Anterior chamber migration of a sustained-release dexamethasone intravitreal implant: A case report and review of literature.

The purpose of the study was to report a case of migration of a dexamethasone intravitreal implant (Ozurdex®) into anterior chamber and review the literature pertaining to the anterior chamber migration of implant. Clinical data were collected from a patient, in whom a dexamethasone intravitreal implant migrated to anterior chamber. A review of literature was conducted to analyze additional reports. A 59-year-old aphakic patient with recalcitrant cystoid macular edema due to chronic idiopathic uveitis was treated with intravitreal injection of dexamethasone implant. Migration of the implant into anterior chamber was noted after a month of injection. Since his cornea was clear and intraocular pressure was normal, he was managed conservatively. Sixteen such reports of migration of implant into anterior chamber was analyzed to look into the possible etiologies and outcome. Disruption of lens capsule, large basal iridectomy, and prior vitrectomy are the primary risk factors for migration of dexamethasone implant into the anterior chamber.

Introduction

Ozurdex® (Allergan Inc., Irvine, CA, USA) is a biodegradable implant which is composed of a mix of polylactic acid and polyglycolic acid polymers (PLGA matrix). The implant contains 700 μg of dexamethasone which is released to the vitreous cavity over a 6-month period and can be administered into the eye using an office-based procedure through a 22-gauge injecting applicator through the pars plana. The PLGA polymer matrix, while releasing dexamethasone to its target tissues, dissolves completely in vivo into its components, lactic acid and glycolic acid, which are in turn converted into carbon dioxide and water.[12] The implant is approximately 0.46 mm in diameter and 6 mm in length. The dexamethasone intravitreal implant (Ozurdex®) got the phase-wise approval from the United States Food and Drug Administration (FDA) for the treatment of macular edema due to retinal vein occlusions, noninfectious uveitis, and diabetic macular edema in 2009, 2010, and in 2014, respectively. The implant showed promising result in the management of macular edema with less deleterious side effects. In this report, we reviewed the literature on anterior chamber migration of dexamethasone intravitreal implant and described a case of dexamethasone implant, which had migrated to anterior chamber in an aphakic patient without causing any corneal dysfunction and was managed conservatively.

Case Report

A 59-year-old aphakic male with a history of vitrectomy and intraocular lens (IOL) removal came to us with chief complaints of diminution of vision for 15 days in the right eye. His left eye was blind for 8 years with absolute glaucoma. He underwent cataract surgery 8 year ago, following which his vision did not improve and he was diagnosed as chronic uveitis elsewhere. He underwent vitrectomy with IOL removal 3 months back, following which his best-corrected visual acuity (BCVA) improved to 6/6 with aphakic correction. On examination, his BCVA in the right eye was 6/60 and no perception of light in the left eye. Fundus examination of the right eye showed cystoid macular edema, which was confirmed by optical coherence tomography with foveal thickness of 853 μ. A sub-Tenon injection of triamcinolone acetonide was administered through superotemporal route in the right eye. At 1 month follow-up, reduction in central foveal thickness was observed (430 μ) with persistent cystoid macular edema. Subsequently, a dexamethasone intravitreal implant – Ozurdex® (Allergan Inc., Irvine, CA, USA) was administered in the right eye. He was reviewed again after 1 month and slit-lamp examination of the right eye showed the implant in anterior chamber at 6 o'clock position. Although the implant was lying in contact with corneal endothelium, cornea of the right eye was normal and we did not notice any corneal edema or folds in Descemet's membrane [Figure 1a]. Intraocular pressure (IOP) in the right eye was 16 mmHg. There was a significant improvement in his BCVA of the right eye (6/9). Optical coherence tomography showed resolution of cystoid macular edema with reduced foveal thickness to 224 μ. As the implant was not obstructing the visual axis and cornea was clear, we decided not to intervene but to observe the patient. At 4 months of follow-up, patient retained the BCVA of 6/9 and his cornea was normal with spontaneous degradation of the implant [Figure 1b]. IOP in the right eye at this visit was 11 mmHg. His endothelial cell count revealed a cell density of 2227 cells/mm2.

