RAP TREATMENT WITH LUCENTIS

1. Case Report of RAP Lesion
Dr. Ajay Dudani
Mumbai Retina Centre

2. Definition
• Yannuzzi et al. coined the term retinal
angiomatous proliferation (RAP) to describe a
variant of neovascular age-related macular
degeneration (NV-AMD) with a presumed
retinal origin1
• Retinal angiomatous proliferation (RAP) is a
distinct form of choroidal neovascularization
which may complicate a wet age related
macular degeneration (AMD)2
• Retinal anastomosis to lesion
• Type 3 CNVM
1. Retina 2001;21:416e34; 2. Curr Drug Targets. 2011 Feb;12(2):199-205.

3. RAP Features
RAP is associated with
• Proliferation of retinal capillaries
• Intraretinal neovascularisation (IRN)
• Surrounding telangiectatic response
Clinical manifestations include
• Pre- and intraretinal haemorrhages
• Exudates
• Intraretinal oedema
• serous detachment of the pigment epithelium
Br J Ophthalmol. 2010;94:672-677

4. Clinical Classification of RAP
• Stage I - Intraretinal neovascularization
(IRN): describes the capillary proliferation
within the retina that originates from the
deep capillary plexus in the paramacular
region. This stage is often accompanied by
intraretinal hemorrhages and edema.

5. Retinal angiomatous proliferation (RAP)
Stage I: intraretinal neovascularization

6. Some More Images
A,
Fluorescein angiogram of an
RAP stage I lesion. Note that
intraretinal neovascularization
(IRN) is bordered by
telangiectatic vessels.
B,
Magnified image of the RAP
lesion.
C,
Indocyanine green angiogram
showing a “hot spot.”
D,
Ophthalmic coherence
tomogram of the same case
shows reflectance and
shadowing by the IRN.
Retina. 2008 Mar;28(3):375-84.

7. Stage II
• Stage II consists of sub retinal
neovascularization (SRN) that occurs
when the IRN extends posteriorly, beyond
the photoreceptor layer of the retina into the
subretinal space. A localized, neurosensory
retinal detachment develops with increasing
intraretinal edema, intraretinal and
preretinal hemorrhages, as well as an
associated serous pigment epithelial
detachment (serous-PED)

8. RAP Stage II: subretinal
neovascularization with a retinal-retinal
anastomosis.

9. Some More Images
A: Fluorescein angiogram of
type 3 neovascularization
stage II with serous pigment
epithelial detachment (PED).
Hyper-fluorescence of the PED
(arrows) corresponds to the
RAP lesion.
B: Indocyanine green
angiogram demonstrates the
“hot spot,” whereas the
serous PED is hypofluorescent
and optically clear.
C: Ophthalmic coherence tomogram (OCT) shows cystic change in the retina,
the intraretinal RAP lesion (arrow), and the serous PED.
D: Fluorescein angiogram of type 3 neovascularization stage II with serous PED.
E: OCT reveals the intraretinal neovascularization and a possible retinal–
choroidal anastomosis (arrow). There is cystoid edema overlying the PED.
Retina. 2008 Mar;28(3):375-84.

10. Stage III
• Stage III describes choroidal
neovascularization seen clinically and
angiographically, sometimes in association
with a vascularized pigment epithelial
detachment (vascularized-PED) . During
the evolution of this vascularized process,
an axonal communication between the
retinal and choroidal circulation forms a
retinal-choroidal anastomosis (RCA)

11. RAP Stage III: Choroidal neovascularization with a
vascularized pigment epithelial detachment and a
retinal-retinal anastomosis.

12. Some More Images
A: Indocyanine green angiogram shows communication among intraretinal,
subretinal, and choroidal neovascularization (retinal– choroidal anastomosis
[RCA]).
B: Optical coherence tomography shows the cascading neovascularization
process with an RCA.
Retina. 2008 Mar;28(3):375-84.

13. CASE PRESENTATION

14. History
• 80 year old male
• Strong family history of AMD
• LE – Diagnosed with AMD 11 years ago,
Underwent 2 TTT’s, 3 PDT’s with IVTA, now
has macular scar with Vn of HM
• RE – Has had 1 PDT (Nov 2005) for extra
foveal RAP lesion and 20 injections of
Lucentis in the past 5 years.

15. Fundus Photos before injections
(sep 2005)
RE
LE

16. Initial OCT (sep 05)

17. Initial ICG (Early) (sep 05)

18. Initial ICG (mid) (sep 05)

19. Initial ICG (late) (sep 05)

20. Initial FFA (EARLY) (sep 05)

21. Initial FFA (mid) (sep 05)

22. Initial FFA (LATE) (sep 05)

23. PDT (sep 05)
• Underwent PDT for RAP lesion
• 2 months later OCT (nov 05)

24. Monthly OCT’s
• Underwent
monthly
OCT’s and
had fluid in
OCT after 6
months. (may 06)

25. FF at this time (may 06)

26. ICG (early) at this time (may 06)

27. ICG (mid) at this time (may 06)

28. ICG (late) at this time (may 06)

29. Lucentis started (may 06)
• Underwent 3
injections of
lucentis at 2
monthly intervals
• Then had
monthly OCT’s
with no fluid and
maintaining
vision of 6/9 N5
for the next 8
months
POST INJECTION OCT

30. OCT 8 months after 3 consecutive
lucentis injections (may 2007)

31. Lucentis
• Undergoing monthly OCT’s since 3 years
now
• Since May 2007, fluid appears on OCT
every 3 months. FFA every year. There is
no change in vision / or metamorphopsia.
• Has received Lucentis every 3 months
since May 2007.

