Dissociations of the Fluocinolone Acetonide Implant: The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study

Abstract

Purpose To describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treatment (MUST) Trial. Design Randomized clinical trial with extended follow-up. Methods Review of data collected on the first implant in the eye(s) of participants. Dissociation was defined as the drug pellet no longer being affixed to the strut and categorized as spontaneous or surgically-related. Results 250 eyes (146 patients) had at least one implant placed. Median time follow-up time after implant placement was 6 years (range 0.5 to 9.2). Thirty-four dissociations were reported in 30 participants. There were 22 spontaneous events in 22 participants; 6-year cumulative risk of a spontaneous dissociation was 4.8% (95% confidence interval (CI): 2.4%–9.1%). The earliest event occurred 4.8 years after placement. Nine of 22 eyes with data had a decline in visual acuity ≥5 letters temporally related to the dissociation. 39 implant removal surgeries were performed, 33 with replacement. Twelve dissociations were noted during implant removal surgeries in 10 participants (26%, 95% CI 15%–48%); 5 of these eyes had a decline in visual acuity ≥5 letters after surgery. The time from implant placement to removal surgery was longer for the surgeries at which dissociated implants were identified than for those without one (5.7 vs 3.7 years, p < 0.001). Overall, visual acuity declined 15 or more letters from pre-implant values in 22% of affected eyes; declines were frequently associated with complications of uveitis or it’s treatment. Conclusion There is an increasing risk of dissociation of Retisert implants during follow-up, the risk is greater with removal/exchange surgeries, but both the risk of spontaneous and surgically related events increase with longevity of the implants. In 22% of affected eyes visual acuity declined by 15 letters. In the context of eyes with moderate to severe uveitis for years, this rate is not unexpected.

Intermediate Uveitis

“…Dissociation increased with duration of implantation in the MUST trial and was associated with decrease in vision in some patients [196]. Cataract is increased in all forms of intravitreal corticosteroid use.…”

Efficacy and safety of intravitreal anti‐tumour necrosis factor drugs in adults with non‐infectious uveitis – a systematic review

“…Secondly, systemic TNF blockade can cause adverse events such as serious infections (notably tuberculosis reactivation), heart failure exacerbation and demyelinating disease (Levy-Clarke et al 2014;Nanau & Neuman 2014;Cordero-Coma & Sobrin 2015). Local treatment of uveitis remains useful, namely with steroids in both adult (Kane et al 2008;Lowder et al 2011;Tempest-Roe et al 2013;Zarranz-Ventura et al 2014;Holbrook et al 2015;Kempen et al 2015a,b;Reddy et al 2016) and paediatric uveitis (Taylor et al 2012; Sella et al 2015;Tomkins-Netzer et al 2016). Thus, the possibility to administer these drugs directly into the eye may minimize systemic adverse effects of anti-TNF drugs, while achieving local therapeutic concentrations (Androudi et al 2010;Farvardin et al 2010;Markomichelakis et al 2012;Hamam et al 2014).…”

Fluocinolone Implant Forceps: Instrument Modification for Enhanced Implant Insertion

“…Dissociation occurs when the adhesive fails to bind the suture strut and the drug pellet together and dislocation occurs when the unbound drug pellet separates from the strut and migrates to a different location in the eye. The rate of spontaneous dissociation ranges from 2.6–4.8% at a mean post-implantation time of 65–77 months with a higher rate of surgically-induced dissociation of 14.2–40.7% 8,9,10,11 . Some patients with dissociated or dislocated implants suffer no visual symptoms while others experience black spots, floaters, or blurred vision.…”

“…Some patients with dissociated or dislocated implants suffer no visual symptoms while others experience black spots, floaters, or blurred vision. Eyes with these problematic implants may have a decrease in visual acuity, recurrent inflammation, or cystoid macular edema but it is nearly impossible to determine whether this is attributable to the dysfunctional implant or the underlying disease process 8,9 . Surgical removal of the dissociated or dislocated implants has resulted in complications including retinal tears 8,11,12 , retinal commotio 12 , suprachoroidal hemorrhage 11 , and corneal endothelial dysfunction and edema 12,13 .…”