SYSTEMIC INTERLEUKIN 1β INHIBITION IN PROLIFERATIVE DIABETIC RETINOPATHY: A Prospective Open-Label Study Using Canakinumab

Abstract

Purpose: To evaluate the effect of systemic interleukin 1β inhibition using canakinumab (Ilaris) on retinal neovascularizations in proliferative diabetic retinopathy.

Methods: Patients with proliferative diabetic retinopathy were enrolled in a prospective uncontrolled pilot study. Canakinumab (150 mg) was given 3 times subcutaneously. The primary end point was the change in the area of neovascularization from baseline to Week 24. Secondary end points were the change in retinal edema measured and best-corrected visual acuity (BCVA), as well as systemic safety evaluation, HbA1c, and systemic inflammatory parameters.

Results: Systemic canakinumab treatment was well tolerated. None of the 8 eyes showed progression of neovascularizations within 24 weeks. Their mean size remained unchanged comparing 0.60 mm at baseline with 0.62 mm at Week 24 (P = 0.944). Median BCVA remained stable with 80 ETDRS letters at baseline and 82 ETDRS letters at Week 24. A not statistically significant reduction in retinal edema was detectable for the foveal central subfield thickness (mean, 313-295 μm). Mean HbA1c improved significantly from 7.92% to 7.30% within the 24 weeks (P = 0.046). Systemic inflammatory parameters remained overall unchanged.

Conclusion: Systemic canakinumab showed no change in neovascularizations in diabetic retinopathy. Promising effects were seen on diabetic macular edema.

Fig. 1

Neovascularization elsewhere at baseline, Weeks 8, 16, and 24 (n = 8). Mean NVE dropped from 0.60 mm² at baseline to 0.50 mm² at Week 8 and 0.36 at Week 16, before increasing again to 0.62 at Week 24.

Fig. 2

Patient 3. A. Fluorescein angiography 7 months before enrollment into the study. B. Fluorescein angiography at baseline showing new hypoperfusion and increased perivascular leakage in the temporal macula and new NVE. C. Fluorescein angiography at Week 24 (8 weeks after the third subcutaneous canakinumab injection) shows that perivascular and NVE-associated leakage is reduced. D. Fluorescein angiography 4 months after the end of the study (no further treatment) shows no relevant change to Week 24.

Fig. 3

Spectral domain optical coherence tomography of Patient 1 shows no change in retinal NVE over 24 weeks. BSL, baseline.

Fig. 4

Spectral domain optical coherence tomography of the right and left eyes of Patient 5 showing subfoveal intraretinal cystoid spaces in both eyes. At Week 8, changes have regressed bilaterally and have disappeared at Weeks 16 and 24. BSL, baseline.

Fig. 5

Fluorescein angiography of Patient 2 showing zone of nonperfusion nasal superior to the disk. A. At baseline, preproliferative changes appear as small hyperfluorescent lesions at the edge of the zone of nonperfusion. At Week 16 (B) and Week 24 (C), FA indicates almost complete regression of preproliferative changes.