Meta-analysis of six randomized controlled trials and one comparative study compared eyes with VH and PDR that underwent PPV alone (142 eyes) to eyes that were pretreated with IVB and then PPV [53]. Intraoperative bleeding was much less in the IVB group. The combined IVB-PPV approach may provide much clearer view of the retina and reduce the likelihood of iatrogenic retinal breaks during the dissection. The incidence of recurrent postoperative VH was less in eyes pretreated with bevacizumab. Also, the time to resolution of postoperative VH was signiÞcantly shorter in these eyes.

Anti-VEGF agents have been used as preoperative surgical adjunctive therapy to PPV for TRD to decrease the risk of intraoperative bleeding during membrane segmentation [51, 54]. Chen et al. [51] reported extensive regression of retinal neovascularization intraoperatively and minimal bleeding during membrane segmentation and delamination following 1.25 mg IVB 1 week before PPV. Also, technically, the delamination was much easier in this eye. Ribeiro et al. [54] evaluated the effect of intravitreal ranibizumab (IVtR), on intraoperative hemorrhage during 23-gauge PPV in a prospective study of 19 eyes with macula-involving diabetic TRD without VH of up to 3-month duration. Nine eyes were given IVtR 1 week before PPV, and nine were given a sham injection. Erythrocyte count at the end of the surgery was calculated to be 65 % lower in the IVtR group. Progression of TRD was seen, however, in one eye within a week of IVtR injection [54].

Timing the interval between intravitreal anti-VEGF injection and PPV remains controversial. Studies have reported progressive contracture of Þbrous tissue leading to a TRD if the time interval between the injection and vitrectomy is long [28, 29]. Many retina specialists believe the time period between the intravitreal antiVEGF injection and PPV should be less than 7Ð10 days to decrease the chances of progressive TRD with increased Þbrosis as neovascularization regresses in eyes with active PDR [51, 55]. The dissection of preretinal membranes becomes more difÞcult with time, with a higher risk of causing iatrogenic retinal breaks.

Histological studies show apoptosis of vascular endothelial cells and overexpression of smooth muscle actin in response to IVB [56]. El-Sabag et al. [57] reported much reduced retinal neovascularization and minimal growth of contractile elements, smooth muscle actin, and collagen by day 10 after IVB injection.

Although PPV removes the anti-VEGF agent from the vitreous cavity, the drug penetrates the retina and choroid as early as 1 day after intravitreal injection and may continue to inhibit VEGF even after PPV, including in post-vitrectomized eyes with silicone oil [58, 59].

5.5.4Silicone Oil Tamponade

Although PPV is effective in managing the severe complications of DR, signiÞcant operative and perioperative complications continue to occur, including recurrent RD due to Þbrovascular proliferation, NV progression with development of neovascular glaucoma (NVG), anterior hyaloidal Þbrovascular proliferation [18, 60] with cyclitic membrane formation and phthisis bulbi, and Þbrinoid syndrome. The

Þbrinoid syndrome is characterized by Þbrin strand formation in the vitreous cavity, condensation of Þbrinoid material on the surface of the retina, eventual development of turbid vitreous gel (or ßuid, in eyes that have undergone vitrectomy), and, often, in progressive TRD [61]. Other features include neovascular glaucoma, pupillary block glaucoma, recurrent hemorrhage, cataract, and ciliary body detachment with hypotony. The incidence of Þbrinoid syndrome in patients undergoing vitrectomy for the complications of PDR is approximately 8 % [18]. Silicone oil can facilitate retinal reattachment by providing extended retinal tamponade (Table 5.1). Intraocular gas has greater surface tension, but it spontaneously resorbs, which in some patients may result in recurrent detachment or in progressive anterior hyaloidal Þbrovascular proliferation and/or NVG. In addition, silicone oil can compartmentalize the eye [78] by retarding the diffusion of angiogenic substances to the anterior segment, thus preventing progressive rubeosis iridis and NVG. Silicone oil also acts as a convection barrier to oxygen, as it prevents reduction in anterior chamber oxygen tension in cats that have undergone lensectomy and vitrectomy [79]. The results of several studies indicate that PPV with silicone oil infusion can salvage useful vision in eyes with an otherwise poor prognosis [62, 65, 66, 68, 69, 74Ð76, 80]. Despite these advantages, silicone oil tamponade is not always successful, and it can be associated with complications such as corneal decompensation, cataract, glaucoma, and peri-silicone proliferation, the latter possibly due to entrapment of retina-derived angiogenic substances between the retinal surface and the silicone oil bubble [81]. Silicone oil tamponade should be considered in diabetic eyes in a variety of circumstances (Table 5.2). In cases with anterior hyaloidal Þbrovascular proliferation, for example, one may need to perform a 360¡ retinectomy in order to relieve the anterior-posterior traction on the retina satisfactorily (Fig. 5.1). In such cases, silicone oil tamponade is typically used to maintain long-term retinal reattachment and to forestall the development of rubeosis iridis (via compartmentalization of the eye) and hypotony [82].

