2. Tx Options in CRVO
| Presentation Title | Presenter Name | Date | Subject | Business Use Only
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Lucentis : Ranibizumab; FDA approved in CRVO
Eylea : Aflibercept; FDA approved in CRVO
Avastin : Bevacizumab; Not approved
Macugen : Pegaptanib; Not approved
IVTA : Triamcinolone Acetonide; Not approved
Ozurdex : Dexamethasone implant;FDA approved in RVO
3. Background: Macular Grid Photocoagulation Vs
Observation in CRVO
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Multicenter randomized controlled clinical trial, 155 patients
Efficacy of Macular Grid photocoagulation in preserving or
improving central vision acuity
Patients with angiographically documented CVO
Best Corrected Visual Acuity 20/50 or poorer
Treatment: Macular grid photocoagulation or No Treatment
4. 4
RESULTS: MACULAR GRID PHOTOCOAGULATION NOT A
TREATMENT OPTION IN CRVO
Treatment Arm Initial Visual
Acuity (median)
Final Visual
Acuity (median)
Macular Grid Photocoagulation (Treated) 20/160 20/200
Observation (Untreated) 20/125 20/160
No difference in visual acuity b/w treated and untreated
eyes at any point during entire Three years follow up
5. Background: SCORE STUDY
IVTA Vs Observation in CRVO
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Multicenter randomized controlled clinical trial of 271 patients
Baseline VA 20/40 to 20/400; OCT ≥ 250 microns
Efficacy & safety of 1 mg and 4 mg dose of IVTA Vs Observation
Main Outcome Measure: Gain in VA of 15 or more letters from
baseline to month 12
6. 6
RESULTS: IVTA Superior to Observation for
treatment of vision loss in CRVO
IVTA: Significantly more number of patients gained 15 letters
Significantly less number of patients lost more than 15 letters.
however No mean vision improvement at end of 1 year.
Compared to Observation (no treatment), IVTA, effective and safe
(1 mg) in the treatment of CRVO
8. GENEVA: Phase III, randomized, double-masked, sham
controlled trial of Dexamethasone implant in RVO
9. Maximum letters gain: 10 letters, at 60 days.
Vision improvement is not sustained. Functional vision gain is for
about two months duration.
No significant vision improvement at the end of 6 months and 12
months(p > 0.05)
10. Dexamethasone implant:
What about Safety?
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Most common Adverse Event: Conjunctival hemorrhage (24.9 %)
Significantly more patients developed cataract in patients who
received Two implants compared to patients with only one implant
Overall, 32.8% patients experienced IOP increase of at least 10
mmHg from baseline.
Laser or surgical procedure to reduce IOP required in 14 study eyes
11. Ranibizumab in CRVO:
CRUISE STUDY
(392 patients)
| Presentation Title | Presenter Name | Date | Subject | Business Use Only
11
12. Treatment schedule
ranibizumab 0.5 mg
ranibizumab 0.5 mg PRN*
ranibizumab 0.3 mg
ranibizumab 0.3 mg PRN*
sham
*Treated if BCVA is 20/40 Snellen equivalent or worse or mean CRT ≥250 µm
BCVA: best-corrected visual acuity, CRT: central retinal thickness, PRN: pro re nata
Sham injection
(n=130)
0 1 2 3 4 5 6 7 8 9 10 11 12
Month 0 1 2 3 4 5 6 7 8 9
Month
Ranibizumab
0.5 mg (n=130)
Ranibizumab
0.3mg (n=132)
Monthly treatment phase PRN treatment phase
Primary endpoint Final assessment
Brown DM et al. Ophthalmology 2010;117:1124–33
13. CRUISE Mean Change from Baseline BCVA
over Time to Month 12
-2
0
2
4
6
8
10
12
14
16
18
2 4 6 8 10 12
0 7
+14.9*
+12.7*
+0.8
*P<0.0001 vs. sham. Earliest statistically significant group difference (P<0.0001 vs. sham) was at Day 7. Vertical bars are ±1 standard error of the
mean. P values for 0.3 mg and 0.5 mg groups vs. sham/0.5 mg group at Month 12 were not calculated. The last-observation-carried-forward method
was used to impute missing data. BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study.
