Spontaneous extrusion of a dexamethasone intravitreal implant (Ozurdex)

Abstract

A 59-year-old man with diabetic macular oedema was treated with a dexamethasone intravitreal implant (Ozurdex) to his right eye. Immediately after injection, the implant was noted to have extruded into the perilimbal subconjunctival space. The remnants of the implant were expeditiously removed the following day to avoid corneal decompensation and permanent corneal oedema. Endothelial decompensation secondary to the migration of dexamethasone implants into the subconjunctival space or anterior chamber is a recognised complication of Ozurdex injection. The patient recovered well postoperatively with no further complications. He was planned for a new Ozurdex implant 1 month later.

Background

Dexamethasone intravitreal implants (Ozurdex) are increasingly being used for the management of diabetic macular oedema, cystoid macular oedema secondary to retinal vein occlusion and non-infectious posterior uveitis. Migration of the implant into the anterior chamber has been described numerous times in the literature with over 80% of cases resulting in corneal oedema.¹ The mechanism by which this occurs is not fully understood. It is proposed that the high dose of dexamethasone may have a cytotoxic effect on corneal endothelial cells and the implant may cause direct mechanical trauma. There has been only one reported case of a dexamethasone implant accidentally injected into the subconjunctival space resulting in the development of corneal oedema 3 weeks later.² Unintentional placement or migration of dexamethasone implants into the subconjunctival space are rare complications which are associated with a significant risk of corneal decompensation and oedema. It is important that the implant is promptly removed to avoid permanent visual impairment due to persistent corneal oedema.

Case presentation

A 59-year-old man presented to the eye clinic of a tertiary hospital with bilateral blurring of vision over the past few months worse in the right eye than the left eye. He had no significant past ocular history. His medical history included type 2 diabetes mellitus for which he was on oral hypoglycaemic agents.

On examination, best-corrected visual acuity was 6/9 in the right eye and 6/6 in the left eye. Anterior segment examination revealed mild nuclear sclerotic and cortical cataracts in both eyes. Intraocular pressures were 14 mm Hg in both eyes. On dilated fundus examination, there was moderate non-proliferative diabetic retinopathy bilaterally with diabetic macular oedema.

Optical coherence tomography (OCT) confirmed diabetic macular oedema in both eyes, worse in the right eye than the left eye with foveal involvement as demonstrated in figures 1 and 2.

Figure 1.

High-definition optical coherence tomography cross of the right eye on initial presentation demonstrating subfoveal intraretinal cystic changes consistent with diabetic macular oedema.

Figure 2.

High-definition optical coherence tomography cross of the left eye on initial presentation demonstrating parafoveal intraretinal cystic changes.

The patient was treated with intravitreal bevacizumab injections with three consecutive injections administered at 1-month intervals. The macular oedema did not resolve after three injections of bevacizumab and the patient’s best-corrected visual acuity declined to 6/12 in the right eye. A dexamethasone intravitreal implant (Ozurdex) was administered to the right eye. Immediately after the Ozurdex injection, it was noted that the implant had extruded into the perilimbal subconjunctival space. The patient was reviewed the following day and the implant had fractured into three pieces as demonstrated in figures 3 and 4.

Figure 3.

Slit lamp photo of the right eye under ×10 magnification demonstrating extrusion of the dexamethasone implant into the subconjunctival space.

Figure 4.

Slit lamp photo of the right eye under ×25 magnification demonstrating the extruded dexamethasone implant in three fragments in the subconjunctival space.

Treatment

The patient was promptly taken to theatre the following day for removal of the Ozurdex implant under local anaesthesia. A radial peritomy at the temporal conjunctiva was performed to enable removal of the three Ozurdex fragments. Each fragment was removed as a whole without further disintegration of the pieces. Washout with balanced salt solution was performed. The conjunctiva was closed with two 7–0 vicryl simple interrupted sutures and subconjunctival cephazolin was administered.

Outcome and follow-up

The Ozurdex implant was successfully surgically removed from the subconjunctival space (figure 5). Postoperatively, the patient was commenced on prednisolone acetate (1%)/phenylephrine hydrochloride (0.12%) (Prednefrin Forte) eye drops and chloramphenicol eye drops four times a day and atropine 1% eye drops two times per day. The patient recovered well and suffered no further complications related to the extruded implant. The patient was planned for a new Ozurdex implant for the right eye 1 month later.

Figure 5.

Slit lamp photo under ×16 magnification postsurgical removal of the dexamethasone implant from the subconjunctival space with no residual fragments.

Discussion

The Ozurdex implant was injected through the inferotemporal sclera. We propose the mechanism of extrusion to be either migration of the implant through the injection site post injection or failure to inject the implant completely through the sclera at the time of injection.

Ozurdex is indicated for diabetic macular oedema, cystoid macular oedema secondary to branch or central retinal vein occlusion and for non-infectious posterior uveitis.³ Migration of Ozurdex implants into the anterior chamber has been described in the literature with close to 30 published cases.¹ It has been recognised that Ozurdex may cause a reduction in corneal endothelial cell density with corneal decompensation and oedema being a significant adverse effect of Ozurdex migration into the anterior chamber.^{1 4 5} Madi et al stated that in 29 cases of Ozurdex implant migration into the anterior chamber, corneal oedema developed in 24 (83%) cases.¹ There has been a single reported case of corneal graft failure 6 weeks following administration of an Ozurdex implant which had been found in the anterior chamber.¹ Risk factors for migration into the anterior chamber include a history of vitrectomy, absent or defective lens capsule or peripheral iridotomy.⁶

The proposed mechanism of endothelial decompensation may be due to drug toxicity from the active ingredient of the Ozurdex implant (dexamethasone) or its chemical contents (lactic acid or glycolic acid) or from direct mechanical trauma to the endothelium.^{1 6} High concentrations of dexamethasone are cytotoxic to the corneal endothelium causing cell apoptosis and necrosis.⁷ There is a higher risk of corneal oedema with early migration (less than 3 weeks).⁶ Late migration has not been associated with corneal oedema possibly due to the lower dose of dexamethasone released after degradation over 3 weeks.

Fenolland et al observed corneal endothelial decompensation with associated decrease in visual acuity in a middle-aged male patient 3 weeks after a dexamethasone implant was inadvertently injected into the subconjunctival space.² The implant was removed immediately with resolution of corneal oedema and complete recovery of visual acuity. We favoured prompt removal of the Ozurdex implant in our patient as its fragments were located in close proximity to the limbus. A higher concentration of dexamethasone would be released from the broken implant due to an increased surface area. Our patient was at high risk of corneal complications and limbal stem cell toxicity.

The literature suggests expeditious surgical removal of a migrated or extruded Ozurdex implant due to the risk of non-resolving corneal oedema.¹ Earlier removal of a migrated dexamethasone implant is associated with a lower risk of permanent corneal oedema.⁶ In a case series describing 14 patients who developed corneal oedema after implant migration, 10 (71%) required corneal transplantation due to permanent oedema.⁶ Due to the risk of limbal stem cell or corneal endothelial damage, we removed the extruded Ozurdex implant within 2 days before the patient developed any corneal oedema and avoided long-term complications.

Learning points.

• Migration or extrusion of dexamethasone intravitreal implants is a rare but significant adverse event.

• Implants in the subconjunctival space or anterior chamber can cause corneal decompensation and corneal oedema due to drug toxicity or mechanical trauma.

• Urgent removal of the migrated or extruded implant is crucial in preventing permanent corneal oedema.