The relationship between dry eye disease and human microbiota: A review of the science.

A complex relationship exists between human microbiota and the risk for ophthalmic disease. While the homeostatic composition of human microbiota is still being established, including what defines dysbiosis (i.e. changes in diversity and abundance), pilot research has begun to identify the potential influence of demographics, geography, and co-morbidities on the microbiota and describe their impact on ocular health. This review specifically focuses on the scientific relationships of the human oral and gut microbiota to dry eye disease (DED), a set of conditions impacting the tear film and ocular surface. Although data are sparse and often conflict across studies, the literature generally supports associations between microbial imbalance (dysbiosis) and DED and alterations in microbial diversity and abundance to specific aspects of DED. This review examines the relevant science and mechanistic relationships linking gut and oral dysbiosis and DED. Various physiochemical factors and therapeutic approaches that alter microbiota, including medications and fecal transplants are examined in relation to DED.

Examining Tear Film Dynamics Using the Novel Tear Film Imager.

PURPOSE: The purpose of this study was to examine Tear Film Imager (TFI, AdOM, Israel) generated parameters across controls and dry eye (DE) subgroups and examine the changes in TFI parameters with contact lens (CL) placement. METHODS: The retrospective study (n = 48) was conducted at the Miami Veterans Hospital. Symptoms were assessed through validated questionnaires and signs of tear function by tear break-up time and Schirmer scores. Participants were grouped as 1) healthy, 2) evaporative, 3) aqueous deficient, and 4) mixed DE based on tear function. Seventeen individuals had a baseline scan and a repeat scan following CL placement. Descriptives were compared across groups and over time. RESULTS: The median age was 27 years, 74% self-identified as White, 45% as male, and 51% as Hispanic. Subjects in the aqueous deficiency category had lower muco-aqueous layer thickness (MALT) (2672 vs. 3084 nm) but higher lipid layer thickness (47.5 vs. 38.3 nm), lipid break-up time (4.4 vs. 2 seconds), and interblink interval (13.9 vs. 5.4 seconds) compared with the evaporative group. Subjects in the evaporative group had the highest MALT values (3084 vs. 2988, 2672, 3053 nm) compared with healthy, aqueous-deficient, and mixed groups. Symptoms were not significantly correlated with TFI parameters. CL placement significantly decreased MALT values (2869 → 2175 nm, P = 0.001). CONCLUSIONS: The TFI provides unique information regarding the dynamic function of the tear film not captured by clinical examination. TFI generated metrics demonstrate a thinner aqueous layer in individuals with aqueous deficiency but highlight a thicker aqueous layer in those with evaporative DE.

The Eye as the Window to the Heart: Optical Coherence Tomography Angiography Biomarkers as Indicators of Cardiovascular Disease.

Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism. Optical coherence tomography angiography (OCTA) studies have specifically identified reduced capillary densities at the level of the retina in several eye diseases including glaucoma. This narrative review examines the published data related to OCTA-assessed microvasculature biomarkers and major systemic cardiovascular disease. While loss of capillaries is being established in various ocular disease, pilot data suggest that changes in the retinal microvasculature, especially within the macula, may also reflect small vessel damage occurring in other organs resulting from cardiovascular disease. Current evidence suggests retinal microvascular biomarkers as potential indicators of major systemic cardiovascular diseases, including systemic arterial hypertension, atherosclerotic disease, and congestive heart failure.

The ocular mathematical virtual simulator: A validated multiscale model for hemodynamics and biomechanics in the human eye.

We present our continuous efforts from a modeling and numerical viewpoint to develop a powerful and flexible mathematical and computational framework called Ocular Mathematical Virtual Simulator (OMVS). The OMVS aims to solve problems arising in biomechanics and hemodynamics within the human eye. We discuss our contribution towards improving the reliability and reproducibility of computational studies by performing a thorough validation of the numerical predictions against experimental data. The OMVS proved capable of simulating complex multiphysics and multiscale scenarios motivated by the study of glaucoma. Furthermore, its modular design allows the continuous integration of new models and methods as the research moves forward, and supports the utilization of the OMVS as a promising non-invasive clinical investigation tool for personalized research in ophthalmology.

Potential measurement error from vessel reflex and multiple light paths in dual-wavelength retinal oximetry.

