Michael Singer

Dexamethasone Intravitreal Implant in Combination with Laser Photocoagulation for the Treatment of Diffuse Diabetic Macular Edema

PURPOSE To evaluate Ozurdex (dexamethasone intravitreal implant [DEX implant]; Allergan, Inc, Irvine, CA) 0.7 mg combined with laser photocoagulation compared with laser alone for treatment of diffuse diabetic macular edema (DME). DESIGN Randomized, controlled, multicenter, double-masked, parallel-group, 12-month trial. PARTICIPANTS Two hundred fifty-three patients with retinal thickening and impaired vision resulting from diffuse DME in at least 1 eye (the study eye) were enrolled. INTERVENTION Patients were randomized to treatment in the study eye with DEX implant at baseline plus laser at month 1 (combination treatment; n = 126) or sham implant at baseline and laser at month 1 (laser alone; n = 127) and could receive up to 3 additional laser treatments and 1 additional DEX implant or sham treatment as needed. MAIN OUTCOME MEASURES The primary efficacy variable was the percentage of patients who had a 10-letter or more improvement in best-corrected visual acuity (BCVA) from baseline at month 12. Other key efficacy variables included the change in BCVA from baseline and the area of vessel leakage evaluated with fluorescein angiography. Safety variables included adverse events and intraocular pressure (IOP). RESULTS The percentage of patients who gained 10 letters or more in BCVA at month 12 did not differ between treatment groups, but the percentage of patients was significantly greater in the combination group at month 1 (P<0.001) and month 9 (P = 0.007). In patients with angiographically verified diffuse DME, the mean improvement in BCVA was significantly greater with DEX implant plus laser treatment than with laser treatment alone (up to 7.9 vs. 2.3 letters) at all time points through month 9 (P ≤ 0.013). Decreases in the area of diffuse vascular leakage measured angiographically were significantly larger with DEX implant plus laser treatment through month 12 (P ≤ 0.041). Increased IOP was more common with combination treatment. No surgeries for elevated IOP were required. CONCLUSIONS There was no significant between-group difference at month 12. However, significantly greater improvement in BCVA, as demonstrated by changes from baseline at various time points up to 9 months and across time based on the area under the curve analysis, occurred in patients with diffuse DME treated with DEX implant plus laser than in patients treated with laser alone. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Efficacy and safety of two or more dexamethasone intravitreal implant injections for treatment of macular edema related to retinal vein occlusion (Shasta study).

Purpose: To evaluate the efficacy, safety, and reinjection interval of dexamethasone intravitreal implant (DEX implant) in branch retinal vein occlusion and central retinal vein occlusion patients receiving ≥2 DEX implant treatments. Methods: Multicenter (26-site), retrospective chart review study. Data were collected from baseline (at first DEX implant) through 3 months to 6 months after last DEX implant. Results: Patients (n = 289) received 2 to 9 (mean, 3.2) DEX implants as monotherapy (29.1% of patients) or with adjunctive treatments/procedures. Mean duration of macular edema before first DEX implant was 18.4 months. Mean reinjection interval was 5.6 months. Mean peak change in best-corrected visual acuity from baseline through 4 weeks to 20 weeks after final DEX implant was +1.0 line (P < 0.001). Best-corrected visual acuity and central retinal thickness improved significantly from baseline after each of the first 6 DEX implant injections (P ⩽ 0.037); 59.7% of branch retinal vein occlusion and 66.7% of central retinal vein occlusion patients achieved ≥2-line best-corrected visual acuity improvement. Intraocular pressure increase (≥10 mmHg) occurred in 32.6% of patients; 29.1% used intraocular pressure-lowering medication to treat increases associated with DEX implant. Only 1.7% of patients required incisional glaucoma surgery. Conclusion: Retinal vein occlusion patients treated with multiple DEX implant injections, either alone or combined with other therapies, had improved central retinal thickness and visual acuity with each subsequent injection. No new safety concerns developed with multiple implants.

Epimacular brachytherapy for neovascular age-related macular degeneration: a randomized, controlled trial (CABERNET).