Figure 1

(a) A dexamethasone intravitreal implant (Ozurdex®) in anterior chamber of the right eye of a patient after 1 month of intravitreal injection (b) slit-lamp photograph of the right eye following resolution of the implant

Discussion

Over the past few years, the intravitreal administration of sustained-release dexamethasone implant has become increasingly popular. Various complications associated with the injection of the implant have been reported in literature. Intraoperative complications include posterior capsular tear (PCT), vitreous loss, and zonular dehiscence. Accidental injection of a dexamethasone intravitreal implant into the crystalline lens has been reported by Fasce et al.[3] Postoperative complications include increase in IOP, posterior subcapsular cataract formation, and secondary ocular infection from pathogens. Anterior migration of dexamethasone implant is relatively rare but has been reported in literature. Pardo-López et al.[4] were the first to report the migration of a dexamethasone intravitreal implant in a patient with iris-fixated IOL. Migration of the implant in aphakic vitrectomized eye was first reported by Bansal et al.[5] Till date, there have been many reports of migration of dexamethasone intravitreal implant into anterior chamber. We performed a comprehensive search for articles, case reports, describing anterior chamber migration of dexamethasone intravitreal implant using MEDLINE. Using the terms “Ozurdex,” “Dexamethasone implant,” and “anterior chamber migration” and limited to “human,” we found 27 articles. After reviewing these articles and their bibliographies, 16 articles were included in this literature review.

Anterior chamber migration of a dexamethasone intravitreal implant has been reported in patients with aphakia,[56] anterior chamber IOL (ACIOL),[78] iris claw lens,[491011] scleral-fixated lens,[121314] and posterior chamber IOL (PCIOL).[1516] In majority of the cases, ruptured capsule has been reported as a primary risk factor for the migration of the implant into anterior chamber.[4567891013] Vitrectomized eyes[56910111216] are at increased risk of migration of the implant to anterior chamber when the other factors described above are present. Peripheral iridectomy, especially basal or inferior which facilitates free passage of aqueous from posterior chamber to anterior chamber, has been described as another risk factor for the passage of implant into anterior chamber.[9101718] The implant, being 0.46 mm × 6 mm in size, can easily pass through the iridectomy wound with aqueous current, if the long axis of the implant is aligned with the conduit. Body postures such as face down or prone positions[9] and long-distance air travel[13] are also described as a risk factor. Pacella et al.[13] reported dexamethasone intravitreal implant migration to anterior chamber in an 83-year-old female following phacoemulsification with scleral-fixated PCIOL, which they attributed to the reduction in air pressure inside the airplane. Most of the case reports observed that the migration of the implant is relatively higher in patients with aphakia and in eyes with disrupted posterior capsule. As result of these observations, in September 2012, FDA instructed Allergan Inc., to include a contraindication for the implant in aphakic eyes and in eyes with ACIOL with PCT. Kocak et al.[19] reported migration of the dexamethasone intravitreal implant into posterior chamber between the iris and PCIOL and attributed it to weak zonules. In another case report, Wai Ch'ng et al.[20] described a case where the implant had moved to anterior vitreous and obtained retrolental position, thereby obstructing the visual axis. Since in both the cases, the implant did not migrate to anterior chamber, we did not include these reports in this review. Table 1 summarizes the published reports on anterior migration of the dexamethasone implants into anterior chamber. The largest series on anterior migration of dexamethasone intravitreal implant to date is by Khurana et al.[21] and included 15 patients who had suffered from 18 episodes of implant migration. Of these 15 patients, six patients were aphakic, four patients with ACIOL, two with scleral-fixated IOL and PCIOL each, and one patient with iris claw lens. All the eyes were vitrectomized and 14 of them had disrupted capsule. Out of 15 patients, 14 developed corneal edema. Corneal edema did not resolve in ten patients even after the removal of implant from anterior chamber and six of them required corneal transplantation.

