Article Date: 3/1/2008

Reimplanting the Fluocinolone Acetonide Sustained Drug-delivery System

Reimplanting the Fluocinolone Acetonide Sustained Drug-delivery System

GLENN JAFFE, MD

Chronic noninfectious posterior uveitis primarily strikes people between the ages of 20 and 50, causing years of vision loss for the individual and eventually leaving about 22% of those afflicted with the disease legally blind in at least 1 eye. Approximately 46% of patients diagnosed with posterior uveitis experience severe visual impairment.1

The drug-delivery system fluocinolone acetonide intravitreal implant 0.59 mg (Retisert, Bausch & Lomb) is the only FDA-approved drug for treatment of noninfectious uveitis affecting the posterior segment. With depletion of fluocinolone acetonide from the implant as evidenced by recurrence of uveitis, the fluocinolone acetonide sustained drug-delivery implant may be replaced.

In this article I will describe when, where, and how to re-implant the drug delivery system.

CONSIDERATIONS PRIOR TO REIMPLANTATION

I insert a fluocinolone acetonide sustained drug-delivery implant with the thought that I am not going to remove it unless the patient has recurrent uveitis for which a new implant would be indicated. Patients who have their first uveitis recurrence after the original implant is inserted have had the implant an average of 3 years (Jaffe GJ, Reimplantation of a Fluocinolone Acetonide Sustained Drug Delivery Implant for Chronic Uveitis. Am J Ophthalmol. 2008 Jan 26; [Epub ahead of print]).

When a patient with an acetonide intravitreal implant develops recurrent inflammation, my immediate goal is to get the acute episode of inflammation under control. I then discuss with the patient whether to continue with medical therapy, or whether to replace the fluocinolone implant. The decision depends on a variety of factors, including the patient's preference, the duration of response to treatment of the recurrent inflammation, the patient's tolerance to medical therapy, and others.

Dr. Jaffe is tenured professor of ophthalmology and a member of the vitreoretinal faculty at Duke University Eye Center. He founded and directs the Optical Coherence Tomography Reading Center at Duke and is the director of the Uveitis Service. He has served as a consultant for SurModics, Merck and Neurotech, and has been on the Advisory Board of Lux Biosciences. He has received research support from B&L in the past.

Figure. Insertion of a fluocinolone acetonide sustained drug-delivery implant.

If a decision is made to replace the implant, I like to achieve a quiet anterior chamber; I don't like to insert an implant if the patient has an inflamed anterior chamber because I worry about postoperative hypotony. Hypotony increases the chance of complications if anterior segment is inflamed to begin with. It doesn't make much difference if there is active posterior segment inflammation, as this doesn't seem to significantly to affect the postoperative course or the outcome. To achieve a quiet anterior chamber prior to inserting a new fluocinolone implant, it may be necessary to administer topical corticosteroid drops frequently, to give a periocular steroid injection, and even to give an intravitreal steroid injection.

It is useful to make an effort to quiet the eye at the first recurrence of inflammation following insertion of the original implant to help determine whether reimplantation is necessary. Some of my patients have been given anti-inflammatory treatment after the first recurrence of uveitis and have had another recurrence soon after the treatment is tapered, in which case I would be more inclined to replace the original implant.

On the other hand, in some cases, it has been possible to control a patient's inflammation with lower doses of medications than what was required in the very beginning, prior to the original implant. It is almost as if the disease is burning itself out or becoming less severe over time, or that the first implant modified the disease and has made the condition easier to control. In these cases, one may opt to continue medical therapy on an ongoing basis and not replace the implant. Finally, some patients have not required ongoing therapy following the initial treatment of recurrent inflammation. Accordingly, these patients have not needed a new implant or chronic medical uveitis therapy.

REIMPLANTATION TECHNIQUE: CHOOSING A SITE

The surgeon has 2 options: remove the original implant and replace it with the new implant, or place the second implant at a separate surgical site and leave the first implant in place. In the days before antiretroviral therapy, when we inserted ganciclovir implants frequently for patients with cytomegalovirus retinitis, it was common to place a second one at a separate site and leave the first one in place when retinitis recurred. If the retinitis reactivated after the second implant was depleted, a third one might be placed in a separate location, or 1 of the first implants could be replaced.

In contrast, with patients who have noninfectious uveitis, I'm reluctant to make multiple incisions in the sclera because as more and more incisions are made, the chance for hypotony is increased. Rather, assuming that the sclera and conjunctiva are healthy at the original implant site, I prefer to remove the original implant and place the second implant through the original scleral incision. However, if there is scarring over the area of the original implant, or the overlying conjunctiva is thin, I will move to a second site.

SURGICAL TECHNIQUE

If the implant is to be placed at a second site and the patient has not had a previous vitrectomy, you may not need an infusion line. However, if the patient has had a previous vitrectomy or if you're replacing the implant at the original site, I feel strongly that an infusion line should be placed at the beginning of the procedure. In eyes with recent inflammation, and low intraocular pressure following the scleral incision, without an infusion line, there is a higher chance for intraocular bleeding, which may be difficult to control. When the infusion is running, it creates positive pressure inside the eye. This positive pressure will prevent ingress of blood into the vitreous cavity at the scleral incision site. In addition, the infusion will serve to facilitate removal of the original implant, which is pushed into the scleral incision by the positive pressure. Without the positive pressure, if the globe is collapsing and there is nothing to push the implant out of the eye, the implant could fall into the vitreous cavity when the anchoring suture on the original implant is cut.

