MIGRATION OF INTRAVITREAL DEXAMETHASONE IMPLANT TO ANTERIOR CHAMBER Vamsi K. Gullapalli, MD, PhD, David A. DiLoreto, MD, PhD
Purpose: To describe two cases of migration of intravitreally injected dexamethasone implant into the anterior chamber. Methods: Charts were reviewed of two patients who received sustained-release dexamethasone implant intravitreally for chronic intractable cystoid macular edema. Results: Both patients had pseudophakic cystoid macular edema and a complicated clinical course before receiving the implant. Treatments before intravitreal injection of implant included topical nonsteroidal anti-inﬂammatory drugs, sub-Tenon triamcinolone injections, vitrectomy, and, in one case, intravitreal bevacizumab. Both patients responded well to triamcinolone injections but required repeated injections. This led to the decision to inject the implant. Within 2 weeks of injection, the implant was noted in the anterior chamber causing pain and decreased vision from corneal edema. Both patients underwent successful removal of the implant. Conclusion: Sustained-release intravitreal injectable implants can migrate freely in vitrectomized pseudophakic or aphakic eyes. Selection of a scleral-ﬁxated steroid implant might be safer in such cases. RETINAL CASES & BRIEF REPORTS 7:111–113, 2013
edema after retinal vein occlusions.4 This implant potentially provides a better alternative to repeated intravitreal injections of triamcinolone in refractory CME. However, the use of steroid implant is not without complications. In addition to the steroid-induced glaucoma and injection-related complications like cataract formation and endophthalmitis, we present two patients in whom the implant migrated to the anterior chamber (AC) and caused corneal decompensation.
From the Flaum Eye Institute, Retina Service, University of Rochester School of Medicine and Dentistry, Rochester, New York.
ostsurgical cystoid macular edema (CME) occurs in 1% to 2% of patients after cataract extraction, especially if the surgery was complicated; it is also seen after other intraocular surgeries.1 It is generally self-limiting, but persistent CME is treated with topical nonsteroidal anti-inﬂammatory agents, sub-Tenon, or intravitreal injection of steroids; in refractory cases, vitrectomy has been attempted to relieve any vitreomacular traction that may be contributing to the macular edema.1,2 Some cases of refractory CME may require multiple injections of intravitreal steroids if the retinal edema returns or if vision worsens.3 A sustained-release biodegradable intravitreal dexamethasone implant has been recently approved by the Food and Drug Administration for the treatment of macular
Case Reports Case 1 A 73-year-old woman underwent extracapsular phacoemulsiﬁcation cataract extraction 7 years ago in her left eye that was complicated by a posterior capsular tear. A sulcus intraocular lens (IOL) was placed at the end of the case. She had persistent postoperative inﬂammation and poor vision at 20/150 at 2 weeks of follow-up. Examination showed large retained lens fragment superior and posterior to a well-centered IOL, with cells in anterior vitreous and CME. One month after the cataract surgery, she underwent 20-gauge pars plana vitrectomy and lensectomy to remove retained lens fragments, and intravitreal triamcinolone. She was also treated with topical ketorolac sodium. Vision improved to 20/50 at 3 months
The authors have no conﬂicts of interest to disclose. Reprint requests: David A. DiLoreto, MD, PhD, Flaum Eye Institute, Retina Service, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 659, Rochester, NY 14642; e-mail: [email protected]
RETINAL CASES & BRIEF REPORTS´ 2013 VOLUME 7 NUMBER 1
postvitrectomy, but recurrent CME reduced vision to 20/70 after 2 months. She responded well to sub-Tenon or intravitreal triamcinolone injections every 4 to 6 weeks. Because of persistent edema and elevated intraocular pressures, a 25-gauge pars plana vitrectomy, epiretinal membrane peel, and an inner limiting membrane peel were performed 3 years after the pars plana lensectomy. Persistent inﬂammation and keratic precipitates with a negative uveitis workup prompted a vitrectomy and IOL exchange with an AC IOL. Anaerobic culture of the lens capsule was positive for Propionibacterium acnes. Vision improved to 20/150, but CME recurred and persisted. Grayish deposits were noted on the AC IOL, raising the possibility of recurrent P acnes infection; in addition, the haptic was lying in a fold of iris rather than in the angle. This prompted the removal of AC IOL, and the patient was left aphakic. Intravitreal vancomycin and ceftazidime were given at the end of the case. Cultures were negative for P acnes. She had persistent mild AC inﬂammation but no change in diffuse CME. Since she had responded well to intravitreal steroids in the past, a sustained-release dexamethasone implant (Ozurdex; Allergan, Irvine, CA) was injected into the left eye in the ofﬁce. At the time of injection, her vision was 2/200. Ten days later, the patient came back complaining of pain in the left eye and seeing a line ﬂoating across the visual ﬁeld. Vision was down to count ﬁngers at 1 foot. She had microcystic edema, Descemet membrane folds, and dexamethasone implant in the AC inferiorly (Figure 1). An attempt was made to displace the implant back into the vitreous cavity in the operating room under sterile conditions after retrobulbar block. On the table, the implant was noted to have displaced to the
