Florian Rensch

Early Intravitreal Bevacizumab for Non-Ischaemic Branch Retinal Vein Occlusion

Purpose: To evaluate the effect of early intravitreal bevacizumab application in patients with macular oedema due to non-ischaemic branch retinal vein occlusion (BRVO). Procedures: The study included 21 patients (21 eyes) with macular oedema due to non-ischaemic BRVO. Inclusion criteria were significant macular oedema as measured by optical coherence tomography, loss of visual acuity and leakage in fluorescence angiography. All patients received 3 intravitreal injections of 1.5 mg bevacizumab. The mean follow-up was 6.2 ± 1.2 months (mean ± standard deviation). The mean duration of the BRVO prior to treatment was 9.2 ± 5.4 days. Results: The visual acuity improved significantly from baseline 0.81 ± 0.53 logMAR to 0.54 ± 0.47 logMAR (p < 0.001) at 1 month, 0.55 ± 0.46 (p = 0.001) at 3 months and to 0.55 ± 0.49 (p = 0.002) at 6 months after the first injection. The mean central retinal thickness decreased significantly (p < 0.001) from 492 ± 113 μm at baseline to 294 ± 117 μm at 1 month after the first injection to 325 ± 127 μm at 3 months (p < 0.001) and to 316 ± 117 μm at 6 months (p < 0.001) after the first injection. The increase in visual acuity correlated significantly (p < 0.01) with the decrease in macular thickness. Conclusions: Early intravitreal injection of bevacizumab may decrease macular oedema and improve visual acuity in eyes with non-ischaemic BRVO.

Early intravitreal bevacizumab for non-ischaemic central retinal vein occlusion

Purpose:  To evaluate the effect of early intravitreal bevacizumab injections for the treatment of macular oedema caused by non‐ischaemic central retinal vein occlusion (CRVO).

Peripapillary atrophy after acute primary angle closure.

Aim: To determine the changes in peripapillary atrophy after episodes of acute primary angle closure (APAC). Methods: Prospective observational study of 40 eyes in 38 patients of predominantly Chinese ethnicity. The mean (SD) intraocular pressure at the time of presentation was 51.7 (12) mm Hg (median, 55 mm Hg) and the mean duration of the symptoms was 37.7 (69.4) hours. A laser iridotomy was undertaken 3.2 (8.4) days after the APAC episode, leading to normalisation of intraocular pressure in all cases. Colour optic disc photographs taken at 2 and 16 weeks after APAC were examined morphometrically. Peripapillary atrophy was divided into α and β zones. Results: Comparing measurements at baseline with week 16, the minimum width of the α zone (0.013 (0.056) v 0.016 (0.001) arbitrary units; p = 0.23), the maximum width of the α zone (1.11 (1.31) v 1.31 (0.79) arbitrary units; p = 0.22), the minimum width of the β zone (0.030 (0.122) v 0.033 (0.166) arbitrary units; p = 0.93), and the maximum width of the β zone (0.62 (0.94) v 0.73 (0.98) arbitrary units; p = 0.42) did not vary significantly. The mean cup to disc ratio increased from 0.56 (0.05) to 0.62 (0.07) (p<0.0001) at the end of follow up. Conclusions: The α and β zones of peripapillary atrophy did not enlarge markedly in patients after APAC, despite an enlargement of the optic cup during a follow up of four months.

Role of vascular endothelial growth factor polymorphisms in the treatment success in patients with wet age-related macular degeneration.

PURPOSE Along with environmental risk factors such as smoking, hypertension, and atherosclerosis, genetic susceptibility is a primary contributor to the development and progression of exudative age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a central angiogenic regulator and there has been general agreement now that it is an important trigger for the progression of exudative AMD. In the present study, we tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with exudative AMD. DESIGN Prospective cohort study. PARTICIPANTS We included 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally administered bevacizumab in this trial. METHODS All patients were aged >50 years and had angiographically verified exudative AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs833061, rs699947, rs3024997, and rs1005230. At each follow-up visit, visual acuity was reassessed and an ophthalmic examination was carried out. Visual acuity outcome, number of retreatments, and overall time of treatment were analyzed in dependence of the VEGF polymorphisms. MAIN OUTCOME MEASURES Mean change in visual acuity at the end of the treatment period. RESULTS The included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment period of 42 to 1182 days. In univariate analysis only the G/G genotypes of rs3024997 and rs2010963 compared with all other 5 single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a significant correlation. CONCLUSIONS The current study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD.

