Shorstein et al. made interesting observations and comments on the location of the sub-Tenon triamcinolone injection. The assumed mechanism for steroid-induced elevation of IOP is that steroids increase aqueous outflow resistance by formation of reversible actin networks as well as by increased deposition of extracellular matrix within the outflow pathway.1 It is very likely that the magnitude of such steroid-induced effects would be in relationship to steroid levels in the aqueous humor. It is well documented that intravitreal triamcinolone causes more frequent IOP elevation than sub-Tenon triamcinolone. Investigators have shown that peak triamcinolone in the aqueous humor was 10 times higher after an intravitreal (4 mg) than after sub-Tenon (40 mg) triamcinolone.2,3 For prophylaxis of macular edema after the cataract procedure in patients with diabetes, posterior sub-Tenon should be the location of choice because the macula is the pharmacological target. Furthermore, to avoid triamcinolone suspension from spilling into the anterior segment, a concentrated smaller volume than the commonly used 1 mL or 500 μL may be preferable and beneficial in reducing the risk of IOP elevation. There is more vessel distribution in the conjunctiva and episclera at the anterior segment than that at the posterior segment. These vessels contribute to not only higher triamcinolone distribution into aqueous but also more triamcinolone absorption into the systemic circulation. With a small volume of a concentrated formulation of triamcinolone (40 or 20 mg in 0.4 mL), peak triamcinolone in systemic circulation is around 1 ng/mL,3 while it is over 30 ng/mL after a commonly used formulation (40 mg in 1 mL).4
In Shorstein et al.’s letter, a 2 mg dose of subconjunctival triamcinolone demonstrated equivalent prophylactic effect against macular edema as well as persistence of postoperative inflammation as compared to the steroid eyedrops, except for a small number of patients who had IOP spikes greater than 30 mm Hg. They observed a smaller or no IOP spike after changing the subconjunctival injection from a small volume (2 mg in 50 μL) to a large volume (3 mg in 300 μL), although the percentage of IOP elevation or statistical significance was not available. One possible explanation for their observation is that a concentrated or small volume injection helps to build up a concentration gradient for the drug to penetrate the eyewall into the aqueous humor or diffuse into arteries supplying the iris and ciliary body. In contrast, a large volume injection with low concentration leads to less intraocular penetration and more drug may diffuse into lower pressured veins at the conjunctiva and episclera with resultant higher systemic drug concentration, although they did not provide triamcinolone levels in the aqueous humor or plasma.
In summary, it seems that a concentrated small volume of triamcinolone suspension at the sub-Tenon of the posterior segment may be a better choice for prophylaxis of macular edema after a cataract procedure in diabetic patients. For alleviation of pain and procedure-related inflammation, anterior sub-Tenon or subconjunctival triamcinolone is of advantage over steroid eyedrops; however, further study is needed regarding the optimal formulation and location of the injection.
Tektas O-Y, Hammer CM, Danias J, Candia O, Gerometta R, Podos SM, Lütjen-Drecoll E. (2010). Morphologic changes in the outflow pathways of bovine eyes treated with corticosteroids. Invest Ophthalmol Vis Sci, 51
, 4060-4066, Available at: http://iovs.arvojournals.org/article.aspx?articleid=2126706
Beer PM, Bakri SJ, Singh RJ, Liu W, Peters GB III, Miller M. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology
Shen L, You Y, Sun S, Chen Y, Qu J, Cheng L. Intraocular and systemic pharmacokinetics of triamcinolone acetonide after a single 40-mg posterior subtenon application. Ophthalmology
Kovacs K, Wagley S, Quirk MT, Ceron OM, Silva PA, Singh RJ, Gukasyan HJ, Arroyo JG. Pharmacokinetic study of vitreous and serum concentrations of triamcinolone acetonide after posterior sub-Tenon's injection. Am J Ophthalmol