4. Case - mrs mir
64 year lady with occult CNVM large PED
Past Interventions:
24 Accentrix
5 Eylea
FIRST Pagenax Injected on 30-10 -20
A SECOND PAGENAX MOTH LATER
12. 4. Hyperreflective Foci
• Particularly adjacent to fluid lesions
• Migrating RPE cells, Pigment-laden macrophages, Microexudates of lipid, fibrin or activated
microglia
• In early AMD, hyperreflective foci are a risk factor for progression to advanced disease
• May be an early sign of Type III (RAP) neovascularization
1. Ritter M, et al. Br J Ophthalmol 2014;98:1629–1635
2. Yun H et al. Graefe's Archive for Clinical and Experimental
Ophthalmology 08:2019
12
19. 7. Pigment Epithelial Detachment
• PED was present in 54%-80% of patients at the time of enrolment in CATT, EXCITE, and VIEW
• A course of three monthly anti-VEGF injections generally reduces the rate of PED by about 25%, in contrast
to a 70% - 80% resolution of sub- and intraretinal fluid
Ross H et al. Springer 10.1038: 09; 2019 19
In the VIEW studies, patients received continuous
anti-VEGF therapy during the first 48 weeks. At 52
weeks, a discontinuous, “as-needed” dosing regimen
was introduced. Only eyes with pigment-epithelial
detachments developing secondary intraretinal
cystoid fluid
33. Clinical Implications
• Patients with nAMD should be diagnosed and treated early
• Patients presenting with extensive foveal cystoid fluid may be counselled that, though they are likely to
experience some gain in VA, even aggressive treatment may not provide similar levels of functional benefit
as in the average patient without such morphologic changes
• Anti-VEGF treatment may be stopped for cystic degeneration (“degenerative IRC”) overlying RPE atrophy or
scarring due to the limited responsiveness of such fluid
Lai TT et al. Scientific reports. 2019 Jan
24;9(1):529
33
34. Differentiation of IRF is most important
• Degenerative – small with underlying RPE atrophy scarring or atrophy, poor response to anti VEGF,
need aggressive therapy and modification of treatment modalities
• Exudative – large, ovoid shaped, quick and good response to anti VEGF, less frequent follow up and can
have more flexible regimen
Business Use Only 34
Lai TT et al. Scientific reports. 2019 Jan 24;9(1):529.
38. CASE-mrs dhaM
• 76 YR LADY
• BE CNVM
• RE SCARRRED -CFCF
• LE 6/12 OCCULT CNVM IPCV WITH RED PED AND EXUDATES
• 3 ACCENTRIX
• NOW PAGENEX
• DAY1 -6/9
• PED REDUCTION BY 200 MICRONS
46. 9. Condition of the Vitreomacular Interface
Studies report that the rate of posterior vitreous detachment in eyes with neovascular AMD ranges from 60% to 74%
Patients with both posterior vitreous detachment and SRF at baseline demonstrated very stable visual acuity benefits
even with infrequent treatment
Eyes without vitreomacular adhesion demonstrated less need for retreatment in a PRN protocol in CATT
Clinical Implications
Patients with complete posterior vitreous detachment, such patients may be recommended a treat and
extend regimen, particularly if SRF is also present at baseline
On the other hand, patients without a complete posterior vitreous detachment should be treated intensively and
aggressively to avoid possible functional losses with infrequent therapy
48. CASE –mr MITR
• 79 YR MALE
• RE OCCULT CNVM SINCE2018-6/12
• MULTIPLE RANIBIZUMAB MONTHLY THEN PRN-2 MONTHLY
• PED WITH SUBRETINAL HAEMORRAGE
• SWICH TO AFLIBERCEPT AND OZURDEX
• GOT COVID IN ICU ETC
• NOW BACK WITH INTRARETINAL AND SUBRETINAL FLUID-PED
• CF 2M –BROLICIZUMAB GIVEN ON 30 TH NOV
56. 5. Subretinal Hyperreflective material and Fibrous scarring
• Particularly in Type II (classic) CNV, new vessels from the choroidal neovascular complex typically proliferate