PURPOSE To evaluate the safety and efficacy of epimacular brachytherapy (EMBT) for the treatment of neovascular age-related macular degeneration (AMD). DESIGN Multicenter, randomized, active-controlled, phase III clinical trial. PARTICIPANTS Four hundred ninety-four participants with treatment-naïve neovascular AMD. METHODS Participants with classic, minimally classic, and occult lesions were randomized in a 2:1 ratio to EMBT or a ranibizumab monotherapy control arm. The EMBT arm received 2 mandated, monthly loading injections of 0.5 mg ranibizumab. The control arm received 3 mandated, monthly loading injections of ranibizumab then quarterly injections. Both arms also received monthly as needed (pro re nata) retreatment. MAIN OUTCOME MEASURES The proportion of participants losing fewer than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline visual acuity (VA) and the proportion gaining more than 15 ETDRS letters from baseline VA. RESULTS At 24 months, 77% of the EMBT group and 90% of the control group lost fewer than 15 letters. This difference did not meet the prespecified 10% noninferiority margin. This end point was noninferior using a 20% margin and a 95% confidence interval for the group as a whole and for classic and minimally classic lesions, but not for occult lesions. The EMBT did not meet the superiority end point for the proportion of participants gaining more than 15 letters (16% for the EMBT group vs. 26% for the control group): this difference was statistically significant (favoring controls) for occult lesions, but not for predominantly classic and minimally classic lesions. Mean VA change was -2.5 letters in the EMBT arm and +4.4 letters in the control arm. Participants in the EMBT arm received a mean of 6.2 ranibizumab injections versus 10.4 in the control arm. At least 1 serious adverse event occurred in 54% of the EMBT arm, most commonly postvitrectomy cataract, versus 18% in the control arm. Mild, nonproliferative radiation retinopathy occurred in 3% of the EMBT participants, but no case was vision threatening. CONCLUSIONS The 2-year efficacy data do not support the routine use of EMBT for treatment-naïve wet AMD, despite an acceptable safety profile. Further safety review is required.

Measuring the precise area of peripheral retinal non-perfusion using ultra-widefield imaging and its correlation with the ischaemic index

Objective To determine the calculated, anatomically correct, area of retinal non-perfusion and total area of visible retina on ultra-widefield fluorescein angiography (UWF FA) in retinal vein occlusion (RVO) and to compare the corrected measures of non-perfusion with the ischaemic index. Methods Uncorrected UWF FA images from 32 patients with RVO were graded manually for capillary non-perfusion, which was calculated as a percentage of the total visible retina (uncorrected ischaemic index). The annotated images were converted using novel stereographic projection software to calculate precise areas of non-perfusion in mm2, which was compared as a percentage of the total area of visible retina (‘corrected non-perfusion percentage’) with the ischaemic index. Results The precise areas of peripheral non-perfusion ranged from 0 mm2 to 365.4 mm2 (mean 95.1 mm2), while the mean total visible retinal area was 697.0 mm2. The mean corrected non-perfusion percentage was similar to the uncorrected ischaemic index (13.5% vs 14.8%, p=0.239). The corrected non-perfusion percentage correlated with uncorrected ischaemic index (R=0.978, p<0.001), but the difference in non-perfusion percentage between corrected and uncorrected metrics was as high as 14.8%. Conclusions Using stereographic projection software, lesion areas on UWF images can be calculated in anatomically correct physical units (mm2). Eyes with RVO show large areas of peripheral retinal non-perfusion.

Monthly Versus As-Needed Ranibizumab Injections in Patients with Retinal Vein Occlusion: The SHORE Study

OBJECTIVE To compare pro re nata (PRN) and monthly injections of 0.5 mg ranibizumab in retinal vein occlusion (RVO) patients stabilized by monthly injections. DESIGN Randomized, open-label, vision-examiner masked, 15-month study. PARTICIPANTS Subjects with macular edema secondary to branch or central RVO. METHODS Subjects received monthly injections of 0.5 mg ranibizumab for 7 months and those meeting stability criteria between months 7 and 14 were randomized (1:1) to PRN injections versus continued monthly injections. Non-randomized (NR) subjects (never met stability criteria) received monthly injections. MAIN OUTCOME MEASURES The primary endpoint was the slope of change in best-corrected visual acuity (BCVA) between months 7 and 15. RESULTS There was no significant difference in the slope of change in BCVA between months 7 and 15 in patients treated PRN versus those treated with monthly injections (P = 0.509). Mean (± standard deviation) change from baseline BCVA in Early Treatment Diabetic Retinopathy Study letter score at month 15 was 21.0 ± 14.1 in the PRN group (n = 82) versus 18.7 ± 14.1 in the monthly group (n = 80) and 14.5 ± 14.7 in NR subjects (n = 13). The percentage of subjects who achieved BCVA ≥ 20/40 at month 15 was 76.8% in the PRN group, 71.3% in the monthly group, and 46.2% in NR subjects. The mean (± standard deviation) change from baseline central subfield thickness was -247.8 ± 207.5 μm in the PRN group, -289.9 ± 177.2 μm in the monthly group, and -93.2 ± 225.2 μm in NR subjects. There were no significant differences in mean BCVA gains or central subfield thickness reductions at month 15 between the PRN and monthly injection groups (all > 0.05). CONCLUSIONS After edema resolution from 7 or more monthly ranibizumab injections in RVO subjects, visual outcomes at month 15 were excellent and not significantly different in subjects treated PRN versus those who continued monthly injections.

