To compare funduscopic and confocal scanning vertical cup-disc ratio (VCDR) assessments and their respective predictive value for estimating functional glaucomatous damage.Data from a single eye of open angle glaucoma patients from the Leuven Eye Study were included: age, gender, intra-ocular pressure, visual acuity, refractive error, visual field mean deviation and pattern standard deviation, funduscopic and HRT III VCDRs as well as mean retinal nerve fibre layer thickness. Non-parametric tests to compare differences within and between diagnostic groups were used, and receiver-operating characteristic curves as well as Bland-Altman plots constructed.Three hundred and one eyes of 301 subjects with primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) were included. The average VCDR assessed with HRT III was significantly smaller than the funduscopic measurement (0.69 ± 0.16 vs. 0.81 ± 0.14, respectively; p < 0.001). The predictive value of both measurement techniques did not differ in NTG patients, but the funduscopic estimate yielded a significantly larger predictive power in patients with severe POAG.Funduscopic and confocal scanner estimates of VCDR differ significantly and should not be used interchangeably. In POAG patients with severe glaucoma, a subjective VCDR predicts functional glaucomatous damage significantly better.
In a retinal detachment, a separation occurs between the retinal photoreceptors and the retinal pigment epithelium (RPE) cells. Sometimes, particularly in young patients, visual recovery is suboptimal, even after successful surgical reattachment of the retina. With optical coherence tomography (OCT), a subfoveal fluid accumulation can be observed in these eyes. The underlying cause of this persistent subfoveal fluid accumulation is still a matter of debate (Wolfensberger & Gonvers 2002). In our opinion, a deficient pump function of the RPE cells is causing the persistent fluid accumulation. In central serous choroidopathy (CSC), a similar subfoveal translucent zone is observed underneath the fovea using OCT. Deficient RPE-cell pump function has previously been shown to cause the fluid accumulation in CSC. Presently, there is no generally accepted treatment for persistent subfoveal fluid accumulation after retinal detachment (Ricker et al. 2011). The pump function of RPE cells is driven by a Na+/K+-ATPase. In human RPE cells, a beta-receptor is present on the apical membrane. The activation of this receptor results in increased pump function from the apical to the basal end (Frambach et al. 1990). Presuming that the pathogenesis of persistent subfoveal fluid accumulation is deficient RPE pump function, the stimulation of this function with a beta-2 agonist should accelerate the resorption of the subretinal fluid, with further recovery of central vision (Wax et al. 1989). Ten male New Zealand albino rabbits were included in the study and received an intravitreal injection of 0.1 ml in the right eye. Five rabbits received an injection of 0.08 μg clenbuterol hydrochloridum (VentipulminⓇ; Boehringer Ingelheim, Ingelheim am Rhein, Germany), and five were injected with a balanced saline solution. The optimal doses of intravitreal clenbuterol in human subjects was calculated based on the volume of a human eye in which an intravitreal injection of 0.08 μg should be appropriate. Because the volume of an adult rabbit eye is only one-third of an adult human eye, the achieved concentration was threefold higher than the concentration suggested for use in a human eye. The rabbits were sacrificed, and the eyes were enucleated. Apoptosis of the retina and pigmented epithelium was investigated using the ApopTag® ISOL Dual Fluorescence Apoptosis Detection Kit (DNase Types I & II) from Millipore (Billerica, MA, USA) (Galluzzi et al. 2009). All examinations were performed by a blinded investigator. No inflammation was observed. The optical media remained clear. The retina and optic nerve appeared unaltered. The intraocular pressure remained normal. In summary, the clenbuterol-treated and placebo eyes did not clinically differ. Light microscopy revealed a normal RPE and a retinal complex with normal structures of all retinal layers, including the ganglion cell layers (Fig. 1A,B). The ganglion cell count in the retina did not differ between eyes in different groups. No picnotic nuclei were found. An analysis with the Dual Fluorescence Apoptosis Detection Kit showed the absence of apoptosis in the RPE and in all retinal layers (Fig. 1C,D). To our knowledge, the safety of intraocular clenbuterol injection has never been reported. This study indicates that 0.08 μg clenbuterol administered intravitreally in rabbit eyes did not display ocular toxicity. The dosage used was threefold higher than the targeted therapeutic level and was shown to be free of side-effects. However, the limitations of this study include the lack of electrophysiological testing, the short follow-up period and the number of rabbits used. Further studies will be required to clearly determine the effective dose of intravitreal clenbuterol and to monitor retinal function using electroretinography. In conclusion, our preliminary study suggests that a 0.08 μg dose of intravitreally injected clenbuterol may be safe for rabbit eyes. Therefore, if proven to be safe by further studies, intraocular clenbuterol might be considered a possible treatment for patients with persistent subfoveal fluid accumulation after retinal detachment surgery.
