Objective: Diabetic macular edema (DME) is a frequent manifestation of diabetic retinopathy,
a leading cause of blindness in the United States. The only proven treatment for DME is laser
photocoagulation. Sirolimus has been shown to inhibit the production, signaling and activity
of many growth factors relevant to the development of diabetic retinopathy. Therefore, this
study will investigate the safety and efficacy of multiple sirolimus injections in patients
with DME.
Study Population: Eligibility criteria include central macular thickening > 260 microns and
visual acuity 20/32 or worse in one or both eyes.
Design: Five participants will be enrolled into this open-label pilot study. After receiving
a 20 μL (440 μg) subconjunctival injection in the study eye at baseline and Month 2, the
participants will be re-evaluated every two months for at least one year for possible
additional injections. During follow-up, participants will not undergo re-injection if they
show significant clinical improvement or treatment success, defined as no intraretinal fluid
or cysts present on optical coherence tomography (OCT) OR 100% reduction in excess retinal
thickness over 260 microns on OCT OR no leakage on fluorescein angiography (FA). Beginning at
Month 4, participants will be assessed for treatment failure, defined as loss of 15 or more
letters of vision compared to baseline at two consecutive visits OR a 50% or greater increase
in total retinal thickness as measured by OCT at two consecutive visits. Individual
participants deemed treatment failures will continue receiving sirolimus injections, but will
be allowed to receive focal laser therapy for any amenable leaking microaneurysms at Month 4.
Beginning at Month 6, focal laser therapy will be permitted for both treatment failures and
participants who do not meet the criteria of a treatment success. Participants will have the
option of continuing treatment until a common termination date of one year.
Outcome Measures: The primary outcome is the change in visual acuity in the study eye at six
months compared to baseline. Secondary outcomes include changes in visual acuity in the study
eye at one year as compared with baseline, changes in retinal thickness as measured by OCT
and changes in fluid leakage in the macula as demonstrated by FA at six months, one year and
throughout the study period in the study and fellow eyes. Safety outcomes include number and
severity of systemic and ocular toxicities, adverse events and infections, and the number of
participants withdrawn from study therapy.