Diabetic Retinopathy: Managing the Extremes. J. Michael Jumper, MD West Coast Retina

Transcription

1 Diabetic Retinopathy: Managing the Extremes J. Michael Jumper, MD West Coast Retina

2 Case 1: EC 65 y.o. HM No vision complaints Meds: Glyburide Metformin Pioglitazone Va: 20/20 OU 20/20

3 Case 2: HS 68 y.o. AF CC: severe vision loss, OU PMH: Type 2 DM, HTN, CAD s/ p MI, ESRD on dialysis, cerebrovascular disease s/p stroke Va: 20/800 OD

4 Case 3: LS 76 y.o. WF No complaints, yearly exam PMH: Type 2 DM, CAD s/p angioplasty, renal cell carcinoma s/p nephrectomy Va: 20/25 OU

5 OD Case 4: SG 31 yo BF CC: gradual vision loss in both eyes PMH: Type 1 DM, HTN, CAD s/p MI, ESRD on dialysis, cerebrovascular disease s/p stroke No prior eye care Va: 4/200 OD; HM OS 4/200 OS HM

6 DR Treatment Landmarks Laser Photocoagulation VEGF Inhibitors DRS 1 ETDRS 2 Pars Plana Vitrectomy DRCRnet 9,10 Bevacizumab BOLT Study 6 Intravitreal Aflibercept Injection VISTA/VIVID Studies 8,11 Ranibizumab FDA Approval RISE/RIDE Studies 7 FDA Approval Protocol S Preliminary report on effects of photocoagulation therapy. The DRS Research Group. Am J Ophthalmol Apr;81(4): ETDRS Research Group. Arch Ophthalmol. 1985;103(12): Diabetic Retinopathy Clinical Research Network. Ophthalmology. 2008;115(9): Campochiaro PA et al. Ophthalmology. 2010;117(7): Boyer DS, Yoon YH, Belfort R, et al. Ozurdex MEAD Study Group. Ophthalmology Michaelides M et al. Ophthalmology. 2010;117(6): Nguyen QD et al. Ophthalmology. 2012;119(4): Korobelnik JF et al. Ophthalmology 2014 DRCR net Writing Committee; Haller JA, Qin H, Apte RS, et al. Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology. 2010;117: Flaxel CJ, Edwards AR, Aiello LP, et al. Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: DRCR network. Retina. 2010;30: Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology Oct;122(10): Panretinal Photocoagulation vs. Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Trial. JAMA 2015; 314(20): 2137=2146. Aflibercept, bevacizumab, or ramibizumab for diabetic macular edema. N Engl J Med Mar 26; 372(13): Wells JA et al. Aflibercept, Bevacizumab, or Ranibizumab for DME Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmolol 2016;123: Triamcinolone Acetonide DRCRnet Protocol B 3 Intravitreal Steroids Fluocinolone Acetonide FAME Study 4 Dexamethasone MEAD Study 5 FDA Approval Protocol T 13,14 Protocol V

7 Clinical Trials in Diabetic Retinopathy Laser Trials Intravitreal injection Trials Vitreoretinal Surgery Trials Medical Rx Trials DRS ETDRS DRCR (Protocol A) DRCR (Protocol B) DRCR (Protocol F) DRCR (Protocol V) DRCR (Protocol I) DRCR (Protocol N) DRCR (Protocol S) DRCR (Protocol T) RISE/RIDE FAME VIVID/VISTA DRCR (Protocol D) DRVS ETDRS Report 17 DCCT/EDIC UKPDS FIELD ACCORD DRCR (Protocol M)

8 Case 1: EC 65 y.o. HM No vision complaints Meds: Glyburide Metformin Pioglitazone Va: 20/20 OU 20/20

9 Diabetic Macular Edema Laser helps (ETDRS) Reduces moderate vision loss* by 50% Laser reduced central thickening in 50% Benefit better for pts with CSME 3 line improvement rare (3%) Anti-VEGF therapy is better (DRCR) letter improvement overall With good visual acuity (20/32-20/40) All drugs similar With worse visual acuity (20/50 or worse) Advantage aflibercept over bevacizumab Difference at 2 years was diminished *Moderate vision loss = doubling of the initial visual angle

10 Diabetic Macular Edema Laser helps (ETDRS) Reduces moderate vision loss* by 50% Laser reduced central thickening in 50% Benefit better for pts with CSME 3 line improvement rare (3%) Anti-VEGF therapy is better (DRCR) letter improvement overall With good visual acuity (20/32-20/40) All drugs similar With worse visual acuity (20/50 or worse) Advantage aflibercept over bevacizumab Difference at 2 years was diminished *Moderate vision loss = doubling of the initial visual angle Mean Change in Visual Acuity Letter Score Mean Change in Visual Acuity Letter Score Aflibercept 20/32 to 20/ Aflibercept Ranibizumab Bevacizumab 20/50 or Worse Ranibizumab Week Bevacizumab

11 DRCR Protocol T Protocol required laser for DME Full Cohort

12 Diabetic Macular Edema Laser helps (ETDRS) Reduces moderate vision loss* by 50% Laser reduced central thickening in 50% Benefit better for pts with CSME 3 line improvement rare (3%) Anti-VEGF therapy is better (DRCR) letter improvement overall With good visual acuity (20/32-20/40) All drugs similar With worse visual acuity (20/50 or worse) Advantage aflibercept over bevacizumab Difference at 2 years was diminished *Moderate vision loss = doubling of the initial visual angle Mean Change in Visual Acuity Letter Score Mean Change in Visual Acuity Letter Score Aflibercept 20/32 to 20/ Aflibercept Ranibizumab Bevacizumab 20/50 or Worse Ranibizumab Week Bevacizumab