To determine the correlation between ocular blood flow velocities and ocular pulse amplitude (OPA) in glaucoma patients using colour Doppler imaging (CDI) waveform analysis.A prospective, observer-masked, case-control study was performed. OPA and blood flow variables from central retinal artery and vein (CRA, CRV), nasal and temporal short posterior ciliary arteries (NPCA, TPCA) and ophthalmic artery (OA) were obtained through dynamic contour tonometry and CDI, respectively. Univariate and multiple regression analyses were performed to explore the correlations between OPA and retrobulbar CDI waveform and systemic cardiovascular parameters (blood pressure, blood pressure amplitude, mean ocular perfusion pressure and peripheral pulse).One hundred and ninety-two patients were included [healthy controls: 55; primary open-angle glaucoma (POAG): 74; normal-tension glaucoma (NTG): 63]. OPA was statistically different between groups (Healthy: 3.17 ± 1.2 mmHg; NTG: 2.58 ± 1.2 mmHg; POAG: 2.60 ± 1.1 mmHg; p < 0.01), but not between the glaucoma groups (p = 0.60). Multiple regression models to explain OPA variance were made for each cohort (healthy: p < 0.001, r = 0.605; NTG: p = 0.003, r = 0.372; POAG: p < 0.001, r = 0.412). OPA was independently associated with retrobulbar CDI parameters in the healthy subjects and POAG patients (healthy CRV resistance index: β = 3.37, CI: 0.16-6.59; healthy NPCA mean systolic/diastolic velocity ratio: β = 1.34, CI: 0.52-2.15; POAG TPCA mean systolic velocity: β = 0.14, CI 0.05-0.23). OPA in the NTG group was associated with diastolic blood pressure and pulse rate (β = -0.04, CI: -0.06 to -0.01; β = -0.04, CI: -0.06 to -0.001, respectively).Vascular-related models provide a better explanation to OPA variance in healthy individuals than in glaucoma patients. The variables that influence OPA seem to be different in healthy, POAG and NTG patients.
Purpose Glaucoma surgery fails in 30% due to excessive scar formation of the constructed channel. Our group found that vascular endothelial growth factor (VEGF) is upregulated in the aqueous humor of glaucoma patients and postoperatively in a rabbit model for trabeculectomy, that VEGF stimulates fibroblast proliferation in vitro whereas bevacizumab can inhibit their growth, and that a single peroperative intracameral injection of bevacizumab improves the surgical outcome of trabeculectomy in a rabbit model. Based on these findings, we set up a clinical trial to study the potential of bevacizumab as an anti-scarring agent after trabeculectomy. Methods This is a prospective, randomized, placebo-controlled, double-blinded experimental study. The effect of peroperative administration of 50 µl of bevacizumab (25mg/ml) on intraocular pressure, bleb characteristics, as well as number of postoperative IOP-lowering medications and surgical interventions is investigated. Patients with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) who are scheduled for primary trabeculectomy are included. Results Inclusions started on April 2009 and are still ongoing. Based on a priori calculations we need to include 124 patients. We already included 97 patients, 54 of which are POAG and 43 are NTG patients. By the end of September the majority will have ended the study. The preliminary results of this group will be presented at EVER. Conclusion This study will provide evidence on effectiveness and safety of single administration of bevacizumab during trabeculectomy to reduce the risk of surgical failure, avoiding or reducing the need for long-term medication use or secondary surgical intervention.
