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Triamcinolone Acetonide for the Treatment of Diabetic Macular Oedema Safety Profile

The safety evaluation of the administration of intravitreal TA has been investigated by several randomised controlled clinical trials. Potential complications are divided into steroid-related and injection-related adverse effects. Steroid-related side effects most commonly include the increase of IOP and cataract formation. Injection-related side effects include endophthalmitis, pseudoendophthalmitis, rhegmatogenous retinal detachment and toxic effects.

Post-injection Infectious Endophthalmitis Infectious endophthalmitis is one of the most serious complications of intravitreal injection of TA, with the reported risk per injection ranging from 0.1 % to 1.6 %.57

development of steroid-induced posterior subcapsular cataract and for the elevation of IOP. A study suggested that a single intravitreal TA induces posterior subcapsular cataract development, whereas multiple injections result in all-layer cataract progression.88

Rhegmatogenous Retinal Detachment

A potential complication of the intravitreal TA injection may be a rhegmatogenous retinal detachment.89

Triamcinolone acetonide, Many studies suggest that this relatively high

rate of infectious endophthalmitis may be attributed to the techniques used for injection. If the injection is performed under sterile conditions, the risk of an infection may be lower.58–65

Patients with

infectious endophthalmitis after intravitreal TA usually present without pain, which is uncommon for infectious endophthalmitis in eyes without intraocular steroids.66

Post-injection Pseudoendophthalmitis

Several studies have described non-infectious endophthalmitis after intravitreal injection of TA.67,68

Post-injection pseudoendophthalmitis is

present if TA crystals are washed from the vitreous cavity into the anterior chamber and settle down in the inferior anterior chamber angle mimicking hypopyon. According to reports, this complication occurs in 0.2–6.7 % of eyes following treatment. TA crystals in the anterior chamber usually disappear spontaneously and may not need to be removed. There have been no reports so far showing corneal endothelial damage or damage to the trabecular meshwork by the crystals.69

Steroid-induced Ocular Hypertension

A number of reports have described IOP elevation as the most common adverse event of intravitreal TA.70–82

Mild to moderate IOP

elevation was seen in 28–42 % of patients, typically within the first three months following injection. This condition is usually controlled with topical agents alone. About 1 % of patients require surgical treatment. Selective laser trabeculoplasty (SLT) is a treatment alternative or adjunct to medical therapy. Comparing studies using different doses of TA for intravitreal injection suggests that the risk of IOP rise appears to be higher due to the prolonged elevated concentrations that are achieved intraocularly. If further studies confirm the assumption that the frequency of secondary ocular hypertension after an intravitreal TA injection may not markedly depend on the dose used, one may assume that even relatively low TA doses are already high enough to occupy all steroid receptors. Some authors suggest that pre-medication with topical steroids may be useful to identify possible steroid responders and excluding them from intravitreal TA treatment may lower the incidence of IOP elevation.83–85

Steroid-induced Cataract

A recent study reported that, in the elderly population, intravitreal high-dose injections of TA led to clinically significant cataract with eventual cataract surgery in about 15–20 % of eyes within about one year of the intravitreal injection.86

Steroid-induced cataract is a common side effect of intravitreal TA.77,86–88

Gillies et al. concluded that

eyes with an elevation of IOP after intravitreal TA have a very high risk of rapidly experiencing posterior subcapsular lens opacification.87 strong association suggests a similar mechanism responsible for the


injected into the vitreous cavity, leads to a change in the structure of the vitreous body and the abnormal vitreous may exert traction on the retina. In particular, this is supposed for the inferior midperipheral area of the vitreo-retinal interface where the TA crystals remain in the preretinal vitreal cortex; for superior midperipheral and peripheral regions where a vitreous traction might be induced by the weight of the TA crystals settled at six o’clock; and for the far periphery of the fundus where the vitreous, incarcerated into the injection site, causes retinal traction.

Toxic Effects

Previous studies in rabbits found that preservatives in the vehicle for suspension of crystalline steroids, rather than steroid itself, could be toxic to the rabbit retina and lens and that the vehicle is not totally responsible for the toxicity, but may initiate TA-dependent toxicity.90,91 Direct toxic effects of TA on the retina and optic nerve have not yet been observed, independently of the dose used.92 to be toxic to retinal pigment epithelial cells in vitro,93 and in vivo95

TA has been shown whereas ex vivo94

studies have failed to show any significant toxicity to the retina. Because TA is a heavy depot formulated suspension, it settles in the inferior vitreous cavity. Whereas there is certainly distribution of the drug throughout the vitreous cavity due to diffusion and constant eye movements, it is possible that the drug does not distribute equally in the vitreous cavity and that the concentration of the drug at the macula is different (presumably lower) than in the inferior retinal periphery.96

causing a significant reduction in cell numbers throughout the whole range of concentrations when retinal pigment epithelium cells were exposed to it for more than one day.97

and hydrocortisone, TA showed the higher relative toxicity.

Safety of Intravitreal Triamcinolone Acetonide Including High-dose Reinjections

In a case series study, Gilles et al. showed that side effects or complications may not occur more frequently after reinjections of TA than after a primary intravitreal high-dose injection.81

Moreover, the

intravitreal high-dose reinjections may be tolerated by eyes within a mean follow-up of about 21 months after the first injection, or about 10 months after the last injection and the increase in IOP may not be more marked after a repeated injection than after the first injection.

Systemic Safety

In the randomised study from comparing laser photocoagulation with ranibizumab in combination with laser and intravitreal TA associated with laser, no evidence suggests that the administration of TA is associated with an increased risk of systemic adverse events, including stroke or cardiac events. Two-year incidence of non-fatal myocardial infarction was 3 % in the laser alone group, 1 % in the ranibizumab–laser group and 3 % in the TA–laser group. Any cardiovascular event, as defined by the Antiplatelet Trialists’ Collaboration (ATC), occurred in 12 % of the laser alone group, 5 % of the ranibizumab–laser group and 6 % of the TA–laser group.31

45 Compared with dexamethasone

Yeung et al. reported a possible cytotoxic effect of TA,

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