Suprachoroidal Triamcinolone Acetonide safe and effective for treatment of Diabetic Macular Edema

Treatment of DME has undergone a major shift over the years. Intravitreal injection (IVI) of steroids has been used for the treatment of DME. This is due to the anti-inflammatory, angiostatic, and anti-permeability properties of corticosteroids. Also, it is due to the inhibition of the expression of vascular endothelial growth factor (VEGF) and key pro-inflammatory genes (eg tumor necrosis factor-alpha [TNF-α]). A slow-release bioerodible dexamethasone implant and an extended-release nonbioerodible fluocinolone acetonide insert are both approved for the treatment of DME and provide the advantage of reduced treatment burden.

Anti-VEGF therapy has replaced laser photocoagulation as the mainstay of treatment. Excellent results of the initial anti-VEGF trial (the RISE/RIDE and VIVID/VISTA) were documented leading to the approval of ranibizumab and aflibercept for the treatment of DME. Currently, the role of triamcinolone acetonide (TA), either alone or combined with laser, could be considered mainly in refractory DME (Best-corrected visual acuity (BCVA) gain ≤5 letters or reduction in CMT ≤ 20% after the loading dose), especially in pseudophakic eyes.

Suprachoroidal injection is a newly developed technique for drug delivery to the posterior segment. The suprachoroidal space (SCS) is a potential space that is located between the sclera and choroid. Injection of drugs into the SCS does not have the risk of intraocular penetration. Animal studies concluded that TA seemed the most promising drug formulation for SCS delivery to treat retinal diseases due to its low solubility and sustained-release property. Thus, it was thought it might be possible to obtain therapeutic levels of TA in the retina and choroid. Animal studies also showed that there were higher amounts of the drug in the retina and the SCS, and minimal amounts in the anterior segment compared with the intravitreal (IV) route. This may decrease complications commonly associated with TA, such as the development of glaucoma and cataract. It is even estimated to have a higher reach to the choroid-retina region than the IV route.

Zakaria et al conducted a prospective interventional study to compare between IV and SCTA in the treatment of DME in terms of efficacy and possible complications. The study suggested the efficacy of SCTA injection using a custom-made syringe compared to the IV route and would provide a safe alternative route of injection as both routes had relatively similar steroid-related complications

This prospective interventional randomized comparative study included 45 eyes of 32 patients, randomly divided into three groups, group I received 4 mg/0.1 mL intravitreal TA (IVTA), group II received 4 mg/0.1 mL suprachoroidal TA (SCTA), and group III received 2mg/0.1 mL SCTA. Patients were followed up for 6 months.

At 1 month, a maximum reduction in CMT was observed, which was associated with the greatest improvement of BCVA in groups I, II, and III, respectively. At 3 months, CMT started to increase, and reduction was not statistically significant compared to baseline, except in group II (4 mg SCTA group) (P-value = 0.013).

At 6 months, CMT and BCVA returned close to baseline except for group II which had a sustained reduction of 60.16 µm from baseline.

Regarding steroid-related complications, IOP elevation of 10 mmHg or more was noted in 1 eye (6.7%), 2 eyes (13.3%), and 1 eye in groups I, II, and III, respectively. Three phakic eyes per group showed cataract progression.

Injection of corticosteroids into the SCS may achieve therapeutic drug levels in the retina while minimizing levels in the anterior chamber, thus, decreasing adverse effects, such as cataract and glaucoma.

This study showed that BCVA improved significantly in the 3 groups at 1 and 3 months. At 1 month, the difference from baseline was significant between the 3 groups, as the 4 mg SC group showed the greatest improvement in BCVA. However, BCVA returned to near baseline values at 6 months, except for the 4 mg SC group. Similarly, CMT significantly decreased in the 3 groups at 1 and 3 months. All groups showed the most significant reduction of CMT after 1 month with a statistically significant difference between the 3 groups, as the 4 mg SC group had the highest reduction. CMT started to increase again after 3 months and returned close to presentation values at 6 months except for the 4 mg SC group, which still had a mean reduction of 60.18 µm.

Regarding IOP elevation and progression of cataract, both routes have insignificantly different effects. The lower dose of SCTA did not show a lower risk of complications of TA.

"Our study suggests the efficacy of SCTA injection using a custom-made syringe compared to the IV route and would provide a safe alternative route of injection as both routes had relatively similar steroid-related complications. An advantage of the SC route over the IV one could be the longer effect on reduction in CMT and improvement of BCVA, which should be further assessed by larger studies for a longer follow-up period. We found the 4 mg dose of SCTA more effective and lasted longer than the 2 mg dose, without having a higher rate of steroid-related complications. However, as CMT had almost returned to baseline values in most of our patients, we believe that reinjection should be considered before 6 months. One of the limitations of the study is the relatively small number of patients and, accordingly, using both eyes of some of our patients, so larger studies would provide stronger results."

Source: Zakaria et al; Clinical Ophthalmology 2022:16

https://doi.org/10.2147/OPTH.S351853