Purpose During posterior vitreous detachment (PVD) the posterior hyaloid remains, for a certain period, attached to the optic disc. It can exert traction with development of optic nerve head hemorrhages (ONHH). ONHH are known to be associated with glaucomatous progression and retinal nerve fiber layer (RNFL) defects. Therefore this study aims at investigating the relationship between PVD formation and ONHH in open angle glaucoma patients. Methods Patients presenting with an ONHH, from November 2014 on, were included. They underwent a comprehensive ophthalmological investigation, automated visual field test, confocal scanner (HRT III), OCT (HRT-Spectralis) scan and stereographic photos of the optic nerve head. This study is part of a larger, clinicaltrial.gov (NCT02290795) registered, study investigating vitreopapillary traction (VPT). Results Eighteen eyes of 18 patients (11 normal tension, 6 primary open angle and 1 secondary open angle glaucoma) were included. Seven out of 18 (38.9%) eyes had concomitant VPT and 7 had a complete PVD. Seven ONHH were located infero-, 5 supero- and 6 temporal. In the non-VPT subgroup 5 out of 11 (45.5%) eyes showed matching retinal nerve fiber layer defects, with 2 out of 7 (28.6%) in the VPT subgroup. Conclusions VPT could be a confounding factor in glaucoma assessment and ONHH development.
Purpose To contrast systemic and ocular vascular parameters in patients with normal‐tension glaucoma (NTG) versus primary open‐angle glaucoma (POAG). Methods Sub‐analysis of a prospective, cross‐sectional, case–control hospital‐based study investigating ocular blood flow in glaucoma patients (Leuven Eye Study). Systemic and ocular vascular parameters, including a questionnaire, blood pressure, dynamic contour tonometry, colour Doppler imaging, retinal oximetry and optical coherent tomography enhanced‐depth imaging, were compared between an age‐matched group of POAG and NTG patients. Results We included 192 NTG and 214 POAG patients. Patients with NTG presented with significantly lower diastolic blood pressure (p = 0.01), decreased acceleration in the central retinal artery (p = 0.02), increased resistive index in the ophthalmic artery and central retinal vein (both p = 0.04), thinner peripapillary choroidal thickness (p < 0.001) and higher retinal venous oxygen saturation (p < 0.001). The odds of suffering from hypotension, migraine and Raynaud were significantly higher for NTG patients [95% confidence interval (CI) 1.30–8.73, 1.13–4.42 and 1.36–3.95 respectively], as were the odds of taking systemic bèta‐blockers, calcium antagonists and angiotensin II receptors blockers (95% CI 1.04–2.67, 1.21–6.62 and 1.18–5.97 respectively). Conclusions Patients with NTG differ significantly on several ocular and systemic vascular parameters from POAG patients. These findings add further support to a higher weight for vascular‐driven neuropathy in NTG vascular etiology in NTG.
Abstract Purpose Purpose: to determine the correlation between ocular blood flow changes throughout the cardiac cycle on ocular pulse amplitude (OPA) in glaucoma patients and healthy subjects. Methods Method: A prospective, case‐control study was designed with dynamic contour tonometry and color Doppler Imaging performed in healthy controls and glaucoma patients. An offline waveform analysis of the Doppler signal was performed by a masked observer for each of the retrobulbar arteries. Linear regression models using intraocular pressure (IOP), age and Doppler waveform variables [(resistance index (RI) and systolic/diastolic velocity ratio (Sm/Dm)] were designed to identify independent variables associated with OPA. Results Results: 192 patients were included [healthy controls: 55; normal tension glaucoma (NTG): 63, primary open‐angle glaucoma (POAG): 74]. OPA showed a significant associated with the constructed model in healthy individuals and in POAG patients (r=0.54, p<0.001; r=0.43, p<0.001, respectively). Short ciliary arteries flow variables were the only vascular‐related parameters independently associated with OPA in these groups (p<0.05). IOP was independently associated with OPA in the POAG group (p<0.001), but not the healthy group (p=0.48). OPA in the NTG group did not correlate with the constructed model (r=0.24, p=0.21). Conclusion Conclusions: OPA seems to reflect blood flow changes in the short ciliary arteries in healthy individuals and POAG patients, but not in NTG patients. In the latter, the ocular pulse may relate to other variables than blood flow velocities.
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