Sham/0.5 mg (n=130) 0.3 mg Ranibizumab (n=132) 0.5 mg Ranibizumab (n=130)
+13.9
+13.9
+7.3
Mean
Change
from
Baseline
BCVA
(ETDRS
Letters)
Month
Day 0–Month 5
Monthly Treatment
Months 6–11
PRN Treatment
14. CRUISE RESULTS: Reading b/w The Lines
•Vision improvement and Sustainability: 14.9 during mandatory
dosing; 13.9 letters during PRN dosing
•Early Tx definitely more beneficial: 7.3 mean letters gain in delayed
Ranibizumab group, compared to 13.9 letters who started RBZ early
Maximum vision gain
14.9 letters at month 5
Mean vision gain
13.9 letters at month 12
Onset-Rapidity of vision gain WOW EFFECT
8 letters gain on as early as day 7
15. • Patients follow up every three monthly
• Mean injections in year one to two: 3.5
• Incidence of ocular SAE 1: %
• Mean BCVA change from Month 12 to 24: -4.1 letters
• CONCLUSION:
- No new safety events were identified
- Reduced follow up & fewer RBZ inj in Second year Decline in vision
- CRVO PATIENTS NEED MORE INDIVIDUALIZED FOLLOW UP AND
DOSING; quarterly follow up is not ideal strategy
16. • Mean Follow Up duration: 51.4 months (FOUR YEARS)
• 44 % patients.... (where edema was resolved)
- Resolution of edema & excellent vision outcomes
- 78% patients gained ≥ 15 letters
- 64 % patients had final VA of 20/40 or better
• About other 56 % patients...(where edema persisted)
- Evidence of Edema
- Required frequent injections even in fourth year
- 33 % gained ≥ 15 letters; 28% had final VA of 20/40 or better
18. • Multicenter, RCT to evaluate intravitreal Aflibercept in CRVO
• 189 patients with macular edema secondary to CRVO
• First Six Months: Aflibercept or Sham Six Monthly injections
• Primary end point: % patients gaining ≥ 15 ETDRS letters at 24 weeks
• After six months: Sham Aflibercept, PRN regimen all patients
Week 24 Week 52
Aflibercept Sham Aflibercept Sham
Aflibercept
≥ 15 letters gain % 56.1 12.3 55.3 30.1
Mean gain 17.9 -4.0 16.2 3.8
19. Ranibizumab in impending CRVO
•Five eyes of impending CRVO
•All had 6/6 vision but blurry
•Disc hot but no macular edema
•Tortous veins with scattered retinal haemorrhages
•All responded to single lucentis
•All features reversed over 1- 2 months
23. 23
•Evaluated effect of PRP in peripheral areas of retinal non-perfusion
imaged with wide angle angiography.
•Study Design
- Prospective study involving 10 patients
- Initially Treatment with Ranibizumab monotherapy (PRN )SIX MONTHS
- After six months, WIDE ANGLE ANGIOGRAPHY PRP in peripheral
retinal non-perfused areas
•Outcome measures: Change in BCVA, num of injections after PRP
24. 24
In this small study, laser photocoagulation to peripheral areas of
non-perfusion as visualized by wide-angle angiography did not result
in either decreased injection frequency or improved VA
POSSIBLE REASONS: Late introduction of PRP, small sample size,
Lack of PRP efficacy?
Before introducing PRP
(0 to 6 months)
After PRP
(6 to 12 months)
No. of injections 3.4 3.1
BCVA 54.2 letters 51.4 letters
25. 25
Objective: To evaluate the effect of combination of Ranibizumab
and Laser photocoagulation to peripheral areas of nonperfusion
in non-ischemic CRVO patients without neovascularization.
Prospective, randomized study, 22 TREATMENT NAIVE patients:
12 in Ranibizumab group (Group R);
10 in Ranibizumab + Laser (Group RL)
3 monthly Ranibizumab, thereafter PRN injections.
6 months follow up study
CoRaLa study
26. 26
R R + L
BCVA change Median, Mean (ETDRS letters) + 6.5, + 2.3 + 14, + 7.3
Mean CRT change (microns) - 159.6 - 178.5
Median num of injections 4 3.5
Mean num of laser tx 0 2.1
Mean Change in non-perfusion areas (DA from
Baseline to six months )
5.8 10.6 4.9 5.7
SELECTIVE LASER PHOTOCOAGULATION OF PERIPHERAL AREAS OF
NON PERFUSION SEEMS TO LEAD TO ADDITIONAL VISION
IMPROVEMENT IN PATIENTS WITH CRVO. LARGE TRIALS REQUIRED
27. SUMMARY OF key CRVO clinical trials
1. Initiated IOP lowering medication 2. subgroup of pseudophakics
28. CONCLUSION
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•Beneficial role of Ranibizumab, Aflibercept, Bevacizumab and
Triamcinolone Acetonide in management of CRVO.
•Mixed results for Dexamethasone implant and Pegaptanib.
•Ranibizumab has the most robust evidence in terms of both
Efficacy and Safety on longer run.
•Steroids: Definite risk of cataract progression & increase in IOP.
•Data on long term efficacy & safety; Head to Head to
comparison, Early identification of Responders is needed.
29. FUTURE RESEARCH
•Cost-effectiveness of Treatment options
•Efficacy and Safety of treatment on longer run
•Newer treatment options for patients able to improve
vision with any available treatment options
31. HISTORY
• 55 year old male presented with complaints of diminution
of vision in left eye since 15 days.
• Patient was a known hypertensive and diabetic.
32. ON EXAMINATION
• BCVA- HM+
• Nv-
• AT- 60
• SLIT LAMP EXAMINATION- corneal oedema,
neovasularization of the iris, shallow AC, Nuclear cataract.
46. HISTORY
• 60 year old female presented to OPD with complaints of
diminution of vision in right eye since 2 months.
• Systemic illness- recently diagnosed hypertensive.
52. CASE 4
65 Year male
1 Eyed
DM + HT+ POAG on xalatan
CRVO 4 years ago
Therapy :
1. Laser
2. Two Macugens
3 Ozurdex led to glaucoma
3. 16 Lucentis inj on PRN basis
4. Nevanac Only (as Steroid Responder)
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62. 2 YEARS HENCE
• Further PRN lucentis injections
• Cataract plus IOL done under lucentis cover
• Vision improved to 6/12
• Still requires injections every 2 months
62
66. CASE 5
•60 yr lady
•Diabetes and hypertension
•CRVO in OS 6 yrs ago
•Underwent vitrectomy with RON in
preVEGF ERA with laser
•Now yet under treatment with PRN avastin
