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Intravitreal ranibizumab and dexamethasone implant injections as primary treatment of diabetic macular edema: simultaneously double protocol.

ABSTRACT:

Purpose

To assess the 12-month efficacy and safety of simultaneously administered intravitreal dexamethasone implant (DEX implant) and ranibizumab (simultaneous double protocol) injections in comparison with ranibizumab monotherapy as the first-line treatment of diabetic macular oedema (DMO).

Methods

Prospective, consecutive, clinical interventional study. Patients were randomized into two groups: 24 naive DMO patients (34 eyes) who received simultaneous double-protocol therapy and 22 DMO patients (34 eyes) who received ranibizumab monotherapy were included. Monthly ranibizumab (0.5 mg) was administered for the first 6 months and later on, an as-needed treatment basis. DEX implant injection was performed at any time during the loading dose of the three consecutive monthly injections of ranibizumab, and with as-needed reinjections of ranibizumab from 6th month onwards. Change in visual acuity was the primary efficacy endpoint. Secondary efficacy endpoints were a gain of ≥15 letters and a change in the central foveal thickness.

Results

Mean BCVA increased from baseline to month 12 in the simultaneously double-protocol therapy group compared with the ranibizumab monotherapy group (21.6 versus 9.6 letters [P < 0.001]). The corresponding proportions of eyes gaining ≥15 letters were 60% versus 29.4% (P < 0.0001). Moreover, the mean reductions in the central foveal thickness were 413 versus 282 µm (P = 0.001). At 12 month, the simultaneous double-protocol therapy decreased a significant number of foveal cysts and subfoveal neuroretinal detachment compared with those by ranibizumab monotherapy.

Conclusions

The simultaneous addition of DEX implant at any time during the three monthly loading doses of ranibizumab in patients with DMO significantly improved the visual outcomes and revealed superior anatomic outcomes than those with the ranibizumab monotherapy.

SUBMITTER: Kaya M

PROVIDER: S-EPMC8027799 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThis retrospective study aimed to compare the efficacy of intravitreal ranibizumab (IVR) and intravitreal dexamethasone implant (IDI) for pseudophakic vitrectomized eyes with diabetic macular edema (DME) in a single institution.MethodsPseudophakic vitrectomized eyes with treatment-naïve center-involved DME were enrolled, with one eye in each patient. They were divided into two groups: one group receiving IDI every 3 to 4 months and another group receiving IVR using 3 monthly plus treat-and-extend injections, all with monthly follow-up for 6 months. Switch of intravitreal drugs or deferred macular laser was not allowed. Primary outcome measures included change in central foveal thickness (CFT) in 1 mm by spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) at Month 6.ResultsTwenty-two eyes were included in the IDI group and 26 eyes in the IVR group. The baseline demographics, glycosylated hemoglobin level, intraocular pressure (IOP), BCVA, and CFT did not significantly differ (p > 0.05). Compared to baseline data, CFT decreased and BCVA improved significantly after either IDI or IVR at Month 6 (p < 0.05). Significantly better mean final BCVA (0.38 logMAR vs. 0.62 logMAR, p=0.04), more mean visual gain (-0.30 logMAR vs. -0.15 logMAR, p=0.02), lower mean final CFT (310.9 μm vs. 384.2 μm, p=0.04), and larger mean CFT decrease (-150.0 μm vs. -60.1 μm, p=0.03) were found in the IDI group compared to those in the IVR group. A smaller mean treatment number (2.6 vs. 5.6, p < 0.001) and higher rate of postinjection ocular hypertension requiring topical hypotensive agent therapy (27.3% vs. 0%, p=0.0002) were demonstrated in the IDI group than those in the IVR group.ConclusionWe concluded that IDI and IVR can both effectively treat vitrectomized eyes with DME. Dexamethasone implants had significantly better visual/anatomical improvement, smaller treatment number, and higher rate of elevated IOP after injection than IVR in pseudophakic vitrectomized eyes with DME in a 6-month period.

Project description: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.

Project description:BackgroundDexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME.MethodsThree-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34-68 Early Treatment Diabetic Retinopathy Study letters (20/200-20/50 Snellen equivalent), and central retinal thickness (CRT) ≥ 300 μm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was ≥ 15-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry.ResultsBaseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n = 261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5% of DEX 0.7 patients versus 11.1 % of sham had ≥ 15-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 μm with DEX 0.7 versus -39.0 μm with sham (P < .001). Cataract-related adverse events were reported in 70.3% of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery.ConclusionsDEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population.Trial registrationClinicalTrials.gov NCT00168337 and NCT00168389, registered 12 September 2005.

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