Diabetic Retinopathy: Recent Advances in Treatment and Treatment Approaches

Transcription

1 Diabetic Retinopathy: Recent Advances in Treatment and Treatment Approaches Dr. David Wong Associate Professor Retina Specialist, Department of Ophthalmology & Vision Sciences, University of Toronto, Canada

2 Pathophysiology of DME/DR Diabetic retinopathy Damage to blood vessels in the retina Ischemia Reduced supply of oxygen to the retina Production of VEGF Process to restore the reduced retina oxygen supply Increased permeability of blood vessels Diabetic Macular Edema (DME) New vessel growth Proliferative Diabetic Retinopathy (PDR)

3 Pathophysiology of DME/DR Diabetic retinopathy Damage to blood vessels in the retina Ischemia Reduced supply of oxygen to the retina Production of VEGF Process to restore the reduced retina oxygen supply Increased permeability of blood vessels Diabetic Macular Edema (DME) New vessel growth Proliferative Diabetic Retinopathy (PDR)

4 DME: milestones in treatment Laser photocoagulation 1980s Intravitreal steroids 2000s 2010s Intravitreal anti-vegf Ranibizumab, Aflibercept, (Bevacizumab*) RESOLVE (2010) 1 DRCR.net (2010) 2 RESTORE (2011) 3 DA VINCI (2011) 4 VIVID 6 VISTA 6 RETAIN 7 Protocol T 8 Key anti- VEGF trials: Ranibizumab Aflibercept Aflibercept / Ranibizumab / (Bevacizumab) RISE (2012) 5 RIDE (2012) 5 *Off-label use 1. Massin P et al. Diabetes Care 2010; 33(11): Elman MJ et al. Ophthalmology 2010; 117(6): Mitchell P et al. Ophthalmology 2011; 118(4): Do DV et al. Ophthalmology 2011; 118(9): Nguyen QD et al. Ophthalmology 2012; 119(4): Korobelnik J.-F. et al., Ophthalmology 2014; 121(11): RETAIN study record detail. Available at clinicaltrials.gov/ct2/show/nct The DRCR.net. NEJM 2015; DOI: /NEJMoa

5 Proportion of eyes (%) with vision loss of 15 ETDRS letters ETDRS Macular laser photocoagulation Deferred laser treatment Macular laser reduced the risk of moderate vision loss by ~ 50% Conclusion: macular laser does not improve vision in CSME, but is effective at preserving vision/preventing further vision loss Time (months) ETDRS Research Group. Arch Ophthalmol. 1985;103:

6 Mean change in BCVA (ETDRS letters) Mean change in BCVA (ETDRS letters) RISE and RIDE RISE Ranibizumab 0.3 mg Ranibizumab 0.5 mg Sham/ranibizumab 0.5 mg RIDE At month 24, sham group crossed over to 0.5 mg ranibizumab Switched group did not achieve comparable improvements at month 36 to patients originally randomized to ranibizumab Time (months) Brown DM, et al. Ophthalmology. 2013;120(10): Nguyen QD et al. Ophthalmology 2012; 119(4):

7 Mean change in BCVA from baseline (ETDRS letters) VIVID / VISTA VIVID aflibercept PRN 1.6 Laser VISTA Primary endpoint q8* q4* q4* 9.4 2q8* 1.2 Laser 0.7 Laser q4* q4* q8* q8* 0.9 Laser 0.2 Laser Laser Aflibercept 2q4 Aflibercept 2q8 aflibercept PRN q8* q4* q8* q4* 1.4 Laser Week *P< vs. laser. Heier JS et al. Ophthalmology 2016; 123 (11):

8 Mean Change in Visual Acuity Letter Score DRCRnet: Protocol T Week Treatment Group Comparison*: Aflibercept vs. Bevacizumab P = 0.02 Aflibercept vs. Ranibizumab P = 0.47 Ranibizumab vs. Bevacizumab P = Weeks Aflibercept Bevacizumab Ranibizumab * P-values adjusted for baseline visual acuity and multiple comparisons

