Update on Prevention, Update on Prevention, Diagnosis & Treatment of Diagnosis & Treatment of Diabetic Macular Edema Diabetic Macular Edema

(DME) Part 3(DME) Part 3

A. Paul Chous, MA, OD, FAAOA. Paul Chous, MA, OD, FAAOSpecializing in Diabetes Eye Care & EducationSpecializing in Diabetes Eye Care & Education

Tacoma, WATacoma, WA

Adjunct Instructor, Nova Southeastern University College Adjunct Instructor, Nova Southeastern University College of Optometryof Optometry

Principal Investigator for the Principal Investigator for the Diabetes Visual Function Diabetes Visual Function Supplement StudySupplement Study (DiVFuSS) (DiVFuSS)

Importance of Early TreatmentImportance of Early TreatmentMean change in BCVA from baseline (pooled)

• With crossover from laser to 1 year of 0.5 mg ranibizumab therapy at With crossover from laser to 1 year of 0.5 mg ranibizumab therapy at third year, original sham (laser) treatment group’s visual gains were lower third year, original sham (laser) treatment group’s visual gains were lower than those seen in first year of ranibizumab-treated groups (than those seen in first year of ranibizumab-treated groups (2.82.8 vs vs 10.610.6 and and 11.111.1 letters) letters)

• Delayed treatment reduced magnitude of VA Delayed treatment reduced magnitude of VA benefits of anti-VEGF therapybenefits of anti-VEGF therapy

RISE and RIDE Research Group. Ophthalmology. 2013;120:2013-2022.

Lucentis

Laser

ET

DR

S l

ett

ers

Week

*P < 0.0001vs. laser

VIVID10.710.72q82q8

10.510.52q42q4

1.21.2 LaserLaser

ETDRS; Compared to baseline; FAS; LOCF;VISTA – Laser: n=154; 2q4: n=154; 2q8: n=151 VIVID - Laser: n=132; 2q4: n=136; 2q8; n=135

*P < 0.0001vs. laser

VISTA 12.512.5 2q42q4

10.7 10.7 2q82q8

0.20.2 LaserLaser

Aflibercept: Mean Improvement in Best-Corrected Visual Acuity v. Laser

Korobelnik JF, et al. Ophthalmology. 2014 Jul 8.

Is It Safe????Is It Safe????

Meta-analysis of 2500 Meta-analysis of 2500 patients shows no significantly increased risk patients shows no significantly increased risk

of CVA, MI, vascular death or mortality with of CVA, MI, vascular death or mortality with Lucentis for DME (but 95% CIs = 0.37 to 4.73)Lucentis for DME (but 95% CIs = 0.37 to 4.73)

There is a dose-dependent increased risk of There is a dose-dependent increased risk of mortality (p = 0.04) that dissipates when mortality (p = 0.04) that dissipates when Lucentis is used pro en reta to p = 0.133Lucentis is used pro en reta to p = 0.133

Retina. 2014 Apr;34(4):629-35

What anti-VEGF is Best for DME?What anti-VEGF is Best for DME?

Avastin, Lucentis & Eylea are now being Avastin, Lucentis & Eylea are now being studied head-to-head – results due in studied head-to-head – results due in 2016 (2016 (DRCR.net Protocol TDRCR.net Protocol T))

Outcomes appear comparable by 15 Outcomes appear comparable by 15 RCTs and 8 observational studies, but RCTs and 8 observational studies, but evidence for superiority is insufficientevidence for superiority is insufficient

Cost-effectiveness is best with AvastinCost-effectiveness is best with Avastin Adverse events with Avastin are under-Adverse events with Avastin are under-

reportedreportedInt J Technol Assess Health Care. 2013 Oct;29(4):392-401

Protocol T – 1 year data

• Aflibercept results in ‘significantly better’ VA versus ranibizumab or bevacizumab

• APTC Events: Eylea = 2%, Avastin = 4%, Lucentis = 5%

• Caution: 1-year data, not published

Regeneron Press Release, 10/17/14

APTC = Antiplatelet Trialists Collaboration

Diabetic Retinopathy Clinical Research Network

Steroids in DMESteroids in DME There is a significant inflammatory There is a significant inflammatory

component to DMEcomponent to DME Steroids result in improved vision in the Steroids result in improved vision in the

short term butshort term but• Invariably result in cataract formationInvariably result in cataract formation• Often result in increased intraocular Often result in increased intraocular

pressure/glaucomapressure/glaucoma

Diabetic Retinopathy Clinical Research Network, Elman MJ et al. Ophthalmology. 2010;117(6):1064-1077.e35.

Improved visual acuity (moreletters on eye chart) from intravitreal steroidinjections wanes over time

Intravitreal Steroid Implants

• Slow release

• Dexamethasone (OzurdexTM)– Lasts up to 6 mos

• Fluocinolone (IluvienTM)– Lasts up to 3 years

•Some recent investigations such as the DRCR.net Protocol I have supported the use of combination therapy in the treatment of DME, including anti-VEGFs, laser & steroids with greater improvements in visual acuity noted* * Ophthalmology. 2010;117:1064-1077.

Grain of rice compared toOzurdex™ implant

Does Good Blood Glucose Control Even Matter Once We Start Using anti-VEGF Agents

for DR/DME?

YES!!