PURPOSE: This study aims to characterize the dependence of measured retinal arterial and venous saturation on vessel diameter and central reflex in retinal oximetry, with an ultimate goal of identifying potential causes and suggesting approaches to improve measurement accuracy. METHODS: In 10 subjects, oxygen saturation, vessel diameter and optical density are obtained using Oxymap Analyzer software without diameter correction. Diameter dependence of saturation is characterized using linear regression between measured values of saturation and diameter. Occurrences of negative values of vessel optical densities (ODs) associated with central vessel reflex are acquired from Oxymap Analyzer. A conceptual model is used to calculate the ratio of optical densities (ODRs) according to retinal reflectance properties and single and double-pass light transmission across fixed path lengths. Model-predicted values are compared with measured oximetry values at different vessel diameters. RESULTS: Venous saturation shows an inverse relationship with vessel diameter (D) across subjects, with a mean slope of -0.180 (SE = 0.022) %/µm (20 < D < 180 µm) and a more rapid saturation increase at small vessel diameters reaching to over 80%. Arterial saturation yields smaller positive and negative slopes in individual subjects, with an average of -0.007 (SE = 0.021) %/µm (20 < D < 200 µm) across all subjects. Measurements where vessel brightness exceeds that of the retinal background result in negative values of optical density, causing an artifactual increase in saturation. Optimization of model reflectance values produces a good fit of the conceptual model to measured ODRs. CONCLUSION: Measurement artefacts in retinal oximetry are caused by strong central vessel reflections, and apparent diameter sensitivity may result from single and double-pass transmission in vessels. Improvement in correction for vessel diameter is indicated for arteries however further study is necessary for venous corrections.

Lessons From The Glaucoma Foundation Think Tank 2023: A Patient-Centric Approach to Glaucoma.

PRCIS: The main takeaways also included that BIG DATA repositories and AI are important combinatory tools to foster novel strategies to prevent and stabilize glaucoma and, in the future, recover vision loss from the disease. PURPOSE: To summarize the main topics discussed during the 28th Annual Glaucoma Foundation Think Tank Meeting "A Patient-Centric Approach to Glaucoma" held in New York on June 9 and 10, 2023. METHODS: The highlights of the sessions on BIG DATA, genetics, modifiable lifestyle risk factors, female sex hormones, and neuroprotection in the field of primary open angle glaucoma (POAG) were summarized. RESULTS: The researchers discussed the importance of BIG DATA repositories available at national and international levels for POAG research, including the United Kingdom Biobank. Combining genotyped large cohorts worldwide, facilitated by artificial intelligence (AI) and machine-learning approaches, led to the milestone discovery of 312 genome-wide significant disease loci for POAG. While these loci could be combined into a polygenic risk score with clinical utility, Think Tank meeting participants also provided analytical epidemiological evidence that behavioral risk factors modify POAG polygenetic risk, citing specific examples related to caffeine and alcohol use. The impact of female sex hormones on POAG pathophysiology was discussed, as was neuroprotection and the potential use of AI to help mitigate specific challenges faced in clinical trials and speed approval of neuroprotective agents. CONCLUSIONS: The experts agreed on the importance of genetics in defining individual POAG risk and highlighted the additional crucial role of lifestyle, gender, blood pressure, and vascular risk factors. The main takeaways also included that BIG DATA repositories and AI are important combinatory tools to foster novel strategies to prevent and stabilize glaucoma and, in the future, recover vision loss from the disease.

Ubiquitin proteasome system and glaucoma: A survey of genetics and molecular biology studies supporting a link with pathogenic and therapeutic relevance.

Glaucoma represents a group of progressive neurodegenerative diseases characterized by the loss of retinal ganglion cells (RGCs) and their axons with subsequent visual field impairment. The disease develops through largely uncharacterized molecular mechanisms, that are likely to occur in different localized cell types, either in the anterior (e.g., trabecular meshwork cells) or posterior (e.g., Muller glia, retinal ganglion cells) segments of the eye. Genomic and preclinical studies suggest that glaucoma pathogenesis may develop through altered ubiquitin (Ub) signaling. Ubiquitin conjugation, referred to as ubiquitylation, is a major post-synthetic modification catalyzed by E1-E2-E3 enzymes, that profoundly regulates the turnover, trafficking and biological activity of the targeted protein. The development of new technologies, including proteomics workflows, allows the biology of ubiquitin signaling to be described in health and disease. This post-translational modification is emerging as a key role player in neurodegeneration, gaining relevance for novel therapeutic options, such as in the case of Proteolysis Targeting Chimeras technology. Although scientific evidence supports a link between Ub and glaucoma, their relationship is still not well-understood. Therefore, this review provides a detailed research-oriented discussion on current evidence of Ub signaling in glaucoma. A review of genomic and genetic data is provided followed by an in-depth discussion of experimental data on ASB10, parkin and optineurin, which are proteins that play a key role in Ub signaling and have been associated with glaucoma.

