Leslie Tobe

Intraocular Pressure, Blood Pressure, and Retinal Blood Flow Autoregulation: A Mathematical Model to Clarify Their Relationship and Clinical Relevance

PURPOSE This study investigates the relationship between intraocular pressure (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and blood flow autoregulation (AR) influence this relationship. METHODS A mathematical model is developed to simulate blood flow in the central retinal vessels and retinal microvasculature as current flowing through a network of resistances and capacitances. Variable resistances describe active and passive diameter changes due to AR and IOP. The model is validated by using clinically measured values of retinal blood flow and velocity. The model simulations for six theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and functional or absent AR (-wAR, -woAR) are compared with clinical data. RESULTS The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg, respectively, whereas LBPwAR patients do not adequately regulate blood flow if IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if IOP changes occur outside of the regulating range, which, most importantly, depend on BP. The model predictions are consistent with clinical data for IOP reduction via surgery and medications and for cases of induced IOP elevation. CONCLUSIONS The theoretical model results suggest that the ability of IOP to induce noticeable changes in retinal hemodynamics depends on the levels of BP and AR of the individual. These predictions might help to explain the inconsistencies found in the clinical literature concerning the relationship between IOP and retinal hemodynamics.

The role of retrobulbar and retinal circulation on optic nerve head and retinal nerve fibre layer structure in patients with open-angle glaucoma over an 18-month period

Background/aims Evidence suggests that vascular abnormalities play a role in the pathogenesis of open-angle glaucoma (OAG) in some patients. This study aims to assess changes in retrobulbar and retinal blood flow over time in patients with glaucoma and examine their relationship to glaucomatous progression, as determined by retinal and optic nerve structure. Methods In this observational study, 103 patients with OAG were examined at baseline and 18 months follow-up. Retrobulbar blood flow was measured by colour Doppler imaging in the ophthalmic, central retinal and temporal posterior ciliary artery (TPCA) and nasal short posterior ciliary artery. Retinal capillary blood flow was measured by confocal scanning laser Doppler. Peripapillary retinal nerve fibre layer thickness was assessed by optical coherence tomography. Non-parametric Wilcoxon signed ranks tests were used to assess for any statistically significant changes between the baseline and 18-month visits for the retrobulbar and retinal flow, as well as the structural parameters. Results In general, retinal and retrobulbar blood flow parameters decreased over 18 months. Thinning of the optic disc rim and increase in cup area were associated with a higher resistance index (p=0.0334) and lower peak systolic velocity of TPCA (p=0.0282), respectively. A higher amount of retinal zero pixel blood flow correlated with a greater increase in cup/disc ratio (p=0.0170). Conclusions Reductions in retrobulbar and retinal blood flow over time were associated with structural glaucomatous progression, as indicated by retinal and optic nerve changes.

Ocular hemodynamics and glaucoma: the role of mathematical modeling.

Purpose. To discuss the role of mathematical modeling in studying ocular hemodynamics, with a focus on glaucoma. Methods. We reviewed recent literature on glaucoma, ocular blood flow, autoregulation, the optic nerve head, and the use of mathematical modeling in ocular circulation. Results. Many studies suggest that alterations in ocular hemodynamics play a significant role in the development, progression, and incidence of glaucoma. Although there is currently a limited number of studies involving mathematical modeling of ocular blood flow, regulation, and diseases (such as glaucoma), preliminary modeling work shows the potential of mathematical models to elucidate the mechanisms that contribute most significantly to glaucoma progression. Conclusion. Mathematical modeling is a useful tool when used synergistically with clinical and laboratory data in the study of ocular blood flow and glaucoma. The development of models to investigate the relationship between ocular hemodynamic alterations and glaucoma progression will provide a unique and useful method for studying the pathophysiology of glaucoma.

Cerebrospinal fluid pressure and glaucoma: regulation of trans-lamina cribrosa pressure

Increased trans-lamina cribrosa pressure difference (TLCPD), the difference of intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSF-P), has been investigated as a possible risk factor in glaucoma pathogenesis. In fact, lower CSF-P in the setting of normal IOP has been implicated as a potential risk factor for normal tension glaucoma. Increased TLCPD has been associated with decreased neuroretinal rim area and increased visual field defects. Furthermore, dysregulation of systemic blood pressure has been associated with changes in IOP. Recent studies have also suggested that increased body mass index (BMI) is associated with decreased prevalence of glaucoma, which may be due to an increased CSF-P with increased BMI found in many studies. Given the interaction of various pressures, their role in glaucoma pathophysiology has come under investigation and warrants further study in order to better understand the aetiology and progression of glaucoma.