12-o’clock position. A paracentesis was made at the 4 o’clock position, and the AC was ﬁlled with viscoelastic. Using a Sinskey hook, the implant was displaced into the vitreous cavity through the pupil. Miochol was injected into the AC after washing out the viscoelastic. The patient was instructed to lie ﬂat till the follow-up the next day. On postoperative Day 1, vision was hand motions; corneal stromal edema and Descemet membrane folds were noted. The patient was treated with pilocarpine 1% three times a day along with polymyxin/trimethoprim eye drops and topical prednisolone acetate at the same frequency. The patient returned for follow-up 1 week later and was noted to have the implant in the AC again. Vision remained the same at count ﬁngers at 1 foot. The patient was taken back to the operating room and, under sterile conditions, a paracentesis was created at the 9 o’clock position, and the AC was injected with viscoelastic. A clear corneal incision was then created at the 2 o’clock position using a 2.6-mm keratome blade and enlarged to 3 mm. A lens glide was inserted across the pupil, and using a blunt tip cannula on a syringe containing viscoelastic, the implant was maneuvered onto the glide. While injecting balanced salt solution through the paracentesis, the glide was gently pulled out with the viscoelastic carrying the implant through the corneal wound. The implant came out in piecemeal. The corneal wound was closed with 10-0 nylon suture and the eye patched after placing neomycin/ polymyxin B/dexamethasone ointment. During the postoperative period, the patient continued to have CME and corneal edema. Postoperative Month 5, the patient had some improvement of vision with count ﬁngers at 6 feet. The patient was offered a corneal transplant and is considering it at the time of this report.
Fig. 1. A. Slit-lamp photograph showing the implant in the anterior chamber inferiorly. The patient has corneal stromal edema and Descemet membrane folds. B. Higher magniﬁcation showing corneal microcystic edema and the implant inferiorly in the anterior chamber.
A 69-year-old woman was referred to the Retina Service for management of persistent pseudophakic CME in her right eye. The cataract extraction was uneventful but was noted to have peaked pupil and vitreous in the AC on postoperative Day 1. By postoperative Month 1, her IOL was tilted with one of the haptics perforating the posterior capsule and lying in the vitreous cavity. Her vision at that time was 20/50. She also had persistent AC inﬂammation and pain. She successfully underwent an IOL exchange with placement of AC IOL. A month after the IOL exchange, the patient had a vision of 20/80 with CME and an epiretinal membrane. Five months after IOL exchange, her vision dropped to 20/150 from CME despite topical ketorolac. A subTenon triamcinolone injection and an intravitreal injection of triamcinolone 3 months later did not resolve the edema but caused her intraocular pressure to increase to 46 mmHg. She underwent pars plana vitrectomy and membrane peel. The membrane was taut. Only 180° of the membrane around the fovea was successfully peeled. Postoperatively, her vision ﬂuctuated between 20/80 and 20/200 with persistent macular edema, responding to intravitreal injections of triamcinolone. She received a total of 8 intravitreal injections over 5 years. In the interim, her intraocular pressure remained high despite topical medications. An Ahmed tube shunt was placed, which reduced the pressure to normal limits. Since she responded well to intravitreal injections, a sustained-release dexamethasone implant (Ozurdex; Allergan) was placed in the right eye. Her vision at that time was 20/200 with signiﬁcant macular edema. Two weeks later, she returned with vision loss to count ﬁngers. The implant was noted in the AC (Figure 2) with severe corneal edema. The implant was successfully removed the same day using the same technique described with the previous case. Since then, her vision has remained at hand motion with bullous keratopathy. She underwent a penetrating keratoplasty at the time of this report.
