Introduction

Fluocinolone acetonide intravitreal microimplant (ILUVIEN®; Alimera, Sciences Limited, Aldershot, UK) is designed to release a continuous, low-dose corticosteroid treatment to the retina for up to 36 months to treat the inflammation associated with diabetic macular edema (DME), retinal vein occlusion and uveitis (Massa et al. 2018; Coelho, Pessoa, and Meireles 2019; Reddy et al. 2016). It is indicated in eyes considered insufficiently responsive to available therapies and have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure (Massa et al. 2018).

We report a case of corneal endothelial decompensation due to unrecognised anterior migration of Iluvien® implant in a pseudophakic eye with Artisan iris-claw intraocular lens (Ophtec BV, and Verisyse, Abbott Medical Optics, Inc.) and compromised posterior capsule. The implant suddenly appeared at the inferior angle of the anterior chamber during penetrating keratoplasty procedure and was completely removed to prevent further damage to the corneal graft.

Case report

A 78-year-old man with Type 2 diabetes mellitus was treated for right chronic diabetic macular edema (DME) following uneventful right cataract extraction in June 2014. The DME was refractory to multiple laser and intravitreal ranibizumab treatments but showed a partial response to intravitreal Alflibercept treatment. In March 2018, he developed subluxation of the right posterior chamber intraocular lens (PCIOL), for which pars plana vitrectomy, removal of the IOL, and implantation of Artisan iris-claw anterior chamber IOL were performed. The DME in the right eye deteriorated rapidly following the surgery and subsequently showed a good response to a combination of intravitreal Ranibizumab and a preservative-free triamcinolone preparation (Triesence®, Alcon). The intra ocular pressure remained stable at 16 mmHg. In October 2019 intravitreal Iluvien® was implanted to achieve a prolonged clinical response. Four weeks later, the vision in the right eye has improved from 6/38 to 6/24 with reduction in central macular thickness from 826 microns to 383 microns. Three months later, the macular edema worsened for which intravitreal injection course of Ranibizumab was resumed. In March 2020, the patient presented to eye emergency department, complaining of blurred vision in the right eye a few days following an intravitreal injection of Ranibizumab. There was no eye pain, discharge or eyelid swelling. The vision was counting fingers in the right eye and 6/9 in the left eye. Examination of the right eye revealed a localised inferior corneal edema, stromal haze, Descemet’s membrane folds and epithelial bullae (Figure 1). The central corneal thickness was 915 microns. There were no keratic precipitates or hypopyon. The anterior chamber was deep and the Artisan iris-claw IOL was secured. Therefore, it was thought that psuedophakic bullous keratopathy was unlikely diagnosis and the corneal edema was of viral aetiology. The intraocular pressure of the right eye was 17 mmHg. The patient was eventually referred to the cornea service. The corneal edema failed to respond to a few weeks treatment of frequent topical steroids and oral acyclovir. Corneal stromal scar worsened over the next three months (Figure 1). The patient was listed for right penetrating keratoplasty. Intra-operatively, Iluvien® implant suddenly appeared in the inferior angle of the anterior chamber (Figure 2). The implant was removed and the penetrating keratoplasty was performed successfully. The graft has settled well postoperatively. The patient is referred back to the medical retina team and further intravitreal Ranibizumab injections have been offered to control the DME in the right eye.

Figure 1
Figure 1.Right eye slit lamp photomicrographs.

A localised inferior corneal decompensation was noted in March 2020 (Figure 1A), which failed to respond to topical steroid eye drops and oral acyclovir. The edema progressively became worse over the course of three months (Figure1B, June 2020). No Iluvein@ implant could be seen in the anterior chamber. A prominent inferior arcus senilis was also observed.

Figure 2
Figure 2.Intraoperative photomicrographs of the right eye during penetrating keratoplasty.

Iluvien® implant was seen clearly at the inferior angle of the anterior chamber (Figure 2A). The implant was maneuvered carefully with 25G anterior chamber (Rycroft) cannula to bring it close to the graft-host junction (Figure 2B). One end of the implant was pushed up through the graft-host junction (Figure 2C) and finally retrieved intact with a fine non-toothed forceps (Figure 2D).

Discussion

The most common recognised complications of Iluvien® implant include the development of cataract in 81% of phakic eyes and raised intraocular pressure in 34% of patients (Massa et al. 2018; Campochiaro et al. 2012, 2011).

Reports of anteriorly migrated intravitreal steroid implants, such as Ozurdex and Iluvien®, have been well documented (Alzaabi, Taguri, and Elbarky 2020; Gunzenhauser, Greven, and John 2022; Rishi, Majumder, and Biswas 2019; El-Ghrably, Saad, and Dinah 2015; Papastavrou et al. 2017; Khurana et al. 2014; Nguyen and Wolfensberger 2019; Pacella et al. 2016; Kishore and Schaal 2013). Risk factors are aphakic patients, eyes with compromised posterior capsule due to a previous complicated cataract surgery, and in vitrectomised eyes with intact posterior capsule. In the latter cases, the implant is believed to migrate through a small zonular dehiscence caused by a previous vitrectomy procedure (Alzaabi, Taguri, and Elbarky 2020; Papastavrou et al. 2017).

The anteriorly dislocated steroid implants can cause sight-threatening complications. These include secondary ocular hypertension, endothelial decompensation, corneal edema and scarring. This condition may be managed by either repositioning it back to the vitreous cavity or by removing it completely (Alzaabi, Taguri, and Elbarky 2020; El-Ghrably, Saad, and Dinah 2015; Kishore and Schaal 2013; Nguyen and Wolfensberger 2019; Tabandeh and Rezaei 2020).