13 Case 1: EC 65 y.o. HM No vision complaints Meds: Glyburide Metformin Pioglitazone Va: 20/20 OU 20/20

14

15

16

17 DRCR Network: Protocol V Comparative Effectiveness Study of Laser, Observation and Ranibizumab for DME in Eyes with Very Good Visual Acuity

18 DRCR Protocol V Randomized, multi-center clinical trial At least one eye meeting all of the following criteria: Central-involved DME on OCT (Cirrus/Spectralis only)* VA letter score 20/25 or better* No prior treatment for DME Prompt anti-vegf Prompt laser + deferred anti-vegf Observation + deferred anti-vegf Primary outcome: Proportion of eyes that have lost 5 letters of VA at 2 years 15

19 Case 2: HS 68 y.o. AF CC: severe vision loss, OU PMH: Type 2 DM, HTN, CAD s/ p MI, ESRD on dialysis, cerebrovascular disease s/p stroke Va: 20/800 OD

20 DME: Our Armamentarium Systemic control Laser ETDRS style Subthreshold Anti-VEGF agents Pegaptanib (Macugen) Bevacizumab (Avastin) Ranibizumab (Lucentis) Aflibercept (Eylea) Steroids Triamcinolone Dexamethasone Fluocinolone Vitrectomy with membranectomy

21 DME: Systemic Factors Blood glucose Hypertension Cardiovascular disease Renal function Serum lipids

22 Corticosteroids for DME 3 choices intravitreal Triamcinolone acetonide (Triesence ) off label Dexamethasone (Ozurdex ) Fluocinolone acetonide (Iluvien ) Mechanism of action: Stabilize, reconstitute the inner blood-retinal barrier Downgrade VEGF production

23 Vitrectomy for DME: DRCR Protocol D 87 pts Little change in mean visual acuity between baseline and 6 months 38% improved by > 10 letters 22% worsened by > 10 letters Marked anatomic improvement OCT central subfield thickness mean from 500 μm to 300 μm Presence of ERM and worse baseline visual acuity were associated with greater VA improvement Diffuse DME Va: 20/160 s/p Avas5n and Kenalog Va: 20/100 s/p Vitrectomy Va: 20/63

24 Case 2: HS s/p multiple Avastin injections s/p intravitreal triamcinolone s/p vitrectomy Va: 20/400 OD Organized exudate Macular fibrosis

25 Case 3: LS Observation Laser Full PRP Targeted PRP Anti-VEGF

26 ETDRS PRP Conclusions Timing PDR with HRC Treat Mild to moderate NPDR Observe Severe NPDR or Early PDR Can observe if f/u reliable Can treat especially Type 2 diabetics Extent When treatment decision made full pattern Diabetic Retinopathy Study Risk factors for severe vision loss Vitreous/preretinal hemorrhage NV NVD Severe NV NVD > 1/3 disc surface (photo 10A) NVE > ½ DA High-risk characteristics (HRC): > 3 factors

27 Targeted PRP?

28 DRCR-Protocol S

29 DRCR-Protocol S Peripheral Visual Field Outcomes 2-Year Visit

30 Different outcomes depending on presence or absence of concomitant CI-DME with VA 20/32 WITH CI-DME ICER = $55,568/QALY Within the realm of accepted cost-effectiveness WITHOUT CI-DME ICER = $662,978/QALY Not cost-effective

31 Case 3: LS Work-up for other causes of peripheral neovascularization negative Targeted peripheral photocoagulation Stable with 4 year follow-up

32 OD Case 4: SG 31 yo BF CC: gradual vision loss in both eyes PMH: Type 1 DM, HTN, CAD s/p MI, ESRD on dialysis, cerebrovascular disease s/p stroke No prior eye care Va: 4/200 OD; HM OS 4/200 OS HM

33 Course Pre-op Right eye vitrectomy/ MP/ endolaser/fax Spotty f/u 6 months later 4/200

34 OD 20/80

35 OD 20/80

36 18 months later OS Can you fix my left eye? HM

37

38 I didn t see her again until 1 year later

39 OD 20/40

40 OD 20/40

41 OS 20/100

42 OS 20/100

43 Conclusions Diabetic retinopathy treatments are mostly guided by evidence-bases studies The great disease variability means there are many instances where there is little evidence backing our treatment decisions Anti-VEGF therapy has become the primary therapy for diabetic macular edema Focal laser therapy was frequently used in addition to anti-vegf in the DRCR Protocol T study (37%-56%) Remember systemic factors and drugs such as thiazolidinediones may influence DME

44 Conclusions Anti-VEGF is effective in the treatment of PDR Especially with concomitant center-involved DME Better central and peripheral vision outcomes Weigh the risk of non-compliance when considering repeat injection therapy vs. single session PRP Future studies will further clarify our treatment options Protocol V CI DME With Very Good Visual Acuity Intravitreous Anti-VEGF Treatment for Prevention of Vision Threatening Diabetic Retinopathy in Eyes at High Risk Intravitreous Anti-VEGF vs. Prompt Vitrectomy for Vitreous Hemorrhage from Proliferative Diabetic Retinopathy Randomized Trial of Intravitreous Aflibercept versus Intravitreous Bevacizumab + Deferred Aflibercept for Treatment of Central- Involved Diabetic Macular Edema