This document discusses the role of anti-VEGF therapy in the management of neovascular age-related macular degeneration (AMD). It outlines various treatment options for neovascular AMD including laser photocoagulation, photodynamic therapy, and anti-VEGF therapy. Anti-VEGF agents like ranibizumab, bevacizumab, and aflibercept are effective at inhibiting VEGF and stabilizing vision in neovascular AMD patients. Clinical trials demonstrate the superiority of monthly ranibizumab injections over sham treatment or verteporfin photodynamic therapy. While bevacizumab has equivalent visual outcomes to ranibizumab, it is not FDA approved and has higher rates of systemic side effects

1. -MANOJIT SARKAR
FINAL PROF
Malda Medical College
Role of anti-VEGF in the management
of AMD

2.  Anti-VEGF therapy :- role in neovascular AMD
 No role in non-neovascular AMD

3. Treatment options for neo-vascular
AMD
 1) Laser Photocoagulation
 2) Photodynamic therapy
 3) Anti-VEGF therapy
 4) Other treatment modalities:- Transpupillary
thermotherapy(TTT), radiotherapy,submacular
surgery to remove subretinal
blood/CNV/both,macular translocation,pneumatic
displacement of haemorrhages.

4. Laser Photocoagulation
 Now a days used rarely
 It is an option for extrafoveal lesions (for which
treating physician believes it is safe and will not
damage foveal center)

5. Photodynamic therapy
 Approved(USFDA) for predominantly classic-CNV
 With the advent of pharmacotherapy,PDT use has
decreased considerably.

6. Anti-VEGF agents available for
neovascular-AMD
 1) Pegaptanib(not used now-days)
 2) Bevacizumab
 3) Ranibizumab
 4) Aflibercept

7. How Anti-VEGF works
 Several angiogenic factors play role :- VEGF(Vascular
endothelial growth factor), FGF, transforming growth factor etc
 Major focus of antiangiogenesis research is on inhibition of
VEGF
 VEGF expression is increased in pigment epithelial cells during
the early stages of AMD. High concentration of VEGF have been
observed in excised CNV from AMD patients as well as in
vitreous
 Treatment of AMD with anti-VEGFs is thus considered to be a
turning point since its emergence has allowed a more direct
approach to choroidal neovascularization and its selective
inhibition.

8. Efficacy of Ranibizumab vs Sham
treatment
 There are many studies
 In MARINA study patients received monthly injections of 0.3
or 0.5 mg of Ranibizumab or Sham treatment continuously
over 24 months
 Results:- At 12 months,95% of Ranibizumab –treated eyes
compared with 62% of Sham treated eyes, lost<15 letters in
Va.
 Visual improvement by >15 letters was found in 34% of eyes
treated with a dose of 0.5mg.
 At 24 months,90% of eyes in the 0.5mg group had continued
to maintain stable vision without loss of > 15 letters compared
with 53% in the control group.

9. PDTwith Verteporfin for
predominantly classic subfoveal
CNV
 ANCHOR Study
 Primary outcome (Visual acuity decline of fewer
than 15 letters from baseline at 12 months), 96.4%
of the 0.5mg group and 64.3% of verteporfin group
avoided this loss. Maintained at 24 months.
 Visual acuity improved by 40.3% in 0.5mg group as
compared with 5.6% in verteporfin group.

10. Bevacizumab vs Ranibizumab
 Visual acuity outcomes when using
Bevacizumab(off-level use) every 4wks were
equivalent to those when using Ranibizumab every
4wks.(The comparison of Age related Macular
Degeneration Treatment Trials- CATT).
 Cost was less in Bevacizumab group but
Bevacizumab groups had higher rate of systemic
serious adverse events than Ranibizumab group.

11. Aflibercept vs Ranibizumab
 Many studies found Aflibercept(Eyelea) given every
4wks for 3 doses followed by every 8wks through
48wks gave equivalent outcomes to Ranibizumab
(Ref:- Twelve-Month Outcomes of Ranibizumab vs. Aflibercept for Neovascular Age-Related
Macular Degeneration: Data from an Observational Study. Ophthalmology;December
2016Volume 123, Issue 12, Pages 2545–2553)
 But VIEW-1 and 2 study found Aflibercept as superior

12. Treatment Schemes
 USFDA approved monthly injections as follows:-
 FDA recommended intravitreal dose of Aflibercept
2.0 mg. The suggested regimen is monthly
injections for the initial 3 months followed by a fixed
dosing every eight weeks.
 For Ranibizumab the approved dose is 0.5 mg of
ranibizumab Monthly
 Bevacizumab not approved
.

13. Treatment Schemes
 Other accepted treatment schemes are:-
 1) treat and observe:- regular treatment is
performed until the macula is mostly free of
exudation,followed by treatment only for signs of
recurrent exudation during the maintenance phase
 2) treat and extend:- regular monthly treatment is
continued until macula is dry,after which treatment
continues at gradually increasing intervals

14. Treatment Schemes
 Several clinical trials are evaluating as-needed
approaches to anti-VEGF
therapy(PrONTO,SAILOR,SUSTAIN,HORIZON
studies). All these studies utilize 3 monthly
injections followed by various as –needed
treatment regimens(based on vision status and
OCT findings).

15. Future Trends
 AMD is multifactorial:- explain the lack or insufficient response to
antiVEGF therapy observed in about 25% of patients.
 Combination therapy such as Low fluence PDT with anti-VEGF
pharmacotherapy is under trial
 Current and future trials are clinically evaluating potentially more
potent anti-VEGF molecules and molecules targeting alternative
growth factors or pathways.
 The drugs in pipelines are- Brolucizumab and DARPins,
Conbercept Tyrosine kinase inhibitors like -pazopanib,
regorafanib and Pan-90806, Anti-platelet-derived growth factor
,Gene therapy,etc.

16. Thank You