Proof of Concept for Combined Insertion of Fluocinolone Acetonide and Glaucoma Drainage Implants for Eyes with Uveitis and Glaucoma

Uveitis is an important cause of visual loss in the developed world and was reported in 1990 to cause 10% of cases of blindness in the United States.^1,2 A substantial number of patients with uveitis find themselves between the “rock” of requiring high-dose or frequently-dosed corticosteroids for control of inflammation and the “hard place” of elevated intraocular pressure (IOP) resulting from this corticosteroid use and/or from the sequelae of uveitis itself. Elevated IOP has been reported to occur in 8% to 26% of patients with acute uveitis and in 11% to 46% of patients with chronic uveitis.^3,4,5,6 Glaucoma surgery usually is the solution to this conundrum, but itself is made more difficult by the uveitis—especially if the uveitis is not consistently controlled.

The fluocinolone acetonide implant (Retisert, 0.59 mg, Bausch & Lomb, Inc., Rochester, NY) has been shown to significantly reduce the uveitis recurrence rates in patients with non-infectious posterior uveitis⁷ and is being compared with systemic therapy for the treatment of posterior uveitis in the National Institutes of Health-sponsored Multicenter Uveitis Steroid Treatment Trial.⁸ A major problem of the fluocinolone implant, is the high rate of IOP elevation seen in eyes receiving the implant. In one study, 71% of eyes receiving this implant experienced a 10 mm Hg increase in IOP compared with baseline IOP, and just over half of eyes developed an IOP of 30 mm Hg or more.⁹ The Kaplan-Meier estimate of the median time from fluocinolone implant insertion to the initiation of glaucoma treatment was approximately one year for glaucoma drops and 36.6% of implanted eyes required glaucoma surgery within three years.⁹ While most eyes which experienced elevated IOP after receiving a fluocinolone implant were successfully controlled with glaucoma medications and/or glaucoma surgery, the impact on a patient’s vision of this IOP elevation and its duration prior to successful lowering may well be negative in some cases. The high rate of IOP elevation and the extent of IOP rise often observed also has led some to believe such implants are contraindicated in uveitic eyes with pre-existing elevated IOP or glaucomatous optic neuropathy, particularly optic nerves at risk of being “snuffed” by a large IOP spike.

In this issue of the American Journal of Ophthalmology, Malone and colleagues report results of combined fluocinolone implant insertion and glaucoma drainage implant insertion in eyes with non-infectious posterior or intermediate uveitis which required maximum medical therapy to achieve acceptable IOP levels or had elevated IOP despite maximum medical therapy.¹⁰ This is a group of patients who would be considered high-risk for post-operative IOP elevation with fluocinolone implant insertion alone. In the study, seven eyes underwent insertion of a fluocinolone implant and an Ahmed glaucoma drainage implant (New World Medical, Inc., Rancho Cucamonga, CA). Similar to observations in previous studies of fluocinolone implants, recurrence of inflammation was significantly reduced, visual acuity improved, and the need for systemic therapy for control of uveitis was reduced in the patients. In addition, the mean IOP decreased from 27.3 mm Hg at baseline to 14.6, 16.4, 16.1, 12.8, and 14.6 mm Hg at one, three, six, nine, and 12 months after surgery, respectively.

The observation that both IOP and uveitis control were achieved early and sustained for nearly three years using combined surgery suggests that insertion of a fluocinolone implant might not always be contraindicated in eyes with uncontrolled IOP or advanced glaucomatous optic neuropathy, if this combined approach can be used. In addition, these results suggest that the presence of the glaucoma drainage implant might not negatively impact the anti-inflammatory effects of the fluocinolone acetonide implant, e.g. by increasing the clearance of the corticosteroid medication from the eye via the tube.

While the combined surgery approach was uniformly effective in a small number of cases, these observations are not sufficient to prove that combined surgery should be routinely performed in these patients. As acknowledged by the authors, a small study easily could have missed important findings (e.g., the upper bound of a 97.5% one-sided exact binomial confidence interval on the observation of 0 vision-threatening complications in seven observations is 41.5%). Complications also may arise with longer-term follow-up, e.g., if replacement of fluocinolone acetonide implants is needed repeatedly. Nevertheless, these findings are in accord with the known effectiveness of fluocinolone acetonide implant therapy for uveitis and of glaucoma drainage devices for control of intraocular pressure, and thus demonstrate an important “proof of concept” that we hope will encourage larger studies into the use of combined surgery in this high-risk population. Combined fluocinolone acetonide implant and glaucoma surgery seems a promising approach for the eye in which sequential surgery carries substantial risks from either intraocular pressure spikes or severe uveitis exacerbations.