Improving quality of life in patients with end-stage age-related macular degeneration: focus on miniature ocular implants

Video abstract Video

Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial.

Purpose: To evaluate the efficacy and safety of dexamethasone intravitreal implant 0.7 mg (DEX) as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration (nvAMD). Procedures: This was a 6-month, single-masked, multicenter study. Patients were randomized to DEX implant (n = 123) or sham procedure (n = 120) and received 2 protocol-mandated intravitreal ranibizumab injections. The main outcome measure was injection-free interval to first as-needed ranibizumab injection. Results: DEX increased the injection-free interval versus sham (50th percentile, 34 vs. 29 days; 75th percentile, 85 vs. 56 days; p = 0.016). 8.3% of DEX versus 2.5% of sham-treated patients did not require rescue ranibizumab (p = 0.048). Visual acuity and retinal thickness outcomes were similar in DEX and sham-treated patients. Only reports of conjunctival hemorrhage (18.2 vs. 8.5%) and intraocular pressure elevation (13.2 vs. 4.2%) were significantly different in the DEX versus the sham treatment groups. Conclusion: DEX reduced the need for adjunctive ranibizumab treatment and showed acceptable tolerability in nvAMD patients.

Comparing bevacizumab and ranibizumab for initial reduction of central macular thickness in patients with retinal vein occlusions

Purpose To examine short-term effects of ranibizumab versus bevacizumab on reduction of optical coherence tomography (OCT) central macular thickness (CMT) in patients with macular edema secondary to retinal vein occlusions (RVOs). Methods This is a retrospective analysis in which patients with RVOs were injected with either bevacizumab or ranibizumab. At 2 weeks, all patients were injected with a dexamethasone intravitreal implant (Ozurdex®). CMT on OCT and best-corrected visual acuity were obtained at baseline, at 2 weeks (just prior to the dexamethasone intravitreal implant), and 6 weeks. Results Sixty-four patients received injections (32 bevacizumab; 32 ranibizumab). At 2 weeks, bevacizumab group had a mean (±standard error of mean [SEM]) CMT reduction of 26.2% ± 3.4% versus 47% ± 3.5% reduction with ranibizumab (P < 0.0001). At 6 weeks, there was a 31.6% ± 3.2% CMT reduction with bevacizumab versus 52% ± 3.2% with ranibizumab (P < 0.0001). At 2 weeks, 15 (9%) of bevacizumab patients versus 25 (78.1%) ranibizumab patients achieved OCT CMT < 300 μm (P = 0.0192). At 6 weeks, 18 (56.3%) of bevacizumab compared to 30 (93.8%) of ranibizumab patients achieved CMT < 300 μm (P = 0.0010). Visual acuity was not significantly different at each time interval between the groups. Conclusion Ranibizumab appears to have a greater effect in the short-term of decreasing macular edema on OCT when compared to bevacizumab in patients with RVOs.

Diabetic macular edema: it is more than just VEGF

Diabetic macular edema is a serious visual complication of diabetic retinopathy. This article reviews the history of previous and current therapies, including laser therapy, anti-vascular endothelial growth factor agents, and corticosteroids, that have been used to treat this condition. In addition, it proposes new ways to use them in combination in order to decrease treatment burden and potentially address other causes besides vascular endothelial growth factor for diabetic macular edema.

Early Evolution of the Vitreomacular Interface and Clinical Efficacy After Ocriplasmin Injection for Symptomatic Vitreomacular Adhesion

BACKGROUND AND OBJECTIVE To determine early evolution of the vitreomacular interface and clinical efficacy and safety profile after ocriplasmin treatment. PATIENTS AND METHODS Retrospective, multicenter, observational case series. Patients with vitreomacular adhesion (VMA) confirmed on optical coherence tomography (OCT) received a single intravitreal ocriplasmin injection. Changes in the vitreomacular interface were evaluated by spectral-domain OCT. Adverse events were monitored at all visits. RESULTS Of 22 patients treated with ocriplasmin, 14 (64%) had VMA resolution, with six (43%) achieving VMA release within the first week. Eight patients (36%) showed improvement in visual acuity (VA) of at least two Snellen lines. Rate of VMA resolution was 79% for VA less than 20/40 and 38% for VA of 20/40 or greater. Safety findings include changes in the ellipsoid layer (n = 3) and transient increases in subretinal fluid (n = 6). CONCLUSION Ocriplasmin was effective for VMA resolution, with a rapid onset of action. Patients with worse baseline VA showed a higher VMA resolution rate.