1. In the name of God

2. Pneumatic & Pharmacologic Vireolysis
Masood Naseripour MD
IUMS

3. VitreoMacular Interface(VMI)
The ILM primarily is composed of type IV collagen.
The extracellular matrix between the ILM and posterior vitreous cortex is rich in glycoproteins, typical extracellular matrix (a glue-like matrix) constituents, and a range of collagen types, each of which is purported to play a role in vitreoretinal adhesion.

4. VMI Various pathologic changes may occur at the VMI. These include:
VMA,
Vitreomacular traction syndrome(VMT),
Epiretinal membrane
Macular hole
CME
Vitreous hemorrhage,
Retinal tear, and even rhegmatogenous retinal detachment.

5. Management Watchful waiting Pars –Plana Vitrectomy
Pneumatic Vireolysis
Pharmacologic Vireolysis

6. “Watchful Waiting”
In patients with tractional VMI disease, “watchful waiting” has been the traditional standard of care.
In some patients, watchful waiting results in favorable outcomes, including spontaneous resolution of VMA.
To date, the spontaneous VMT resolution has been well documented in different series, with a rate ranging from 11% to 53%

7. “Watchful Waiting”
Using fundus photography, a population-based study of 3654 persons showed that
only 29% of ERMs progressed over 5 years;
26% regressed
and 39% remained approximately the same.

8. Natural Course
The majority of ERMs will remain relatively stable and do not require therapy.
In patients who have areas of VMT of 1500 μm or less, the incidence of spontaneous release of traction from the macula occurs in approximately 30% to 40% of eyes over a follow-up of 1 to 2 years.

9. Natural Course
This study has several strengths, including that it is the largest (556 eyes of 400 patients, Belgium) cohort of patients and eyes with VMI. Other observational cohorts ranged in size from 11 to 214.
Almost 40 % of all patients had bilateral involvement, which was higher in this group of patients than anticipated.
In this study, a high percentage of patients underwent PPV—more than 85 % in each of the MH groups and more than 25 % in the VMT group
Graefes 2016 : Peter Stalmans: A retrospective cohort study in patients with tractional diseases of the vitreomacular interface (ReCoVit)

10. Natural Course
A total of 5 % of eyes with VMT developed a new macular hole, almost half in the first month after diagnosis, and the majority of those new macular holes progressed to a threshold where the patient opted for PPV.
Moreover, none of the MH with VMT cases showed a spontaneous closure, even if 15.1 % showed a spontaneous VMT release, rendering them unsuitable for treatment with pharmacological vitreolysis that could potentially induce a nonsurgical closure.

11. Natural Course
Although metamorphopsia alone was not the indication for vitrectomy, it was one of the key symptoms bringing patients to the clinic, and therefore, was one of the factors considered when choosing PPV.
NICE in the UK has officially stated that having metamorphopsia has the same burden on the quality of life as a 2-line decrease in VA.
In this study, having metamorphopsia was a strong independent predictor of vitrectomy in eyes with VMT, tripling the odds of a patient opting to undergo PPV.

12. Natural Course
In conclusion, this retrospective analysis confirmed that metamorphopsia is a hallmark symptom of vitreomacular pathology, and that both vision loss and metamorphopsia increase with disease stage severity.
Our findings suggest there is no clinical benefit in watchful waiting, and the delay in treatment may result in poor visual outcomes even after restoration of the anatomical defect.

13. Natural Course
Our findings suggest there is no clinical benefit in watchful waiting, and the delay in treatment may result in poor visual outcomes even after restoration of the anatomical defect.

14. PPV
Vitrectomy surgery is often indicated in patients who are affected with a decrease in visual acuity, metamorphopsia, double vision, or difficulty using their eyes together.
On average, the visual acuity improves by two lines or more after surgery.
The visual results are highly variable, however; some patients have more visual acuity gain, yet 10% to 20% of them will have unchanged or worse vision following surgery.

