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Diabetic Vitrectomy – An Update
where media opacities such as cataract or vitreous haemorrhage appears to be limited to date. They can be grouped into four main
prevent the application of laser. There are also cases of proliferative categories: pharmacological vitreolytics, aids to intra-operative removal
retinopathy that do not respond to PRP alone, where anti-VEGF agents of haemorrhage, suppressors of post-operative inflammation and
may be a useful additional therapy. The pre-operative use of suppressors of post-operative haemorrhage.
intravitreal bevacizumab has been shown to speed the clearance
of vitreous haemorrhage prior to surgery and to reduce the risk of Pharmacological Vitreolytics
intraocular bleeding during surgery.
43,44
It has also been shown to Traction associated with incomplete vitreoretinal separation and
reduce operating time, with anecdotal reports that fibrovascular vitreoschisis are thought to be important to the pathophysiology of a
membranes become less adherent. The risk of early post-operative number of retinal diseases, including PDR and cystoid macular
haemorrhage also appears to be reduced,
42,45
although there is some oedema (CMO). Complete vitreous separation offers many potential
evidence of late re-bleeding. This may reflect the pharmacokinetics of advantages.
48
First, surgery would be easier and safer, and in some
bevacizumab
46
or its removal with the vitreous at the time of surgery. cases even unnecessary. Second, the vitreous remnants often left
It is therefore recommended that vitrectomy be followed by after surgery act as a scaffold for subsequent cellular proliferation
supplementary PRP. The role of top-up intravitreal bevacizumab at the and would be removed. Third, the induction of posterior vitreous
end of surgery remains unclear.
42
detachment (PVD) before onset of neovascularisation in PDR would
avoid some of the complications of advanced disease. Finally, there is
A potential risk of anti-VEGF agents is the progression of TRD, with some evidence that removal of the vitreous improves retinal
Arevalo et al. reporting a 5.2% (11 from 211 eyes) incidence of oxygenation, and it is possible that the same effect would be
progression of TRD following intravitreal bevacizumab.
47
The authors achieved by pharmacological vitreous liquefaction.
8
speculated that this may reflect the natural history of rapid involuting
fibrovascular complexes rather than a risk specific to anti-VEGF agents. Many pharmacological agents have been studied with the aim of
Avery et al. have shown that eyes with diabetic retinopathy may be aiding the separation of vitreous from the retina. Early trials of tissue
particularly sensitive to bevacizumab, with an effect noted at doses as plasminogen activator (tPA) given by intravitreal injection 15 minutes
low as 6.2µg and as early as 24 hours after injection.
44
It is unknown before diabetic vitrectomy failed to induce vitreoretinal separation.
43
whether a higher dose results in a longer duration of action or a greater However, more promising results have been obtained using plasmin
risk of TRD, but with evidence to suggest that such low doses are and the more stable recombinant microplasmin, which have both
efficacious, there may be an argument for lowering the dose to reduce been shown to be capable of inducing PVD and may aid removal of
the potential risk of systemic side effects and TRD progression. the posterior hyaloid in TRD and CMO.
49
This is the subject of the
ongoing Microplasmin Intravitreal Administration in Patients with
To our knowledge no studies have been published on the effects Vitreomacular Traction Scheduled for Vitrectomy (MIVI) trial. Other
of ranibizumab (Lucentis) on proliferative diabetic retinopathy, candidate agents include chondroitinase,
50
dispase,
51
hyaluronidase
52
although early experience in animal models suggests that both and combined plasmin with hyaluronidase.
53
posterior and anterior neovascularisation are very sensitive. Work
on the pharmacokinetics of ranibizumab and bevacizumab has Aids to Removal of Haemorrhage
demonstrated a vitreous half-life of 2.88 days for 0.5mg intravitreal The removal of tenacious pre-retinal haemorrhage during vitrectomy
ranibizumab and 4.32 days for 1.25mg bevacizumab. Ranibizumab surgery can be difficult, and several pharmacological agents have
(48kDa) is a smaller molecule than bevacizumab (149kDa), and may been suggested to aid this process. However, the literature is limited.
thus penetrate the retina more quickly and be cleared from the A single case report describes a good result with heparin.
54
Although
systemic circulation more rapidly. The implications for treatment in tPA has been used more widely for this purpose,
55
there are reports of
diabetic retinopathy remain to be demonstrated, but the longer half- retinal toxicity, and caution is advised.
56
life of bevacizumab may be advantageous.
46
Suppression of Post-operative Inflammation
There are currently no published studies that have investigated the The role of thrombin is central to post-operative outcome in diabetic
optimal timing of surgery following intravitreal bevacizumab. vitrectomy, where it may play both a beneficial role by suppressing
However, Yeoh et al. reported that bevacizumab given within 14 days post-operative haemorrhage and a deleterious role by promoting post-
of surgery caused regression of new vessels without maturation and operative inflammation.
thickening of the fibrous component.
42
Their shortest duration
between injection and surgery was six days, when the new vessels Formation of intraocular fibrin has been reported in approximately
were already sufficiently regressed. Avery et al. found that all patients one-third of vitrectomies (the data include non-diabetic vitrectomy)
with neovascularisation demonstrated by fluorescein angiography and is severe in about 12% of cases, when it can be associated
had a reduction in leakage within one week, and that 59–82% showed with pupil block glaucoma and reproliferation in PDR.
57
Several
complete cessation. In addition, they reported involution, with pharmacological adjuvants have been suggested to suppress fibrin
reduced calibre and perfusion of neovascular fronds. Recurrence of formation. tPA is a potent fibrinolytic, but its association with
fluorescein leakage was variable, but was seen as early as two weeks increased risk of intraocular haemorrhage and possible retinal toxicity
in one case.
43
On the basis of the available evidence, surgery one to suggest that it should be reserved for severe cases rather than
two weeks post-injection would seem to be optimal. prophylaxis.
58
Furthermore, a dose of 10µg has been recommended,
58
which is lower than the commonly used dose in clot lysis (typically
Other Adjuvants 30–100µg).
18,59
Unfractionated heparin has also been investigated and,
A number of other adjuvant agents have been proposed. Although some although effective at reducing post-operative fibrin formation, it is
have shown promise, their widespread adoption in clinical practice associated with a mild increase in intra- and post-operative
EUROPEAN OPHTHALMIC REVIEW 89
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