Dexamethasone implant (Ozurdex®) migration to anterior chamber through a congenital iris coloboma: A case report

Background: Ozurdex® 0.7 mg (dexamethasone 0.7 mg implant, Allergan, Dublin, Ireland), an intravitreal biodegradable implant indicated for cystoid macular edema due to variable causes. One of its known complications is implant migration to the anterior chamber, causing corneal edema that in some cases might be irreversible. Reported risk factors for device migration are open or defective lens capsule and prior history of vitrectomy. We present a case of dexamethasone implant migration through a congenital iris coloboma in a pseudophakic patient with intact lens capsule. Case presentation: 56-year-old pseudophakic man with a history of congenital iris coloboma, myopia, retinal tears and a Branch Retinal Vein Occlusion (BRVO) with subsequent Cystoid Macular Edema (CME) which was resistant to anti-VEGF medications but responsive to corticosteroids. He presented with sudden painless decreased vision in his left eye, eight weeks after dexamethasone implant (Ozurdex®) injection to the same eye. Upon presentation he was diagnosed with corneal edema caused by anterior chamber migration of the implant. He was referred for immediate surgical intervention and the implant was extracted, with the edema completely resolved within two weeks post-op. Conclusions: This is the first case reported of implant migration through an iris coloboma in the setting of intact posterior capsule. In addition, we describe a novel approach for implant removal surgery that is simple and efficient. This case sheds a light on another risk factor that should be taken into consideration in the management of this patient population.

lens capsule and prior history of vitrectomy. We present a case of dexamethasone implant migration through a congenital iris coloboma in a pseudophakic patient with intact lens capsule. Case presentation: 56-year-old pseudophakic man with a history of congenital iris coloboma, myopia, retinal tears and a Branch Retinal Vein Occlusion (BRVO) with subsequent Cystoid Macular Edema (CME) which was resistant to anti-VEGF medications but responsive to corticosteroids. He presented with sudden painless decreased vision in his left eye, eight weeks after dexamethasone implant (Ozurdex®) injection to the same eye. Upon presentation he was diagnosed with corneal edema caused by anterior chamber migration of the implant. He was referred for immediate surgical intervention and the implant was extracted, with the edema completely resolved within two weeks post-op. Conclusions: This is the first case reported of implant migration through an iris coloboma in the setting of intact posterior capsule. In addition, we describe a novel approach for implant removal surgery that is simple and efficient. This case sheds a light on another risk factor that should be taken into consideration in the management of this patient population.

Background
Ozurdex® 0.7 mg (dexamethasone 0.7 mg implant, Allergan, Dublin, Ireland) is a 0.46 mm diameter and 6 mm length biodegradable implant, injected into the vitreous cavity for the treatment of macular edema due to several conditions, among them cystoid macular edema (CME) due to branch or central vein occlusion (1) (4,5), suggesting it could be the migration route. It is of note, that all the reported cases had, in addition 3 to the Iris defect, a defective lens capsule. Migration in the setting of intact posterior capsule have also been reported, in which migration was speculated to occur through weak or ruptured zonules (6).
When anterior chamber migration occurs, and corneal edema begins to develop, it is crucial to remove the implant promptly. If not taken out expeditiously, implant migration can lead to permanent corneal compromise (2,3). We present a case of dexamethasone implant migration through a congenital iris coloboma in a pseudophakic patient with intact lens capsule. After ruling out other causes for corneal edema, it was determined that that the cause was implant migration. A literature review on such cases was preformed, concluding the prompt extraction of the implant is needed to avoid persistent corneal decompensation. The patient was than referred for surgical intervention within 24 hours from presentation.

