Kenacort-A and Kenalog (Bristol-Myers Squibb)
9 16 39 42 43 are formulated BA-preserved TA suspensions, and both contain TA 40 mg/mL and BA 9 mg/mL as the preservative. They were developed for intra-articular or intramuscular injection and were only recently formulated for off-label use as ocular medications. For visualizing and removing the vitreous-posterior hyaloid-ERM-ILM, TA contacts the retina for only 10 to 30 minutes, whereas in therapeutic intravitreous TA injection, TA particles, together with their vehicle, are retained within the eye for weeks or months. Based on our finding in this study that TA is associated with subtle, early ultrastructural changes in RPE cells after only 5 minutes of exposure to the vehicle, we urge removal of the vehicle as completely as possible before the TA suspension is used in the eye, particularly during macular hole surgery. Concurring with our result that TA particles without vehicle were not toxic to RPE cells, Enaida et al.
45 reported no apparent adverse effect in a patient with submacular deposition of TA particles after TA-assisted vitrectomy for rhegmatogenous retinal detachment. The authors concluded that the damage attributable to subretinal TA deposition was not significant either morphologically or functionally; however, they were still concerned about the potentially harmful effects on retinal structure and function of the vehicle in commercial TA suspensions.
We recently described three methods to remove the vehicle from cTA.
27 The first, described by Jonas et al.,
1 is the “standstill” method in which the TA suspension is drawn into a syringe that is held vertically for 30 minutes to allow sedimentation of TA crystals; the upper layer is ejected and the settling procedure is repeated twice more before the suspension is used. Because this procedure takes hours, it is not practical when a TA suspension is unexpectedly needed intraoperatively. Hernaez-Ortega and Soto-Pedre
46 separated the TA particles from the vehicle by density-gradient centrifugation at 3000 rpm for 5 minutes. This method is simple and rapid, with little loss of TA particles; however, almost no operating rooms are equipped with density-gradient centrifuges. The third method for removing the vehicle from cTA, introduced by Kumagai
19 and Burk et al.,
16 involves repeatedly passing the TA suspension through syringe filters (Millipore Acrodisc 32-mm Syringe Filter, Pall Corp.) and resuspending the TA particles in saline solution (BSS; Alcon Laboratories). These filters are available in most ophthalmic operating rooms, and so this method seems the most practical for routine clinical use. However, about half of TA particles would be trapped on the 0.2-μm-pore filter paper.
6 47 Therefore, it is necessary to titrate the solution to determine the exact concentration using this method, particularly for intravitreous injection of TA to treat various vitreoretinal diseases.
Even though the vehicle of TA is removed, we recommend additional safety measures to prevent adverse effects of any vehicle residue on the retina. First, the intravitreous injection of TA should be directed away from the macula, particularly the fovea, unless it is being injected to enhance visualization during macular surgery. For macular hole surgery, we suggest preventing direct exposure of TA to the RPE by application of autologous blood or serum or viscoelastic substance within the macular hole. Second, when an intravitreous injection of TA is used to treat ocular inflammatory or vessel-leaking diseases, the patient should maintain a head-up position most of the time for weeks to avoid settling of the TA suspension and the residual vehicle over the macular area, particularly for the first several days in vitrectomized eyes.