Desegmentation of Ozurdex implant in vitreous cavity

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Clinical science

Desegmentation of Ozurdex implant in vitreous cavity: report of two cases Rupesh Agrawal, Guillermo Fernandez-Sanz, Susmita Bala, Peter K F Addison Medical Retina Service, Moorfields Eye Hospital, London, UK Correspondence to Peter K F Addison, Medical Retina Service, Moorfields Eye Hospital, 253 City Road, London EC1V 2PD, UK; Peter. Addison@moorfields.nhs.uk Received 1 January 2014 Revised 1 February 2014 Accepted 17 February 2014 Published Online First 19 March 2014

ABSTRACT Purpose To report two cases of desegmentation or fracture of the Ozurdex implant observed immediately after routine intravitreal implantation for macular oedema. Patients In two patients receiving intravitreal Ozurdex implant injection, a rare complication of fracture of implant was noted immediately after the injection. No additional complication was noted in either of the patients. On follow-up, the macular oedema had resolved and there were no further complications. Discussion We shared our experience with the manufacturer, and it was confirmed that, during the normal degradation process, the implant may become soft and break into pieces. Allergan shared their unpublished data on in vivo and in vitro drug release profile of one piece versus three pieces of implant, which is presented in this case report. Conclusions With more and more microsurgical implantation procedures, clinicians should be well aware of these unusual although rare complications. Even though the desegmented implants do not appear to cause more intraocular complications compared with single-piece implants, patients with defragmented implants should be followed up carefully to monitor for unexpected complications. Ozurdex (Allergan Pharmaceuticals) is a sustained release biodegradable steroid ocular implant containing dexamethasone and is licensed for the treatment of macular oedema secondary to retinal vein occlusion and for the treatment of non-infectious posterior segment uveitis. It is commercially available in a complete drug delivery system ready for transscleral intravitreal injection. The biodegradable implant contains 700 μg of dexamethasone, which is released with an initial high-dose pulse and then a sustained release with efficacy for up to 6 months.1 2 We report two cases of desegmentation or fracture of Ozurdex implant observed immediately after routine intravitreal implantation.

the applicator parallel to the limbus, the sclera was engaged at an oblique angle with the bevel of the needle facing up and a shelved scleral path was made 4 mm posterior to the limbus. The needle tip was advanced transsclerally for approximately 1 mm, before redirecting towards the centre of the eye to complete entry into globe. The actuator button was slowly depressed until an audible click was heard. Before withdrawing the applicator from the eye, it was confirmed that the actuator button was fully depressed and was locked flush with the applicator surface. The needle was removed using the reverse technique compared with entry. On postprocedure fundus examination, the patient was noted to have an implant fractured into two pieces (figure 2A), which was otherwise stable and had not caused any iatrogenic vitreoretinal damage. On follow-up, his vision improved and the macular oedema resolved. The fractured implant did not cause any intraocular inflammation or infection. At 1 month postimplantation, the fractured pieces of implant looked stable. Visual acuity had already improved to 6/9 in the right eye and the macular oedema had decreased to 278 μ on OCT scan At 2 months postimplantation, visual acuity was stable and the central macular thickness had reduced further to 218 μ (figure 1B). The fractured pieces of implant were smaller in size but were still present in the vitreous cavity and were not causing any intraocular inflammation

CASE 1

To cite: Agrawal R, Fernandez-Sanz G, Bala S, et al. Br J Ophthalmol 2014;98:961–963.

A 69-year-old man was referred to Medical Retina clinic. His visual acuity at presentation was 6/24 in the right eye and 6/9 in the left eye. He was diagnosed with right eye non-ischaemic central retinal vein occlusion with cystoid macular oedema. His known risk factor was controlled hypertension. Optical coherence tomography (OCT) scan revealed macular oedema with a central macular thickness of 656 μ (figure 1A). After obtaining fully informed consent, the patient underwent intravitreal implantation of Ozurdex. The standard technique was used.1 While aligning the long axis of

Agrawal R, et al. Br J Ophthalmol 2014;98:961–963. doi:10.1136/bjophthalmol-2014-304866

Figure 1 Preimplant and postimplant optical coherence tomography (OCT) scans for case 1. Preimplant OCT scan showing the presence of macular oedema (A), which improved postimplant at 2 months (B). 961


Clinical science Figure 2 Fractured implant in two pieces immediately after injection (A) and at 2 months follow-up (B).

(figure 2B). By 3 months postimplantation, there was recurrence of macular oedema with a reduction in visual acuity. A second Ozurdex implantation was arranged and delivered 4 months after the first one. This implant did not fracture.

CASE REPORT 2 A 66-year-old woman was consented for a second Ozurdex implant in her right eye for branch retinal vein occlusion with macular oedema. Her visual acuity in the right eye was 6/24

with central macular thickness of 549 μ (figure 3A). Her first Ozurdex implantation was 4 months before, and there was recurrence of macular oedema for which a second implant was recommended. The procedure was carried out in the same way as that in case report 1. On postprocedure fundus examination, the implant was noticed to be fragmented into three pieces inside the vitreous cavity (figure 4A,B). However, there were no immediate complications warranting removal of the implant. The patient was informed and followed up closely to monitor

Figure 3 Preimplant and postimplant optical coherence tomography (OCT) scans for case 2. Preimplant OCT scan showing the presence of macular oedema (A), which improved at 1 month (B).

