MultiSDGAN: Translation of OCT Images to Superresolved Segmentation Labels Using Multi-Discriminators in Multi-Stages.

Optical coherence tomography (OCT) has been identified as a non-invasive and inexpensive imaging modality to discover potential biomarkers for Alzheimer's diagnosis and progress determination. Current hypotheses presume the thickness of the retinal layers, which are analyzable within OCT scans, as an effective biomarker for the presence of Alzheimer's. As a logical first step, this work concentrates on the accurate segmentation of retinal layers to isolate the layers for further analysis. This paper proposes a generative adversarial network (GAN) that concurrently learns to increase the image resolution for higher clarity and then segment the retinal layers. We propose a multi-stage and multi-discriminatory generative adversarial network (MultiSDGAN) specifically for superresolution and segmentation of OCT scans of the retinal layer. The resulting generator is adversarially trained against multiple discriminator networks at multiple stages. We aim to avoid early saturation of generator model training leading to poor segmentation accuracies and enhance the process of OCT domain translation by satisfying all the discriminators in multiple scales. We also investigated incorporating the Dice loss and Structured Similarity Index Measure (SSIM) as additional loss functions to specifically target and improve our proposed GAN architecture's segmentation and superresolution performance, respectively. The ablation study results conducted on our data set suggest that the proposed MultiSDGAN with ten-fold cross-validation (10-CV) provides a reduced equal error rate with 44.24% and 34.09% relative improvements, respectively (p-values of the improvement level tests .01). Furthermore, our experimental results also demonstrate that the addition of the new terms to the loss function improves the segmentation results significantly by relative improvements of 31.33% (p-value .01).

Toxic Anterior Segment Syndrome with Intracameral Moxifloxacin: Case Report and Review of the Literature.

A case of severe anterior segment toxicity secondary to high-volume, undiluted intracameral moxifloxacin for endophthalmitis prophylaxis is reported. We examine the other reported cases of toxicity after intracameral moxifloxacin, as well as iris depigmentation and transillumination syndromes after oral and topical fluoroquinolone exposure. Additionally, we review the literature on safety, efficacy, and appropriate dosing of intracameral antibiotics with a focus on moxifloxacin.

Subepithelial Corneal Deposits Associated with Exemestane.

This is a case report of corneal deposits noted in a 69-year-old female patient taking the aromatase inhibitor, exemestane, after undergoing a mastectomy and chemotherapy for breast cancer. The patient presented to our eye clinic for a new-onset floater in one eye, and bilateral subepithelial opacities were found incidentally on exam. The patient completed a 5-year course of the medication shortly after her initial visit with us and was noted to have a slight improvement in the density of the opacities on a follow-up visit 3 months later. We believe these corneal changes were most likely secondary to exemestane. The effect of aromatase inhibitors on the eye deserves further exploration as an increasing number of patients are prescribed these medications.

Vascular Dysfunction in Diabetes and Glaucoma: A Complex Relationship Reviewed.

Open-angle glaucoma (OAG) is a multifactorial disease characterized by progressive retinal ganglion cell death and visual field loss. Intraocular pressure, ocular perfusion pressure, and systemic vascular irregularities have all been identified as contributing factors for glaucoma onset and progression. Focal and systemic vascular abnormalities have also been well documented in diabetic patients. The relationship between diabetes mellitus and OAG remains enigmatic in the literature. As the pathogenesis of both diabetes mellitus and OAG involves compromised vascular regulation, this review was undertaken to further investigate their precise relationship. A literature review of published population-based studies was performed, with a focus on studies regarding blood flow abnormalities. Although current studies support the role of vascular contributions to both diseases, the association between glaucoma and diabetes yields contrasting results.

Parameters characterizing age-dependent retrobulbar circulation in healthy subjects measured by color Doppler ultrasonography.

PURPOSE: The aim of this study was to analyze age-related effects influencing retrobulbar blood flow parameters. MATERIALS AND METHODS: The study enrolled healthy volunteers (162 eyes) with a mean age of 49.64 years (SD ± 17.50). Participants were divided into 5 groups (G1-G5) based on 12-year age spans (means from 25.41 to 73.87 years). Peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV), pulsatility index (PI) and resistive index (RI) of the ophthalmic (OA), central retinal (CRA) and posterior ciliary arteries (PCAs) were measured by color Doppler ultrasonography (CDU). In addition, systemic blood pressure (BP), ocular perfusion pressure (OPP) and intraocular pressure (IOP) were evaluated. Statistical analysis was performed using the Shapiro-Wilk, Levene's, Spjotvoll-Stoline and analysis of variance tests (p ≤ 0.05 was considered statistically significant). RESULTS: In the oldest group, significantly lower PSV, EDV in the CRA and PCAs as well as MV in the CRA were confirmed. Significantly increased RI in the OA, CRA and PCAs in regard to age was recorded. CONCLUSIONS: CDU has considerable potential for evaluating hemodynamic changes in the retrobulbar circulation in relation to age. Age laboratory standards for a specific CDU device should be established for further analyses of blood flow in ocular diseases of vascular origin.

