemia, edema, and significant ocular morbidity. It affects men and women equally and occurs predominantly in persons over the age of 65 years.,, Population-based studies report the prevalence of CRVO at 0.1%–0.4%.,,
Intravitreal corticosteroids are gaining popularity in managing macular edema (ME) of RVO attributed to their anti-angiogenic, anti-edematous, anti-inflammatory, anti-apoptotic, and anti-proliferative effects. Intravitreal delivery allows the steroids to bypass blood-retinal barrier, leading to higher concentration and prolonged action. Commonly used intravitreal steroids are triamcinolone-acetonide and 0.7 mg dexamethasone implant. Earlier studies have established both steroids to mitigate the risk of vision loss and improve ME secondary to CRVO.,,
Our study compares the efficacy and safety of intravitreal triamcinolone (IVTA) and intravitreal dexamethasone implant (IVD) over 6 months.
| Materials and Methods|| |
This comparative, prospective, interventional, randomized study was carried out at Army Hospital Research and Referral Ophthalmology Clinic between September 2012 and May 2014. The study is conducted in accordance with the Declaration of Helsinki and approved by the Institutional Research Board. Informed consent was obtained from all patients before enrolling in the study. At baseline and follow-up, patients were evaluated for best-corrected visual acuity (BCVA; Snellen chart at 6 m), intraocular pressure (IOP; Goldmann Tonometer), slit-lamp examination of anterior segment, indirect ophthalmoscopy. Forty patients of nonischemic CRVO with significant ME (>330 μm) of <3 months were included. The clinical diagnosis was confirmed by Fundal Photography, Fundal Fluorescein Angiography (FFA) and Optical Coherence Tomography (OCT) (Spectralis, Cirrus) pre and post injection of IVD Ozurdex Implant for one group of 20 patients (12 men, 8 women). and another group of 20 patients (11 men, 9 women) who received IVTA Injections (Kenacort A®, BMS) for ME secondary to CRVO. [Figure 1], [Figure 2], [Figure 3], [Figure 4] and [Figure 5] and [Figure 6] The exclusion criteria were the existence of other retinal vascular diseases (diabetic retinopathy, age-related macular degeneration), glaucoma, previous treatments for CRVO (intravitreal or laser-photocoagulation), iris neovascularization and >10-disc retinal ischemia in FFA. The Same drugs were used during the whole study period. Follow-up was at day 1 and weeks 4, 8, 12, and 24. Reinjections were based on CMT measured on OCT. Recurrence of ME was defined as a decrease in VA ≤2 lines or an increase in intraretinal or subretinal fluid, with ME ≥320 μm. IVD and IVTA were administered as and when required. The primary outcomes were BCVA, CMT on OCT, IOP, and cataract progression.
|Figure 2: FFA pre- and postinjection ozurdex showing resolving macular oedema|
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|Figure 3: Optical coherence tomography macula pre- and postinjection ozurde|
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|Figure 5: FFA pre and post injection triamcinolone showing resolving macular oedema with capillary non perfusion areas and enlarged and distorted foveal avasular zone|
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|Figure 6: Optical coherence tomography macula pre and post injection triamcinolone|
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Statistical analysis was performed using Stata90 (Electronics Manufacturing Services, Inc., College Station, TX, USA). Data is presented as median (minmax) or number (%) as appropriate. Continuous baseline characters were compared between groups using the Wilcoxon-Rank sum test, and categorical baseline characteristics were compared using Fisher's exact test. The outcomes variable such as BCVA, IOP, CMT were compared between groups using the Wilcoxon rank sum test and within-group using the Wilcoxon Signed-Rank sum test as the sample size is small. The value of P < 0.05 was considered statistically significant. VA is converted into logarithm of the minimum angle of resolution (logMAR) for statistical analysis.
| Results|| |
Of the 40 patients, 20 (11 men, 9 women) received IVTA and 20 (12 men, 8 women) received IVD for ME secondary to CRVO. The sex distribution was similar between groups (P = 0.502), as was the mean patient age (58.6 ± 10.41 years vs. 57.9 ± 8.77 years; P = 0.342). The mean follow-up time is 6 months in both groups. Mean baseline measurements in IVDvs. IVTA group are BCVA (logMAR) (1.06 ± 0.13 vs. 0.99 ± 0.15), CMT (551 ± 17.16 μm vs. 547.5 ± 13.79 μm) and IOP (16.7 ± 1.16 mmHg vs. 16.1 ± 2.60 mmHg), respectively, and were not statistically significant [Table 1]. Arterial hypertension was diagnosed in ten patients (IVD group-4 patients; IVTA group-6 patients). Seven patients had hyperlipidemia (IVD group-3 patients; IVTA group-4 patients). Eight patients were cigarette smokers in IVD-group and nine smokers in IVTA-group. Two patients in IVD-group required 2 IVD injections during the first 6 months of therapy. Four patients in the IVTA-group required 2 IVTA injections during the first 6 months of therapy.
