Elsevier

Ophthalmology

Volume 113, Issue 9, September 2006, Pages 1533-1538
Ophthalmology

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

Presented in part at: Association for Research in Vision and Ophthalmology meeting, May 2005, Fort Lauderdale, Florida.
https://doi.org/10.1016/j.ophtha.2006.02.065Get rights and content

Objective

To report 2-year safety and efficacy outcomes from a trial of intravitreal triamcinolone acetonide (TA) injections (4 mg) in eyes with diabetic macular edema and impaired vision that persisted or recurred after laser treatment.

Design

Prospective, double-masked, placebo-controlled, randomized clinical trial.

Participants and Controls

Sixty-nine eyes of 43 patients were entered into the study, with 34 eyes randomized to receive active treatment and 35 placebo. Two-year data were available for 60 of 69 (87%) eyes of 35 of 41 (85%) patients; 9 eyes of 6 patients were lost to follow-up, of which 6 received a placebo and 3 received intravitreal TA.

Intervention

Triamcinolone acetonide (0.1 ml) was injected through the pars plana using a 27-gauge needle. Eyes randomized to placebo received a subconjunctival injection of saline.

Main Outcome Measures

Improvement of best-corrected logarithm of the minimum angle of resolution visual acuity (VA) by ≥5 letters after 2 years and incidence of moderate or severe adverse events.

Results

Improvement of ≥5 letters’ best-corrected VA was found in 19 of 34 (56%) eyes treated with intravitreal TA, compared with 9 of 35 (26%) eyes treated with the placebo (zgeneralized estimating equation = 2.73, P = 0.006). The mean improvement in VA was 5.7 letters (95% confidence interval, 1.4–9.9) more in the intravitreal TA–treated eyes than in those treated with the placebo. An increase of intraocular pressure (IOP) of ≥5 mmHg was observed in 23 of 34 (68%) treated versus 3 of 30 (10%) untreated eyes (P<0.0001). Glaucoma medication was required in 15 of 34 (44%) treated versus 1 of 30 (3%) untreated eyes (P = 0.0002). Cataract surgery was performed in 15 of 28 (54%) treated versus 0 of 21 (0%) untreated eyes (P<0.0001). Two eyes in the intravitreal TA–treated group required trabeculectomy. There was one case of infectious endophthalmitis in the treatment group.

Conclusion

Intravitreal TA improves vision and reduces macular thickness in eyes with refractory diabetic macular edema. This beneficial effect persists for up to 2 years with repeated treatment. Progression of cataract and elevation of IOP commonly occur but appear manageable. Spontaneous improvement over years can still occur in eyes that are apparently severely affected by diabetic macular edema.

Section snippets

Patient Enrollment

This study was conducted in accordance with the Declaration of Helsinki and was approved by the South Eastern Sydney Area Health Service and University of Sydney research ethics committees. Safety data were reviewed by an independent safety-monitoring committee. Patients were recruited from the retina clinics of Sydney Eye Hospital, a major public tertiary referral center, from March 2002 to April 2003. Patients with severe (involving the central fovea11) diabetic macular edema, diffuse or

Results

A total of 69 eyes from 41 patients were included in the trial, of which 34 eyes were randomized to receive intravitreal TA and 35 to a placebo. Figure 1 shows the flow of patients through the study. Two-year data were available for 60 of 69 (87%) eyes of 35 of 41 (85%) patients; 9 eyes of 6 patients were lost to follow-up, of which 6 received the placebo and 3 received intravitreal TA. For the 27 patients with both eyes receiving different treatments, the average age was 64 years, and 13 (48%)

Discussion

This study demonstrates for the first time that treatment with intravitreal TA reduces thickening and improves vision for up to 2 years in eyes with advanced diabetic macular edema. Previous short-term uncontrolled studies could not address the possibility of spontaneous improvement that may occur in diseases such as diabetic retinopathy, nor did they take account of the effect of removal of steroid-induced cataract, which might eventually leave eyes worse off because cataract surgery is known

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      The interval between injections has also been reported to be dose-dependent, ranging from 6 to 9 months and 2–4 months for a 20 mg and 4 mg dose, respectively [99]. In a 2-year, randomized, placebo-controlled trial, repeated intravitreal injection of 4 mg TA in patients with refractory DMO resulted in the improvement of visual acuity and reduction of macular thickness [100]. After 5 years, the majority of patients that had initially improved with this therapy, were able to maintain their gains [101].

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    Manuscript no. 2005-994.

    This study was funded by grants from the Sydney Eye Hospital Foundation, Sydney, Australia; Ophthalmic Research Institute of Australia, Surry Hills, Australia; Juvenile Diabetes Research Foundation, New York, New York; and Diabetes Australia Research Trust, Canberra, Australia. The study was investigator initiated and unsupported by the pharmaceutical industry.

    2

    Dr Gillies is included as an inventor on patents relating to the formulation of triamcinolone for ocular use and its use for the treatment of retinal neovascularization but not macular edema.

    3

    Drs Sutter, Simpson, and Larsson; Ms Ali; and Dr Zhu have no conflicting or proprietary interests.

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