Differences in ocular blood flow in glaucoma between patients of African and European descent.

PURPOSE: To investigate differences in ocular blood flow in individuals of African descent (AD) and European descent (ED) with open angle glaucoma (OAG). PATIENTS AND METHODS: A retrospective data analysis was performed on OAG patients of AD and ED who were previously examined for ocular blood flow within the Department of Ophthalmology at Indiana University School of Medicine. Data analysis included blood pressure, heart rate, visual fields, intraocular pressure, ocular perfusion pressure, and color Doppler imaging of retrobulbar vessels. Color Doppler imaging measurements were performed on ophthalmic, central retinal, and nasal and temporal short posterior ciliary arteries, with peak systolic (PSV) and end diastolic velocities (EDV) as well as the Pourcelot vascular resistive index calculated for each vessel. Two-sample t tests of unequal variance were performed with P values <0.05 considered statistically significant. RESULTS: OAG patients of AD had statistically significant lower retrobulbar blood flow values than patients of ED including lower ophthalmic artery PSV (P=0.0001), ophthalmic artery EDV (P=0.0008), central retinal artery PSV (P=0.01), temporal short posterior ciliary artery PSV (P=0.0037), and nasal short posterior ciliary artery PSV (P<0.0001). No significant differences were found in terms of intraocular pressure or visual field parameters. CONCLUSIONS: Significantly lower blood flow values were identified in all retrobulbar blood vessels in AD compared with ED OAG patients. These findings suggest that the contribution of ocular blood flow to the disease process may be different in AD compared with ED OAG patients.

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.

Vascular considerations in glaucoma patients of African and European descent.

Glaucoma is the leading cause of blindness in individuals of African descent (AD). While open-angle glaucoma (OAG) disproportionately affects individuals of AD compared with persons of European descent (ED), the physiological mechanisms behind this disparity are largely unknown. The more rapid progression and greater severity of the disease in persons of AD further raise the concern for identifying these underlying differences in disease pathophysiology between AD and ED glaucoma patients. Ocular structural differences between AD and ED patients, including larger optic disc area, cup:disc ratio and thinner corneas, have been found. AD individuals are also disproportionately affected by systemic vascular diseases, including hypertension, cardiovascular disease, stroke and diabetes mellitus. Abnormal ocular blood flow has been implicated as a risk factor for glaucoma, and pilot research is beginning to identify localized ocular vascular differences between AD and ED OAG patients. Given the known systemic vascular deficits and the relationship between glaucoma and ocular blood flow, exploring these concepts in terms of glaucoma risk factors may have a significant impact in elucidating the mechanisms behind the disease disparity in the AD population.

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.

Novel therapies for open-angle glaucoma.

Open-angle glaucoma is a multifactorial optic neuropathy characterized by progressive loss of retinal ganglion cells and their axons. It is an irreversible disease with no established cure. The only currently approved treatment is aimed at lowering intraocular pressure, the most significant risk factor known to date. However, it is now clear that there are other risk factors involved in glaucoma's pathophysiology. To achieve future improvements in glaucoma management, new approaches to therapies and novel targets must be developed. Such therapies may include new tissue targets for lowering intraocular pressure, molecules influencing ocular hemodynamics, and treatments providing neuroprotection of retinal ganglion cells. Furthermore, novel drug delivery systems are in development that may improve patient compliance, increase bioavailability, and decrease adverse side effects.

Theoretical analysis of vascular regulatory mechanisms contributing to retinal blood flow autoregulation.

PURPOSE: To study whether impaired retinal autoregulation is a risk factor for glaucoma, the relationship between vascular regulatory mechanisms and glaucoma progression needs to be investigated. In this study, a vascular wall mechanics model is used to predict the relative importance of regulatory mechanisms in achieving retinal autoregulation. METHODS: Resistance vessels are assumed to respond to changes in pressure, shear stress, carbon dioxide (CO2), and the downstream metabolic state communicated via conducted responses. Model parameters governing wall tension are fit to pressure and diameter data from porcine retinal arterioles. The autoregulation pressure range for control and elevated levels of IOP is predicted. RESULTS: The factor by which flow changes as the blood pressure exiting the central retinal artery is varied between 28 and 40 mm Hg is used to indicate the degree of autoregulation (1 indicates perfect autoregulation). In the presence of only the myogenic response mechanism, the factor is 2.06. In the presence of the myogenic and CO2 responses, the factor is 1.22. The combination of myogenic, shear, CO2, and metabolic responses yields the best autoregulation (factor of 1.10). CONCLUSIONS: Model results are compared with flow and pressure data from multiple patient studies, and the combined effects of the metabolic and CO2 responses are predicted to be critical for achieving retinal autoregulation. When IOP is elevated, the model predicts a decrease in the autoregulation range toward low perfusion pressure, which is consistent with observations that glaucoma is associated with decreased perfusion pressure.

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.

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.

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.

Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents.

