http://www.tvrs.gr/

1. ATHANASIOS NIKOLAKOPOULOS
PAPANIKOLAOU HOSPITAL
THESSALONIKI-GREECE

2. Diabetic macular edema (DME) is a major source of vision loss in
people with diabetes mellitus.
DME affects up to 25% of people after 10 years of diagnosis of
diabetes and will develop in more than 40% of patients with type 1
diabetes over the course of their lifetimes.
Klein R, Klein B, Moss S, Cruickshanks KC. The Wisconsin Epidemiologic Study of Diabetic
Retinopathy XV. The long term incidence of macular edema. Ophthalmology 1995; 102: 7-16.
Javitt JC, Canner JK, Sommer A. Cost effectiveness of current approaches to the control of
retinopathy in type I diabetes. Ophthalmology 1989; 96: 255-264.

3.  Laser photocoagulation (focal/grid)
 Anti-VEGF agents
 Combined therapy (laser photocoagulation + anti- VEGF)
Early Treatment Diabetic Retinopathy Study Research Group. Focal photocoagulation
treatment of diabetic macular edema. Relationship of treatment effect to fluorescein
angiographic and other retinal characteristics at baseline. ETDRS report number 19.
Arch Ophthalmol. 1995; 113: 1144-1155.
Elman MJ, Aiello LP, Beck RW et al. Diabetic Retinopathy Clinical Research Network.
Randomized trial evaluating ranibizumab plus prompt of deferred laser or triamcinolone
plus prompt laser for DME. Ophthalmology 2010; 117: 1064-1077.

4. Nasrallah et al (1988): the incidence of PVD was lower in patients with
DME.
Hikichi and colleagues (1997): after PVD spontaneous resolutionof DME
in 55% of diabetic patients
ATTACHED VITREOUS RISK FACTOR FOR DME
Lewis et al 1992: vitrectomy can improve visual prognosis in some eyes
with DME and macular traction (“taut posterior hyaloid”)

5. It is known that the diabetic vitreous is abnormal with
enzyme-mediated vitreous collagen crosslinking and non-
enzymatic glycation; with reduced permeability
potentially increasing the concentration of a pre-macular
growth factor soup.
Sebag J. Abnormalities of human vitreous structure in diabetes. Graefes Arch Clin Exp
Ophthalmol 1993; 231(5): 257–260.
Sebag J, Buckingham B, Charles MA, Reiser K. Biochemical abnormalities in vitreous of
humans with proliferative diabetic retinopathy. Arch Ophthalmol 1992; 110(10): 1472–1476.
Sebag J, Nie S, Reiser K, Charles MA, Yu NT. Raman spectroscopy of human vitreous in
proliferative diabetic retinopathy. Investig Ophthalmol Vis Sci 1994; 35(7): 2976–2980.

6.  Transvitreal oxigenation
 Relief of vitreomacular traction
 Improved growth factor diffusion away from the
perimacular area
Cambridge Ophthalmology Symposium
Eye (2008) 22, 1337–1341; doi:10.1038/eye.2008.84; published online 25 April 2008
Vitrectomy for diabetic macular oedema
D A H Laidlaw

7.  Edema duration
 Expansion of laser scars
 Extent of ischemia and exudation
 Permanent photoreceptore and capillary damage which
precludes anatomical or visual benefits
Laidlaw

8. FUNDUS EXAMFUNDUS EXAM
FAGFAG
OCTOCT

10. Vitreous base
Optic disc
Perifoveal/macular region
Vessels
Posterior lens - Weigert’s ligament

11. SURGICAL TREATMENT (25GPPV)
Release any vitreomacular traction
Remove the vitreous cortex (kenalog assisted)
Remove as much vitreous gel as possible
Peel off any ERM
ILM peeling BB assisted

12. Caused by partial posterior vitreous detachment: the posterior
hyaloid is incompletely detached from the posterior pole and
remains attached to the optic disc and the foveal center exerting
traction on the foveal tissue.
Traction on macular tissue produces gradual anatomic and
functional deterioration in proportion to traction forces
(anterior-posterior or tangenzial) and their duration of action.