"Typically, the original fluocinolone implant exerts its anti-inflammatory effect for approximately 3 years."

I place the infusion line on the side opposite the implant site because if the infusion line is on the side where you are performing manipulations for the implant, it gets in the way. For example, if the implant site is inferotemporal, I will place the infusion line inferonasally.

BEGINNING STEPS

After I have inspected the conjunctiva and sclera, I carefully examine the retina and pars plana region with an indirect ophthalmoscope and scleral depression to identify any pathology that would influence my choice of implant site. In patients with intermediate uveitis, a common type of pathology is snowbanking, a combination of inflammation and scar material. You do not want to insert an implant through the snowbank because sometimes the retina will be tractionally elevated in that area and you could convert the traction retinal detachment to a rhegmatogenous retinal detachment. If a snowbank is present, I choose an area well away from this region to avoid causing a rhegmatogenous retinal detachment.

If I have decided to replace the implant at the original site, I perform a peritomy, and elevate the conjunctiva over the implant. I then gently dissect any tissue that's over the previous incision and make an incision on either side of the original implant's anchoring suture with a micro-vitreoretinal blade. Next, I open the sclera right over the original implant, cut the anchoring suture, and identify the suture strut on the implant (the suture strut is secured to the sclera with an 8-0 polypropylene anchoring suture). Remember to keep the infusion going while you remove the implant.

Usually the scleral incision ends up being a little bit bigger than the wound that was made to insert the original implant. It is critical that the incision length is adequate – you need to have enough room to maneuver so that you can easily remove the implant without the pellet getting hung up on the edge of the wound. If you're pulling on the strut and the pellet is hung up inside the wound, you can strip the pellet right off the suture strut, making it harder to retrieve the pellet.

SUTURES FOR THE NEW IMPLANT

My suture technique for the replacement implant is identical to that used for the original implant: I use 8-0 polypropylene for the anchoring suture because I like to have as much bulk to the suture as possible to avoid suture degradation. Unlike ganciclovir implants, fluocinolone implants do not usually develop a capsule surrounding the suture strut. So if the suture were to dissolve, it's very possible that the implant would just fall into the eye. In fact, we've now gone to using prolene suture for ganciclovir implants because we have observed that some ganciclovir implants are spontaneously dislocating 3 years after the original implant surgery. I've now replaced quite a few fluocinolone implants and was interested to see how the sutures have held up over the 3-year period, as a nylon suture would have almost dissolved. The prolene has held up extremely well, and there has not been any appreciable degradation.

The replacement implant is prepared by passing the double-armed 8-0 polypropylene suture through the suture strut. A single throw is placed over the suture strut, the new implant is inserted into the scleral incision, full-thickness scleral bites are taken on either side of the wound, and the anchoring suture is then tied tightly. Interrupted 9-0 polypropylene sutures are passed on either side of the anchoring suture (usually 2 or 3 on either side of the anchoring suture), and the sutures are tied over the tails of the anchoring suture. I clamp the infusion line as I tie down each of the interrupted sutures. The infusion is begun (although I usually restart it as I pass each interrupted suture. The interrupted sutures are then rotated to bury the knots. I use 9-0 polypropylene suture rather than 8-0 polypropylene, because the 9-0 sutures rotate much more easily than the 8-0 sutures. I close the wound tightly, and if the patient has had a vitrectomy, it's critical that the wound be closed very carefully because there's no vitreous on the inside to plug the wound. Having the infusion going will allow you tell whether there's any leakage from the wound. Then, I look inside the eye to make sure that the implant is where it's supposed to be and that there are no complications such as suprachoroidal implantation, vitreous hemorrhage, or retinal detachment. I trim the tails on the anchoring suture so that they lie flat on the sclera, because if the ends are sticking up they will protrude through the conjunctiva and can become a site of infection.

I like to put a pre-placed suture around the infusion cannula to make it easy at the end of the case. After I've closed everything up over the implant, I can take the infusion line out as I'm tying down the pre-placed suture. That way, the eye never gets soft.

I then close the conjunctiva with buried interrupted plain gut sutures. I usually give a subconjunctival antibiotic such as cefazolin for infectious prophylaxis, and a short-acting subconjunctival steroid, usually Decadron (Merck & Co., Inc.).

Save the old implants after removing them. You can send them to Bausch & Lomb and they'll measure the amount of drug that is remaining in the pellet. If the implant still has drug in it and the patient is having recurrences, for whatever reason, you know the steroid isn't enough to control the inflammation at that point.

CONCLUSION

Typically, the original fluocinolone implant exerts its anti-inflammatory effect for approximately 3 years. When the original fluocinolone acetonide implant is depleted of drug, if inflammation recurs, replacement of the original implant can be considered. With careful attention to surgical technique, implant replacement is feasible. To date, results with the replacement implant have been similar to the original implant; inflammation is controlled, visual acuity is maintained and ancillary anti-inflammatory medications can be decreased. Further experience with this approach, and longer follow-up duration will help to better define the outcomes with reimplantation. RP

REFERENCE

  1. Hudson, H. Retisert: A step forward in treating chronic noninfectious posterior uveitis. Retinal Physician. 2005;2(4):22-24.


Retinal Physician, Issue: March 2008