MIGRATION OF DEXAMETHASONE IMPLANT
Fig. 2. Slit-lamp photograph of Case 2 showing corneal edema, AC IOL. The implant can be seen inferiorly in the anterior chamber in front of the AC IOL.
Discussion Cystoid macular edema is an important cause for suboptimal vision after cataract surgery. The incidence of CME is around 1% to 2%.5 Intravitreal implants are very useful and convenient in cases of CME that are responsive to steroid but require re-injections. There are currently at least four different corticosteroid-based implants: injectable and biodegradable dexamethasone implant (Ozurdex), helical triamcinolone acetonide implant (I-vation, Surmodics, Eden Prairie, MN), ﬂuocinolone acetonide (Retisert, Bausch & Lomb, Rochester, NY), and injectable ﬂuocinolone acetonide (Medidur, Alimera Sciences, Alpharetta, GA/pSivida, Watertown, MA). Only the ﬁrst implant has been approved by the Food and Drug Administration for use in macular edema resulting from vein occlusions. This implant contains 0.7 mg of dexamethasone in a poly (D,L-lactide-co-glycolide) (PLGA) intravitreal polymer matrix. Intravitreal injection of the implant as an ofﬁce procedure offers the advantage of giving a smaller dose of steroid in a sustained delivery closer to the retina. Potential complications of steroid use include cataract formation and glaucoma despite the use of smaller amounts of steroid. There is also a small risk of endophthalmitis from the intravitreal injection. In the clinical trials conducted using the dexamethasone implant, adverse effects like eye pain, vitreous ﬂoaters, vitreous hemorrhage, elevated intraocular pressure, AC cell and ﬂare, and cataract were reported. Migration of the implant was not noted.6,7 In fact, patients with history of vitrectomy were excluded from the study. In both the cases presented in this report, all other treatment options had been attempted before use of
intravitreal implant. Both patients responded well to steroids and were good candidates for a sustainedrelease intravitreal implants. Because of the quick migration of the implant into the AC and subsequent corneal decompensation within 2 weeks of injection, it could not be determined if the implant was effective in reducing CME. Both the eyes implanted were previously vitrectomized, which may have facilitated the migration of the implant. The presence of AC IOL did not prevent the migration of the implant in the second case; the implant was noted to be in front of the IOL in the AC. No other cases have been reported with similar migration of the implant in nonvitrectomized eyes. It is not known if a highly syneretic vitreous would lead to the same problem. Injectable implants are, by design, small linear structures consisting of the drug and the matrix. These are more prone to migration since they are free ﬂoating in the vitreous. Implants that are secured to the sclera (Retisert or I-vation) are unlikely to have this issue, although they are associated with a different set of issues like surgical implantation, cost, and breakage. In conclusion, sustained-release intravitreal injectable implants can migrate freely in aphakic or pseudophakic eyes that have undergone vitrectomy. Proper choice of the case and the appropriate implant (injectable vs. scleral ﬁxated) are important for a successful outcome. Key words: intravitreal triamcinolone implant, macular edema, migration of implant. References 1. Ray S, D’Amico DJ. Pseudophakic cystoid macular edema. Semin Ophthalmol 2002;17:167–180. 2. Pendergast SD, Margherio RR, Williams GA, et al. Vitrectomy for chronic pseudophakic cystoid macular edema. Am J Ophthalmol 1999;128:317–323. 3. Boscia F, Furino C, Dammacco R, et al. Intravitreal triamcinolone acetonide in refractory pseudophakic cystoid macular edema: functional and anatomic results. Eur J Ophthalmol 2005;15:89–95. 4. Haller JA, Bandello F, Belfort R Jr, et al. Randomized, shamcontrolled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010;117:1134–1146,.e1133. 5. Rotsos TG, Moschos MM. Cystoid macular edema. Clin Ophthalmol 2008;2:919–930. 6. Kuppermann BD, Blumenkranz MS, Haller JA, et al. Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol 2007;125:309–317. 7. Williams GA, Haller JA, Kuppermann BD, et al. Dexamethasone posterior-segment drug delivery system in the treatment of macular edema resulting from uveitis or Irvine-Gass syndrome. Am J Ophthalmol 2008;147:1048–1054,.e2.