UME is frequently encountered in patients with uveitis (20.5% in the clinic)2,3 and can cause permanent vision loss. The management strategies vary significantly as no optimal strategy exists. Periocular injections or intraocular injections of TA and intraocular sustained-release glucocorticoid implants have been previously reported in detail9,11. Recently, the POINT trial compared the effectiveness of 3 methods of administering regional corticosteroids for UME, including periocular injections of 40mg TA (periorbital floor or posterior sub-Tenon’s approach), intraocular injections of 4mg TA and a 0.7 mg dexamethasone intravitreal implant. The results showed that all treatment groups had clinically meaningful reductions in central subretinal thickness compared with baseline12. However, subconjunctival injections of TA have rarely been reported13,19,23.
CMT
In our study, subconjunctival injection of TA was effective in controlling UME, particularly in patients with unilateral macular edema and in those with bilateral UME under systemic medication who still exhibited aggravated unilateral ME. In these cases, topical TA injection could prevent systemic glucocorticoids side effects.
In the first month after 20 mg TA injection, 62/71 eyes (87.32%) showed a reduction in CMT. In addition, 59/71 eyes (83.09%) showed an obvious reduction in CMT (at least 20%).
A previous article27 compared the efficacy and tolerability of subconjunctival injection of TA, subtenon TA and intravitreal dexamethasone implants and showed improvements in CMT of 88% at one month with no significant differences among the three groups. Bae et al.14 reported that 53.1% of the eyes treated with peribulbar injections of 40 mg TA showed reductions in CMT after 1 month. However, the curative effect declined after 3 months. Similarly, Henry A. Leder et al.15 also reported that 53% of the eyes treated with a single posterior-subtenon TA injection had clinically resolved 1 month after the injection, and 57% of the eyes had clinically resolved 3 months after the injection. However, another recent study administered periocular injections of 40 mg TA using a periorbital floor or posterior subtenon approach, and the percentage of CMT reduction was only 23% after 2 months9.
Although our study reduced the dose of TA by half, the efficacy and persistence were similar or even better than those reported previously.
Relapse
Twenty-two eyes (22/83, 26.51%) had UME relapse within 6 months; 10 patients received a second injection and still effective. Among these eyes, 5 eyes (22.73%) relapsed at 2 months, 7 eyes (31.82%) relapsed at 3 months and 10 eyes (45.45%) relapsed at 6 months. In one patient in the present study, the effect of the first injection lasted for 6 months, but the effect of the second injection 1.5 years later lasted for only 2 months. However, over the past decade, we did not observe any other similar cases. One patient received 7 injections within 10 years with a good response to TA every time, and the injection had an efficacy that lasted for more than 6 months. Furthermore, no correlation was found between the duration of TA efficacy and the number of injections.
During the follow-up, 5 patients did not respond to the therapy. One patient was diagnosed with Vogt-Koyanagi-Harada (VKH) disease complicated by choroidal neovascularization, but ME resolved after an anti-VEGF injection.
IOP
In this study, elevated IOP was the only side effect of subconjunctival TA injections. An elevated IOP was observed in 21/83 eyes (25.30%). However, Byun et al.17 reported that 18 eyes (11.3%) required glaucoma medications after a posterior-subtenon injection. Another study reported that 34.9% of the patients after a posterior-subtenon injection had elevated IOPs, and 4.7% of the patients needed trabeculectomy after a posterior-subtenon injection with 40 mg TA18.
Previous literature reported that an anterior subtenon injection of TA was 2.4 times more likely (95% CI, 1.02–5.9) to cause elevated IOPs than a posterior subtenon injection16. A higher level of aqueous humor triamcinolone may be associated with a higher incidence of IOP elevation. However, our data showed similar rate of IOP elevation as posterior subtenon injection, and thus, further randomized controlled trials are needed to verify these findings.
According to our clinical experience, the elevated IOP can be well controlled. The Kaplan-Meier survival analysis of the patients with an IOP > 21mmHg is illustrated in Figure 3, which indicated that elevated IOP was more frequently observed within the first 2 months after the injection. Therefore, IOP should be closely monitored every 2 weeks within the first 2 months after the injection.
For patients with elevated IOP, topical IOP-lowering agents should be applied first. For example, topical beta-blockers, carbonic anhydrase inhibitors, and alpha-agonists are the usual first-line treatments. For patients with IOP above 35 mmHg that cannot be controlled with topical eye drops, removal of the TA deposit is suggested. In our study, 7 eyes (7 patients) underwent removal of the subconjunctival TA deposit, and IOP of all 7 eyes returned to normal within 1 month after TA deposit removal.
Subconjunctival hemorrhage is also a well-known but trivial side effect. One case25 of conjunctival ulceration caused by a subconjunctival injection of 40 mg triamcinolone has been reported; other reported side effects of subconjunctival triamcinolone acetonide include infectious scleritis, blepharoptosis, mydriasis, conjunctival ischemia23 and conjunctival necrosis26. These side effects were not observed in our patients, which may be due to the halved dose.
There are some limitations in our study, including missing data due to the retrospective nature of the study and the different follow-up intervals. The efficacy rate may be influenced by confounding factors, such as the presence of cataracts or epiretinal membrane.
From our point of view, subconjunctival injection, which could be performed in the outpatient department, is much easier to administer than posterior subtenon injection and intravitreal injection, which must be performed in the operating room. On the other hand, subconjunctival injections are more likely to cause IOP elevation, although elevated IOP could be well controlled by application of 1 or 2 types of topical IOP-lowering agents. Furthermore, subconjunctival TA deposit removal may cause less damage than intravitreal injection or posterior subtenon injection in patients suffering IOP elevation who require pars plana vitrectomy or trabeculectomy.