Boris Knyazer

Anatomy and Physiology of the Blood-Brain Barrier

Essential requisite for the preservation of normal brain activity is to maintain a narrow and stable homeostatic control in the neuronal environment of the CNS. Blood flow alterations and altered vessel permeability are considered key determinants in the pathophysiology of brain injuries. We will review the present-day literature on the anatomy, development and physiological mechanisms of the blood-brain barrier, a distinctive and tightly regulated interface between the CNS and the peripheral circulation, playing a crucial role in the maintenance of the strict environment required for normal brain function.

Prognostic factors in posterior open globe injuries (zone-III injuries)

Purpose:  The aim of this study is to describe and identify clinical characteristics, prognostic factors and visual outcome in a group of patients with posterior open globe injuries (zone III injury).

Cell-free DNA--a marker to predict ischemic brain damage in a rat stroke experimental model.

BackgroundThe animal model of stroke that is most frequently used is a rat model of focal brain ischemia caused by middle cerebral artery occlusion (MCAO). Several studies have reported a link between levels of cell-free DNA (CFD) and neurologic outcome in human stroke. The purpose of this study was to assess brain injury and measure CFD levels in 2 models of MCAO in rats, and to determine whether brain injury correlates with CFD. MethodsA total of 60 rats were used for this study. Twenty rats underwent a sham procedure, 20 rats had MCAO using a monofilament, and 20 rats had MCAO with a silicon-coated filament. Groups were further divided into 2 subgroups. In 1 subgroup of 10 rats, neurologic performance [measured as a neurologic severity score, (NSS)] was measured at 1 and 24 hours after the procedure, and brain edema and infarct volume were determined at 24 hours. In the second subgroup of 10 rats, CFD was measured at 0, 1, 2, 4, 8, 12, and 24 hours and at 2, 3, 4, and 5 days. Neurologic performance (measured as a NSS) was measured at 1 and 24 hours after the procedure. ResultsThe main finding was a significant increase in CFD levels observed 24 hours after the onset of MCAO. The correlation between the total infarct volume and CFD levels of the 3 groups was R=0.78, P<0.0001. Brain edema and NSS also were strongly correlated with CFD levels at 24 hours after MCAO (R=0.91, P<0.0001 and R=0.73, P<0.0001, respectively). ConclusionsWe found that CFD levels correlate well with the extent of ischemic injury, brain edema, and neurologic outcome in rats 24 hours post-MCAO. We have also shown that CFD correlates well with the expected temporal progression of ischemic injury. These findings place CFD in a unique place as a biomarker for stroke, both experimentally and possibly clinically.

Acute eclipse retinopathy: A small case series

We present four young patients with acute severe solar retinopathy after observation of the total eclipse on January 4, 2011 without appropriate eye protection. Funduscopic findings were accompanied by optical coherence tomography (OCT) investigation of the macula. All our patients were young (range 14-29 years). In three of the four patients we have been able to repeat OCT evaluation revealing that the retinal changes were reversible, but delineating mild pathology in the retinal pigment epithelium and photoreceptors. Best-corrected visual acuity in the fourth case was 6/24. In addition, macular edema, which has been previously described in literature, could not be demonstrated by OCT. In the two cases we performed an early fluorescein angiogram, no pathology was seen.

Link between retinopathy and nephropathy caused by complications of diabetes mellitus type 2

While the correlation and chronology of appearance of diabetic nephropathy and retinopathy is well known in diabetes mellitus (DM) type 1 patients, in DM type 2 this correlation is less clear. A retrospective study including 917 patients with type 2 diabetes. Diabetic retinopathy (DR) was diagnosed based on fundus photographs taken with a non-mydriatic camera. Diabetic nephropathy (DN) was diagnosed based on urinary albumin concentration in a morning urine sample. Statistical analysis was performed with a seemingly unrelated regression (SUR) model. Our SUR model is statistically significant: the test for “model versus saturated” is 2.20 and its significance level is 0.8205. The model revealed that creatinine and glomerular filtration rate (GFR) have strong influence on albuminuria, while body mass index (BMI) and HbA1c have less significant impact. DR is affected positively by diabetes duration, insulin treatment, glucose levels, and HbA1c, and it is affected negatively by GFR, triglyceride levels, and BMI. The association between DR and DN was statistically significant and had a unidirectional correlation, which can be explained by chronological order; that is, DN precedes DR. The present study indicates that the level of renal impairment is proportional to the level of damage to the eye. Furthermore, such an association has a chronological aspect; the renal injury precedes retinal damage.