El- Ghrablya et al. described a simple and novel technique to reposition anteriorly migrated Iluvien® implant back into the vitreous cavity in eyes with compromised posterior capsule. Using 23-gauge flute needle, the dislocated Iluvien® implant is retrieved safely without compromising implant integrity (El-Ghrably, Saad, and Dinah 2015). A less invasive approach has been described to remove Ozurdex pellet from the anterior chamber using a 23-g needle aligned with the axis of the implant through a paracentesis (Nguyen and Wolfensberger 2019). In patients with disrupted anterior-posterior segment border and steroid implant-related problems including migration, Herold et al. described a simple surgical technique of scleral fixation of Iluvien® implant (Herold et al. 2020). The implant was prepared using 10-0 nylon suture to create a knot and two loops around its middle part. Then, 1.5-mm sclerotomy at a distance of 3.5 mm from the limbus was created using vitreoretinal knife. The implant was pushed a minimum of 3 mm in order to create some distance from the ciliary body. Finally, the thread was fixed to the sclera and the conjunctiva was closed. The technique proved to be safe and reversible. Published data on demographic, clinical features and management of the anteriorly migrated Iluvien implant is summarized in table 1.

Table 1.Published data on demographic, clinical features and management of the anteriorly migrated Iluvien® implant
Author(s); year Age and sex of patient(s) Indication Risk factor(s) Complication(s) Treatment to complication interval Management
Alzaabi and associates, 2020 60, female DME
  • PPV for vitreous haemorrhage (PC intact)
 Raised IOP 6 months
  • Surgical removal of the implant via anterior approach
  • Glaucoma drainage device surgery
El-Ghrably and associates, 2015 74, male DME
  • PC rupture
  • PPV for dropped nucleus
  • Sulcus IOL
 Raised IOP 13 days
  • Surgical repositioning of the implant into vitreous cavity via anterior approach
Papastavrou and associated, 2016 77, female DME
  • PXF
  • PC rupture
  • Sulcus IOL
  • PPV for RRD
 No complications (First migration)
Corneal edema (second migration)
  • 7 days (First migration)
  • 6 weeks (second migration)
  • Surgical removal of the AC implant via anterior approach and reinsertion into vitreous cavity via par plana approach (first migration)
  • Removal of the implant via paracentesis (second migration)
47, male DME
  • PC rupture
  • Artisan iris-claw IOL
  • PPV for ERM
 Corneal edema
Raised IOP		 2 months
  • Surgical repositioning of the implant into vitreous cavity via anterior approach
Gunzenhauser and associates, 2019 61, male DME
  • PC rupture
  • PPV for retained lens fragments
  • Sulcus IOL
 Raised IOP
Increased central corneal thickness		 3 months and subsequent implant free movement between AC and vitreous
  • IOP lowering eye drops
  • Reposition the implant into the vitreous cavity via supine posturing and topical pilocarpine eye drops
Tabandeh and associated, 2020 83, male DME
  • PC rupture
  • PPV for retained lens fragments
  • Sulcus IOL
 Corneal edema 4 months (recurrent migration of the implant)
  • Scleral fixation of the implant via posterior approach

DME=Diabetic macular edema, PPV=pars plana vitrectomy, PC=posterior capsule, IOP=intraocular pressure, PXF=Pseudoexfoliation, RRD= Rhegmatogenous retinal detachment, ERM=Epiretinal membrane.

In our patient, we believe that corneal endothelial decompensation of the right eye was likely due to the toxicity and/or mechanical damage induced by the migrated Iluvien® implant into the anterior chamber, which surprisingly was not visible on slit-lamp examination during several pre-operative clinic visits. However, gonioscopic examination hasn’t been documented and the presence of the implant lodged in the inferior angle couldn’t be ruled out. The Localised corneal edema and arcus senilis, both of them were prominent inferiorly, could have impaired the visibility of the implant in the anterior chamber. A compromised endothelial cells (EC) count was another important factor, which possibly contributed to the acute presentation and subsequently chronic decompensation in our patient. Despite the lack of documentation of EC count and morphology before and after the acute presentation, it is likely that the EC count is affected. Cataract surgery, vitrectomy, IOL explanation and anterior chamber secondary IOL implantation are all possible iatrogenic causes of EC compromise in our patient.

Interestingly, two previous case reports observed frequent Iluvien® implant re-migration in their patients, who had a compromised posterior capsule as a result of a prior complicated cataract surgery (Papastavrou et al. 2017). The potential free movement of the implant between the anterior chamber and the vitreous cavity could theoretically increase the chance of missing the diagnosis during the follow up period.

The risk of Iluvien® implant migration is higher than Ozurdex due to the fact that the shell of Iluvien® implant is non-biodegradable and its smaller in size (Iluvien® 3.5mm x 0.37mm vs Ozurdex 6 mm x 0.46 mm). In addition, vitrectomized eyes carry a higher risk of migration, because the implant would not be tethered by the vitreous (Papastavrou et al. 2017).

In conclusion, we here describe a case report of corneal edema and bullous keratopathy due to anteriorly migrated Iluvien® implant which was only discovered at the time of corneal transplantation. In patients with an unexplained corneal endothelial decompensation, a prior history of an intravitreal steroid implant is etiologically relevant. Gonioscopy is an important part of the ophthalmic examination in this clinical setting.

Funding/Support

None.

Conflict of interest

No conflicting relationship exists for any author.

Financial Disclosures

Mouhamed Al-Aqaba: None

Darren Ting: None

Dalia G Said: None

Harminder S. Dua: Honoraria and Travel expenses from Dompe, Croma, Santen, Allergan, Thea. Shares in NuVision and Glaxosmithkline.