|Table 1: Baseline parameters in patients with central retinal vein occlusion|
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The mean BCVA improved from 1.06 ± 0.13 to 0.63 ± 0.54 (P < 0.001) in the IVD-group and from 0.99 ± 0.15 to 0.50 ± 0.45 (P < 0.001) in the IVTA group at the end of 6 months [Table 2]. The BCVA at baseline (P = 0.392) and at the end of follow-up (6 months) (P = 0.582), however, were similar, as was the gain in visual acuity in the two groups [Table 3]. Within both the groups, there was a significant improvement in visual acuity at each follow-up visit [Table 3]. CMT decreased significantly in both groups, from 551 ± 17.16 μm to 237 ± 20.71 μm in the IVD-group (P < 0.001) and from 547.5 ± 13.79 μm to 232.6 ± 18.54 μm in the IVTA-group (P = 0.001) at the end of 6 months; thus, at the final follow-up, CMT was similar in both groups (P = 0.4244) [Table 2]. There was no statistical difference between the groups in retinal thickness at 6 months [Table 4]. Within the group, there was a statistically significant reduction of CMT at each follow-up visit in both the treatment arms [Table 4].
|Table 2: Comparison of baseline and end-of-follow-up parameters in patients with central retinal vein occlusion|
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|Table 3: Comparison of logarithm of the minimum angle of resolution best-corrected visual acuity between ozurdex and triamcinolone at each follow-up visit|
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|Table 4: Comparison of central macular thickness between Ozurdex and Triamcinolone at each follow-up visit|
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A significant increase in IOP at 6 months was observed only in the IVTA-group [Table 2]. IOP lowering medication was initiated in 12 eyes (60%) in the IVTA-group and in 5 eyes (25%) in IVD-group in 6 months. All the 5 eyes in the IVD-group had IOP of <26 mmHg and was readily controlled by single antiglaucoma medication and reached baseline by 6 months. Peak IOP was recorded in the 2nd month of follow-up. In IVTA-group IOP lowering medication was initiated in 12 eyes (60%). Five eyes (41.6%) had IOP of >35 mmHg. Eight eyes (66.6%) needed combination eye drops and did not normalize by 6 months of the study. The statistical analysis of IOP comparison between dexamethasone and triamcinolone was significant at 12 and 24 weeks with triamcinolone group showing increased IOP [Table 5]. Within the ozurdex group, the change in IOP from baseline was statistically significant up till 12 weeks, but by the end of 24 weeks, this change became statistically insignificant, but in the triamcinolone group, this was statistically significant by the end of 6 month period [Table 5].
|Table 5: Comparison of Intraocular pressure between ozurdex and triamcinolone at each follow-up visit|
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Among eyes that were phakic at baseline 7 eyes (35%) in the IVTA-group either had new-onset lens opacity or progression of an existing opacity through month 6 as compared to 2 in the IVD-group. In the IVTA-group, 5 eyes (71.5%) of the 7 eyes with significant cataract progression required cataract surgery at the end of follow-up period. Through month 6, there were no reports of infectious endophthalmitis in either group. Minor ocular adverse events related to injection procedures such as vitreous floaters and conjunctival hemorrhage occurred in a similar number of eyes in both groups.
| Discussion|| |
Studies related to the tricarboxylic acid (TCA) done by Cekiç et al. reported average gain in VA in patients treated with TCA is 1.3 Snellen lines (range, −3–7) for 10 months. Of 24, 10eyes gained ≥2 lines of VA, 3 eyes improved 1-line, 7 eyes remained the same, and 4 eyes worsened. There was no correlation between improvement in foveal thickness and corresponding visual gain. The SCORE study group concluded that of 271 patients, 27% of participants in 4-mg TCA group achieved ≥15-letters improvement from the baseline. Jonas et al. reported an improvement in VA by at-least 2 Snellen lines and 3 Snellen lines, respectively, in 8 (62%) eyes and 5 (38%) eyes treated with triamcinolone. VA measurements at 1 month (P = 0.038) and 3 months (P = 0.046) after the injection were significantly higher than the baseline values. The increase in VA was higher in the nonischemic subgroup than the ischemic subgroup. Patel et al. reported VA improvement ≥2 Snellen lines in eight (62%) eyes with mean VA improvement of 0.46 LogMAR with TCA intervention. The studies related to dexamethasone done by GENEVA study group reported 22% of participants in 0.7 mg dexamethasone group achieved ≥15-letters improvement from baseline. Joshi et al. reported mean change in VA at 12 months with ozurdex compared to baseline for CRVO was 11.5 ± 11.0 EDTRS letters, 30% of eyes gained ≥15 letters. Visual outcomes are similar to those previously seen with TCA in the SCORE study.
