vmt e ocriplasmin francesco barca stanislao rizzo daniela bacherini azienda ospedaliero...
TRANSCRIPT
VMT e Ocriplasmin
Francesco BarcaStanislao Rizzo
Daniela Bacherini
Azienda Ospedaliero Universitaria Careggi Firenze
Simpson et al Surv Ophthalmol 2012
VMA: focal adhesion of the vitreous face within the macula region without any associated retinal distortion
VMT: VMA causing focal tractional distortion of the macula. This image has been proposed as a photographic standard to define VMT
VMT: VMA causing focal tractional distortion of the macula.
Goal of therapy …
To RELEASE vitreous TRACTION on the macula thereby resolving the underlying
condition BEFORE structural retinal damage has occurred!
Vision Improvement
Microplasmin for Intravitreous Injection Traction Release without Surgical Treatment
2 randomized, placebo-controlled Phase 3 studies:
TG-MV-006 and TG-MV007
MIVI-TRUST
Ocriplasmin: truncated form of human plasmin
Plasmin Ocriplasmin
Ocriplasmin acts on Laminin and Fibronectin, molecolar glues between PVC and ILM
Posterior vitreous cortex
ILM
Vitreous
Therefore … Release of VMT!
Indication
Ocriplasmin is a truncated form of Human Plasmin
Trattamento della TVM, compresa quella associata a MH di diametro ≤ 400 microns
Stalmans P, Benz MS, Gandorfer A, et al; MIVI-TRUST Study Group. N Engl J Med. 2012;367:606-615.
n=19 123
PlacebooN=188
OcriplasminN=464
p<0.001
Jetrea (ocriplasmin)Resolution of VMT at Day 28
Patie
nts,
%
Placebo N=188 (10.1%)
OcriplasminN=464 (26.5%)
Placebo 1 : 10
Ocriplasmin 1 : 4
Jetrea (ocriplasmin)Resolution of VMT at Day 28
Independent Baseline Features Predictiveof Pharmacologic VMT Resolution
FTMH present
VMT diameter ≤1500 μm
ERM absent
Phakic
Age <65 years
% with VMA Resolutionp-valuePatient Type OcriplasminPlacebo
<0.001Symptomatic VMT 26.510.1
0.006+ FTMH 50.025.5
0.026+ age <65 years+ diameter ≤1500 μm
60.026.2
0.017+ no ERM 66.435.0
0.020+ phakic status 70.540.0
Ocriplasmin
Placebo
100%
100%
Positive Predictors Criteria
Enzyme impact on small adhesions is expected to be
maximal
Focal adhesion (≤1.500 μm)
Positive Predictors Criteria
Enzyme impact on small adhesions is expected to be
maximal
Focal adhesion (≤1.500 μm)
No epiretinal membrane (ERM)
Enzyme does not dissolve membranes
Younger age
Phakic
Probably selection bias: patients pseudophakic or
aged>65 years would already have developed a spontaneous
PVD, therefore patients enrolled might be more resistant cases of VMA
- 35 subjects with symptomatic VMA.- Retrospective interventional case series
- Resolution of VMT 43%
Predictive factors of VMA resolution:
• age<65 years (p 0.04)
• Retinal comorbidity absence (p 0.02)
• Adhesion diameter <1500 micron (p 0.005)
• VMA duration (p 0.03)
Proportion of Patients With FTMH Closure at Day 28
Day 28
Patie
nts
With
FTM
H C
losu
re, %
Placebo (n=47)
Ocriplasmin(n=106)
p<0.001
n=43n=5
Stalmans P, Benz MS, Gandorfer A, et al; MIVI-TRUST Study Group. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med. 2012;367:606-615.
< 400: 48.8%
< 250: 58.3%
safety
1) ACUTE REDUCTION VISUAL ACUITY
Visual acuity loss was attributed to:
- progression of the associated macular pathology (vitreomacular traction and/or fullthickness macular hole)
- or to onset of a subretinal fluid at the fovea despite VMA resolution
Premarketing, or clinical trial, data (n = 999 inj.) 6-month study end point.
Postmarketing reports through July 16, 2013 (n = 4,387 injections)
26% were ongoing or resolving< 35% resolution status unknown.
- Foveolar lucencies observed by OCT are a common finding after macular hole surgery (26%).
- They occur with and without ICG-assisted ILM peeling and irrespective of the type of gas used for tamponade in this small group of eyes.