The Outcomes of Primary Scleral Buckling during Repair of Posterior Segment Open-Globe Injuries

Objective. To compare visual outcomes of eyes which underwent primary scleral buckling (PSB) treatment during posterior segment open-globe injury (OGI) repair with eyes not treated with PSB. Methods. We retrospectively reviewed 38 eyes which underwent a posterior segment OGI repair with no preoperative evidence of retinal detachment (RD) at Soroka University Medical Center (1995–2010). 19 (50%) underwent scleral repair alone (control group) and the other 19 eyes were treated with PSB also (PSB group). We compared visual outcomes in these two groups and rates of subsequent postoperative complications. Results. Baseline characteristics of the groups were similar. Compared with the control group, the PSB group had statistically significant lower rates of proliferative vitreoretinopathy (PVR) (5.3% versus 38.4%, P < 0.05) and a trend towards lower rates of RD (15.8% versus 41.1%, P = 0.1). PSB group eyes had a statistically significant improvement of their best distance visual acuity (BDVA) with lower means of final BDVA-grade (P < 0.05) and logMAR vision (P < 0.05). Eyes in the control group had no improvement in these parameters. Conclusion. PSB procedure during posterior segment OGI repair may decrease the risk of subsequent retinal complications and improve final visual outcome.

Novel Fluorescein Angiography-Based Computer-Aided Algorithm for Assessment of Retinal Vessel Permeability

Purpose To present a novel method for quantitative assessment of retinal vessel permeability using a fluorescein angiography-based computer algorithm. Methods Twenty-one subjects (13 with diabetic retinopathy, 8 healthy volunteers) underwent fluorescein angiography (FA). Image pre-processing included removal of non-retinal and noisy images and registration to achieve spatial and temporal pixel-based analysis. Permeability was assessed for each pixel by computing intensity kinetics normalized to arterial values. A linear curve was fitted and the slope value was assigned, color-coded and displayed. The initial FA studies and the computed permeability maps were interpreted in a masked and randomized manner by three experienced ophthalmologists for statistical validation of diagnosis accuracy and efficacy. Results Permeability maps were successfully generated for all subjects. For healthy volunteers permeability values showed a normal distribution with a comparable range between subjects. Based on the mean cumulative histogram for the healthy population a threshold (99.5%) for pathological permeability was determined. Clear differences were found between patients and healthy subjects in the number and spatial distribution of pixels with pathological vascular leakage. The computed maps improved the discrimination between patients and healthy subjects, achieved sensitivity and specificity of 0.974 and 0.833 respectively, and significantly improved the consensus among raters for the localization of pathological regions. Conclusion The new algorithm allows quantification of retinal vessel permeability and provides objective, more sensitive and accurate evaluation than the present subjective clinical diagnosis. Future studies with a larger patients’ cohort and different retinal pathologies are awaited to further validate this new approach and its role in diagnosis and treatment follow-up. Successful evaluation of vasculature permeability may be used for the early diagnosis of brain microvascular pathology and potentially predict associated neurological sequelae. Finally, the algorithm could be implemented for intraoperative evaluation of micovascular integrity in other organs or during animal experiments.

The effect of Nd:YAG laser posterior capsulotomy on ocular wave front aberrations