The study shows that the likelihood of a gain in VA letter score of ≥15 at 6 months is similar in IVTA and IVD groups. At all-time points through 6 months, mean VA improvements are comparable between IVD and IVTA groups. At 6 months, mean improvement in BCVA was 0.43 and 0.49 LogMAR in IVD and IVTA groups, respectively, and was not statistically significant between groups [Table 3]. Within both groups, there was a significant improvement in VA at each follow-up visit. In our study, 8/20 subjects (40%) in both groups achieved ≥15 letters improvement from baseline to 24 weeks. This is in concurrence with other studies that have reported that steroids improve VA in patients of ME due to CRVO.
There was no statistical difference between groups in CMT at 6 months [Table 4]. In both treatment arms, 18/20 (90%) patients achieved CMT of ≤250 μ at the end of 6 months. In the GENEVA study for dexamethasone implant 40% of patients achieved CMT <250 μ at 6 months, whereas the SCORE study group reported 38% patients with CMT of ≤250 μ at 6 months. Cekiç et al. reported that in TCA treated patients the mean CMT decreased to 55% of preinjection values ([n = 23] 635 vs. 352 μm, respectively; P < 0.001). Ip et al. reported that mean baseline CMT before TCA injection was 590 μm and improved to 281 μm at 6 months in 13 patients. Patel et al. reported that CMT decreased significantly by 259 μm (45% improvement) at best after treatment (standard deviation 94 μm; P = 0.000017), with five eyes achieving a thickness ≤250 μm in 13 patients injected with triamcinolone.
In our study at 6 months, the mean improvement in CMT was 323 μm and 322 μm in IVD and IVTA groups, respectively. In both treatment arms, 18/20 (90%) patients achieved CMT of ≤250 μm at 6 months and was statistically similar between groups. Comparatively greater proportion of patients achieved a reduction in CMT. This may be attributed to selective inclusion of patients with shorter duration of ME of <3 months yielding better prognosis than patients with a longer period ME. Within groups, there was a statistically significant reduction of CMT at each follow-up in both treatment arms [Table 5].
In regard to safety outcome for dexamethasone-implant, GENEVA study reported that 15% study eyes showed IOP elevation of at least 25 mmHg peaking at day 60 and normalizing by day 180. While triamcinolone in SCORE study reported 35% of study eyes with IOP rise and eight subjects having IOP >35 mmHg. Cekiç et al. reported that 9/18 patients without a history of glaucoma developed ocular hypertension and required glaucoma medication during post-TCA injection follow-up. Trabeculectomy was performed on 2 eyes with glaucoma. Ip et al. reported that out of 13 patients on TCA, 1 patient experienced an IOP rise that was controlled with two aqueous suppressants. Jonas et al. reported that in the TCA-group, IOP increased significantly (P = 0.018) from 14.4 ± 3.9 mmHg to a mean maximal value of 21.6 ± 9.2 mmHg (range, 10–44 mmHg) and decreased (P = 0.012) toward the end of 10 months follow-up to 15.3 ± 5.1 mmHg (range, 10–21 mmHg). Patel et al. reported an IOP rise in 8/13 (62%) eyes during follow-up. Four eyes achieved a maximum IOP <30 mmHg. The highest IOP recorded was 40 mmHg with two eyes and both treated adequately with topical medication. In total, five eyes (38%) required IOP lowering medication at the end of follow-up.
In our study, there is a higher frequency of initiating IOP-lowering medications in the IVTA-group compared to IVD-group. Twelve cases (60%) in IVTA-group showed elevated IOP, of which 8 (66.6%) were managed with combination eye drops, and the difference was statistically significant from baseline at 6 months [Table 3]. However, in IVD-group IOP rise was manageable with single antiglaucoma medication and returned to baseline by 6 months [Table 3].
There were no cases of infectious/noninfectious endophthalmitis with intravitreal procedures in either group. Seven phakic eyes (35%) in IVTA-group either had new-onset lens opacity or progression of an existing opacity through month 6 as compared to 2 (10%) in the IVD-group. In the IVTA-group, 5 of 7 (71.4%) with significant cataract progression required cataract surgery at 6 months while none required cataract surgery in IVD-group.
Thus, our study demonstrates that dexamethasone0.7 mg sustained-release implant and triamcinolone-acetonide are effective in restoring vision in patients of early CRVO, with a high proportion (40%) gaining ≥3 lines. In terms of safety, drug-induced IOP rise 35% lesser with dexamethasone implant compared to IVTA. With IVTA, there is the probability of 42% of patients experiencing IOP rise >35 mmHg and about 67% requiring combination anti-glaucoma medications and fail to normalize at 6 months. Cataract progression and propensity for cataract surgery is 25% and 100% lesser with dexamethasone implant at 6 months' therapy. Our sample size is small, with the longest follow up of 18 months, a much larger study with an appropriate sample size and longer follow up is needed to establish these results.
| Conclusion|| |
Intravitreal steroids are effective in managing ME of RVO, while the newer formulation of sustained-release dexamethasone implant is significantly safer than IVTA.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]