Figure 4 Fractured implants in three pieces immediately after injection (A, B) and at 1 month follow-up (C). 962



Clinical science

Figure 5 Comparison of in vitro release of 1-piece versus 3-piece dexamethasone implant in rabbit eyes (courtesy of Allergan Inc.). for efficacy and adverse effects. At 1 month post-Ozurdex, her visual acuity had improved to 6/12 and the macula oedema had resolved, with central macular thickness reduced to 197 μ (figure 3B). There were no complications of the fractured implant (figure 4C). At 2 months postimplantation, visual acuity and OCT central macular thickness had further improved to 6/9 and 190 μ, respectively. At 4 months, all three fragments of the implant were absorbed without leaving any residual pieces or adverse sequelae.

DISCUSSION Intraoperative or intraprocedure breakage of ophthalmic surgical devices has been described with anterior and posterior segment operations and, increasingly so, with the advent of microgauge vitreoretinal surgery.3 Ozurdex is a microsurgically implanted device. It is available in an applicator preloaded with biodegradable dexamethasone implant with fixed size and concentration.1 2 In the published studies, the most common adverse effects reported with Ozurdex implant were conjunctival haemorrhage (20%), eye pain (7%), cataract (7%), conjunctival hyperaemia (7%), maculopathy (5%), and ocular hypertension (4%).4 There were no cases of breakage of implant reported in any of the published studies on dexamethasone implant, except a recently published single case report by Rishi et al,5 where the authors reported a similar case of breakage of Ozurdex implant during the procedure and another case report published very recently by Donmez et al.5 The desegmentation of Ozurdex apparently seems to be innocuous without any immediate or early intraocular complications. Similar to the cases described by Rishi et al5 and Donmez et al,6 there were no consequential adverse effects of fractured Ozurdex implant in either of the cases reported here. The efficacy of the drug normally reduces at 2 months, and this was observed in both our cases. A possible mechanism of intraprocedure desegmentation of Ozurdex implant is manufacture defect. The manufacturer had a random quality control (QC) system in place, and after the initial check postmanufacturing, implants are checked randomly for quality assurance as per Allergan Inc. Allergan confirmed

that fractured implants in the applicator have not been found to date during this QC process. The therapeutic effect of broken Ozurdex implant pieces is unknown. Of note, the Ozurdex implant matrix consists of biodegradable ingredients. It degrades into water and carbon dioxide over months. During the normal degradation process, the implant may become soft and break into pieces. Allergan shared their unpublished data on in vivo and in vitro drug release profile of one piece versus three pieces of implant. In the experiments performed on rabbit eyes, investigators determined that the in vivo and in vitro pharmacokinetic behaviour of dexamethasone released from the implant was not affected by whether the drug was delivered in one piece or three pieces (figure 5).7 Neither longevity nor efficacy of the drug was affected because of fragmentation.7 The possibility of a fragmented piece of implant being injected into the eye with the other part remaining in the applicator was also discussed with Allergan. This is unlikely both from the manufacturer perspective and from our own clinical observation in both cases that all the fragmented pieces were inside the eye. The delivery of the implant from the applicator is based on a positive pressure mechanism whereby the whole contents of the applicator are pushed into the vitreous cavity. To the best of our knowledge, these are the only cases of fractured implant after the cases reported by Rishi et al5 and Domez et al.6 In addition, our cases demonstrate normal efficacy of implants in two and three pieces over time. With more and more microsurgical implantation procedures, clinicians should be well aware of these unusual although rare complications. Even though the desegmented implants do not appear to cause more intraocular complications compared with singlepiece implants, patients with defragmented implants should be followed up carefully to monitor for unexpected complications. Acknowledgements We acknowledge the advice and sharing of the pharmacokinetics data from the manufacturer of the implant, Allergan Inc. Contributors We have all equally contributed to the data collection, writing and editing of the article and also the intellectual inputs. Funding This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. Dr Rupesh Agrawal is on an overeseas NMRC research training fellowship funded by MOH, Singapore. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed. Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Data sharing statement The current manuscript in its form is not published or submitted to any other journal at this moment of time. The data are not available to any other scientist or researcher besides the team.

REFERENCES 1 2

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5 6 7

Anon. Advance notification document: Dexamethasone 700 μg intravitreal implant in applicator (OZURDEX™) for retinal vein occlusion. Allergan, 2009. Haller JA, Bandello F, Belfort R, et al. Ozurdex Geneva Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010;117:1134–46. Udoetuk JD, Javey G, Carvounis PE. Intraoperative breakage of a disposable 23-Gauge trocar tip. Retina Cases Brief Rep 2013;7:50–1. Haller JA, Bandello F, Belfort R, et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010;117:1134–46. Rishi P, Mathur R, Rishi E. Fractured ozurdex implant in the vitreous cavity. Indian J Ophthalmol 2012;60:337–8. Donmez O, Parlak M, Yaman A, et al. Splitting of a Dexamethasone Implant (Ozurdex) following the Injection. Case Rep Ophthalmol Med 2013;2013:247949. Allergan; data on file—fractured implants, 2003.


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Desegmentation of Ozurdex implant in vitreous cavity: report of two cases Rupesh Agrawal, Guillermo Fernandez-Sanz, Susmita Bala and Peter K F Addison Br J Ophthalmol 2014 98: 961-963 originally published online March 19, 2014

doi: 10.1136/bjophthalmol-2014-304866 Updated information and services can be found at: http://bjo.bmj.com/content/98/7/961

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