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The purpose of this study was to report a rare case of subretinal lodgement of Ozurdex® implant (Allergan Inc., Irvine, CA, USA) and its effect on macular edema in a case of central retinal vein occlusion (RVO).
A rare complication of subretinal lodgement of Ozurdex® implant without retinal perforation was encountered in a case of RVO with intractable macular edema. As associated retinal perforation was not noted, no intervention was done. The patient was regularly followed up at 1 month, and the effect on macular edema and intraocular pressure was analyzed.
The corticosteroid pellets got disintegrated and totally absorbed with a subtle chorioretinal scar by the 3rd follow-up month without any intervention. Even though subretinal, it was capable of reducing macular edema by 181 microns at 1 month postinjection, and its effect started wearing off by 2 months.
Subretinal lodgement of Ozurdex® implant is rare and preventable, yet a potential complication of intravitreal implants which is now in vogue. We speculate a too acute angle of injection or incomplete insertion of the drug delivery system applicator (DDS) away from the limbus or perhaps less refined previous DDS applicator to be a cause for subretinal delivery of the implant. The early disintegration of implant occurred due to breach in structural integrity that caused loss of controlled drug release and rapid absorption. It reduced macular edema up to 2 months without elevating intraocular pressure.
A more widespread application of any technology always portends a more significant risk for complications, and an ophthalmologist should be aware of this potential risk. Though subretinal, corticosteroid implant was capable of reducing macular edema by 181 microns by 1 month and its effect wore off by 2 months.
The corticosteroid implant (0.7 mg Ozurdex, Allergan Inc., Irvine, CA, USA) offers sustained release of dexamethasone in the vitreous cavity and has an ever-expanding role in treating a wide spectrum of vitreo-retinal diseases. It was initially approved by the Food and Drug Administration in 2009 for treating retinal vein occlusions (RVOs) and noninfectious posterior uveitis. However, it now finds its therapeutic use in various retinal pathologies. Mishaps such as migration of the implant into the anterior chamber and consideration for prompt removal to prevent corneal endothelial decompensation and edema[2,3,4] have been documented. Complications such as inadvertent injection of the dexamethasone implant into the crystalline lens also have been reported.[5,6]
We report a case of central RVO with macular edema, for which Ozurdex® implant was injected subretinal albeit fortuitously and its effect on the macular edema was analyzed. To the best of our knowledge, this is the first case of subretinal lodgement of Ozurdex® implant reported in the literature.
A 51-year-old hypertensive female presented to the outpatient department with defective vision in the left eye (OS) for 1 year. Best-corrected visual acuity in the right eye (OD) was 6/6, and in OS, it was 6/36 using Snellen test type. Previous ocular history revealed that she was a diagnosed case of OS central RVO, for which pan retinal photocoagulation had been performed. Fundus fluorescein angiography was performed to confirm the diagnosis. Spectral domain ocular coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Heidelberg, Germany) OS showed epiretinal membrane (ERM), cystoid macular edema with hard exudates, and a central macular thickness (CMT) of 610 microns. Intravitreal avastin (bevacizumab 1.25 mg, Genentech) was injected, and CMT after 1 month was found to be 592 microns. Due to this inadequate response to antivascular endothelial growth factor injection, Ozurdex® injection was planned and injected following the routine standard procedure. Indirect ophthalmoscopic examination with a 20 diopter lens immediately postinjection showed fractured pellets of Ozurdex® implant located subretinal, with no associated retinal perforation [Figure 1]. The patient was closely observed and regularly followed up fortnightly, and the effect on macular edema as recorded by SD-OCT and intraocular pressure using Goldmann applanation tonometer was analyzed.
Fractured pellets of Ozurdex® implant were seen clinically by indirect ophthalmoscopy. The intraocular pressure 2 weeks postinjection was recorded to be 20 mm Hg, and the injection site was found to be stable. Fundus examination at 1 month showed resolving Ozurdex® pellets. SD-OCT at 1 month demonstrated a reduction in CMT to 429 microns. At 2 months, the pellets were shrunken and CMT was recorded to be 476 microns. At 3 months, the pellets were totally disintegrated, a subtle chorioretinal scar was noted at the implant site, and IOP was stable at 14 mmHg. The CMT, however, shot up to 604 microns and further raised to 800 microns at the end of 5 months. A pars plana vitrectomy with ERM peeling and intravitreal triamcinolone acetonide was then planned.
Corticosteroid implants are of proven efficacy for treating recalcitrant macular edema in RVO cases.[7,8] Injection techniques and drug delivery system (DDS) applicators are evolving to improve its safety profile even in eyes that are often considered to have relative contraindications to its use, further extending its application. The associated complications may be drug-related such as secondary glaucoma and cataract progression or due to the procedure per se such as endophthalmitis. Migration of Ozurdex® implant in the anterior chamber and its adverse effects on the corneal endothelium is also well documented.[2,3,4] We encountered an unusual complication perhaps related to the improper injection technique which led to subretinal delivery of the implant. We speculate a too acute angle of injection or incomplete insertion of the DDS applicator at a distance of more than 4 mm from the limbus to be a cause for subretinal delivery of the implant. As retinal perforation was not noted, any intervention was deferred, and the patient was kept under close observation.
The improper delivery of drug implant may also be attributed to the DDS applicator. The previous DDS needle required a high penetration force and had a prolonged friction phase while insertion as compared to the modified sharper 22-G DDS applicator which achieves less resistance to the sclera even with low piercing and cutting forces and with a chevron-shaped incision, thus ensuring a proper wound closure even in vitrectomized eyes. This adverse event occurred with the previous, less refined DDS applicator.
It is reported that Ozurdex® may stay in the vitreous cavity for as long as 6 months with peak levels of dexamethasone attained by 2 months. Subretinal Ozurdex® implant was completely disintegrated and was not clinically detectable as early as 3 months in our case. This could have occurred due to breach in structural integrity of the implant and its disruption into pieces as documented [Figure 1] that dramatically affected the controlled drug release and enhanced its rapid absorption. Close approximation of the implant to choroidal vasculature might have also contributed to early biodegradation.
Ozurdex® although subretinal decreased the macular edema in the 1st month. Its effect, however, weaned off by 2 months. This was evidenced by a gradual rise in CMT on subsequent OCT scans. Subretinal Ozurdex® implant, thus, failed to deliver sustained release of dexamethasone for prolonged period.
Iatrogenic lodgement of Ozurdex® implant in subretinal space was a rare therapeutic misadventure, though had an uneventful course, which could be easily prevented by correct injection technique and modified DDS applicators. Subretinal corticosteroid implant was capable of reducing macular edema by 181 microns by 1 month following injection and its effect wore off by 2 months. It reflects that a more widespread application always portends a more significant risk for complications, and an ophthalmologist should be aware of this potential risk.
There are no conflicts of interest.