Table 1

Review of literature on anterior migration of a dexamethasone intravitreal implant-Ozurdex® into anterior chamber excluding the largest series of 16 patients by Khurana et al.

Author	Age/sex	Risk factors	Cornea*	IOP*	Management	Outcome
Pardo-López et al.[4]	68/male	Iris claw lens, PCT, anterior vitrectomy	Corneal edema	18	Surgical removal	Required corneal transplantation
Bansal et al.[5]	47/male	Aphakia, vitrectomized eye	DM folds with corneal edema	11	Conservative	Improvement in BCVA
	13/male	Aphakia, vitrectomized eye	Corneal edema	33	Surgical removal	Corneal edema decreased, but persisted
	15/male	Aphakia, vitrectomized eye	Clear	18	Conservative	Improvement in BCVA
Bernal and Estévez[6]	68/male	Aphakia, vitrectomized	Corneal edema, DM folds	35	Partial surgical removal	Corneal decompensation
Ruiz-Casas et al.[7]	64/male	ACIOL	Corneal edema	10	Surgical removal	NA
Kishore and Schaal[8]	89/female	ACIOL	Nil	22	Pharmacological dilatation, head positioning	NA
Malclès et al.[9]	69/female	Iris claw lens, vitrectomized eye, inferior iridectomy	Corneal edema	14	Surgical removal	Corneal decomposition
	50/male	Iris claw lens, vitrectomized eye, superior iridectomy	Corneal edema	20	Surgical removal	Corneal decomposition
	56/male	Vitrectomized eye, PCIOL, PCT	Corneal edema	40	Conservative	NA
Stepanov et al.[10]	65/male	Iris-claw lens, vitrectomized eye, Inferior iridectomy	Corneal edema	40	Surgical removal	NA
Vela et al.[11]	65/female	Iris claw lens, vitrectomized eye, inferior iridectomy	Cornea clear	NA	Repositioned with a needle	NA
Laplace et al.[12]	54/male	SFIOL, Vitrectomized eye	Corneal edema	NA	Surgical removal	Improvement in BCVA
Pacella et al.[13]	83/female	SFIOL	Corneal edema	11	Surgical repositioning	Resolution of corneal edema, improved BCVA
Srinivasan et al.[14]	60/male	SFIOL, Vitrectomized eye	Corneal edema, DM folds	NA	Pharmacological dilatation, head positioning	Resolution of corneal edema, improved BCVA
Daudin and Brézin[15]	NA	PCIOL	Clear	NA	Surgical removal	NA
Collet[16]	84/male	3-piece PCIOL, vitrectomized eye	Corneal edema	18 (valve#)	Head positioning and tapping	Improvement in BCVA
Stelton et al.[17]	59/male	PCIOL, PCT, large inferior iridectomy	Corneal edema	26	Surgical removal	Deterioration, required DSEK
Eadie et al.[18]	48/male	Superior iridectomy	Cornea clear	18	Conservative	Improvement in BCVA
Present Case	59/male	Aphakia, vitrectomized eye	Cornea clear	16	Conservative	Improvement in BCVA

*Examination findings of cornea and IOP measurement (mm of Hg) at the time presentation with implant in anterior chamber, #Eye with Ahmed glaucoma valve. IOL: Intraocular lens, DSEK: Stripping Endothelial Keratoplasty, PCIOL: Posterior chamber intraocular lens, ACIOL: Anterior chamber intraocular lens, PCT: Posterior capsular tear, SFIOL: Scleral fixated intraocular lens, DM: Descemet’s membrane, BCVA: Best-corrected visual acuity, IOP: Intraocular pressure, N/A: Not available

