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Khaled Nassar, Ayceguel Tura, Julia Lueke, Matthias Lueke, Salvatore Grisanti; The Novel Use of LY364947 (LY), a TGF-ß Type I Receptor Inhibitor, In Prevention of Proliferative Vitreoretinopathy (PVR). Invest. Ophthalmol. Vis. Sci. 2012;53(14):893.
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© ARVO (1962-2015); The Authors (2016-present)
This study evaluates the effect of LY364947 (LY), a TGF-ß Type I Receptor Inhibitor, in an experimental rabbit model for PVR.
Traumatic PVR was induced in 30 rabbits divided into six groups (n = 5). One group (G1) received only trauma and reveals a control. In G2 only 20 µmol LY was injected intravitreally. G3-G6 received phacovitrectomy at 2 weeks. In G3,rabbits receive only phacovitrectomy. In G4, 0.1 ml of the drug vehicle was intravitreally injected at the end of the surgery. G5 and G6 received 5µmol and20 µmol LY, respectively. PVR severity was scored from 0 to 4. The amount of fibrosis was quantified using JMicrovision software.
The control group (G1) developed severe PVR with tractional retinal detachment (TRD); (PVR score ≥ 2) in 80%. Neither vitrectomy nor vehicle alone had a positive effect on PVR development. The best results were obtained with LY that reduced both the PVR score and fibrosis development significantly (p value < 0.05). TRD was prevented in 93.3 % (14 out of 15) of LY treated rabbits and PVR development was completely prevented (PVR score =0) in (9 out of 15) rabbits. 20 µmol intravitreal LY (G2) improved the trauma out come compared to G1 and G3 (p value < 0.05). 5 µmol adjuvant treatment (G5) significantly prevent PVR development compared to trauma (p value < 0.001); vitrectomy (p value < 0.05) and vehicle (p value < 0.05). 20 µmol treatment (G6) significantly prevent PVR development compared to trauma and vitrectomy (p value < 0.05). Only 5 µmol adjuvant treatment (G5) was superior to 20 µmol intravitreal treatment, (p value < 0.05). There were no drug related toxic effects evident on clinical and histopathological examination.
In this rabbit model of PVR, both intravitreal and adjuvant LY application during vitrectomy effectively reduce PVR and TRD development. In conjunction with no obvious side effects this seems a promising substance to inhibit PVR reactions.
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