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