Vascular imaging findings in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a vascular disease among preterm infants involving incomplete or abnormal retinal vascularization and is a leading cause of preventable blindness globally. Measurements of ocular blood flow originating from a variety of imaging modalities, including colour Doppler imaging (CDI), fluorescein angiography (FA) and ocular coherence tomography angiography (OCTA), have been associated with changes in ROP patients. Herein, we discuss and summarize the relevant current literature on vascular imaging and ROP reviewed through December 2022. Differences in vascular imaging parameters between ROP patients and healthy controls are reviewed and summarized. The available data identify significantly increased peak systolic velocity (PSV) in the central retinal artery and ophthalmic artery as measured by CDI, increased vascular tortuosity as measured by FA, smaller foveal avascular zone (FAZ) as measured by FA and OCTA, and increased foveal vessel density (VD) and reduced parafoveal VD as measured by OCTA in ROP patients compared with controls. None of the above findings appear to reliably correlate with visual acuity. The studies currently available, however, are inconclusive and lack robust longitudinal data. Vascular imaging demonstrates the potential to aid in the diagnosis, management and monitoring of ROP, alongside retinal examination via indirect ophthalmoscopy and fundus photography.

Ocular blood flow biomarkers may predict long-term glaucoma progression.

BACKGROUND/AIM: To examine the relationship between baseline blood flow biomarkers and long-term open-angle glaucoma (OAG) progression. METHODS: 112 patients with early to moderate OAG (mean age 64.9±11.0 years; 68 female) were evaluated at baseline and every 6 months from 2008 to 2013. Biomarkers of retinal capillary blood flow were assessed by Heidelberg retinal flowmetry. Functional disease progression was monitored via Humphrey visual field examinations, defined as two consecutive visits with a mean deviation decrease ≥2 decibels and/or Advanced Glaucoma Intervention Study score increase ≥2 compared with baseline. Structural progression was monitored with optical coherence tomography and Heidelberg retinal tomograph, defined as two consecutive visits with retinal nerve fibre layer thickness decrease ≥8% and/or horizontal or vertical cup/disk ratio increase ≥0.2 compared with baseline. Mixed-model analysis of covariance was used to test for significant change from baseline to 5-year follow-up. Times to functional and structural progression were analysed using Cox proportional hazards models. RESULTS: Lower HRF retinal capillary blood flow in the superior retina was significantly associated with structural progression (p=0.0009). CONCLUSION: In our OAG sample, baseline lower retinal capillary perfusion in the superior retina was predictive of structural progression after 5 years. TRIAL REGISTRATION NUMBER: NCT01145911.

Regional Vessel Density Reduction in the Macula and Optic Nerve Head of Patients With Pre-Perimetric Primary Open Angle Glaucoma.

PRCIS: Capillary and neuronal tissue loss occur both globally and with regional specificity in pre-perimetric glaucoma patients at the level of the optic nerve and macula, with perifovea regions affected earlier than parafovea areas. PURPOSE: To investigate optic nerve head (ONH) and macular vessel densities (VD) and structural parameters assessed by optical coherence tomography angiography in pre-perimetric open angle glaucoma (ppOAG) patients and healthy controls. MATERIALS AND METHODS: In all, 113 healthy and 79 ppOAG patients underwent global and regional (hemispheric/quadrants) assessments of retinal, ONH, and macular vascularity and structure, including ONH parameters, retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness. Comparisons between outcomes in ppOAG and controls were adjusted for age, sex, race, BMI, diabetes, and hypertension, with P <0.05 considered statistically significant. RESULTS: In ppOAG compared with healthy controls: RNFL thicknesses were statistically significantly lower for all hemispheres, quadrants, and sectors ( P <0.001-0.041); whole image peripapillary all and small blood vessels VD were statistically significantly lower for all the quadrants ( P <0.001-0.002), except for the peripapillary small vessels in the temporal quadrant (ppOAG: 49.66 (8.40), healthy: 53.45 (4.04); P =0.843); GCC and inner and full macular thicknesses in the parafoveal and perifoveal regions were significantly lower in all the quadrants ( P =0.000- P =0.033); several macular VD were significantly lower ( P =0.006-0.034), with the exceptions of macular center, parafoveal superior and inferior quadrant, and perifoveal superior quadrant ( P >0.05). CONCLUSIONS: In ppOAG patients, VD biomarkers in both the macula and ONH, alongside RNFL, GCC, and macular thickness, were significantly reduced before detectable visual field loss with regional specificity. The most significant VD reduction detected was in the peripheric (perifovea) regions. Macular and ONH decrease in VD may serve as early biomarkers of glaucomatous disease.

Deep Learning for Localized Detection of Optic Disc Hemorrhages.

