Pagenax rapidly resolves fluid and improves vision in refractory nAMD cases

Cases With
Pagenax
Prof. Ajay Dudani
Mumbai Retina Centre
SANTACRUZ
MUMBAI

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

30th Oct 2020
Pagenax Injection given
Current VA 6/ 60

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

31st Oct 2020
After 1 day
of Injection

One week after
Pagenax Injection given
Current VA 6/ 24

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

• 100micron less
• Day 10
• 6/18

Case- mrs thill
• 80 yr lady
• Occult CNVM -2003
• 2 PDT
• LUCENTIS 40 INJ –PRN
• 2 OZURDEX
• VISION CF 3M –DRILL, RETINAL CYSTS, SHREM,SR FIBROSIS
• LATEST PAGENAX
• 3 DAYS LATER 6/60 MAGIC-PED REDUCTION BY 200 MICRONS

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

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.

1 month
• Foveal contour
• First time ever
• No IRF PED SHREM

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

CASE –mr ira
• 78 YR PARSI
• BE SOFT DRUSENIOD PED 6/6
• DV 15 DAYS 6/12
• LARGE PED
• PAGENEX DONE
• NO CHANGE IN 1 WEEK
• ? SOLID PED

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

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

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

• 1 week
• 6/60
• No IRF

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

• LE PED
• DOUBLE HUMP
• IPCV

• OD-CNVM
• IPCV
• SCARRING

• F U 1 WEEK
• PED <200MICRON

CASE – mrs SAMa
• 70 OLD LADY
• OCCULT CNVM
• MULTIPLE RANIBIZUMAB INJECTIONS LOADING AND PRN
• SWITCHED TO BROLICIZUMAB ON 30 NOV

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)

CASE –mrs KAR
• 80 YRS FEMALE
• RE OCCULT CNVM ?IPCV -6/12 –CONICAL PED
• 80 ACCENTRIX OVER 10 YRS STARTING 2010
• LE SCARRED CNVM- AMD
• POST LOCKDOWN 9 MONTHS VN DROPPED 6/60 BOTH EYES
• RE- IRF ,PED-MULTILAYER,PACHYCHORIOD,SHREM
• LE- PED
• BE PAGENAX
• DAY 1 PT FEELS BETTER- FLUID LESS

• PRE
• PAGENAX
• RE
• IRF INCREASED

• RE- DAY 15
• 6/36
• ZERO FLUID

• RE –FLAT
• NO IRF
• PACHYCHOROID

• LE –PED FLAT
• 6/36
• YAG DONE

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.

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.

Take home message
• When to use Pagenax
 In case of recalcitrant patients
 In De-novo patients
 In non responsive / Chronic patients

Take home message
• When to switch to Pagenax
 Non Responders
 Tachyphylactic

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

Take home message
• Advantages of Pagenax
 Long acting drug (3Months)
 Small molecule better penetrative power
 Excellent Drying

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

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

Case- mr path
80 yr male, High myopic, Le CVNM-TYPE2
Cf1 m
One Accentrix
One Pagenax
Cf5 m
Pt says better than last injections Scotoma
reduced

• 1 MONTH
• POST INJ
• FLAT

Case –mr dub
55 year male
RE 6/9
CNVM
4 accentriX
OCT-INTRARETINAL SPLIT AT EZ ELM
Last Pagenax

10th Nov 2020
After 1 day
of Injection
on 10th Nov

10th Nov 2020
After 1 day
of Injection
on 10th
Nov-ELM
back

CASE - mrs HAR
• 54 YR LADY
• CHRONIC CSCR WITH MACULAR CNVM
• ACCENTRIX GIVEN
• SWITCHED TO BROLICIZUMAB

• 1 WEEK
• 6/6 N6
• DRYING
• ATROPHIC

CASE –mr MALK
• 45 YR MALE
• BILATERAL CNVM
• BIETTE’S CRYSTALLINE RETINAL DEGENERATION
• MULTIPLE INJ OF RANIBIZUMAB AND AFLIBERCEPT -10 YRS
• VISION OD-6/60, OS- CF 5 M
• ? OS BROLICIZUMAB

Pagenax rapidly resolves fluid and improves vision in refractory nAMD cases

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