15. PPV
Pars plana vitrectomy (PPV) remains the treatment of choice in eyes affected by VMT, with an anatomical resolution up to 75% -85 % of cases .
Although usually effective to relieve symptoms and improve visual function, surgery is costly and cannot be considered a risk-free procedure.
Furthermore, in some cases it may be related to secondary development of fibrocellular epiretinal membranes, cataract, infection, hemorrhage and so on.

16. Vitreolysis
Given these limitations, there is a great interest in developing pharmacologic or minimally invasive, methods for the induction of PVD, especially in patients affected with VMT syndrome.

17. Vitreolysis
Several agents have been proposed to induce the so-called pharmacologic vitreolysis such as ocriplasmin .
Some authors also suggested the use of a single intravitreal gas injection as primary treatment of VMT .

18. SF6 for the treatment of stage 2 MH
PVD at the macula was achieved in 19 of 20 eyes (95%). Ten cases (50%) had anatomical closure of the hole with intravitreous gas injection alone.
The remaining 10 cases (50%) achieved anatomical closure of the hole after subsequent vitreous surgery.
Ophthalmology 2007

19. SF6 for VMT
Retina : Day et al reported the results of intravitreal injection of 100% SF6 gas for the treatment of symptomatic VMT syndrome.
They found a 55.6% rate of release of VMT within the first month after injection with a significant decrease in mean central subfield thickness.
Although there was improvement in mean logMAR visual acuity, this was not statistically significant.

20. C3F8 for VMT
AJO 2013: Rodrigues et al recently published a case series describing the use of expansile perfluoropropane (C3F8) gas for the treatment of VMT syndrome in 15 eyes of 14 patients.
One month following treatment, vitreomacular traction was released in 6 eyes (40%).
Three further eyes (20%) had resolution of vitreomacular traction within 6 months.
The pneumatic release of VMT is believed to be due to the buoyant force of the gas bubble causing a mechanical separation of the posterior hyaloid face from the macula

21. C3F8 and Lucentise
From the results of the current study, gas-assisted VMA release showed good efficacy in the eyes with obvious VMA.
However, the treatment outcomes such as visual outcome were not significantly improved after VMA release.
Recent study suggests that the presence of VMA seems to have a significant influence on the intervals of anti-VEGF injections, but not visual acuity or exudative control outcomes

22. Pharmacologic Vitreolysis
Vitreolysis involving an enzyme that has activity against the molecular substrates responsible for vitreomacular adhesion is a potential nonsurgical, biologic approach to the treatment of this disorder.

23. Pharmacologic Vitreolysis
One of the classifications of enzymes used for pharmacological vitrectomy was proposed in 1998 by Sebag.
He divided the enzymes into those acting specifically on a given substrate (eg, chondroitinase, hyaluronidase, and collagenase) and those acting non-specifically, eg, plasmin and dispase.

24. Pharmacologic Vitreolysis
Substances directed against biochemical components of the vitreomacular interface, such as chondroitinase, dispase, and hyaluronidase, have been tested but were abandoned because of insufficient clinical efficacy, complications, or both.

25. Ocriplasmin
Ocriplasmin is a recombinant protease with activity against fibronectin and laminin, components of the vitreoretinal interface.
It has been approved by the FDA in 2012 for intravitreal injection for the treatment of symptomatic vitreomacular adhesion (VMA).
Phase III clinical trials demonstrated that a single intravitreal treatment with ocriplasmin induced a posterior vitreous detachment in 26.5% of eyes versus 10.1% of placebo controls.

27. MIVI-TRUST Study Group
652 eyes were treated: 464 with ocriplasmin and 188 with placebo.
Total posterior vitreous detachment was more prevalent among the eyes treated with ocriplasmin than among those injected with placebo (13.4% vs. 3.7%, P<0.001).
Nonsurgical closure of macular holes was achieved in 40.6% of ocriplasmin-injected eyes, as compared with 10.6% of placebo injected eyes (P<0.001).

