deteriorated to no light perception vision and 1 patient required enucleation.56,57

Noninfectious (sterile) endophthalmitis following intravitreal triamcinolone acetonide injection has been described in several studies. This sterile inflammatory reaction could be secondary to a component of the drug formulation or to bacterial toxins that could be present even in sterile solutions.44 Additionally, the triamcinolone acetonide crystals themselves may migrate into the anterior chamber, creating a picture of pseudoendophthalmitis.

Cataract

Intravitreal triamcinolone acetonide has been associated with posterior subcapsular cataract formation. A study by Gillies et al.58 has demonstrated that steroid-related cataracts are more likely to form in patients who are steroid responders. These authors reported a strong association between the mechanism responsible for the development of steroidinduced posterior subcapsular cataract and raised IOP.

Thompson studied by linear regression analysis lens scores from lens opacity standards in evaluating 93 eyes with intravitreal injection of 4 mg triamcinolone acetonide. Lens opacities were graded using the Lens Opacity Classification System II (LOCS II) scale. Thompson found that nuclear sclerosis increased at a rate of 0.175 U/year, posterior subcapsular cataracts at 0.423 U/year, and cortical cataracts at 0.045 U/year.59

Retinal detachment

Although traumatic retinal holes with resultant detachment are theoretical risks associated with intravitreal injection, no case reports could be found in the peer-reviewed literature. The risk of retinal tears and retinal detachment associated with intravitreal injection of steroids has not been shown to be common.

FUTURE CONSIDERATIONS AND ONGOING STUDIES

THE SCORE STUDY

The SCORE study is a multicenter, randomized, phase III trial to compare the effectiveness and safety of standard care versus triamcinolone acetonide injection for the treatment of macular edema associated with CRVO and BRVO. Standard care is defined as observation of macular edema in CRVO and for BRVO immediate observation of eye with dense macular hemorrhage and then grid photocoagulation when clearing of hemorrhage permits or immediate grid photocoagulation in eyes without dense macular hemorrhage.

The primary outcome is improvement by 15 or more letters from baseline in best corrected ETDRS visual acuity score at the 12-month visit. Secondary outcomes include changes from baseline in best corrected ETDRS visual acuity score, changes in retinal thickness as assessed by stereoscopic color fundus photography and OCT, and adverse ocular outcomes. The SCORE study has completed its subject recruitment and is expected to report results when all patients have completed primary endpoints.

STEROID-SUSTAINED RELEASE DEVICES

The STRIDE study

The prospective, randomized, double-masked Sustained Triamcinolone Release for Inhibition of Diabetic Macular Edema (STRIDE) trial is assessing the safety and tolerability of the I-vation triamcinolone acetonide (SurModics, Irvine, CA) in 30 patients. In the study, patients are randomized to either a slow-release or fast-release implant, each con-

taining 925 g triamcinolone. They also were stratified by baseline visual acuity and by presence or absence of prior laser treatment.

From screening to 6 months, the proportion of patients with visual acuity of at least 70 ETDRS letters (in the study eye) increased from 14% to 46% in the slow group and from 18% to 41% in the fast group. A gain of more than 15 letters occurred in 8% of patients in the slow group and 18% in the fast group. Both implant formulations were associated with improvements in macular thickness. Further studies with I-vation triamcinolone acetonide have been suspended as the roles of triamcinolone are being evaluated by the sponsors.

FLUOCINOLONE ACETONIDE DEVICE

In 2005, the Food and Drug Administration approved a fluocinolone acetonide-containing intraocular implant (Retisert, Bausch & Lomb, Rochester, NY) for the treatment of chronic noninfectious uveitis, affecting the posterior segment of the eye. The Retisert is implanted into the eye via a surgical procedure entailing a 3.5-mm circumferential incision through the pars plana and the implant is sutured to the eye wall.

The fluocinolone implant investigated in the uveitis study has also been studied in a multicenter, randomized, controlled clinical trial for the treatment of diabetic macular edema. Patients in the study were randomized 2 : 1 to receive either a 0.59-mg fluocinolone implant or standard of care, defined as repeat laser treatment or observation.

Pearson and colleagues reported that, at 36 months, the implant resolved edema at the center of the macula and produced a 3-line or more improvement in visual acuity in a significant proportion of eyes studied (n = 197).60 At 36 months, no evidence of edema was present in 58% of implanted eyes compared with 30% of eyes that received the standard of care (P < 0.001). Visual acuity improvements of 3 lines or more occurred more frequently in implanted eyes (28% versus 15%, P < 0.05).

The most common serious adverse events in the implanted eyes were cataract development, requiring extraction, and increase in IOP. Ninetyfive percent of phakic implanted eyes required cataract surgery, and 35% of implanted eyes experienced increased IOP. A filtering procedure was necessary in 28% of implanted eyes, and explantation was performed in 5% of eyes to manage IOP.

NEW-GENERATION FLUOCINOLONE DEVICE

A second fluocinolone acetonide sustained-delivery device has been developed. The injectable Medidur/Iluvien FA (Alimera Sciences Inc., Alpharetta, Ga./pSivida, Watertown, MA) does not require sutures and can be inserted in a physician’s office (Figure 30.5).

Enrollment in the phase III Fluocinolone Acetonide in diabetic Macular Edema (FAME) trial, which is evaluating a daily dose of 0.2 g

Medidur Retisert Vitrasert

Figure 30.5  Comparative sizes of Medidur, Retisert, and Vitrasert.

Diseases Retinal in Mechanisms and Drugs • 4 section