Progression of tractional retinal detachment following intravitreal bevacizumab.

Editor, S ince the landmark study by Rosenfeld and colleagues on the efficacy of intravitreally administered bevacizumab for the treatment of exudative age-related macular degeneration (ARMD) (Michels et al. 2005; Rosenfeld et al. 2005), bevacizumab has become a globally used intravitreal medication. Soon after its first application for the treatment of exudative ARMD, intravitreal bevacizumab was administered as an adjunct for the treatment of neovascular and oedematous changes in eyes with ischaemic retinopathies such as diabetic retinopathy and ischaemic retinal vein occlusions (Grisanti et al. 2006; Iliev et al. 2006; Mason et al. 2006; Silva Paula et al. 2006; Chilov et al. 2007; Dell’omo et al. 2007; Jonas et al. 2007; Lee & Koh 2007; Minnella et al. 2007; Ruiz-Moreno et al. 2008; Shima et al. 2008; Soliman et al. 2008; Tonello et al. 2008; Yazdani et al. 2007). The observed anti-neovascular effect of intravitreal bevacizumab on iris and retinal neovascularization was unprecedented. As in any new therapy, however, unknown side-effects may occur. It was the purpose of the present study to report on such an unexpected side-effect of intravitreal bevacizumab. A 27-year-old female patient suffering from insulin-dependent diabetes mellitus experienced a loss of vision and discomfort in her left eye. Visual acuity was 0.10 (right eye) and 0.60 (left eye), and intraocular pressure measured 12 mmHg (both eyes). Ophthalmoscopy showed a tractional retinal detachment caused by a retinovitreal neovascular membrane, extending from the optic disc to the temporal superior vascular arcade. After informing the patient about the experimental character of the therapy and receiving informed consent, the patient was given an intravitreal injection of bevacizumab to reduce the intraocular neovascularization, to prevent the development of iris neovascularization and neovascular glaucoma, and to prepare the eye for a planned panretinal laser coagulation. Within 1 week of the injection, the patient noticed a rapidly progressing paracentral scotoma in her left visual field. Ophthalmoscopy revealed an almost complete closure of the blood vessels in the papillovitreal neovascular proliferation with a secondary shrinkage of the membrane leading to a progression of the tractional retinal detachment in the direction of the fovea. In view of the rapidly progressing retinal detachment and the threat of central fixation, a pars plana vitrectomy was performed with the removal of the retinovitreal neovascular membrane, silicone oil endotamponade and panretinal endolaser coagulation. The findings suggest that intravitreal bevacizumab can lead to the progression of a tractional retinal detachment in patients with pre-existing diabetic tractional retinal detachment. The present report agrees with another recent study on 11 out of 211 patients with proliferative diabetic retinopathy who developed or showed a progression of tractional retinal detachment after the intravitreal administration of bevacizumab (Arevalo et al. 2007). The reason for the progression of the retinal detachment may be shrinkage of the neovascular retinovitreal membrane leading to a contraction and further elevation of the retina. In conclusion, intravitreal bevacizumab injections may lead to the progression of a tractional retinal detachment and loss of vision in patients with proliferative ischaemic retinopathies and pre-existing tractional retinal detachments. In view of the increasing use of intravitreal bevacizumab in the treatment of neovascular glaucoma (Grisanti et al. 2006; Iliev et al. 2006; Mason et al. 2006; Silva Paula et al. 2006; Chilov et al. 2007; Dell’omo et al. 2007; Yazdani et al. 2007), the complication of the progression of a tractional retinal detachment may have to be taken into account.

INTRAVITREAL BEVACIZUMAB FOR MYOPIC CHOROIDAL NEOVASCULARIZATION

BACKGROUND AND OBJECTIVE To evaluate the effect of intravitreal bevacizumab on visual acuity in patients with myopic choroidal neovascularization. PATIENTS AND METHODS The retrospective case series study included 13 patients with myopic choroidal neovascularization who received three intravitreal injections of 1.5 mg of bevacizumab. RESULTS At 1, 3, and 6 months after the first injection, mean visual acuity improved significantly from 0.63 +/- 0.41 logarithm of the minimum angle of resolution units (LogMAR) to 0.39 +/- 0.22 (P< .001), 0.47 +/- 0.49 (P= .002), and 0.52 +/- 0.49 LogMAR (P = 0.009), respectively. The increase in visual acuity was correlated with a significant decrease in central retinal thickness (P = .003) as measured by optical coherence tomography. Mean intraocular pressure did not change significantly (P> .05) during follow-up. CONCLUSION Intravitreal injections of bevacizumab may be a therapeutic option for exudative myopic macular degeneration.

