Effects of topical clonidine versus brimonidine on choroidal blood flow and intraocular pressure during squatting

PURPOSE. Clonidine and brimonidine, two ␣-2 agonists, have been shown to reduce intraocular pressure (IOP) in patients with glaucoma. Little is known, however, about the exact role of ␣ receptors in the control of ocular blood flow in the posterior pole of the eye. Hence, the study was conducted to investigate the effects of topical clonidine versus topical brimonidine on choroidal blood flow and intraocular pressure during squatting. METHODS. This was a randomized, double-masked, controlled, two-way crossover study. Twelve healthy male nonsmoking volunteers, aged between 19 and 35 years were included in the study. Two drops of clonidine or brimonidine were administered in the subjects' study eyes. Continuous measurement using the compact laser Doppler flowmeter was performed during a 6-minute squatting period, to assess choroidal blood flow regulation during an increase in ocular perfusion pressure. RESULTS. Both substances induced a pronounced but comparable (P ϭ 0.8) decrease in IOP. Squatting increased mean arterial pressure (MAP) and ocular perfusion pressure (P Ͻ 0.01). This increase was comparable between the clonidine and the brimonidine study day (P ϭ 0.88). Squatting induced an increase in choroidal blood flow that was less pronounced than the increase in ocular perfusion pressure. Compared with baseline the ␣-2 agonists decreased choroidal blood flow during squatting (P ϭ 0.0026) to a comparable degree (P ϭ 0.86). Vascular resistance increased at baseline and during squatting after administration of the ␣-2 agonists (P Ͻ 0.01) in both groups to a comparable degree (P ϭ 0.56). CONCLUSIONS. Topical ␣-2 agonists may induce changes in choroidal blood flow, even after a single administration. Long-term studies are needed to study potential effects of brimonidine and clonidine in the clinical setting. (Invest Ophthalmol Vis Sci. 2007;48:4220 -4225

Effects of Pentoxifylline and Alprostadil on Ocular Hemodynamics in Healthy Humans

PURPOSE. Alprostadil, a prostaglandin (PG)E 1 analogue and pentoxifylline, an alkylxanthine derivate, have been shown to exert vasodilatory effects in several vascular beds. The purpose of the present study was to investigate the effect of PGE 1 and pentoxifylline on the ocular circulation. METHODS. A placebo-controlled, double-masked, three-way, crossover study was performed in 15 healthy male subjects. Subjects received pentoxifylline (300 mg), PGE 1 (alprostadil 60 g), or placebo intravenously over 2 hours on three trial days. Choroidal red blood cell flow was assessed with laser Doppler flowmetry and pulsatile choroidal blood flow with laser interferometric measurement of fundus pulsation amplitude (FPA). Retinal blood cell flow was calculated based on the measurements of maximum erythrocyte velocity in a retinal vein assessed with bidirectional laser Doppler velocimetry, and diameter measurements of retinal vessels were obtained with a retinal vessel analyzer. RESULTS. Pentoxifylline increased FPA by 15.4% Ϯ 1.1% (P Ͻ 0.001 versus placebo and baseline). Alprostadil tended to increase FPA, but this effect did not reach the level of significance (P ϭ 0.07 versus placebo). Choroidal blood flow as measured with laser Doppler flowmetry tended to increase during pentoxifylline and PGE 1 infusion by 8.9% Ϯ 2.9% (P ϭ 0.062) and 4.5% Ϯ 6.2% (P ϭ 0.29), respectively, but none of these effects was significant. The drugs under study had no effect on mean red blood cell velocity in retinal veins, on retinal vessel diameters, intraocular pressure, blood pressure, or pulse rate. CONCLUSIONS. PGE 1 did not alter the parameters of retinal or choroidal circulation in healthy subjects. Pentoxifylline increased FPA, but did not change choroidal blood flow as measured with laser Doppler flowmetry and did not affect retinal blood flow parameters. Accordingly, neither pentoxifylline nor PGE 1 appears to be suitable to improve ocular blood flow in healthy subjects. Whether long-term treatment with alprostadil would improve choroidal blood flow in patients with vascular disease remains to be established. (Invest Ophthalmol Vis Sci

Exploring Consensus on Preventive Measures and Identification of Patients at Risk of Age-Related Macular Degeneration Using the Delphi Process

BACKGROUND: Early identification of AMD can lead to prompt and more effective treatment, better outcomes, and better final visual acuity; several risk scores have been devised to determine the individual level of risk for developing AMD. Herein, the Delphi method was used to provide recommendations for daily practice regarding preventive measures and follow-up required for subjects at low, moderate, and high risk of AMD evaluated with the Simplified Test AMD Risk-assessment Scale (STARS(®)) questionnaire. METHODS: A steering committee of three experts drafted and refined 25 statements on the approach to be recommended in different clinical situations [general recommendations (n = 2), use of evaluation tools (n = 4), general lifestyle advice (n = 3), and AREDS-based nutritional supplementation (n = 5)] with the help of a group of international experts, all co-authors of this paper. Thirty retinal specialists from Europe and the US were chosen based on relevant publications, clinical expertise, and experience in AMD, who then provided their level of agreement with the statements. Statements for which consensus was not reached were modified and voted upon again. RESULTS: In the first round of voting, consensus was reached for 24 statements. After modification, consensus was then reached for the remaining statement. CONCLUSION: An interprofessional guideline to support preventive measures in patients at risk of AMD based on STARS(®) scoring has been developed to aid clinicians in daily practice, which will help to optimize preventive care of patients at risk of AMD