Corneal edema and raised IOP are the major side effects associated with migration of the sustained-release dexamethasone implant into anterior chamber. Cause of corneal edema can be multifactorial – it can result from toxicity due to chemical ingredient of the implant or due to mechanical irritation by the implant on corneal endothelium. mRNA encoding glucocorticoid receptor in corneal endothelium was detected by immunohistochemistry studies,[2223] and high dose of dexamethasone has been reported to cause apoptosis and necrosis of corneal endothelial cells.[24] However, another sustained-release dexamethasone implant made up of almost similar composition with relatively lower dose of dexamethasone (Surodex, Oculex Pharmaceuticals, Inc., Sunnyvale, CA, USA, made up of 60 mg DEX with PLGA matrix) has been used as an anterior chamber implant to control postoperative inflammation following cataract surgery.[2526] No corneal complication was reported with this implant, thereby reducing the chance of PLGA-associated injury to the corneal endothelium with the dexamethasone intravitreal implant. Furthermore, no corneal complications were reported following intracameral application of dexamethasone at the end of cataract surgery and in patients with endothelial immune reactions after penetrating keratoplasty.[2728] In the largest series of 15 patients with dexamethasone implant migration into anterior chamber by Khurana et al.,[21] 14 patients had corneal edema. Among these 14 patients, the corneal edema did not resolve despite implant removal in ten patients, and keratoplasty was required in six patients. They concluded that the endothelial decompensation was primarily due to mechanical trauma rather than chemical toxicity caused by the implant. In accordance with the Khurana et al., various case reports have detected specular microscopy demonstrating corneal endothelial cell loss in eyes where the migrated implant was rubbing the corneal endothelium. Corneal edema was reported to resolve in many patients with the removal or displacement of the implant. However, many case reports including ours have observed no corneal abnormality even with the dexamethasone intravitreal implant lying in close contact with the corneal endothelium. It is not clear whether corneal endothelial loss due to prior surgical intervention has any role to play in these conditions. The duration of the contact between implant and corneal endothelium seems to be crucial in determining the incidence of corneal involvement, and many authors suggested that any delay in removing the implant may lead to irreversible changes in cornea.[911]

Management of a migrated dexamethasone intravitreal implant (Ozurdex®) into anterior chamber can be discussed under two broad headings.

Cornea not involved: Even if cornea is not involved, the primary aim of the treatment should be to reduce the duration of mechanical rubbing of corneal endothelium by the implant. This can be achieved by proper positioning such as asking the patient to lie supine and dilating the pupil in aphakic eyes. There is a report of repositioning the implant using a needle under slit-lamp[11] or with gentle tapping in head-back position.[16] Yttrium aluminum garnet laser can be used to fragment the implant to facilitates its dislodgment into posterior segment, especially in conditions where the implant is lodged in the pupillary plane between iris and IOL[21]

Corneal involvement: In the presence of corneal edema, the implant has to be removed from anterior chamber as early as possible to prevent endothelial decompensation. Khurana et al.[21] observed that earlier removal of implant had reduced the likelihood of permanent corneal endothelial damage. Various techniques of removing the implant from anterior chamber have been described. Largely method of removal is based on the structural integrity of the implant – whether the implant is friable or not. A friable implant will disintegrate into numerous fragments with minimal manipulation with a surgical instrument. Special care should be taken while removing such an implant.

Thus, it is the combination of disruption of posterior lens capsule and a history of prior vitrectomy that make the eye vulnerable to anterior migration of dexamethasone implant. Large peripheral iridectomy is another important risk factor. It is of paramount importance to understand that the presence or type of IOL alone cannot prevent migration of the implant in the presence of a disrupted posterior lens capsule. In the presence of these risk factors, suturing the implant to the sclera using a 10-0 nonabsorbable polypropylene suture can be considered.[29]

This review aims to elevate awareness of the possibility of the migration of dexamethasone implant into anterior chamber. Our report suggests that clinicians need to carefully select the patients for intravitreal dexamethasone implant. Due to the potential risk of corneal decompensation associated with anterior chamber migration of the implant, these patients should be carefully followed after intravitreal injection. It is equally advisable to explain the patients about this rare, but vision-robbing complication of intravitreal injection of dexamethasone implant before administration, especially in the presence of risk factors.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.