9 Proportion of patients with VA of 20/32 or better at Year 1 (%) Baseline VA is associated with VA outcomes at 1 year The relationships between various baseline characteristics and VA outcomes at 1 year following treatment with ranibizumab were analyzed in a DRCR.net study Patients with VA of 20/32 or better at Year /320 20/100 20/320-20/100 20/80-20/63 20/80 20/63 20/50 20/40 Baseline VA 75 n=69 n=79 n=63 n=65 Adapted from Bressler SB et al. (2012) supplementary table 2. Eyes with lower VA at baseline were more likely to achieve larger gains in VA but less likely to reach near-normal VA DRCR.net, Diabetic Retinopathy Clinical Research Network; VA, visual acuity. Bressler SB et al. Arch Ophthalmol 2012; 130 (9):

10 Mean number of injections Change from baseline in VA (letters) Sustained gains in VA with Ranibizumab with a reduced injection frequency long-term DRCR.net 1,2 Ranibizumab + deferred laser Ranibizumab + prompt laser DRCR.net 1,2 Ranibizumab + deferred laser Ranibizumab + prompt laser * Year 1 Year 2 Year Week Reduced injection frequency while average visual acuity gains at 6 months are maintained for at least 3 years Includes study participants completing the 3-year (156-week) visit

11 Mean change in visual acuity through 5 years following DRCR.net retreatment strategies And it does so with few injections after year 2! *Only eyes that completed 5-year visit 11

12 Pathophysiology of DME/DR Diabetic retinopathy Damage to blood vessels in the retina Ischemia Reduced supply of oxygen to the retina Production of VEGF Process to restore the reduced retina oxygen supply Increased permeability of blood vessels Diabetic Macular Edema (DME) New vessel growth Proliferative Diabetic Retinopathy (PDR)

13 PDR: milestones in treatment Laser photocoagulation Intravitreal anti-vegf Ranibizumab*, Aflibercept 1980s 2000s 2015s Ongoing DRCR.net : Protocol S CLARITY Key anti- VEGF trials: Ranibizumab Aflibercept *Off-label use Writing Committee for the Diabetic Retinopathy Clinical Research Network. JAMA 2015;314:

14 EVENT RATES/100 DRS - PDR LASER (PRP) 40 CONTROL (all visits) CONTROL (original protocol) TREATED (original protocol) TREATED (all visits) PRP superior to control (no treatment) Reduced severe visual loss by 50% Main treatment MONTHS OF FOLLOW-UP Ophthalmol 88: , 1981

15 DRCRnet: Protocol S Ranibizumab non-inferior to PRP Writing Committee for the Diabetic Retinopathy Clinical Research Network. JAMA 2015;314:

16 Diabetic retinopathy severity score (DRSS) Level ETDRS DRSS Description 1 10 DR absent 2 20 DR questionable, microaneurysms only 3 35 Mild NPDR 4 43 Moderate NPDR 5 47 Moderately severe NPDR 6 53 Severe NPDR 7 61 Mild PDR 2-step improvement in DRSS From DRSS 53, severe NPDR (Level 6) to DRSS Level 43, moderate NPDR (Level 4) 2-step improvement in DRSS From DRSS Level 53, severe NPDR (Level 6) 8 65 Moderate PDR 9 71 High-risk PDR High-risk PDR DR, diabetic retinopathy; NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy. Davis MD et al. Invest Ophthalmol Vis Sci 1998; 39 (2):

17 ETDRS Va change from baseline All Cohorts RWE and RCT Real World Protocol T Vivid Vista Rise Ride Bevacizumab Ranibzumab Aflibercept Ciulla et a. :Presented ASRS 2017l.

18 Take away messages Anti VEGF superior but requires more frequent treatment /monitoring compared to laser Retinopathy can be regressed to an earlier stage Real World Evidence shows we undertreat Treating early leads to better outcomes: Patients should be educated and aware Referral process should be efficient Effective use of guidelines and protocols

19 Thank You