Safety and Effectiveness of Intravitreal Dexamethasone Implant (Ozurdex^®) for the Treatment of Refractory Cystoid Macular Oedema (CMO) in Galway University Hospital

1. INTRODUCTION

Diabetic eye disease has long been considered an inflammatory process [1], with mediators, such as VEGF and ICAM-1, shown to have a strong association with vascular permeability and the severity of diabetic macular oedema (DMO) [2]. Similarly, inflammatory mediators, such as VEGF, ICAM-1, and IL-6, have been implicated in the pathogenesis of retinal vein occlusions (RVO), leading to a recent interest in the use of intravitreal steroid preparations in the management of these conditions [3].

Ozurdex, an implant containing 700 micrograms of dexamethasone, was approved in 2010 for the management of macular oedema secondary to retinal vein occlusions, diabetic eye disease as well as non-infectious uveitis [4]. Its efficacy in diabetic macular oedema (DMO) has been evidenced by previous studies showing an 83% increase in the proportion of patients achieving >15 letter gain compared to sham [5] and non-inferiority compared to anti-VEGF agents in achieving the same outcome [6]. In these studies, the rate of adverse events was higher in the Ozurdex treatment arm, with 30-40% having a significant IOP rise and 40–70% showing the progression of cataracts. On subgroup analysis, outcomes of Ozurdex compared to anti-VEGF were more favourable in pseudophakic eyes, leading to recommendations from the National Institute for Health and Care Excellence (NICE) to consider Ozurdex as a second-line agent in selected patients [7].

Similar efficacy has been shown in the management of macular oedema secondary to retinal vein occlusions (RVO). In a recent systematic review, intravitreal injection of Ozurdex showed similar efficacy to anti-VEGF agents, with effects lasting 3-5 months. However, up to 20% of patients receiving Ozurdex had a significant IOP rise or progression of cataract [8].

In University College Hospital Galway (UCGH), Ozurdex is used in the management of patients with refractory macular oedema secondary to diabetes or retinal vein occlusions. Prior research has indicated that Ozurdex may improve Central Subfield Thickness (CST) but leads to limited visual acuity gain [9, 10]. The purpose of this study is to assess the effectiveness and risk profile of intravitreal Ozurdex implant for the treatment of macular oedema secondary to retinal vein occlusions and diabetic eye disease in Ireland.

2. MATERIALS AND METHODS

3. RESULTS

Overall, 36 patients met the eligibility criteria of the study (mean age 68.0 years, 69% male). Of these patients, 77.8% had clinically significant CMO secondary to DED and 22.2% had CMO secondary to RVO. Mean ETDRS letter score at baseline was 57.25 (SD 14.4) and mean CST at baseline was 444.2 (SD 139.3). The mean follow-up duration was 5.6 months. Prior to intravitreal Ozurdex implant, 30.6% and 88.9% of patients had received focal laser treatment and intravitreal anti-VEGF injections, respectively, in the previous 12 months. None of the included patients had previously undergone a vitrectomy. The mean number of intravitreal injections was 4.6 (SD 2.55), and at baseline, 80% of patients were phakic. Four patients did not have final visual acuity recorded due to non-attendance at the clinic and were not included in the analysis of the primary outcome.

In all included patients, there was a 1.66 mean letter gain (SD 11.8) with 3.5 letter (SD 6.2) and 1.04 letter (SD 6.0) gains in the RVO and DED groups, respectively. The proportion of patients who gained >10 letters was 15.6% overall, 12.5% in the RVO group and 16.7% in the DED group. Overall mean reduction in CST was 110.6um (SD 255.7), 129.3um (SD 239.3) in the RVO group, and 105.2um (SD 139.3) in the DED group. In the linear regression analyses, no variables were found to be significantly associated with a change in visual acuity.

In terms of adverse events, 14.3% of patients had significant cataract progression and 20.6% of patients had a significant rise in IOP following intravitreal Ozurdex implant, which required treatment. No cases of endophthalmitis were observed, nor were there any instances of significant post-operative pain or vitreous bleeding reported during the follow-up period.

4. DISCUSSION

In patients receiving intravitreal Ozurdex for the treatment of refractory cystoid macular oedema, the mean visual acuity gain was 1.66 letters (SD 11.8) and the mean reduction in central subfield thickness was 110.6um (SD 255.7), as measured with SD optical coherence tomography. These findings are consistent with previous studies showing improvements in anatomical outcomes seemingly uncorrelated to visual acuity or visual function [9, 10]. In terms of adverse effects, our findings were consistent with previous studies indicating that 20-27% of patients receiving Ozurdex experience a significant IOP rise [8, 12-14]. In previous studies, reduction of IOP to baseline levels with topical treatment was the most common outcome and <1% of patients required trabeculectomy or tube shunt surgery [5, 15].

This study is limited by its short follow-up period, which may have underestimated the rate of adverse events, such as cataract development. In a large multicentre randomised controlled trial, 67.9% of patients developed cataracts within 3 years compared to 20.4% in the sham injection group, and other studies with longer follow-up durations have estimated this rate to be between 30 to 60% [16, 17]. Furthermore, our relatively small sample size limited our assessment of possible predictors of visual acuity, particularly with pseudophakic lens status, which was previously shown to be independently associated with visual acuity gain [5]. None of the patients in our study reported significant post-operative pain, and no cases of vitreous haemorrhage were recorded. Again, this may be a reflection of our small sample size, but additionally, our study used the newer iteration of the Ozurdex drug delivery system, which has a reduced penetration force compared to the original version [18]. The fact that none of the patients in our study had previously undergone a vitrectomy may also have contributed to this finding due to the greater drag force in the vitreous body [19].

CONCLUSION

Overall, the safety profile and effectiveness of Ozurdex were within expectations, supporting it as a safe drug to use in patients with macular oedema secondary to diabetic eye disease and retinal vein occlusion. As some patients had better visual improvements, further studies with larger patient samples should be carried out to evaluate the possible predictors of visual acuity outcome.

REFERENCES