- Foveolar lucencies gradually decrease and eventually resolve over 3 to 11 months without further surgical intervention.
- Disappearance of the foveolar lucency correlateswith further improvement of visual acuity.
It remains uncertain as to why the foveolar lucencies took so much time to resolve (3–11 months) and what the material within lucencies consists of.
Retrospective, single-center, observational case series In 38 eyes with VMT (10 with concomitant full-thickness macular hole),
- Subretinal fluid in the macular region was observed in 36.8% of eyes 1 day afterinjection, with resolution by day 42
VMT RESOLUTION
2) ERG CHANGES
3) DYSCHROMATOPSIA
4) RETINAL TEAR/DETACHMENT
•RBs in: 1.1% (23/1862 eyes)
Retinal Tears in Macular Surgery: 23-25 Gauge Cannula System
2) ERG CHANGES
3) DYSCHROMATOPSIA
4) RETINAL TEAR/DETACHMENT
5) LENS SUBLUXATION/PHACODONESIS
Case Reports
REVERSIBLE VISION LOSS AND OUTER RETINAL ABNORMALITIES AFTER
INTRAVITREAL OCRIPLASMIN INJECTIONThanos et al. Retinal cases and Brief
reports 2014
A 55-year-old woman experienced acute severe vision loss 2 days after the treatment with ocriplasmin, recovered over a 3-month period after the injection
a 97 year old patient with vision reduction after 1 day ocriplasmin inj; resolution after 56 days
A 71-year-old woman with vision loss after ocriplasmin: improvement after 4 months, with persistent discontinuity of the ellipsoid zone
a 63-year-old woman with acute panretinaldysfunction after intravitreous ocriplasmin injection for a small macular hole with VMA. A 67-year-old female with VMA, ERM and macular hole . One week following intravitreal ocriplasmin visual acuity had decreased to 20/400. 3 weeks later: persistence of the macular hole
Alterations of Ellipsoid Zone
Presence of Subretinal Fluid
ELLIPSOID ZONE
INTERDIGITATION ZONE MYOID ZONE
OUTER RETINAL FINDINGS
Transient loss or disruption of the ellipsoid zone: discontinuity of the IS/OS layer
Diffuse loss of this bandDay 2
Strong ellipsoid zone bandDay 0
Return of the ellipsoid zoneDay 32
Subretinal fluid: often associated with VMT resolution
The same isoform of laminin found in the internal limitation membrane is also expressed in the IPM
(InterPhotoreceptor Matrix)
Ocriplasmin may penetrate through the retina and react with the laminin located within the IPM
IPM is known to play a major role in mediating retinal adhesion to the RPE
- 35 subjects with symptomatic VMA.- Retrospective interventional case series
- Resolution of VMT 43%
Predictive factors of VMA resolution:
• age<65 years (p 0.04)
• Retinal comorbidity absence (p 0.02)
• Adhesion diameter <1500 micron (p 0.005)
• VMA duration (p 0.03)
• Transient outer retinal attenuation: •28.6%•Broadest VMA diameter•Resolved in all cases at mean 24.2 days after IVI •p 0.008
VMA Resolution Rate (%)Overall rate of
MH Closure
(%)Overall
VMA Diameter≤1500 μm
No ERMFTMH
Present
Phase 3 Trials 26.5 34.7 37.4 50 40.6
Bascom Palmer 42.1 50 54.5 66.7 50
Cole Eye 47.1 61.5 50 NR 80
California Retina
56 n/a 56.5 72.7 36.4
NJ Retina 35 38* 41.5 73.3 32
Real-World Clinical Experience Summary
Real-Italy Clinical Experience Summary
VMA Resolution Rate: 57%
FTMH Closure Rate: 62.5%
Presence of ERM: 45%
No ERM: 64.8%
Tips For Using Ocriplasmin
Consider injecting as posteriorly as possible – bury the ½-inch needle to the hub
Consider laying the patient back for up to 30 minutes after the injection
Use the predictor of response guidelines
• Ocriplasmin is not the same as other intravitreal agents we are currently utilizing in clinical practice
• Who, how and when we inject may be important…
• Patient selection plays a role in the success rate of therapy
• The majority of adverse events associated with ocriplasmin therapy:
• Have an acute onset: Days 0–7
• Are mild/moderate in severity
• Are transient and self-limiting
Conclusions
JETREA:Classe Hfarmaci a carico del Servizio Sanitario Nazionale
utilizzati o forniti in ambito ospedaliero
05/03/2015
grazie