Discussion
Ophthalmic corticosteroids elicit numerous potent anti-inflammatory effects and are a standard of care for the management of ocular inflammation. This retrospective pilot study was designed to assess the safety and efficacy of a novel ICD drug-delivery suspension for treating intraocular inflammation following a variety of posterior segment surgeries involving PPV. This analysis found that study eyes in the test group treated with ICD at the conclusion of the surgery were more likely to have complete clearing of anterior chamber inflammatory cells at POD 7 than study eyes of case-matched control patients treated with topical ophthalmic prednisolone acetate. Complete clearing of ACC at POD 7 was observed in 66.7% of test patents and 37.0% of the matched controls, p≤0.05.
The improved control of postoperative intraocular inflammation in the ICD test group was observed as early as POD 1. Twelve of the 27 (44.4%) eyes treated with ICD had no ACCs on the first PODversus 6 (22.2%) of the 27 eyes treated topically with corticosteroid drops, p≤0.05. The differences in anterior chambers free of inflammatory cells were no longer significant at days 30 and 90.
Agarwal et al used a LFM to determine the level of anterior chamber inflammation in 50 eyes for 30 days following 25-gauge vitrectomy surgery. They reported that 22 (44%) out of 50 patients had sufficient anterior chamber flare (≥50 photons/ms) to warrant treatment with topical corticosteroids, which successfully returned the flare to preoperative levels. Multivariate analysis suggested that patients with higher preoperative anterior chamber flare, and men, were most likely to reach this threshold. No other variables were predictive of patients who would experience this level of postoperative inflammation.3
The lower rate of anterior chamber inflammation reported in the aforementioned study compared with the present study may have several explanations. Agarwal et al reported rates of clinically significant inflammation, defined as LFM measurements ≥50 photons/ms, while the present study reported rates of any inflammation, defined as greater than 0 ACCs. Additionally, triamcinolone acetonide was used as a visualising agent in nearly half of the eyes in the Agarwal study, whereas it was not used during surgery performed in the present study.
Supporting the notion of a depot approach to perioperative steroid treatment, a 2007 study by Paccola et al randomised 40 patients to treatment with either topical prednisolone acetate or subtenons triamcinolone acetate following 20-gauge PPV. This study found that there was no difference in the severity of ACC and flare, or other signs and symptoms of ocular inflammation, between the two treatments.6 The current study used ICD in a much smaller volume to achieve similar clinical efficacy.
The topical corticosteroid, 0.1% betamethasone, was compared with 0.1% diclofenac, a topical NSAID, for the treatment of postoperative inflammation in 200 patients who had combined cataract and 25-gauge vitreoretinal surgery. Although there were no overall differences in the severity of postoperative inflammation, eyes treated with the steroid were less impacted by the length of the surgery than eyes treated with the NSAID. This study also found that patients being treated for macular holes and epiretinal membranes had more IOP elevation in the betamethasone group.7 In the current study, we did not observe a difference in inflammation rates or severity between different indications for primary vitrectomy surgery, although the exact duration of each case was not recorded and topical NSAIDs were not prescribed to any patient.
Postoperative IOP elevation is a known complication of both vitrectomy surgery and corticosteroid use. Risk factors for elevated IOP following vitreoretinal surgery have been reported to include the number of photocoagulations, the severity of postoperative vitreous haemorrhage, and the use of gas tamponade.8 Using 15 years of Medicare claims data, Stein et al reported glaucoma rates of 6% to 8% following PPV.2 Atchison and Pollack performed a retrospective comparison of post-PPV treatment with subconjunctival dexamethasone plus topical steroids in 146 patients versus subconjunctival triamcinolone without drops in 135 patients. They reported IOP elevations ≥10 mm Hg occurring at rates of 14% and 20%, respectively.4 The rates of clinically significant IOP elevation in this study, 7.4% in the ICD group and 11.1% in the topical corticosteroid group, were both within the previously reported ranges.
Cataract progression in phakic eyes was frequently observed in this group of patients and is a known side effect of both PPV1 and steroid use. Other AEs were observed less frequently and were primarily those expected following intraocular surgery.
This is the first report of the use of this ICD formulation for treatment of inflammation following PPV and retinal surgery. Donnenfeld and Holland have reported on the safety and efficacy of the same formulation following cataract surgery. Their placebo-controlled trial enrolled 394 patients and reported nearly the same rate of complete ACC clearing (66%) at POD 8 as was observed in this cohort. The finding of a statistically significant benefit of the ICD treatment out to POD 30 in their trial, versus only to day 7 in the current trial, is likely due to the active treatment of the control group with topical corticosteroids in the present study.9
The delivery of a corticosteroid, using a single administration after the completion of surgery, eliminates the potential for compliance problems that can compromise postoperative treatment outcomes when patients self-administer eye drops. This formulation immediately begins treating intraocular inflammation without the need to penetrate the cornea. The 5 µL droplet injected into the eye after surgery forms a surface tension-based sphere, and the drug is released into the eye as the droplet is absorbed. When the drug depot is fully absorbed, drug delivery stops. The concentration of drug delivered is highest on the day of application, and as the medication dissipates, the concentration in the anterior chamber should taper slowly at the same time as the need for anti-inflammatory therapy decreases.9
The retrospective nature of this study, in addition to the modest sample size, are limitations. The comparison of real-world outcomes to a known standard of care, although using only one brand of topical corticosteroid, does provide useful information to clinicians. These data can provide the proof of concept for designing a randomised, prospective trial comparing ICD to topical postoperative treatments following PPV.
In this case-controlled retrospective study, dexamethasone drug-delivery suspension placed in the anterior chamber at the conclusion of vitreoretinal surgery was more effective in controlling inflammation than a standard corticosteroid eyedrop regimen. The nature of the AEs recorded was consistent with the profile expected following these posterior segment surgeries. Treatment of postoperative inflammation with this ICD suspension may offer clinical benefits to retinal surgeons and their patients.