Case Presentation
The operation comprised of making two paracentesis 180 degree apart; introducing an AC maintainer of basic salt solution through one and a spatula gently opening the second paracentesis directly across. Due to pressure gradient and stream created by the maintainer the dexamethasone implant was navigated toward the second paracentesis and easily ejected from the AC. following the extraction of the implant an intracameral Cefuroxime was injected and incision hydration was made.
One day post-op on eye examination the corneal edema was still evident, anterior chamber was deep and quiet, intra ocular pressure was 15 mmHg. On examination two weeks post-op, the patients' LE BCVA was 20/400 and corneal edema had resolved completely. As the steroidal treatment was interrupted by implant removal, on macular OCT we witnessed a deterioration in the macular edema with CMT increasing from 342 µm to 477µm. After careful deliberation (elaborated in "Discussion") we found that the best course of action would be renewal of the previous treatment. The patient underwent a third Ozurdex® injection to his LE. In a follow-up up to this day, 4 months post injection, there hasn't been recurrence of implant migration.

Discussion 5
Ozurdex® implant anterior chamber migration is a rare complication that can lead to permanent corneal decompensation. In a retrospective study, Khurana and colleagues showed that early removal of the implant is essential for corneal recovery (3). The "classical" risk factors for implant migration identified in that pivotal study were (1) History of pars plana vitrectomy, and (2)  Congenital iris colobomas arise from incomplete closure of the embryonic fissure during fetal development. A "typical" congenital iris coloboma is located at the inferonasal quadrant and therefore must be considered a risk factor for AC dexamethasone implant migration, with this being the first report of Ozurdex® implant migration through an iris coloboma. It is essential to inform these patients of having an increased risk for implant migration and the importance of seeking an immediate medical consultation with any sudden change of vision as early removal of the implant increases corneal recovery rates (3).
Following the migrating implant removal, we faced exacerbation of the CME condition. Our team of experts came together for convergent thinking process with several alternatives considered. First 6 option considered was to reinitiate injections of anti VEGF agents. However, As mentioned earlier, our patient has already exhausted all anti-VEGF treatment options therefore repeating trial with one of these drugs would probably be infertile. Second alternative considered was implanting a different intraocular steroidal implant. Fluocinolone acetonide 0.59mg (Retisert, Bausch & Lomb, Rochester, New York, USA) and fluocinolone acetonide 0.19mg (Iluvien, Alimera Sciences, Alpharetta, Georgia, USA) are two steroidal implants available for intraocular use. Although Iluvien is designed to provide sustained therapy for a longer period of time, it is also free-floating, but smaller in size than Ozerdex, making it even more susceptible for implant migration. Only two reports of Iluvien migration have been published, with two patients suffering from consequent corneal edema (7,8). Retisert, despite being anchored to the sclera, has also been reported to dislocate to the AC, inducing corneal edema, possibly resulting from medication reservoir dissociation from its sutured strut (9)(10)(11). Furthermore, we considered iris coloboma repair (Pupilloplasty). Despite being a tempting alternative, pupilloplasty is an additional AC surgery, which involves a considerable risk to a cornea that has already gone through a considerable amount of procedures thus jeopardizing it again. At that point, our decision was to recommend repeating Ozurdex® injection since this treatment had a substantial effect on the patient's CME and improved his VA. We concluded that any other alternative would carry either the same or a greater risk to the patient's eye. The patient accepted our recommendation and underwent a third Ozurdex® implantation. The patient was instructed to return at any sudden change of vision.
As mentioned, in a follow-up of 4 months post injection, implant migration had not recurred.

Conclusion
We have presented a case of dexamethasone implant migration to the AC through a congenital coloboma, resulting in corneal edema. This is the first case reported of implant migration in the setting of intact posterior capsule. We described a novel approach for implant removal surgery that is Availability of data and material: not applicable.
Competing interests: The authors declare that they have no competing interests.
Funding: no financial support was received for the submission.
Authors contribution: YG contributed to manuscript conception, design and acquisition. EC and SS contributed to acquisition, analysis and interpretation of data. All authors have been involved in drafting the manuscript or revising it critically and have given final approval of this version to be published and agreed to be accountable for all aspects of the work.