Intravitreal Triamcinolone for Refractory Diabetic Macular Edema
Two-Year Results of a Double-Masked, Placebo-Controlled, Randomized Clinical Trial

Gillies M, Sutter F, Simpson J, Larsson J, Ali H, Zhu M. Ophthalmology. 2006;113:1533-1538.

Diabetic macular edema (DME) is with a manifestation of diabetic retinopathy (DR), for which laser treatment of sight-threatening disease is the standard therapeutic method. However, previous studies have described laser treatment as being a destructive procedure as well as being ineffective in restoring previously deteriorated vision. Recent studies have demonstrated increased inflammation in the pathogenesis of DR, possibly actuated by elevated levels of vascular endothelial growth factor (VEGF). The use of anti-VEGF treatments, such as intravitreally injected steroids, has yielded promising results in eyes with impaired vision caused by DME. This study describes the 2-year results of a double-masked, placebo-controlled, randomized clinical trial in which intravitreal triamcinolone acetonide (TA) injections were administered and subjects were monitored for vision improvement.

Patients recruited from the retina clinics of Sydney Eye Hospital were randomized to receive either intravitreal TA or placebo. Inclusion criteria consisted of severe diffuse or focal DME ≥3 months after at least 1 session of laser treatment, and best-corrected visual acuity (BCVA) in the affected eye(s) of 20/30 or worse. Exclusion criteria were uncontrolled glaucoma, loss of vision due to other causes, systemic treatment with >6 mg prednisolone daily, intercurrent severe systemic disease, or any condition affecting follow-up or documentation. Using these criteria, 34 eyes were allocated to the intravitreal TA treatment group and 35 eyes were allocated to placebo. For patients with both eyes eligible for entry, the assigned treatment was administered to the right eye while the other treatment was given to the left eye.

The primary outcome measures as determined by the Early Treatment Diabetic Retinopathy Study (ETDRS) charts were the percentage of eyes in which the best corrected logMAR score improved by the equivalent of ≥5 letters and the percentage of eyes with moderate or severe adverse events. Secondary outcome measures were any changes in visual acuity (VA) from baseline and in macular thickness as determined by optical coherence tomography (OCT). A significant elevation in intraocular pressure (IOP), as measured through tonometry, was defined as an increase of >5 mm Hg compared to baseline. Additionally, a ≥2-step increase in Age Related Eye Disease Study Grades demonstrated significant cataract progression. The degree of DME at the fovea was determined at baseline using contact lens biomicroscopy and was defined as absent, mild, moderate, or severe. Intravitreal TA (0.1 mL of 40 mg/mL TA) was administered at the time baseline VA measurements were collected. Vision loss of ≥5 letters from the previous peak value and persistent central macular thickness >250 µm received retreatment with study medication. Moreover, fluorescein angiography was performed if VA did not improve by ≥5 letters and excessive macular thickness persisted within 4 weeks.

Two-year data were available for 31 eyes in the intravitreal TA group and 29 eyes in the placebo group. Eyes treated with intravitreal TA received more treatments with the study medication compared to placebo, leading to a greater risk of requiring glaucoma medication (44%) and cataract surgery (54%); however, these eyes were significantly less likely to require further macular laser treatment (1 intravitreal TA vs 16 placebo). Twice as many eyes treated with intravitreal TA (56%) improved ≥5 letters BCVA than eyes treated with placebo (26%). Additionally, only 18% of the treated eyes lost ≥5 letters compared to 37% of eyes receiving placebo. Mean improvement was 5.7 letters more in treated eyes than in untreated eyes, with a correlation of 4.6 between the paired eyes. Sensitivity analysis, performed on the primary outcomes, was robust to missing treatment data. At 2 years, foveal thickness measured by OCT decreased by 59 µm more in treated eyes than in untreated eyes. Some adverse events included an increase in IOP ≥5 mm Hg, cataract progression by ≥2 grades, endophthalmitis, and corneal decompensation. Eyes that received intravitreal injections did not incur any lens damage or retinal detachment.

This study shows the potential efficacy of using an anti-VEGF agent, intravitreal TA, for reducing macular thickening and improving vision. The use of a 5-letter improvement criterion rather than the conventional 10-letter improvement requirement allowed the inclusion of patients with less advanced disease. The study medication demonstrated a significant effect on both further deterioration and vision improvement. Moreover, a notable number of placebo-treated eyes showed unexpected improvement, which suggests that there is a continued need for patient education and disease control.