Dexamethasone intravitreal implant in the treatment of diabetic macular edema

Abstract

Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory reaction, and is characterized by blood-retinal barrier (BRB) breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana) injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours) and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048) from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg) administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA) and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%). Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients), intraocular pressure elevation ≥25 mmHg (29.7%), conjunctival hemorrhage (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis) were infrequent (<2%). Dexamethasone intravitreal implant offers a viable treatment option for DME, especially in cases that are persistent or treatment (anti-vascular endothelial growth factor/laser) refractory.

Keywords: corticosteroids; dexamethasone; diabetic retinopathy; implant; intravitreal; macular edema.

Figure 1

A 64-year-old male diagnosed with diabetic macular edema in the right eye. Notes: Color and red-free fundus photographs of the RE indicate thickening of the fovea, as well as intraretinal small hemorrhages and microaneurysms (A and B). After ten monthly bevacizumab injections, optical coherence tomography indicates marked macular thickening, while fluorescein angiography fails to identify any treatable lesions (C and D). Intravitreal injection of dexamethasone implant reduces central macular thickness from a baseline (post-bevacizumab) level of 412 µm (BCVA 6/12) (E) to 286 µm (BCVA 6/10) at 6 weeks (F), 285 µm (BCVA 6/12) at 12 weeks (G), and 309 µm (BCVA 6/15) at 18 weeks postinjection (H). Images courtesy of Dr A Loewenstein. Abbreviation: BCVA, best-corrected visual acuity.

Figure 2

A 62-year-old patient with cystoid macular edema in the left eye previously treated with three monthly injections of intravitreal bevacizumab. Notes: Early- and late-phase fluorescein angiograms indicate diffuse leakage temporal to the fovea, and distortion of the foveal avascular zone with some non-perfusion (A and B). Optical coherence tomography images indicate a decrease in central macular thickness from a baseline (post-bevacizumab) level of 475 µm (C) to 235 µm at 3 months after dexamethasone implant injection (D), with improvement in BCVA from 20/60 to 20/40 over this period. Images courtesy of Dr A Loewenstein. Abbreviation: BCVA, best-corrected visual acuity.

Figure 3

A 72-year-old patient with diabetic macular edema in the right eye previously treated with three monthly injections of intravitreal bevacizumab. Notes: Color and red-free fundus photographs (A and B) and fluorescein angiograms (C and D) of the right eye show multiple microaneurysms, as well as leakage primarily in the temporal fovea, with accumulation in a cystoid pattern. Optical coherence tomography images indicate a central macular thickness of 525 µm on presentation (E), which transiently decreases to 269 µm at 1 month after dexamethsone implant injection (F) before returning to pretreatment levels (534 µm) at 3 months postinjection (G). Images courtesy of Dr A Loewenstein.

Figure 4

A 65-year-old female with regressed proliferative diabetic retinopathy in the right eye previously treated with three monthly injections of intravitreal bevacizumab. Notes: Early- and late-phase fluorescein angiograms reveal significant leakage, with accumulation in a cystoid pattern, and multiple-scatter scars (A and B). Optical coherence tomography images indicate a decrease in central macular thickness from a baseline (post-bevacizumab) level of 846 µm (BCVA 6/30) (C) to a trough of 209 µm (BCVA 6/15) at 11 weeks after the first dexamethasone implant injection (D), with reversal of effect occurring by week 20 (CMT 752 µm; BCVA 6/15) (E). Consistent, marked reductions in central macular thickness to trough levels of 222 µm (BCVA 6/12), 209 µm (BCVA 6/30), and 235 µm (BCVA 6/15) were recorded 9–12 weeks after the second, third, and fourth dexamethasone implant injections, respectively (F–H). Images courtesy of Dr A Loewenstein. Abbreviation: BCVA, best-corrected visual acuity.