directly in the subretinal space after initially penetrating Bruch's membrane
• Usually associated with an active CNV lesion, including subretinal haemorrhage and lipid or fluid exudation
1. Vinnie P et al RETINA 34:1281–1288, 2014
2. Erfurth U et al. Progress in Retinal and Eye Research 50 (2016) 1-24 56
Baseline presentation of patient
with nAMD
SHRM
Presentation following long term VEGF
inhibition
SHRM and
PED have
condensed
into a spindle
shaped fibrous
scar
60. CASE-mr FEDL
• 80 YR MALE
• RE –CF 2M LE -6/18
• BE OCCULT CNVM IPCV WITH PED RE 2010 LE 2018
• BE- MULIPLE AVASTIN,AFLIBERCEPT, RANIBIZUMAB
• LE- BROLICIZUMAB -2DEC 20 FOR OCCULT DOUBLE PED
76. 5. Outer Retinal Tubulations
Hyporeflective, branching tubular structure surrounded by a hyperreflective ring, located in the
outer nuclear layer of the retina and often overlying fibrous scarring
Outer retinal tubulation may be misdiagnosed as intraretinal or subretinal fluid, which lacks the
hyperreflective border
1. Karen B et al. RETINA 35:1339–1350, 2015
2. Erfurth U et al. Progress in Retinal and Eye Research 50 (2016) 1-24
76
ORT
Open ORT (An
ovoid cross-section
lacking
hyperreflectivity on
its outer
aspect (adjacent to
the scar)
99. Post-Hoc Analysis Conclusions
• Brolucizumab 6 mg is associated with greater and sustained reduction
in SHRM and PED compared with aflibercept .
• Although the majority of patients treated with brolucizumab achieve
complete drying of IRF, SRF, and Sub RPE fluid ,most still demonstrate
residual Type1 MNV.
• A Maximum reduction in SHRM with persistence of a PED without
exudation may be the preferred anatomic configuration for the
optimal long-term visual outcomes.
• As this is the post-hoc analysis, observations needs to be confirmed in
future long-term prospective studies.
100.
101.
102.
103.
104. Summary
• Brolucizumab is an potent addition to our treatment armamentarium
for patients with Neovascular AMD.
• Appears to have superior drying and consequently superior durability
over other currently available agents.
• Severe intraocular inflammation and occlusive retinal vasculitis with
vision loss, is uncommon (prob<1/100), but requires comprehensive
discussion with the patient prior to use ,weighing this risk against the
risk of vision loss with persistent activity.
105. Take home message
• When to use Pagenax
In case of recalcitrant patients
In De-novo patients
In non responsive / Chronic patients
106. Take home message
• When to switch to Pagenax
Non Responders
Tachyphylactic
107. Take home message
• When to avoid using Pagenax (in which type of patients)?
H/O Old Thrombosis
H/O of IOI
Any Ocular surgery / Interventions
108. Take home message
• Advantages of Pagenax
Long acting drug (3Months)
Small molecule better penetrative power
Excellent Drying
109. AAO 20-PAGENAX
• IRIS REGISTRY 1200 PATIENTS OF BEOVUE
• RETINAL VASCULITIS- RV AND RETINAL VASCULAR OCCLUSION-RO
• HIGHEST RISK IN 6 MONTHS
INTRAOCULAR INFAMMATION-IOI
• OR PRIOR RO IN 12 MONTHS BEFORE FIRST BEOVUE
• OVERALL RISK OF RV OR RO -0.46%
• INCREASED TO 3.97% -PRIOR IOI OR RO
110. AAO 20 -PAGENAX
• 50% WET AMD-UNRESOLVED FLUID
• 1/3 RD NEED MONTHLY INJECTIONS
• UNMET NEED IN WET AMD FOR BEOVUE
• HAWK HARRIER DATA-INCREASED RV/RO IN EYES WITH TREATMENT
EMERGENT-BOOSTED /INDUCED-ANTI DRUG ANTIBODIES-ADAs
• GREATER AND SUSTAINED REDUCTION IN PED AND SUBRETINAL
HYPER-REFLECTIVE MATERIAL VS AFLIBERCEPT
• FIRST SINGLE CHAIN ANTIBODY FRAGMENT –SMALLER SIZE 26
KDA,TISSUE PENETRATION,RAPID CLEARANCE,HIGHER
CONCENTRATION 6 MG,MORE ACTIVE BINDING TO VEGF RECEPTORS
