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.