Karel Van Keer

Ocular blood flow in glaucoma – the Leuven Eye Study

Elevated intra‐ocular pressure (IOP) has been identified as a major risk factor for glaucoma. Additionally, extensive literature depicts a vascular dysfunction to exist in these patients. However, a large ocular blood flow‐oriented trial to integrate these findings in the clinical setting is lacking. This study would likely help to identify which of these vascular data can be used as a clinical tool for screening and disease stratification.

Correlation Between Peripapillary Choroidal Thickness and Retinal Vessel Oxygen Saturation in Young Healthy Individuals and Glaucoma Patients.

PURPOSE To investigate the correlation between peripapillary choroidal thickness (CT) and retinal vessel oxygen saturation (SO2) in young healthy individuals and open-angle glaucoma (OAG) patients. METHODS Fifty-four young healthy volunteers (aged 21.6 ± 1.1 years) and 48 OAG patients (aged 72.0 ± 9.1 years, visual field mean deviation -9.0 ± 8.1 dB) were included. Peripapillary CT was obtained using enhanced depth imaging optical coherence tomography (EDI-OCT). Arterial (SaO2) and venous (SvO2) retinal oxygen saturation were measured by a spectrophotometric retinal oximeter. RESULTS Arterial and SvO2 retinal oxygen saturation were significantly higher in the glaucoma group (95.1 ± 3.3% vs. 92.3 ± 3.0% and 60.8 ± 6.3% vs. 55.4 ± 4.6%, P < 0.001, respectively), while arteriovenous oxygen difference was significantly lower (34.4 ± 6.0% vs. 36.8 ± 3.8%, P = 0.014). Arterial and SvO2 retinal oxygen saturation were positively correlated with peripapillary CT in the healthy group (Spearmans ρ = 0.48, P < 0.001 and ρ = 0.41, P = 0.002, respectively), but not in the glaucoma group (P > 0.05). Multivariate analysis confirmed that these findings were independent of age, intraocular pressure, and mean arterial blood pressure and revealed a negative correlation between arteriovenous oxygen difference and CT in the healthy group (β = -0.337, P = 0.03). CONCLUSIONS In this study, we found a significant positive correlation between retinal vessel SO2 and peripapillary CT in young healthy individuals, but not in open-angle glaucoma patients. Further research is warranted to investigate whether the lack of correlation reflects a disturbance in the blood flow regulation in glaucoma patients. (ClinicalTrials.gov number, NCT01840202.).

Review on Dynamic Contour Tonometry and Ocular Pulse Amplitude

Intraocular pressure (IOP) measurement is the cornerstone of the management of glaucoma patients. The gold standard for assessing IOP is Goldmann applanation tonometry (GAT). Recently, the dynamic contour tonometer (DCT) has become available. While both devices provide reliable IOP measurements, the results are not interchangeable. DCT has the advantage of measuring an additional parameter: ocular pulse amplitude (OPA). OPA is defined as the difference between systolic and diastolic IOP and represents the pulsatile wave front produced by the varying amount of blood in the eye during the cardiac cycle. It has been shown to vary with ocular structural parameters, such as axial length, corneal thickness, and ocular rigidity, as well as with systemic variables like heart rate, blood pressure, and left ventricular ejection fraction. Although the existence of some of these associations is still controversial, the clinical relevance of OPA has been consistently suggested, especially in glaucoma. Further research on this intriguing parameter could not only provide insight into glaucoma pathophysiology but also help integrate this variable into clinical practice.

More Than Meets the Eye: Klebsiella pneumoniae Invasive Liver Abscess Syndrome Presenting with Endophthalmitis

BACKGROUND Endophthalmitis is a feared complication of pyogenic liver abscesses caused by hypervirulent Klebsiella pneumoniae strains. First described in East Asia in the 1980s, this invasive syndrome is only recently emerging in Europe and America. CASE REPORT We describe an 84-year-old man who presented to the emergency department with fever, orbital cellulitis, and bilateral visual loss. Although the patient had no overt abdominal symptoms, computed tomography scan revealed a pyogenic liver abscess. Blood cultures were positive for K. pneumoniae. Initial treatment consisted of intravenous ceftriaxone and intravitreal ceftazidime. A unilateral vitrectomy was performed. The patient survived with severe visual sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: K. pneumoniae pyogenic liver abscess with metastatic endophthalmitis is a relatively new syndrome that should be considered in patients presenting with acute vision loss who appear septic, with or without abdominal complaints. Early recognition prohibits delays in lifesaving treatment.

Non-invasive assessment of cerebral oxygenation: A comparison of retinal and transcranial oximetry

Background To investigate the correlation between cerebral (SO2-transcranial), retinal arterial (SaO2-retinal) and venous (SvO2-retinal) oxygen saturation as measured by near-infrared spectroscopy (NIRS) and retinal oximetry respectively. Methods Paired retinal and cerebral oxygen saturation measurements were performed in healthy volunteers. Arterial and venous retinal oxygen saturation and diameter were measured using a non-invasive spectrophotometric retinal oximeter. Cerebral oxygen saturation was measured using near-infrared spectroscopy. Correlations between SO2-transcranial and retinal oxygen saturation and diameter measurements were assessed using Pearson correlation coefficients. Lin’s concordance correlation coefficient (CCC) and Bland-Altman analysis were performed to evaluate the agreement between SO2-transcranial as measured by NIRS and as estimated using a fixed arterial:venous ratio as 0.3 x SaO2-retinal + 0.7 x SvO2-retinal. The individual relative weight of SaO2-retinal and SvO2-retinal to obtain the measured SO2-transcranial was calculated for all subjects. Results Twenty-one healthy individuals aged 26.4 ± 2.2 years were analyzed. SO2-transcranial was positively correlated with both SaO2-retinal and SvO2-retinal (r = 0.44, p = 0.045 and r = 0.43, p = 0.049 respectively) and negatively correlated with retinal venous diameter (r = -0.51, p = 0.017). Estimated SO2-transcranial based on retinal oximetry showed a tolerance interval of (-13.70 to 14.72) and CCC of 0.46 (95% confidence interval: 0.05 to 0.73) with measured SO2-transcranial. The average relative weights of SaO2-retinal and SvO2-retinal to obtain SO2-transcranial were 0.31 ± 0.11 and 0.69 ± 0.11, respectively. Conclusion This is the first study to show the correlation between retinal and cerebral oxygen saturation, measured by NIRS and retinal oximetry. The average relative weight of arterial and venous retinal oxygen saturation to obtain the measured transcranial oxygen saturation as measured by NIRS, approximates the established arterial:venous ratio of 30:70 closely, but shows substantial inter-individual variation. These findings provide a proof of concept for the role of retinal oximetry in evaluating cerebral oxygenation.

