To investigate the clinical and electrophysiologic effect of a single intravitreal injection of bevacizumab for neovascular glaucoma (NVG) after ischemic central retinal vein occlusion (iCRVO).
Nineteen eyes from 19 patients with NVG secondary to iCRVO were randomly allocated to either an intravitreal bevacizumab injection and panretinal photocoagulation (PRP) (10 eyes) or PRP alone (9 eyes). The primary outcome measure was the change in the total retinal function 6 months after treatment, demonstrated by full-field electroretinography (ERG). Secondary outcomes included visual acuity, intraocular pressure (IOP), glaucoma medication, additional IOP-lowering treatment, and the presence of ocular neovascularization before treatment, and 1 week, 2 months, and 6 months after treatment.
The regression of ocular neovascularization in the bevacizumab/PRP group was confirmed 1 week after injection. Patients in both study groups had very poor visual acuity at baseline. This remained unchanged. There was no significant difference in the mean IOP between the groups at any point in time. The a-wave amplitudes of combined rod-cone response were significantly decreased after 6 months in the bevacizumab/PRP group (p=0.028), compared with the baseline values. The a- and b-wave amplitudes of combined rod-cone response and the b-wave amplitudes of the 30-Hz flicker response were also markedly reduced compared with the PRP group (-60%, -43%, -47% vs +23%, -36%, -16%, respectively).
This study suggests that intravitreal injection of bevacizumab is valuable in the treatment of NVG by hastening the resolution of neovascularization, while the full-field ERG results indicate that bevacizumab may reduce the photoreceptor function in NVG patients.
"At a minimum, our findings suggest that risks to patients with glaucoma may need to be more systematically and rigorously assessed. Based on full-field electroretinographic results, it was recently reported that VEGF neutralization with bevacizumab regressed neovascularization and also reduced photoreceptor function in patients with neovascular glaucoma.49 Furthermore, a study observing 49 patients with age-related macular degeneration found that, in eyes treated with ranibizumab, nerve fiber layer thickness was significantly reduced after 1 year of treatment, whereas untreated control eyes displayed no change.50 "
[Show abstract][Hide abstract] ABSTRACT: Vascular endothelial growth factor A (VEGF-A) is a validated therapeutic target in several angiogenic- and vascular permeability-related pathological conditions, including certain cancers and potentially blinding diseases, such as age-related macular degeneration and diabetic retinopathy. We and others have shown that VEGF-A also plays an important role in neuronal development and neuroprotection, including in the neural retina. Antagonism of VEGF-A function might, therefore, present a risk to neuronal survival as a significant adverse effect. Herein, we demonstrate that VEGF-A acts directly on retinal ganglion cells (RGCs) to promote survival. VEGF receptor-2 signaling via the phosphoinositide-3-kinase/Akt pathway was required for the survival response in isolated RGCs. These results were confirmed in animal models of staurosporine-induced RGC death and experimental hypertensive glaucoma. More important, we observed that VEGF-A blockade significantly exacerbated neuronal cell death in the hypertensive glaucoma model. Our findings highlight the need to better define the risks associated with use of VEGF-A antagonists in the ocular setting.
American Journal Of Pathology 02/2013; 182(4). DOI:10.1016/j.ajpath.2012.12.032 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To determine the incidence rate as well as causative diagnoses and surgical indications of enucleation in Iceland during the years 1992-2004.
A retrospective population-based incidence study involving the entire population of Iceland. Medical records of all patients who underwent enucleation in Iceland from January 1992 through December 2004 were reviewed. The annually updated Icelandic census was used as a denominator data.
Fifty-six eyes were enucleated during 1992-2004. No eviscerations were done, and the three exenterations performed were not included in the study. The mean annual age-adjusted incidence rate of enucleation in Iceland was 1.48 enucleations per 100 000 population in comparison with 2.66 enucleations per 100 000 for the time period 1964-1991. With advancing age, a significant increasing linear trend existed (p < 0.001). The median age at enucleation was 51 years (SD 22; mean 55 years; 16-91 years). The three most common surgical indications for enucleation were blind painful eye, suspected ocular malignancy and acute trauma. The most common causative diagnosis for enucleation was traumatic lesion (39%). The annual incidence was 2.00 enucleations per 100 000 for men and 0.95 for women. There were significantly more men in the traumatic lesion group (p < 0.001), but no gender predominance was found in the other groups of causative diagnoses (p = 0.8).
The overall mean annual incidence of enucleation in Iceland is continually decreasing, although the incidence of severe ocular trauma and ocular malignancy is fairly stable.
[Show abstract][Hide abstract] ABSTRACT: Neovascular glaucoma (NVG) is a potentially blinding secondary glaucoma. It is caused by the formation of abnormal new blood vessels which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) agents are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGFs for the control of intraocular pressure (IOP) in NVG.
To compare the IOP lowering effects of intraocular anti-VEGF agents to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment of NVG.
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 January 2013.
We included randomized controlled trials (RCTs) and quasi-RCTs of people treated with anti-VEGF agents for NVG.
Two authors independently assessed the search results for trials to be included in the review. Discrepancies were resolved by discussion with a third author. Since no trial met our inclusion criteria, no assessment of risk of bias or meta-analysis was undertaken.
No RCTs were found that met the inclusion criteria for this review. Two RCTs of anti-VEGF agents for treating NVG were not included in the review due to the heterogeneity and uncontrolled assignment of adjunct treatments received by the study participants.
Currently available evidence is insufficient to evaluate the effectiveness of anti-VEGF treatments, such as intravitreal ranibizumab or bevacizumab, as an adjunct to conventional treatment in lowering IOP in NVG. Well designed RCTs are needed to address this issue, particularly trials that evaluate long-term (at least six months) benefits and risks since the effects of anti-VEGF agents may be short-term only. An RCT comparing anti-VEGF agents with no anti-VEGF agents taking into account the need for co-interventions, such as panretinal photocoagulation (PRP), glaucoma shunt procedures, cyclodestructive procedures, cataract surgery, and deep vitrectomy, could be of use to investigate the additional beneficial effect of anti-VEGF agents in treating NVG. Since decisions for when and which co-interventions should be used are based on clinical criteria, they would not be appropriate for randomization. However, the design of a study on this topic should aim to balance groups by stratification of co-intervention at time of randomization or by enrolling a sufficient number of participants to conduct subgroup analysis by co-interventions (ideally 15 participants per treatment group for each subgroup). Alternatively, the inclusion criteria for a trial could limit participants to those who receive the same co-intervention.
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