Correlation of optic disc morphology and ocular perfusion parameters in patients with primary open angle glaucoma

Purpose:  Little information is available about the relationship between glaucomatous visual field defects, morphological changes of the optic disc and ocular blood flow. In this study, ocular blood flow parameters were correlated with parameters of optic nerve head (ONH) morphology and visual field performance in a cross‐sectional study.

Combined intravitreal bevacizumab and triamcinolone in exudative age‐related macular degeneration

Acta Ophthalmol. 2010: 88: 630–634

Diffuse diabetic macular oedema treated with intravitreal bevacizumab or triamcinolone acetonide

Editor, O ne of the most frequent complications of diabetic retinopathy is diabetic macular oedema (DMO) (Klein et al. 1984). Therapeutic recommendations for the therapy of DMO usually include intensive glycaemic control (Diabetes Control and Complication Trial Research Group 1993; UK Prospective Diabetes Study [UKPDS] Group 1998), arterial blood pressure control (Gray et al. 2002) and focal or grid retinal photocoagulation, as demonstrated by the Early Treatment Diabetic Retinopathy Study [ETDRS] Research Group (1985). During the last 10 years, additional therapeutic modalities have been proposed, such as pars plana vitrectomy (Lewis et al. 1992) and intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents such as pegabtanib (Macugen Diabetic Retinopathy Study Group 2005) and bevacizumab (Browning et al. 2006; Haritoglou et al. 2006; Arevalo et al. 2007; Fang et al. 2008; Soliman et al. 2008a, 2008b) or triamcinolone acetonide (Jonas & Söfker 2001; Audren et al. 2006; LecleireCollet et al. 2007; Vinten et al. 2007; Margolis et al. 2008). As the effects of intravitreal bevacizumab and intravitreal triamcinolone on visual acuity (VA) and macular thickness have not been compared, it was the purpose of the present pilot study to compare the drugs. The study included 27 patients (27 eyes) with DMO, who received either two intravitreal injections of 1.5 mg bevacizumab with an interval of 6 weeks between them (n = 12 patients) or one intravitreal injection of about 25 mg triamcinolone acetonide (n = 15 patients). Inclusion criteria were clinically significant macular oedema as shown by loss of VA and macular thickening as imaged by optical coherence tomography (OCT), and leakage in fluorescence angiography. The decision to inject triamcinolone or bevacizumab depended on the ophthalmologist examining the patient (UHMS for bevacizumab, JBJ for triamcinolone). Each patient was examined at baseline, and at 1, 3 and 6 months after the first injection. Follow-up examinations included VA measured by Snellen charts, intraocular pressure (IOP) measured by applanation tonometry and central retinal thickness (CRT) measured by OCT. All patients were fully informed about the experimental character of the treatment and gave signed informed consent. All patients in both groups attended all four examinations. At baseline, the bevacizumab and triamcinolone study groups did not vary significantly in age (58.2 ± 6.8 years [mean ± standard deviation] and 57.3 ± 8.6 years, respectively; p = 0.76), VA (1.00 ± 0.44 logMAR and 0.85 ± 0.24 logMAR, respectively; p = 0.29), macular thickness (469 ± 126 lm and 379 ± 154 lm, respectively; p = 0.12) or length of follow-up (6.2 ± 0.2 months and 6.1 ± 0.2 months, respectively). In the bevacizumab group, mean VA increased from 1.00 ± 0.44 logMAR at baseline to 0.84 ± 0.50 logMAR at 1 month after the first injection, 0.71 ± 0.30 logMAR at 3 months after the first injection (reflecting a significant increase: p = 0.03) and 0.69 ± 0.26 logMAR at 6 months after the first injection (p = 0.02). In the triamcinolone acetonide group, VA increased significantly from 0.85 ± 0.24 logMAR at baseline to 0.60 ± 0.11 logMAR (p = 0.001) at 1 month, 0.64 ± 0.13 logMAR (p = 0.004) at 3 months and 0.64 ± 0.15 logMAR (p = 0.004) at 6 months after injection. The increase in VA measured at 1 month (p = 0.48), 3 months (p = 0.57) and 6 months (p = 0.43) after baseline did not vary significantly between the two study groups. Mean CRT in the bevacizumab group was 469 ± 126 lm at baseline and decreased significantly to 331 ± 94 lm (p = 0.004) at 1 month after the first injection, 361 ± 157 lm (p = 0.05) at 3 months and 361 ± 125 lm (p = 0.005) at 6 months. In the triamcinolone group, mean CRT was 380 ± 155 lm at baseline and decreased significantly to 262 ± 83 lm (p = 0.006) at 1 month, 277 ± 98 lm (p = 0.003) at 3 months and 321 ± 129 lm (p = 0.009) at 6 months. The decrease in macular thickness measured at 1 month (p = 0.71), 3 months (p = 0.93) and 6 months (p = 0.22) did not vary significantly between the two study groups. The decrease in macular thickness was significantly correlated with the increase in VA at 1 month (p = 0.003), 3 months (p = 0.05) and 6 months (p = 0.004). No systemic or intraocular side-effects were observed in either group. Mean IOP in the bevacizumab group was 15.0 ± 2.4 mmHg at baseline, 15.8 ± 2.0 mmHg at 1 month after injection (non-significant: p = 0.13), 15.3 ± 1.9 mmHg (p = 0.70) at 3 months and 14.8 ± 2.1 mmHg (p = 0.69) at 6 months. In the triamcinolone group, IOP increased slightly, but not statistically significantly, from 15.0 ± 2.2 mmHg at baseline to 17.1 ± 5.0 mmHg (p = 0.13) at 1 month, 15.7 ± 3.3 mmHg (p = 0.45) at 3 months and 15.7 ± 3.5 mmHg (p = 0.40) at 6 months. The results suggest that, in the patients with diffuse DMO included in the present study, both intravitreal bevacizumab and intravitreal triamcinolone significantly improved VA and reduced macular thickness. There were no major differences between the study groups. These findings agree with the results of a recent study by the Diabetic Retinopathy Clinical Research Network (2008) (DRCR.net) in which mean VA had significantly improved at 4 months after baseline. In the DRCR.net study, the visual improvement was significantly better in the study group that received 4 mg triamcinolone than in the study groups that received macular laser therapy (p < 0.001) or an intravitreal injection of 1 mg triamcinolone (p = 0.001) (Diabetic Retinopathy Clinical Research Network 2008). The results of the present study also agree with previous studies in terms of showing a significant improvement in Acta Ophthalmologica 2010