28. Ocriplasmin It works best to release vitreous traction in
younger patients (<65 years),
eyes without an ERM,
eyes with a full-thickness macular hole and associated VMA,
phakic eyes,
eyes with a focal VMA of 1500 μm or less.

29. Ocriplasmin
In the MIVI-TRUST, resolution of VMA was found in 50% of small macular holes (,400 mm), 37.4% of eyes that lacked an epiretinal membrane, and 34.7% of eyes with small adhesions (,1500 mm).
Similarly, available aftermarket data have shown efficacy in achieving separation of the posterior hyaloid ranging from 42% to 62.5%.

30. Complications of Ocriplasmin
A review of the adverse effects included 465 eyes treated with ocriplasmin and 187 eyes treated with placebo.
During the first week after injection, the ocriplasmin group had about a 10% risk of developing vitreous floaters and photopsia, eye pain, and a combination of either blurred vision or decreased vision. Most of these early symptoms resolved

31. Ocriplasmin and Anti-VEGF injections
The investigators concluded that ocriplasmin treatment seemed to be well tolerated in most of the patients and led to greater VMA resolution and a reduced need for anti-VEGF injections, although the statistical power of the study was limited.
In addition, the rescue treatment group required fewer injections after VMA release.

32. Complications of Ocriplasmin (IVO)
􀂋 Decreased visual acuity
􀂋 Retinal tears and Floaters
Temporary ellipsoid zone attenuation
􀂋 Blue-yellow vision, dyschromatopsia, or dark vision
􀂋 Photopsias
􀂋 Disruption of the photoreceptor layers
􀂋 Visual field abnormalities
􀂋 Electroretinography changes
􀂋 Weakening of zonular fibers and possible lens subluxation

33. Vitx VS Ocriplasmin
A study compared the costs of surgery versus ocriplasmin for the treatment of VMT using data from multiple surgical papers and the MIVI-TRUST study.
The conclusion was that vitrectomy surgery was more cost-effective than ocriplasmin for the primary treatment of VMT.
Overall, the results of these calculations suggest that ERM surgery is a very cost-effective procedure when compared with other interventions across medical subspecialties.

34. rTPA
Recombinant tissue plasminogen activator (rTPA) (Actilyse, manufactured by Boehringer Ingelheim Pharma KG, Ingelheim, Germany) is a specific serin protease.
TPA converts plasminogen to plasmin due to its ability to break a peptide bond between arginine 560 and valine 561.
This enzyme acts specifically in the presence of fibrin.
Drug Design, Development and Therapy 2015

35. rTPA
0.1 mL (ie, 50 μg) of the rTPA preparation was injected intravitreously using an insulin needle, 3.5–4 mm from the corneal limbus.
Each group consisted of 30 people (30 eyes). The observation period was 6 months.
In both groups some of the VRTs had dissolved. In the TPA group the traction dissolved in 10 patients (33.33%) and in the control group only in 5 (16.67%).

36. Meta-Analysis
Twenty-three of 131 prospective or retrospective and consecutive articles ( ) for VMT and VMA were included.
Sixty-three eyes were treated with PV, 726 eyes were treated with intravitreal ocriplasmin, and 253 eyes were characterized as the control group (saline injection).
RETINA 0:1–11, 2015

37. Meta-Analysis
The weighted rate of VMT resolution for the control group was 0.09 (95% confidence interval [CI]: 0.06–0.13), PV(Pneumatic vitreolysis) was 0.84 (95% CI: 0.76–0.92), and intravitreal ocriplasmin was 0.26 (95% CI: 0.23–0.29).
Conclusion: Our analysis found that PV releases VMT in most patients and suggest that PV may be as effective or superior to nonsurgical options for VMTr at Day 28 with a similar risk profile.
RETINA 0:1–11, 2015

38. Conclusion
These reported studies indicate that there is still much to be learned about the specific effects of pharmacologic vitreolysis particularly ocriplasmin.

39. Thank you