Funduscopic versus HRT III Confocal Scanner Vertical Cup-Disc Ratio Assessment in Normal Tension and Primary Open Angle Glaucoma (The Leuven Eye Study).

Purpose: To compare funduscopic and confocal scanning vertical cup-disc ratio (VCDR) assessments and their respective predictive value for estimating functional glaucomatous damage. Methods: 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. Results: 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. Conclusion: 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.

Choroidal abnormalities in café‐au‐lait syndromes: A new differential diagnostic tool ?

The best known café‐au‐lait syndrome is neurofibromatosis type 1 (NF1). Legius syndrome (LS) is another, rarer syndrome with café‐au‐lait macules (CALMs). In young patients their clinical picture is often indistinguishable. We investigated the presence of choroidal abnormalities in syndromes with CALMs as a candidate tool for a more efficient diagnosis.

Towards a Glaucoma Risk Index Based on Simulated Hemodynamics from Fundus Images

Glaucoma is the leading cause of irreversible but preventable blindness in the world. Its major treatable risk factor is the intra-ocular pressure, although other biomarkers are being explored to improve the understanding of the pathophysiology of the disease. It has been recently observed that glaucoma induces changes in the ocular hemodynamics. However, its effects on the functional behavior of the retinal arterioles have not been studied yet. In this paper we propose a first approach for characterizing those changes using computational hemodynamics. The retinal blood flow is simulated using a 0D model for a steady, incompressible non Newtonian fluid in rigid domains. The simulation is performed on patient-specific arterial trees extracted from fundus images. We also propose a novel feature representation technique to comprise the outcomes of the simulation stage into a fixed length feature vector that can be used for classification studies. Our experiments on a new database of fundus images show that our approach is able to capture representative changes in the hemodynamics of glaucomatous patients. Code and data are publicly available in https://ignaciorlando.github.io.

New Normative Database of Inner Macular Layer Thickness Measured by Spectralis OCT Used as Reference Standard for Glaucoma Detection

Purpose This study examines the capacity to detect glaucoma of inner macular layer thickness measured by spectral-domain optical coherence tomography (SD-OCT) using a new normative database as the reference standard. Methods Participants (N = 148) were recruited from Leuven (Belgium) and Zaragoza (Spain): 74 patients with early/moderate glaucoma and 74 age-matched healthy controls. One eye was randomly selected for a macular scan using the Spectralis SD-OCT. The variables measured with the instruments segmentation software were: macular nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) volume and thickness along with circumpapillary RNFL thickness (cpRNFL). The new normative database of macular variables was used to define the cutoff of normality as the fifth percentile by age group. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of each macular measurement and of cpRNFL were used to distinguish between patients and controls. Results Overall sensitivity and specificity to detect early-moderate glaucoma were 42.2% and 88.9% for mRNFL, 42.4% and 95.6% for GCL, 42.2% and 94.5% for IPL, and 53% and 94.6% for RNFL, respectively. The best macular variable to discriminate between the two groups of subjects was outer temporal GCL thickness as indicated by an AUROC of 0.903. This variable performed similarly to mean cpRNFL thickness (AUROC = 0.845; P = 0.29). Conclusions Using our normative database as reference, the diagnostic power of inner macular layer thickness proved comparable to that of peripapillary RNFL thickness. Translational Relevance Spectralis SD-OCT, cpRNFL thickness, and individual macular inner layer thicknesses show comparable diagnostic capacity for glaucoma and RNFL, GCL, and IPL thickness may be useful as an alternative diagnostic test when the measure of cpRNFL shows artifacts.

Retinal Toxicity of Medical Devices Used during Vitreoretinal Surgery: A Critical Overview

Retinal toxicity/biocompatibility of medical devices in direct contact with the retina is an important subject for clinicians and scientists. As these effects are not very frequent, there is also a relative lack of information for many clinicians. The past has taught us multiple times that there is a significant safety problem associated with severe loss of vision in affected patients. In this review, we want to classify medical products that are used in the back of the eye, describe recent examples of toxicity, critically reflect on the regulations that exist and suggest improvements that can be done to ensure patient safety without hindering innovation. Methods: Critical review of the recent papers and personal experience of the authors in this issue. Medical devices used in the back of the eye and recent examples of toxicity are described, regulations that exist are critically reflected and improvements suggested that can ensure patient safety without hindering innovation. Results: There is clear evidence of toxicity after intraocular surgery in any category. Some cytotoxic indirect methods have failed in detecting this toxicity. Some ISO rules do not seem appropriate. Postmarketing safety is missing. There is little data on this issue. Conclusions: The absence of a clear regulation of the production, purification and evaluation of the toxic effects of the medical devices supposes the possibility that products are not sufficiently safe to obtain the CE mark.