Optic Nerve Head Change in Non-Arteritic Anterior Ischemic Optic Neuropathy and Its Influence on Visual Outcome

Purpose To evaluate changes in cup/disc (C/D) diameter ratios and parapapillary atrophy in patients with non-arteritic anterior ischemic optic neuropathy (NA-AION), using morphometric methods. Methods The clinical non-interventional study included 157 patients with unilateral or bilateral NA-AION. Optic disc photographs taken from both eyes at the end of follow-up were morphometrically examined. Results Follow-up was 86.3±70.3 months. Horizontal and vertical disc diameters (P = 0.30;P = 0.61, respectively), horizontal and vertical C/D ratios (P = 0.47;P = 0.19,resp.), and size of alpha zone and beta zone of parapapillary atrophy (P = 0.27;P = 0.32,resp.) did not differ significantly between affected eyes and contralateral normal eyes in patients with unilateral NA-AION. Similarly, horizontal and vertical disc diameters, horizontal and vertical C/D ratios, and size of alpha zone and beta zone did not vary significantly (all P>0.05) between the unaffected eyes of patients with unilateral NA-AION and the eyes of patients with bilateral NA-AION. Optic disc diameters, C/D ratios, size of alpha zone or beta zone of parapapillary atrophy were not significantly associated with final visual outcome in the eyes affected with NA-AION (all P>0.20) nor with the difference in final visual acuity between affected eyes and unaffected eyes in patients with unilateral NA-AION (all P>0.25). Conclusions NA-AION did not affect C/D ratios nor alpha zone and beta zone of parapapillary atrophy. Optic disc size was not related to the final visual acuity outcome in NA-AION.