Risk of intraocular pressure elevation associated with triamcinolone acetonide administration via different routes in macular edema: a systematic review andnetwork meta-analysis of randomized controlled trials
Kexin Liu1, Jinyang Yi1,2, Juan Xu1,3,Zhong Li1,4, and Na Su 1,5*
1 Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China, 2 Department of Pharmacy, Suining First People’s Hospital, Suining, China, 3 Pharmacy Department of Zizhong County People’s Hospital, Zizhong, China, 4 Department of Clinical Pharmacy,The People’s Hospital of Zhongjiang , Zhongjiang, China. 5 West China School of Pharmacy, Sichuan University, Chengdu, China,
Abstract Aims:Despite their overall favourable safety profile, the intraocular pressure increases after any routes of triamcinolone acetonide application are not rare. We designed a systematic review and network meta-analysis to compare risk of IOP elevation among TA for different routes of administration used by patients diagnosed with macular edema.
Methods: We obtained data from the PubMed, MEDLINE, Embase, and Cochrane Library. We performed random-effects model and consistency model network meta-analyses to summarize the evidence. The Bayesian approach was used for direct and indirect comparisons, and the treatments were ranked by the surface under the cumulative ranking curve. The study was registered with PROSPERO, CRD42022366513
Results: Sixteen studies were included in the network meta-analysis. There was a significant difference in IOP between IVTA and STiTA (MD, 1.67 [95% CrI, 0.25, 3.15]) at the 12th week. At the 24th week, compared with the placebo group, IVTA, SCTA and STiTA had statistically significant effect on IOP (MD, 1.35 [95% CrI, 0.23, 2.30], 2.42 [95% CrI, 4.53, 0.19], and 1.31 [95% CrI, 2.49, 0.02]). The probabilities of rankings and SUCRA showed that IVTA and SCTA were generally considered the higher risk of IOP elevation than the other routes of injection therapy. In addition, RITA was shown to be safer.
Conclusion: IVTA and SCTA appeared as the least safe routes of injection therapy for ME, which being more prone to increase the risk of IOP elevation. RITA demonstrated a safer profile. However, more high-quality randomized controlled trials will be necessary to further confirm this.
KEYWORDS
triamcinolone acetonide, macular edema, network meta-analysis, intraocular pressure, Bayesian framework
1 INTRODUCTION
Macular edema (ME) is secondary to many different ocular and systemic disease processes and is defined as the accumulation of intra and/or subretinal fluid in the macular region.1-2 It can occur in several retinal conditions, such as diabetic retinopathy (DR), agerelated macular degeneration (AMD), retinal vascular disorders, and many other ocular and systemic diseases resulting in visual impairment.3-4At present, anti-vascular endothelial growth factor (anti-VEGF) drugs, glucocorticoids, and laser photocoagulation alone or in combination are mostly used to reconstruct the blood-retinal barrier in patients with macular edema in clinical practice.5-6 In their midst, glucocorticoids have both angiostatic and anti-inflammatory effects, so they have been recommended by guidelines for intravitreal injection or implantation as a second-line therapy for diabetic retinal vein occlusion (RVO) and diabetic macular edema (DME).7-8 Sometimes glucocorticoids are even a first-line treatment, e.g. patients with high-risk cardiovascular disease, poor compliance, severe edema (>500 mm), patients with pseudolenses, patients scheduled for cataract surgery, and patients with a history of vitrectomy.8
Glucocorticoids have long been used in the treatment of macular edema; systemic glucocorticoids are effective but are associated with adverse events, including adrenal insuffciency, Cushing’s syndrome, diabetes, cardiovascular disease, osteoporosis, and immunosuppression. Local application of glucocorticoids results in much lower systemic concentrations of the drug and reduces the incidence of adverse events associated with systemic therapy. However, these come with their own set of risks, most commonly an increased risk of cataracts and elevations in intraocular pressure (IOP).9 In comparison with other glucocorticoids, because triamcinolone acetonide (TA) is a minimally water-soluble steroid in a suspension form, it can maintain a long-term intraocular concentration for an expanded period of time. TA has been reported to be present in the eye for as long as six months after the injection, and it is present in measurable concentrations up to 1.5 years after intravitreal injections of triamcinolone acetonide (IVTA).10 The incidence of IOP increase after IVTA may be as high as 83.3% in the literature.11 The most recent meta-analysis indicated that sub-Tenon’s capsule injection of TA injection has a comparable effect to the intravitreal injection of TA injection and carries a lower risk of intraocular complications.12
At present, there is no comparison of the safety of triamcinolone acetonide in the treatment of macular edema with different routes of administration, and no recommendations are provided. Therefore, we conducted this systematic review and network meta-analysis (NMAs) to comprehensively evaluate and compare the safety of triamcinolone acetonide administration via different routes in patients with macular edema.