13. Ocriplasmin (microplasmin)
is a truncated form of the human serine protease plasmin that retains its
enzymatic properties.
 is believed to primarily target the fibronectin, laminin, and type IV
collagen fibers that adhere the vitreous to the retina.
designed specifically for use in the eye is delivered via an intravitreal
injection.
The goal of any pharmacologic separation of the vitreoretinal interface is to
create a clean separation of the posterior vitreous cortex and the inner
limiting membrane (ILM) of the retina.

14. Offers complete PVD without mechanical manipulation at the retina
thereby minimizing the risk of iatrogenic damage
An intravitreal injection is less traumatic than vitrectomy and can be
given early before advanced stages of the disease have developed
Cleaving the vitreous cortex from the retina changes the molecular
flux across the vitreoretinal interface and improves both oxygen supply
to and clearance of vascular endothelial growth factor from the retina1.
Gandorfer A, Putz E, Welge-Lüssen U, Grüterich M, Ulbig M, Kampik A. Br J Ophthalmol.
2001;85(1):6-10.
2. Sakuma T, Tanaka M, Mizota A, Inoue J, Pakola S. Invest Ophthalmol Vis Sci.2005;46(9):3295-3299.

15. The ocriplasmin (microplasmin) phase III program, consists of 2
multicenter, randomized, placebo controlled, double-masked trials.
These trials were designed to evaluate a single dose of 125μg
ocriplasmin vs placebo administered intravitreally for the treatment
of patients with sVMA
The primary end point of these trials was looking at pharmacologic
resolution of symptomatic vitreomacular adhesion.
652 patients were enrolled in these trials at 90 centers in 7 countries
across the United States and Europe

16. Both TG-MV-006 (US only) and TG-MV-007 (EU and US) trials of
ocriplasmin vs placebo:
Met the primary end point: achieving a statistically and clinically
significant improvement in the resolution of VMA
26.5% of subjects had pharmacological resolution of VMA at day
28
Demonstrated pharmacological resolution of VMA in 34% of
subjects without an epiretinal membrane
40.6% of subjects had pharmacological closure of FTMH at day
28, which was mainained at month 6
13.4% of subjects had inductionof total PVD
Visual acuity and visual function questionnaire outcomes favored
ocriplasmin
Ocriplasmin was generally well tolerated

17.  28-49% SHOWED AN IMPROVED VISUAL OUTCOME
 REMOVAL OF EPIRETINAL MEMBRANES MAY
FAVORABLY EFFECT VISUAL OUTCOME OF
VITRECTOMY
Diabetic Retinopathy Clinical Research Network Writing Committee on behalf of the
DRCR.net, Haller JA, Qin H, Apte RS, Beck RW, Bressler NM, Browning DJ,
Danis RP, Glassman AR, Googe JM, Kollman C, Lauer AK, Peters MA, Stockman
ME. Vitrectomy outcomes in eyes with diabetic macular edema and
vitreomacular traction. Ophthalmology. 2010 Jun;117:1087-1093.e3

18.  VITREOUS AND TRACTION REMOVAL IN ALMOST
ALL CASES
 REMOVAL OF THE EPIRETINAL TISSUE AND ILM
 PERMANENT RESULTS IF SUCCESFULL

19. JUST AN INTRAVITREAL INJECTION
POSSIBLE EARLIER USE ?
A STAGE BEFORE VITRECTOMY?

20. From the literature the strongest indication for vitrectomy in DME is when
there is also macular traction.
Better visual outcomes in patient when we remove the epiretinal
membranes with or without ILM.
The early Results of ocriplasmin showed that can also remove the traction
with an injection only in more than 30%.
But we have to wait to see if it can be used in an early, pre - vitrectomy
stage, or in combination treatments for DME.
If VITREOUS IS A RISK FACTOR in DME both can create a better
access for further anti-VEGF treatment in eyes with resistance to anti-
VEGF due to attached vitreous and the perifoveal area membranes