32. Lucentis Protocol followed
• Initially 3 injections at 2 month intervals
• Monitored with monthly OCTs – Fluid was
noted 8 months later – Injection given.
• Underwent cataract surgery under cover of
Lucentis injection – 1 week before and 2
more injections, monthly, after surgery.
• Further monitored on monthly basis and
has developed fluid consistently every 3
months warranting an injection.

33. RECENT OCTs
(2008- till date)
• OCT (Sep 08) : Fluid
with thickening always in
same area- infero – nasal
extra foveal region.
• Vision 6/9
• No metamorphopsia
Lucentis given

34. OCT (Oct 08):
• Post injection-
no fluid / no thickening

35. OCT (Dec 08)
• 3 months post
injection-
Infero-nasal extra foveal
thickening.
No fluid.
FFA done.
Vision 6/9
No metamorphopsia
LUCENTIS GIVEN

36. (Dec 08) FFA: Early

37. FFA: Mid

38. FFA: Late

39. OCT – Jan 09
• No fluid
No Thickening
Vision 6/9
• Needed injection
again in march 09

40. March 09 to
May 09
 Injection lucentis
every 3 months
 There is infero-
nasal thickening
in para foveal
region just prior
to fluid
appearing

41. On May 09
• Vision: RE 6/9, N5
LE HM
reduced contrast vision
• Bilateral pseudophakia
• RE: Confluent drusen with RPE atrophy
• LE: Extensive macular scar with serous
elevation.
• We now inject 2 weeks prior to 3 months
and then extend so that we inject just
before the fluid appears

42. QUESTIONS
• Is it a RAP lesion and is there any role
of PDT / Green laser in this case?
• What are the risks of RPE atrophy with
repeated Lucentis injections?

43. Lucentis Protocol followed (RE)
• Initially 3 injections at 2 month intervals
• Monitored with monthly OCTs – Fluid was
noted 8 months later – Injection given.
• Underwent cataract surgery under cover of
Lucentis injection – 1 week before and 2
more injections, monthly, after surgery.
• Further monitored on monthly basis and
has developed fluid consistently every 3
months warranting an injection.
• Treat and extend

44. Fundus Photos before injections (sep
2005)

45. Serial angiography
Sep
2005
(FFA)
May 2006
(ICG)
Oct
2008
(FFA)

46. Serial OCTs
Sep 05 – PDT
done
May 06 – post lucentis –
3 injections at 2 monthly
intervals
May 06 – fluid 6
months later –
Lucentis started

47. Serial OCTs
May 07 – Fluid 8 months
after last injection – needed
injection every 3 months
since..
Jan 09 – eg of OCT post
injection
March 09 – fluid in 3
months – Thickening
of same parafoveal
area every 3 months

48. Serial SLO photos
Aug 2010
Mar 2009
Sep 2008
May 2011

49. Discussion
• RPE atrophy progressed in last 4 years
• Reduced contrast vision
• Protocol:
 Judicial use of Lucentis
 Extend the interval between injections based on
fluid on OCT.

50. Yannuzzi’s Opinion
• Complimented on accurate diagnosis
• The Retinal Angiomatous Proliferation
which was on the nasal side of the fovea in
the left eye soon became associated with
pigment epithelial detachment.
• Macula is flat, but there is regressed and
consolidated neovascularization
• Only a few intraretinal cystic changes are
present

51. Yannuzzi’s Opinion
• The primary concern is well known and manifested
in the paramacular region with globular atrophy.
• For some reason, this particular variant of
neovascular age-related macular degeneration
becomes associated with a virulent type of
progressive atrophy.
• Cause of the above is not known clearly
• According to Dr. K. Bailey Freund and me
(Yannuzzi) atrophic progression can be beyond
insidious in nature
• I do not believe that is associated with the
injections, but certainly we don’t have absolute
information regarding that.

52. Yannuzzi’s Opinion
• With an acuity of 20/25+, medication interval at
3 months should be used on experiencing
recurrent exudation for a shorter period.
• Maintenance of your systemic blood pressure,
avoidance of chronic exposure to the sun and
smoking, and supplemental anti-oxidant
medications would be supportive measures
within the group.
• There is no evidence regarding the Lutein, but
Omega 3 and of course the standard anti-
oxidants are rational supplemental
medications.