Management of Fluocinolone Implant Dissociation During Implant ExchangeFluocinolone Implant Dissociation During Exchange FREE

The fluocinolone acetonide (FA) implant (Retisert; Bausch and Lomb, Rochester, New York) is a sustained-release corticosteroid delivery device that has demonstrated efficacy for the treatment of chronic, noninfectious uveitis. The US Food and Drug Administration–approved FA implant contains 0.59 mg of medication, which is delivered for up to 30 months following implantation. Results from a 3-year, historically controlled trial showed a reduction in uveitis recurrences from 62% in the 1-year preimplantation period to 4%, 10%, and 20% in the 1-, 2-, and 3-year postimplantation periods.¹ Complications associated with FA implantation include the development of cataract, which occurs in more than 90% of implanted eyes, and glaucoma requiring filtration surgery, which is required in approximately 40% of patients.¹ Rarely reported complications include retinal detachment and endophthalmitis. Spontaneous dissociation of the medication-containing silicone reservoir from the anchoring strut has been reported and was attributed to an adhesive process used in older implants that has since been modified.

Separation of the medication reservoir from its anchoring strut was also reported in 2 of 10 patients undergoing FA reimplantation in one series.² In this series, both patients required only limited vitrectomy, and intraocular foreign body (IOFB) extraction techniques were not required.² In a series of 17 eyes of 14 patients who underwent FA reimplantation, separation of the medication reservoir from its anchoring strut was not observed.³ We describe the intraoperative management of 3 cases of FA medication reservoir dissociation from the anchoring strut during reimplantation surgery; the management of this complication following the improved FA implant adhesive process has not been reported previously to our knowledge. In 2 cases, pars plana vitrectomy (PPV) and IOFB removal techniques were required to retrieve the dissociated implants; in 1 case, PPV and IOFB removal were averted by grasping the fractured reservoir and the anchoring strut simultaneously at the time of explantation.

A 27-year-old woman with an 8-year history of multifocal choroiditis with panuveitis complicated by recurrent choroidal neovascularization in the right eye was managed with FA implant placement and 6 subsequent bevacizumab injections. This allowed her mycophenolate mofetil dosage to be tapered; however, she later developed cataract and glaucoma requiring cataract extraction and tube shunt placement. Because of the prior success of the FA implant in allowing the patient to avoid systemic immunosuppressive medications, an FA implant exchange was performed 3 years following the initial implantation. Preoperative visual acuity was 20/400 OD. Ophthalmic evaluation showed scarring involving the macula but no evidence of active vitritis.

During FA implant exchange surgery, the prior inferotemporal sclerotomy site was identified, the anchoring sutures were removed, and the FA implant was visualized. At the time of attempted device removal with 0.3-mm forceps, the reservoir separated from the anchoring strut and descended into the midvitreous cavity despite attempts to grasp the device with the forceps. The implant sclerotomy was temporarily closed and a complete PPV was performed with an inferonasal infusion. The viscoelastic Healon 5 (Advanced Medical Optics, Inc, Santa Ana, California) was used to elevate the reservoir from the posterior pole, and the dislocated reservoir was retrieved with alligator forceps through the inferotemporal sclerotomy. The new FA implant was sutured into the inferotemporal sclerotomy without complication. Postoperative visual acuity at 1 month's follow-up was 20/400 and the patient's ophthalmic examination remained stable.

A 46-year-old woman with a 2-year history of recurrent bilateral idiopathic panuveitis worse in the left eye was managed with FA implantation. She was subsequently treated with cataract extraction and trabeculectomy in the left eye 1 and 2 years later. Six years after FA implantation, her intraocular pressure was controlled in the left eye with brimonidine tartrate, 0.15% (Alphagan P) and dorzolamide hydrochloride–timolol maleate (Cosopt) twice daily. Although the inflammation had initially been controlled following the FA implantation, immunosuppression with 60 mg of prednisone and 100 mg of azathioprine sodium daily was required to suppress inflammation.

In an effort to reduce the need for systemic immunosuppression, FA implant exchange was performed in the left eye. Intraocular pressure was maintained with a 25-gauge infusion cannula as the prior inferotemporal sclerotomy site was opened to a full 4 mm using a microvitreoretinal blade, and the FA implant was visualized. The prolene anchoring suture was divided, the FA implant was engaged with nontoothed forceps, and on removal of the anchoring strut the medication reservoir remained in the vitreous. The patient underwent 25-gauge PPV with perfluorocarbon (Perfluoron) to elevate the medication reservoir above the retina for removal with Rappazzo intraocular forceps (Bausch and Lomb Surgical, St Louis, Missouri) via the inferotemporal sclerotomy (Figure). The new FA implant was then sutured into this site without complication. One month after surgery, no signs of inflammation were present and visual acuity was stable at 20/50.

A 45-year-old man with a history of bilateral multifocal choroiditis and panuveitis had persistent vitritis despite the use of cyclosporine, methotrexate, chlorambucil, cyclophosphamide, and FA implantation with subsequent replacement in the right eye (2002, 2005). Although the patient's daily requirement of prednisone was 35 mg/d, tapering below 30 mg/d of prednisone resulted in recurrence of vitritis. Thirty-one months after the initial FA exchange, a second exchange was performed.