Open angle glaucoma (OAG) is a severe ocular disease characterized by progressive and irreversible vision loss. While elevated intraocular pressure (IOP) is a well-established risk factor for OAG, the progression of OAG in many cases, despite IOP treatment, suggests that other risk factors must play significant roles in the development of the disease. For example, various structural properties of the eye, ocular blood flow properties, and systemic conditions have been identified as risk factors for OAG. Ethnicity has also been indicated as a relevant factor that affects the incidence and prevalence of OAG; in fact, OAG is the leading cause of blindness among people of African descent. Numerous clinical studies have been designed to examine the possible correlation and causation between OAG and these factors; however, these studies are met with the challenge of isolating the individual role of multiple interconnected factors. Over the last decade, various mathematical modeling approaches have been implemented in combination with clinical studies in order to provide a mechanical and hemodynamical description of the eye in relation to the entire human body and to assess the contribution of single risk factors to the development of OAG. This review provides a summary of the clinical evidence of ocular structural differences, ocular vascular differences and systemic vascular differences among people of African and European descent, describes the mathematical approaches that have been proposed to study ocular mechanics and hemodynamics while discussing how they could be used to investigate the relevance to OAG of racial disparities, and outlines possible new directions of research.

Delivery of intraocular triamcinolone acetonide in the treatment of macular edema.

Macular edema (ME) is one of the eventual outcomes of various intraocular and systemic pathologies. The pathogenesis for ME is not yet entirely understood; however, some of the common risk factors for its development have been identified. While this investigation will not discuss the numerous etiologies of ME in detail, it appraises the two most widely studied delivery modalities of intraocular corticosteroids in the treatment of ME-intravitreal injection (IVI) and sub-Tenon's infusion (STI). A thorough review of the medical literature was conducted to identify the efficacy and safety of IVI and STI, specifically for the administration of triamcinolone acetonide (TA), in the setting of ME in an attempt to elucidate a preferred steroid delivery modality for treatment of ME.

The Effect of Diluted Penetration Enhancer in Nebulized Mist versus Liquid Drop Preparation Forms on Retrobulbar Blood Flow in Healthy Human Subjects.

The aim of this study was to compare the effects of nebulized mist and liquid drop applications on retrobulbar blood flow. A prospective, non-randomized clinical trial was used to collect data from 40 healthy human eyes. Color Doppler Imaging determined peak systolic (PSV) and end diastolic (EDV) blood flow velocities and resistance index (RI) in the ophthalmic artery after both applications. Measurements were taken at baseline and at 1 min post-treatment in both eyes with 5 min measurements in the treatment eye only. p values ≤ 0.05 were considered statistically significant. Mist application to treatment eye produced an increase in 1 min and 5 min PSV and EDV (0.001 < p < 0.03) and a decrease in 5 min RI (p = 0.01), with no significant changes in PSV, EDV or RI of control eye or in treatment eye 1 min RI (p > 0.05). Drop application to treatment eye produced an increase in PSV (p < 0.001) and EDV (p = 0.01) at 1 min, with an increase in control eye 1 min PSV and EDV (p = 0.03). There were no statistically significant changes in treatment eye PSV, EDV and RI after 5 min (p > 0.05). The use of nebulized mist may provide an effective alternative to liquid drop medication application.

Should Men and Women be Managed Differently in Glaucoma?

INTRODUCTION: To assess differences in associations of ocular perfusion pressure (OPP) as well as retinal and retrobulbar blood flow between men and women with primary open angle glaucoma (OAG). METHODS: A total of 116 patients with OAG (age 66.9 ± 10.9 years, 70 females) participating in the Indianapolis Glaucoma Progression Study were assessed for OPP, retinal microcirculation, and retrobulbar blood flow. Confocal scanning laser Doppler flowmetry measured peripapillary retinal capillary blood flow. Color Doppler imaging measured peak systolic (PSV) and diastolic blood flow velocities and vascular resistance in the ophthalmic (OA), central retinal (CRA), and nasal and temporal short posterior ciliary arteries (N/T PCA). Bivariate Spearman correlation and multivariate linear regression analyses were performed. RESULTS: In female patients with OAG, inferior retinal capillary flow was associated with OPP (r = 0.246, P = 0.044). In men, superior and inferior sector retinal blood flow was associated with OPP (r = -0.402, P = 0.006 and r = -0.357, P = 0.016, respectively). There was no statistically significant association between OPP and retrobulbar blood vessel flow velocities in male patients with OAG but there was an association between OA and TPCA PSV and OPP in female patients with OAG (r = 0.290, P = 0.015 and r = 0.357, P = 0.002, respectively). In female patients with OAG, multivariate regression showed no statistically significant effect of any variable on the superior retinal capillary blood flow, with CRA PSV as a sole predictor to the inferior retinal sector (partial rho = 0.302, P = 0.015) and in male patients with OAG, superior sector retinal capillary blood flow was independently associated with intraocular pressure (partial rho = -0.371, P = 0.016) and OPP (partial rho = -0.456, P = 0.002) with a trend of association with OPP in the inferior retina (partial rho = -0.301, P = 0.053). CONCLUSIONS: There was a positive linear association between retinal microcirculation and OPP in females and a negative association in males. Male and female patients with OAG may differ in their vascular autoregulation in response to changes in OPP.