OBJECTIVE To assess the effect of Nd:YAG laser posterior capsulotomy on ocular wave front aberrations. STUDY DESIGN Retrospective comparative study. PARTICIPANTS Twenty-four eyes of 24 consecutive pseudophakic patients with symptomatic PCO, who presented for Nd:YAG laser posterior capsulotomy at our clinic, were included in this study. METHODS The wave front aberrations of the entire optical path of 24 pseudophakic eyes of 24 patients before, and 1 month after, Nd:YAG laser posterior capsulotomy were measured using the Nidek Optical Path Difference (OPD) scan aberrometer. Total, tilt, and high-order aberrations, and total coma, total trefoil, total tetrafoil, total spherical, and total high astigmatism aberrations were analyzed statistically. Secondary measures included changes in visual acuity and refraction, and repeatability of wave front measurements in the fellow eye. RESULTS Before Nd:YAG laser posterior capsulotomy, the total higher-order aberrations root mean-square (RMS) wave front aberration was 2.08 (SD 2.20) microm, with total trefoil being a major contributor at 1.19 (SD 1.15) microm. One month after the procedure, significant decreases in total, tilt, and high-order aberrations, and total trefoil, total tetrafoil, total spherical, and total high astigmatism aberrations were noted (p< 0.05). No significant changes in total coma aberrations were found (p > 0.05). Additionally, significant improvement in visual acuity without significant change in refraction was observed. No statistically significant differences were detected in any of the RMS values of wave front measurements taken 1 month later in the fellow eye. CONCLUSIONS Nd:YAG laser posterior capsulotomy causes significant decrease in ocular wave front aberrations measured using the Nidek-OPD scan aberrometer, which can account for a better optical quality after the procedure. Further research to examine the impact of wave front aberrations in visual function after Nd:YAG laser posterior capsulotomy is needed.

Angiographic evidence of proliferative retinopathy predicts neuropsychiatric morbidity in diabetic patients

INTRODUCTION Diabetic retinopathy (DR) is a common vasculopathy categorized as either non-proliferative (NPDR) or proliferative (PDR),characterized by dysfunctional blood-retinal barrier (BRB) and diagnosed using fluorescein angiography (FA). Since the BRB is similar in structure and function to the blood-brain barrier (BBB) and BBB dysfunction plays a key role in the pathogenesis of brain disorders, we hypothesized that PDR, the severe form of DR, is likely to mirror BBB damage and to predict a worse neuropsychiatric outcome. METHODS A retrospective cohort study was conducted among subjects with diabetes (N=2982) with FA-confirmed NPDR (N=2606) or PDR (N=376). Incidence and probability to develop brain pathologies and mortality were investigated in a 10-year follow-up study. We used Kaplan-Meier, Cox and logistic regression analyses to examine association between DR severity and neuropsychiatric morbidity adjusting for confounders. RESULTS Patients with PDR had significantly higher rates of all-cause brain pathologies (P<0.001), specifically stroke (P=0.005), epilepsy (P=0.006) and psychosis (P=0.024), and a shorter time to develop any neuropsychiatric event (P<0.001) or death (P=0.014) compared to NPDR. Cox adjusted hazard ratio for developing all-cause brain impairments was higher for PDR (HR=1.37, 95% CI 1.16-1.61, P<0.001) which was an independent predictor for all-cause brain impairments (OR 1.30, 95% CI 1.04-1.64, P=0.022), epilepsy (OR 2.16, 95% CI 1.05-4.41, P=0.035) and mortality (HR=1.35, 95% CI 1.06-1.70, P=0.014). CONCLUSIONS This is the first study to confirm that angiography-proven microvasculopathy identifies patients at high risk for neuropsychiatric morbidity and mortality.

Epiretinal membrane in diabetes mellitus patients screened by nonmydriatic fundus camera.

OBJECTIVE To determine the prevalence of epiretinal membrane (ERM) in patients with type 2 diabetes mellitus (T2DM) and to assess the associated risk factors. DESIGN Retrospective, cross sectional study. METHODS Patients with T2DM, seen for annual follow-up between 2009 and 2010, were evaluated by digital nonmydriatic retinal photography for the detection of diabetic retinopathy. Retinal photographs were assessed by a retina specialist. RESULTS ERM was present in 102 of 1550 patients with T2DM (6.5%). Of the participants, 1443 had sufficient documented data to conduct statistical analysis for variant risk factors. The prevalence of ERM was significantly associated with age (p < 0.001; 1.2% for <49 years, 4% for 50-59 years, 8.2% for 60-69 years, and 9.6% for >70 years), cataract surgery (p < 0.001), diabetic nephropathy (p < 0.001), and chronic renal failure (p = 0.039). Prevalence was similar for both sexes (53% females, 47% males; p = 0.33). In logistic regression models, the prevalence of ERM was significantly associated with increasing age (p = 0.018), cataract surgery (p < 0.001), and diabetic nephropathy (p = 0.011). CONCLUSIONS The prevalence of ERM in patients with T2DM in the present study was not significantly different than that of the general population. ERM was significantly associated with age, diabetic nephropathy, and cataract surgery.