At the time of removal of the FA implant, the FA medication reservoir separated from its anchoring strut. Two 0.3-mm toothed forceps were used to engage the medication reservoir and its anchoring strut simultaneously while an assistant retracted the anterior lip of the sclerotomy. Both pieces of the device were subsequently removed without complication. Following removal of this device, a new FA implant was secured into place. At 4 weeks' follow-up, visual acuity remained stable at 20/70.

This retrospective case series describes the management of an uncommon complication associated with the FA implant. Manipulation of the FA implant at the time of explantation resulted in the unanticipated dissociation of the silicone medication reservoir from its anchoring strut; in 2 of 3 cases, PPV was required to retrieve the device. Both 20-gauge and 25-gauge PPV were useful during device removal from the vitreous cavity. An ophthalmic viscosurgical device (ie, Healon 5) and perfluorocarbon were each used to elevate the reservoir from the posterior pole to facilitate removal. Because of some technical difficulties in grasping the implant owing to its round shape, large IOFB forceps were necessary to engage the medication reservoir in both cases. Other intraocular forceps (eg, basket forceps, intraocular end-grasping forceps) are available and could have also been considered for removal of this IOFB.

In the multicenter study of FA implants in 278 patients, 22 subjects underwent surgical removal of their FA implant for various reasons (eg, uncontrolled elevated intraocular pressure, hypotony, spontaneous dissociation of the implant from its strut). Spontaneous dissociation of the FA implant from its anchoring strut requiring explantation occurred in 3 of these patients. All 3 of these implants had been produced prior to the adoption of an improved adhesive process.¹ Five patients from this multicenter trial underwent uncomplicated FA implant exchange owing to medication depletion.

Taban et al² reported the loosening of the polymer holding the cup to the anchoring suture strut in 2 of 10 patients who underwent FA reimplantation. The cup was able to be retrieved just beneath the wound without complication following limited vitrectomy around the medication cup. It is notable that this complication was thought to be unique to the FA implant received by patients in the phase 3 clinical study from which their series of patients was derived. The 3 patients described in our study received their FA implants outside the context of the multicenter trial following the improved adhesive process but nonetheless developed this unusual complication.

Jaffe³ reported a series of successful, uncomplicated FA reimplantation in 17 eyes of 14 patients. The mean time from the first implantation to a uveitis recurrence was 38 months, which is consistent with the 30-month drug delivery period of the FA implant. In their series, patients who received reimplantation of the FA device experienced a modest benefit in visual acuity and a decrease in inflammation recurrences. However, 1 patient experienced a recurrence of uveitis, which occurred 3 years after FA reimplantation. These data suggest that inflammatory episodes may occur after drug depletion of the FA implant despite periods of disease quiescence, and strategies to curb inflammation after the 30-month drug delivery period such as FA exchange should be anticipated.

Separation of the medication reservoir from its anchoring strut at the time of reimplantation has also been reported with the ganciclovir implant,⁴ a similar implant used to successfully treat cytomegalovirus retinitis.⁵ Although the manufacturer's labels for both the ganciclovir implant and the FA implant advise handling the implant only by the anchoring strut, these precautions would appear to be more applicable to the initial implant procedure.^{6 - 7} A skilled assistant may be valuable in grasping the medication cup with toothed forceps or retracting the scleral wound edges at the time of device extraction. Although it may be technically difficult to grasp both the medication reservoir and strut simultaneously without substantially enlarging the sclerotomy site, the surgeon should be prepared to engage the medication reservoir if descent of a fractured FA implant into the vitreous cavity is imminent.

Because of the possibility of dissociation of the FA implant during explantation, we recommend opening the implant sclerotomy to a full 4 mm and retracting the scleral edges wide enough to decrease any potential shearing force on the medication reservoir during explantation. A 20- or 25-gauge infusion line placed prior to device removal is advisable to maintain the intraocular pressure and to prevent wound collapse, thereby allowing improved visualization of the implant. The fluid flow of a preplaced infusion line may also prevent the medication cup from falling deep into the vitreous cavity. Only 1 of 3 patients (patient 2) had a preplaced infusion line prior to device extraction in this series. Although the preplaced infusion line was unable to prevent the medication reservoir from falling into the vitreous cavity in this patient, we recommend a preplaced infusion line to maintain intraocular pressure, to improve visualization of the implant, and in anticipation of this unusual complication.

As patients with uveitis experience depletion of their medication after the 30-month drug delivery period, FA exchange procedures will likely be performed more frequently. During the preoperative visit, patients undergoing FA explantation or exchange should be counseled regarding this potential complication. The surgeon performing the procedure should be aware of this complication and have vitreoretinal personnel and instrumentation available if additional posterior segment surgery is required. However, if dissociation of the medication from its anchoring strut occurs, PPV with IOFB removal techniques may be successful in FA implant retrieval.

Corresponding Author: Christina J. Flaxel, MD, Department of Ophthalmology, Casey Eye Institute, Oregon Health Sciences University, 3375 SW Terwilliger Blvd, Portland, OR 97239 (flaxelc@ohsu.edu).

Submitted for Publication: November 19, 2008; final revision received January 14, 2009; accepted January 23, 2009.

Financial Disclosure: None reported.

Funding/Support: This work was supported by an unrestricted grant to the Casey Eye Institute from Research to Prevent Blindness.