sulfated glycosaminoglycans with mainly heparan sulfate, improved proteinuria in type 1 diabetics (Gambaro 1998), but did not improve proteinuria or retinopathy among type 2 diabetics (van der Pijl et al 1999). The incidence of cataract is higher among diabetics than the general population and cataract extraction may be required to improve visual function and/or to improve the view to the retina for diagnostic and therapeutic purposes. DR may limit the visual prognosis after cataract extraction, especially in the presence of severe NPDR or PDR (Chew et al 1999). While newer phacoemulsiﬁcation techniques are associated with a lower incidence of DR progression, post-operative macular edema may still limit visual outcomes after cataract surgery (Krepler et al 2002). An association was found between progression of NPDR and rapid pre-operative glycemic control, suggesting that cataract surgery should be delayed until prolonged glycemic control has been achieved (Suto et al 2006). In the US, African American and Latino populations have an increased incidence and severity of DR that cannot be explained by glycemic control alone. The great variability in severity of DR among populations with similar environ- mental factors has fueled the search for genetics factors that may contribute to the development of DR (Uhlmann et al 2006). Variations at several genetic loci have been implicated in DR, including VEGF, α2β1 integrin, ALR2 , angiotensin II receptor 1, RAGE, and PPARγ2 (Uhlmann et al 2006). However, the interpretation of the results of many of these studies is confounded by conﬂicting reports that have failed to conﬁrm such an association and the limited racial diversity of each of the study populations. Conventional treatments Traditional treatment of diabetic retinopathy has been shaped by the results of a few large prospective clinical trials. The Early Treatment Diabetic Retinopathy Study (ETDRS) sought to determine the efﬁcacy of photocoagulation in the treatment of diabetic macular edema (Anonymous 1991). Patients with mild, moderate, or severe NPDR or low- risk PDR were randomized to immediate or delayed focal macular laser (FML) and immediate or delayed panretinal laser photocoagulation (PRP) for the treatment of clini- cally signiﬁcant macular edema (CSME). Immediate FML decreased moderate vision loss by 50% in patients with CSME, while immediate PRP with delayed FML in patients with NPDR and CSME responded least favorably. The study group concluded that FML for CSME should be performed before scatter PRP in patients with NPDR. In patients with high-risk PDR and CSME, eyes should receive immediate Clinical Ophthalmology 2008:2(2) Diabetic retinopathy PRP beginning nasally and inferiorly (to limit progression of macular edema) concurrently with FML. The Diabetic Retinopathy Study (DRS) was designed to determine the efﬁcacy of PRP in preventing severe visual loss in eyes with advanced DR (Anonymous 1981). Study subjects with bilateral PDR or severe NPDR (ie, preproliferative DR) were given PRP in the ﬁrst eye and no treatment in the fellow eye. PRP reduced the risk of severe vision loss by 50% or more in preproliferative and proliferative retinopathy (7% versus 3%). The effect was most marked in high risk PDR (26% versus 11%), as deﬁned by the presence of any neovascularization of the disc (NVD) or retina with VH, or severe NVD with or without VH. The authors concluded that for severe NPDR, PDR, and especially high risk PDR, PRP is essential in preventing blindness. Side effects of treatment included peripheral visual ﬁeld constriction and nyctalopia. Additional complications of PRP include exacerbation of DME and contraction of retinal ﬁbrosis, exacerbating TRD and/or causing retinal breaks. The Diabetic Retinopathy Vitrectomy Study (DRVS) was designed to compare early versus delayed pars plana vitrec- tomy (PPV) in patients with PDR, active neovascularization, and vitreous hemorrhage (Anonymous 1988). Patients with Type 1 DM, but not Type II DM, with dense non-clearing vitreous hemorrhage, had better outcomes with early vitrec- tomy. The study group recommended early PPV for vitreous hemorrhage in the setting of Type 1 DM or for eyes with useful vision and advanced active PDR. An important caveat to this study is that endolaser (intraoperative PRP) was not used in this study, possibly limiting the applicability of the results to current clinical practice. Although practice patterns vary widely, current indica- tions for vitrectomy in the setting of DR include non-clearing VH, TRD threatening or involving the macula, or combined tractional and rhegmatogenous retinal detachment. A number of techniques may be employed for TRD repair, including the use of long-acting intraocular gas or silicone oil, that may improve anatomic and functional outcomes (Mason et al 2006). Vitrectomy has also been used in the treatment of recalcitrant DME, especially when a tractional component is present, although its beneﬁt has not been proven in a ran- domized, controlled clinical trial (see below). Treatments currently under clinical investigation Despite these proven treatments for retinal complications of diabetes, patients with diabetic retinopathy continue to experience visual loss. A number of off-label non-FDA 427