Ординатура / Офтальмология / Английские материалы / Diabetic Retinopathy_Lang_2007

Fig. 5. a–d Baseline visit: magnification of retinal neovascularization elsewhere (a), red-free photograph showing the location of the neovascularization along the inferotemporal arcade (b), fluorescein angiograms with areas of capillary nonperfusion in the early phase (c), and leakage from the neovascularization elsewhere in the late-phase frame (d ). e–h Thirty-six weeks after 6 periodic pegaptanib injections (and 6 weeks since most recent injection): regression of neovascularization elsewhere on red-free photographs (e, f ), with less apparent microaneurysms in the early-phase frame ( g) and regression of leakage from neovascularization elsewhere in the late phase (h). i–l Fifty-two weeks after study entry and 22 weeks since the last pegaptanib injection: reappearance of neovascularization elsewhere on red-free photographs (i, j ), with reappearance of leakage from neovascularization elsewhere in the early- (k) and late-phase (l ) frames. With permission from Macugen Diabetic Retinopathy Study Group [118].

after intravitreous injection among 652 injections (0.15%) administered in the pegaptanib arms, and there was no evidence of cataract formation/progression, sustained intraocular pressure elevation, or serious systemic events associated with pegaptanib therapy. Importantly, there was no evidence that pegaptanib

treatment was associated with systemic thromboembolic events or the cardiac, gastrointestinal or hemorrhagic complications noted with pan-VEGF blockade.

Conclusions

Current treatment options for diabetic retinopathy are primarily restricted to laser photocoagulation and pars plana vitrectomy, both of which are destructive and do not address the underlying pathological mechanisms involved in the development of diabetic retinopathy. Preclinical studies support the concept of blocking the actions of VEGF165 in the eye as a sound therapeutic approach to the treatment of diabetic retinopathy. These concepts have been validated by a recent phase II study that demonstrated the clinical benefits of the VEGF165- blocking aptamer, pegaptanib, in the treatment of DME. Outcomes included improvements in VA and a reduction in retinal thickness. Moreover, a separate retrospective analysis in a subset of these subjects who had concomitant retinal neovascularization demonstrated regression of neovascularization in 61% of eyes treated with pegaptanib. Confirmation of these findings and the more subtle effects of VEGF165 blockade upon the severity of underlying retinopathy, as well as the effects upon capillary nonperfusion await the results of definitive phase III trials that are under way.

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Carla Starita, MD, PhD

Pfizer Global Research and Development, Building 508/1.75 IPC 613 Ramsgate Road, Sandwich

CT13 9NJ Kent (UK)

Tel. 44 1304 642915, Fax 44 1304 652540, E-Mail Carla.starita@pfizer.com

Table 1. Enzyme candidates for pharmacologic vitreolysis

Chondroitinase

A 240-kDa chondroitin sulfate proteoglycan is associated with the vitreoretinal interface [3]. The greatest immunoreactivity of this proteoglycan has been observed in regions of firm vitreoretinal adhesion, such as the vitreous base and the papillary margin, suggesting a major role in vitreoretinal adhesion. The enzyme chondroitinase cleaves this proteoglycan and has been studied as an adjunct in vitrectomy in 2 human donor eyes and in 57 cynomolgus monkeys [3]. Intravitreal injection of the enzyme separated the vitreous from the retina without damaging the inner limiting membrane (ILM). Three monkeys have been followed for 14–16 months after surgery without any adverse effects [3]. Chondroitinase has also been utilized to detach epiretinal membranes in 4 monkeys, providing evidence that chondroitin sulfate proteoglycan participates in the adhesion of epiretinal membranes to the ILM [3]. Unfortunately, no clinical results have been reported yet.

Hyaluronidase

Hyaluronan represents one of the two major macromolecules of the vitreous [4–6] and is supposed to maintain the 3-dimensional structure of the vitreous gel by coating the collagen fibrils and by bridging them with interconnecting filaments [7]. Hyaluronidase (Vitrase®) cleaves hyaluronan and has been suggested to liquify the vitreous.

A recently published phase III clinical trial shows that 55 IU of highly purified ovine hyaluronidase (Vitrase) helps to clear eyes with vitreous