Nanotechnology and glaucoma: a review of the potential implications of glaucoma nanomedicine

The purpose of this review is to discuss the evolution of nanotechnology and its potential diagnostic and therapeutic applications in the field of ophthalmology, particularly as it pertains to glaucoma. We reviewed literature using MEDLINE and PubMed databases with the following search terms: glaucoma, nanotechnology, nanomedicine, nanoparticles, ophthalmology and liposomes. We also reviewed pertinent references from articles found in this search. A brief history of nanotechnology and nanomedicine will be covered, followed by a discussion of the advantages and concerns of using this technology in the field of glaucoma. We will look at various studies concerning the development of nanomedicine, its potential applications in ocular drug delivery, diagnostic and imaging modalities and, surgical techniques. In particular, the challenges of assuring safety and efficacy of nanomedicine will be examined. We conclude that nanotechnology offers a novel approach to expanding diagnostic, imaging and surgical modalities in glaucoma and may contribute to the knowledge of disease pathogenesis at a molecular level. However, more research is needed to better elucidate the mechanism of cellular entry, the potential for nanoparticle cytotoxicity and the assurance of clinical efficacy.

Generic medications in ophthalmology

The purpose of this review is to discuss the process of genericisation of medications in the US and Europe with a focus on ophthalmic drugs. Regulatory guidelines of the US Food and Drug Administration and the European Medicines Agency will be discussed, and the advantages and concerns of genericisation will be explored. We will look at various studies concerning the safety and efficacy of generic drugs compared to their branded counterparts. In particular, the challenges of assuring bioequivalence and therapeutic equivalence in topical ophthalmic drugs will be examined.

Retinal oxygen saturation and metabolism: how does it pertain to glaucoma? An update on the application of retinal oximetry in glaucoma

Purpose To discuss the techniques and mechanisms of retinal oximetry with a focus on utilization of retinal oximetry in the assessment of retinal oxygen saturation in glaucoma. Methods We reviewed recent literature found by searching combinations of the following search terms: glaucoma, retinal oximetry, ocular blood flow, retinal blood flow, oxygen saturation. We also reviewed pertinent references from articles found in this search. Results Retinal oximetry offers the potential for directly assessing oxygen saturation in retinal tissue. This capability can contribute to the knowledge of ocular blood flow and its role in the pathogenesis of glaucoma. Conclusions Recent research has shown that retinal oximetry could become an important clinical tool in glaucoma. However, more research is needed to validate the reliability and reproducibility of retinal oximetry, and to fully deduce its clinical role in ocular diseases.

The influence of retinal blood flow on open-angle glaucoma in patients with and without diabetes

Purpose To evaluate the impact of retinal blood flow on optic nerve head (ONH) morphology in patients with open-angle glaucoma (OAG) with and without diabetes mellitus (DM). Methods A total of 66 patients with OAG (14 with DM, 52 without DM) were assessed at baseline and 3-year follow-up for retinal capillary blood flow using confocal scanning laser Doppler and ocular structure using Heidelberg retinal tomography and optical coherence tomography. Results Change in retinal tissue with zero blood flow in the superior and inferior retina was found to have a strong correlation with ONH changes in diabetic patients (r≥0.90, p≤0.03); however, no relation was found in the nondiabetic cohort. There were also significant changes in inferior mean flow that strongly correlated with changes in cup area (r = 0.97, p = 0.0029), cup/disc area ratio (r = 0.96, p = 0.0070), linear cup/disc ratio (r = 0.93, p = 0.0172), rim area (r = −0.97, p = 0.0036), and rim volume (r = −0.95, p = 0.0084) in diabetic patients only, while changes in the superior mean flow were only significantly associated with cup area (r = −0.30, p = 0.0498), cup volume (r = −0.36, p = 0.0178), and rim volume (r = 0.35, p = 0.0193) in nondiabetic patients. Conclusions In this cohort of patients with OAG, changes in retinal capillary blood flow correlated more strongly with changes in ONH morphology in patients with DM than in those without DM. These data suggest that changes in retinal blood flow may play a larger role in glaucomatous ONH progression in patients with OAG with DM.

Differences in Ocular Blood Flow Between People of African and European Descent With Healthy Eyes.

Purpose:To investigate differences in ocular blood flow between people of African descent (AD) and European descent (ED) with healthy eyes. Materials and Methods:Retrobulbar and retinal capillary blood flow was assessed in 1 eye of 58 participants (24 AD, 34 ED) with healthy eyes with systemic blood pressure lower than 140/90. Retrobulbar blood flow was measured in the ophthalmic artery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA) and temporal posterior ciliary artery (TPCA). Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were assessed. Retinal capillary blood flow was assessed using mean retinal flow and avascular space defined as the percent of area measured with no blood flow. Groups were compared using t tests and Pearson correlations were compared using Fisher r-to-z transformation. Results:Compared with people of ED, people of AD had significantly lower EDV in the NPCA (P=0.01), and higher RI in the CRA (P=0.04) and TPCA (P=0.01). No significant differences were observed in mean retinal capillary flow or avascular area. In the CRA, a significant negative correlation was observed between pattern standard deviation and peak systolic velocity (P=0.02) in the AD group and this correlation was significantly different from that observed in the ED group (P=0.01). A significant correlation was also observed between pattern standard deviation and EDV (0.04) in the AD group. Conclusions:This study suggests that retrobulbar blood flow is lower in healthy eyes in persons of AD compared with ED. This may provide a mechanism through which people of AD are at increased risk for ophthalmic diseases such as glaucoma.