CorneaNet : fast segmentation of cornea OCT scans of healthy and keratoconic eyes using deep learning

Deep learning has dramatically improved object recognition, speech recognition, medical image analysis and many other fields. Optical coherence tomography (OCT) has become a standard of care imaging modality for ophthalmology. We asked whether deep learning could be used to segment cornea OCT images. Using a custom-built ultrahigh-resolution OCT system, we scanned 72 healthy eyes and 70 keratoconic eyes. In total, 20,160 images were labeled and used for the training in a supervised learning approach. A custom neural network architecture called CorneaNet was designed and trained. Our results show that CorneaNet is able to segment both healthy and keratoconus images with high accuracy (validation accuracy: 99.56%). Thickness maps of the three main corneal layers (epithelium, Bowman’s layer and stroma) were generated both in healthy subjects and subjects suffering from keratoconus. CorneaNet is more than 50 times faster than our previous algorithm. Our results show that deep learning algorithm scan be used for OCT image segmentation and could be applied in various clinical settings. In particular, CorneaNet could be used for early detection of keratoconus and more generally to study other diseases altering corneal morphology.Published versio

Cationic Emulsion-Based Artificial Tears as a Mimic of Functional Healthy Tear Film for Restoration of Ocular Surface Homeostasis in Dry Eye Disease

Dry eye disease (DED) is a complex multifactorial disease that affects an increasing number of patients worldwide. Close to 30% of the population has experienced dry eye (DE) symptoms and presented with some signs of the disease during their lifetime. The significant heterogeneity in the medical background of patients with DEs and in their sensitivity to symptoms renders a clear understanding of DED complicated. It has become evident over the past few years that DED results from an impairment of the ocular surface homeostasis. Hence, a holistic treatment approach that concomitantly addresses the different mechanisms that result in the destabilization of the tear film (TF) and the ocular surface would be appropriate. The goal of the present review is to compile the different types of scientific evidence (from in silico modeling to clinical trials) that help explain the mechanism of action of cationic emulsion (CE)-based eye drop technology for the treatment of both the signs and the symptoms of DED. These CE-based artificial tear (AT) eye drops designed to mimic, from a functional point of view, a healthy TF contribute to the restoration of a healthy ocular surface environment and TF that leads to a better management of DE patients. The CE-based AT eye drops help restore the ocular surface homeostasis in patients who have unstable TF or no tears

In vivo tear film thickness measurement and tear film dynamics visualization using spectral domain optical coherence tomography

Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the tear film. Traditional methods used for the evaluation of tear film stability are invasive or show limited repeatability. Here we propose a new non-invasive fully automated approach to measure tear film thickness based on spectral domain optical coherence tomography and on an efficient delay estimator. Silicon wafer phantom were used to validate the thickness measurement. The technique was applied in vivo in healthy subjects. Series of tear film thickness maps were generated, allowing for the visualization of tear film dynamics. Our results show that the in vivo central tear film thickness measurements are precise and repeatable with a coefficient of variation of about 0.65% and that repeatable tear film dynamics can be observed. The presented approach could be used in clinical setting to study patients with dry eye disease and monitor their treatments.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Assessment of choroidal neovascularization perfusion: a pilot study with laser speckle flowgraphy

Purpose: The purpose of this study was to quantify perfusion in the area of choroidal neovascularization (CNV) using laser speckle flowgraphy (LSFG) before and after intravitreal anti-vascular endothelial growth factor (VEGF) injection. Methods: Retrospective case series. Fifteen eyes of 15 patients with treatment-naïve CNV due to age-related macular degeneration (AMD) and with available LSFG images were included. The main outcomewas themean blur rate (MBR) quantified as ameasure of perfusion within the CNV area observed on indocyanine green angiography. Twelve patients had available longitudinal data until one month after the injection, used to evaluate changes in perfusion, central macular thickness (CMT), visual acuity, and ocular perfusion pressure. Reproducibility of LSFG measurements was investigated at each time point from two images taken within five minutes. Results: Intraclass correlation coefficients for LSFG measurements were higher than 0.8 indicating excellent reproducibility. There was a significant decrease in perfusion after oneweek (-26.4±14.4%; P=0.027),whereas, after onemonth, perfusion was no longer significantly different from baseline (P = 0.121). CMT showed a progressive decrease over the follow-up period. Changes in perfusion were strongly correlated with changes in CMT after one week, but not thereafter. Conclusions: This pilot study suggests a method to select a region in the CNV area to quantify perfusion using LSFG. MBR could represent a parameter possibly related to regrowth of the CNV after anti-VEGF treatment. Large-scale studies are needed to assess the usefulness of LSFG in defining re-treatment criteria for neovascular AMD