5.5.4.1Viscodissection

Viscodissection [83] facilitates dissection of epiretinal membranes. The technique involves injecting a viscous ßuid (e.g., Healon¨) between the retina and epiretinal tissue, typically using a 27-gauge cannula with a bent tip attached to a syringe or with a viscodissector (BD Visitec¨ 20-gauge × 1-in. cannula with a 30-gauge x 3/16-in. tip extension) (Fig. 5.2). A variety of viscoelastic materials have been used, including 1 % methylcellulose, Healon¨, and Healon¨ GV [84Ð86]. Healon¨ has an average molecular weight of 4 × 106 Da and contains 10 mg/ml sodium hyaluronate dissolved in physiological buffer. Healon¨ GV contains 14 mg/ml sodium hyaluronate, has an average molecular weight of 5 × 106 Da, and has ten times greater viscosity than Healon¨. In general, lower molecular weight preparations are preferred because the risk of hydraulic retinal perforation during dissection is less. In the largest study on viscodissection published to date, Grigorian et al. [86] found that viscodissection was not associated with a signiÞcantly greater frequency of retinal breaks compared to conventional membrane dissection, despite the fact that the case complexity was greater among the cases undergoing viscodissection.

Table 5.1 Results and postoperative complications after silicone oil infusion in eyes with severe proliferative diabetic retinopathy

Reproduced with permission from Grigorian et al. [77]

aC cataract, CD corneal decompensation, FR Þbrinoid reaction, G glaucoma, H hypotony, IOP↑ elevation of intraocular pressure, IMD irreversible macular damage, MP macular pucker, NVG neovascular glaucoma, ON/RA optic nerve and retina atrophy, RFVP re-proliferation FVP, RI rubeosis iridis, SAC silicone oil in the anterior chamber, SE silicone oil emulsiÞcation, SSR silicone oil in subretinal space

Table 5.2 Some potential indications for the use of silicone oil tamponade in eyes with severe diabetic retinopathy

Indication

Functionally one-eyed patient requiring retinal tamponade

Vitrectomy for an eye with the Þbrinoid syndrome

Retinal tamponade required for an eye with numerous retinal breaks or in which not all retinal breaks can be treated fully with retinopexy

Compartmentalization of the posterior segment to reduce the development or progression of rubeosis iridis or NVG

Vitrectomy for an eye with anterior hyaloidal Þbrovascular proliferation (to reduce the chance for clinically signiÞcant postoperative hypotony)

c

Fig. 5.1 Retinectomy and silicone oil infusion for management of severe complications of diabetic retinopathy. A 67-year-old woman underwent vitrectomy elsewhere for complications of proliferative diabetic retinopathy and was referred with total retinal detachment, anterior hyaloidal Þbrovascular proliferation, proliferative vitreoretinopathy, and vitreous hemorrhage. Vision was bare light perception. The patient underwent pars plana vitrectomy, membrane peel, 360¡ retinectomy, panretinal laser photocoagulation, and silicone oil infusion. (a) Preoperative B-scan echography demonstrates posteriorly closed funnel retinal detachment (arrows) with anterior loop traction secondary to anterior hyaloidal Þbrovascular proliferation. Image artifact (asterisk) is due to the intraocular lens. (b) Fundus photograph collage at postoperative week 1 demonstrates reattached retina and fresh laser treatment burns. (c) Fundus photograph collage at postoperative month 1 demonstrates reattached retina with mild peripapillary hemorrhage. The retina has remained reattached for more than 1 year with hand motions vision