Hongting Liu

Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1.

In this study, we used small interfering RNA (siRNA) directed against vascular endothelial growth factor receptor 1 (vegfr1) mRNA to investigate the role of VEGFR1 in ocular neovascularization (NV). After evaluating many siRNAs, Sirna-027 was identified; it cleaved vegfr1 mRNA at the predicted site and reduced its levels in cultured endothelial cells and in mouse models of retinal and choroidal neovascularization (CNV). Compared to injection of an inverted control sequence, quantitative reverse transcriptase-PCR demonstrated statistically significant reductions of 57 and 40% in vegfr1 mRNA after intravitreous or periocular injection of Sirna-027, respectively. Staining showed uptake of 5-bromodeoxyuridine-labeled Sirna-027 in retinal cells that lasted between 3 and 5 days after intravitreous injection and was still present 5 days after periocular injection. In a CNV model, intravitreous or periocular injections of Sirna-027 resulted in significant reductions in the area of NV ranging from 45 to 66%. In mice with ischemic retinopathy, intravitreous injection of 1.0 μg of Sirna-027 reduced retinal NV by 32% compared to fellow eyes treated with 1.0 μg of inverted control siRNA. These data suggest that VEGFR1 plays an important role in the development of retinal and CNV and that targeting vegfr1 mRNA with siRNA has therapeutic potential.

New Treatment Options for Noninfectious Uveitis

Autoimmune uveitis is a group of sight-threatening inflammatory diseases associated with an exacerbated immunological response to ocular proteins. The Standardization of Uveitis Nomenclature Working Group Guidelines have recommended the use of corticosteroids as the first line of therapy for patients who present with active uveitis. However, long-term use of corticosteroids is associated with numerous adverse effects including cataract, glaucoma and metabolic disorders. In this context, new drugs developed to treat rheumatic diseases, and other autoimmune diseases, are being employed often as monotherapy or combined with other immunosuppressive drugs in order to decrease the corticosteroid burden on patients and to manage refractive uveitis. These drugs are currently being evaluated in the framework of uveitis and may open a new horizon with less side effects and more responsiveness for chronic cases. Among others, calcineurin inhibitor voclosporin, mammalian target of rapamycin inhibitor sirolimus, and the IL-1 trap rilonacept, are among these new agents and will be scrutinized in detail in this chapter. More efficient modes of drug delivery are also being employed to deliver high concentration of drug locally and to minimize systemic side effects. The new modes of drug delivery that we will describe in the index chapter include nanoparticles and iontophoresis.

Association of retinal vessel calibre and visual outcome in eyes with diabetic macular oedema treated with ranibizumab.

PurposeThe study aims to identify the association between the baseline retinal vascular calibre and visual outcome of patients with diabetic macular oedema (DMO) treated with intravitreal ranibizumab.MethodsThe 1-M field (as defined in the ETDRS study) of the digital colour fundus photographs of DMO patients who had been treated primarily with ranibizumab in a clinical trial was assessed. Of the 84 patients, 25 had gradable retinal photographs that could be subjected to analyses by the Interactive Vessel Analysis (IVAN) software at baseline. The average retinal vascular calibre of the six largest venules (CRVE) and the six largest arterioles (CRAE) in the peripapillary area (0.5 and 1 disc diameter from the optic disc margin) was measured. The relationship between CRVE and CRAE at baseline and the change in visual acuity at month 12 was assessed using the Mann–Whitney U test.ResultsTen eyes from 10 patients who had shown an improvement of ≥2 lines of best corrected visual acuity (BCVA) at month 12 had a wider baseline CRVE (248.3±24.5 μm) compared with the 15 eyes from 15 patients who did not show the improvement of ≥2 lines (226.6±44.8 μm, P<0.05). The baseline CRAE did not differ significantly in these patients (156.1±22.7 vs 142±17.5 μm, P=0.17).ConclusionsA wider baseline retinal venular calibre may be a predictor of better visual outcome in DMO eyes treated with ranibizumab. Further prospective studies with a larger sample size and a broader range of disease severity and visual acuity are needed to confirm this finding.

Longitudinal comparison of visual acuity as measured by the ETDRS chart and by the potential acuity meter in eyes with macular edema, and its relationship with retinal thickness and sensitivity

PurposeTo evaluate the relationship between visual acuity as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart and by the potential acuity meter (PAM) with retinal thickness and sensitivity measured by a combined microperimetry/optical coherence tomography system (OCT).MethodsForty-four patients with macular edema (ME) were included in a prospective observational study. Visual acuity (VA) was assessed using the ETDRS chart (with best correction) as well as by the PAM. Retinal thickness and sensitivity was measured by an automatic fundus perimetry/tomography system.ResultsBest-corrected VA using the ETDRS chart ranged from 20/20 to 20/400 (median: 20/50). VA measured by the PAM without correction ranged from 20/20 to 20/400 (median: 20/40). The mean retinal thickness was 369.57 μm (s.d.: 140.28 μm) on spectral domain-OCT and the mean retinal sensitivity was 8.12 decibels (dB) (s.d.: 5.78 dB). The mean LogMAR value using the ETDRS chart was 0.43, whereas it was 0.38 using the PAM (P-value: 0.009).ConclusionsVA values measured by the PAM were statistically significantly better than those measured by the ETDRS chart in eyes with ME secondary to various retinal vascular and uveitic diseases. VA measured by the PAM may be a more sensitive predictor of macular function than that obtained by ETDRS testing in eyes with ME.