PURPOSE: To develop an automated deep learning system for detecting the presence and location of disc hemorrhages in optic disc photographs. DESIGN: Development and testing of a deep learning algorithm. METHODS: Optic disc photos (597 images with at least 1 disc hemorrhage and 1075 images without any disc hemorrhage from 1562 eyes) from 5 institutions were classified by expert graders based on the presence or absence of disc hemorrhage. The images were split into training (n = 1340), validation (n = 167), and test (n = 165) datasets. Two state-of-the-art deep learning algorithms based on either object-level detection or image-level classification were trained on the dataset. These models were compared to one another and against 2 independent glaucoma specialists. We evaluated model performance by the area under the receiver operating characteristic curve (AUC). AUCs were compared with the Hanley-McNeil method. RESULTS: The object detection model achieved an AUC of 0.936 (95% CI = 0.857-0.964) across all held-out images (n = 165 photographs), which was significantly superior to the image classification model (AUC = 0.845, 95% CI = 0.740-0.912; P = .006). At an operating point selected for high specificity, the model achieved a specificity of 94.3% and a sensitivity of 70.0%, which was statistically indistinguishable from an expert clinician (P = .7). At an operating point selected for high sensitivity, the model achieves a sensitivity of 96.7% and a specificity of 73.3%. CONCLUSIONS: An autonomous object detection model is superior to an image classification model for detecting disc hemorrhages, and performed comparably to 2 clinicians.

Differences in structural parameters in patients with open-angle glaucoma, high myopia and both diseases concurrently. A pilot study.

PURPOSE: To evaluate the differences in structural parameters in patients with open-angle glaucoma (OAG), high myopia (M), and both diseases (OAG-M) concurrently. METHODS: 42 subjects with OAG (n = 14), M (n = 14) and OAG-M (n = 14) were included in a prospective pilot study. Mean peripapillary retinal nerve fiber layer (RNFL) thickness, RNFL in superior, temporal, inferior, nasal quadrants, macular ganglion cell complex (GCC) and its' layers, vessel density (VD) of optic nerve head (ONH) and macula were evaluated. RESULTS: The OAG-M group showed significantly lowest thickness of mean peripapillary RNFL 89 (49-103) µm (p = 0.021), temporal quadrant 64.5 (51-109) µm (p = 0.001) and inferior quadrant 107 (64-124) µm (p = 0.025). The macular RNFL was thinnest in the OAG-M group (p <0.001). Macular VD in inferior quadrant was lowest in OAG-M group at superficial capillary plexus 45.92 (40.39-51.72) % (p = 0.014) and choriocapillaris 51.62 (49.87-56.63) % (p = 0.035). The lowest ONH VD of temporal quadrant was found in the OAG-M group 52.15 (35.73-59.53) % (p = 0.001) in the superficial capillary plexus. Similarly, the lowest VD of inferior quadrant was found in OAG-M group in the choriocapillaris 54.42 (46.31-64.64) % (p<0.001). CONCLUSIONS: The M group showed the least thinning in the peripapillary RNFL thickness in the temporal quadrant and macular RNFL compared to other two groups. The highest macular VD in the inferior quadrant was in the M group in the superficial capillary plexus, deep capillary plexus and choriocapillaris. The M group showed highest VD in the temporal quadrant and in total VD of ONH at the superficial capillary plexus and in total VD of ONH at the deep capillary plexus. PRACTICAL RECOMMENDATIONS: The observed decrease in peripapillary RNFL thickness of the temporal quadrant, macular RNFL thickness, the decrease of macular VD at the inferior quadrant and decrease in VD of the ONH temporal quadrant in deep capillary plexus could be beneficial for diagnosing glaucoma in high myopia.

The role of conventional and unconventional adaptive routes in lowering of intraocular pressure: Theoretical model and simulation.

In this article, we propose a theoretical model leveraging the analogy between fluid and electric variables to investigate the relation among aqueous humor (AH) circulation and drainage and intraocular pressure (IOP), the principal established risk factor of severe neuropathologies of the optic nerve such as glaucoma. IOP is the steady-state result of the balance among AH secretion (AHs), circulation (AHc), and drainage (AHd). AHs are modeled as a given volumetric flow rate electrically corresponding to an input current source. AHc is modeled by the series of two linear hydraulic conductances (HCs) representing the posterior and anterior chambers. AHd is modeled by the parallel of three HCs: a linear HC for the conventional adaptive route (ConvAR), a nonlinear HC for the hydraulic component of the unconventional adaptive route (UncAR), and a nonlinear HC for the drug-dependent component of the UncAR. The proposed model is implemented in a computational virtual laboratory to study the value attained by the IOP under physiological and pathological conditions. Simulation results (i) confirm the conjecture that the UncAR acts as a relief valve under pathological conditions, (ii) indicate that the drug-dependent AR is the major opponent to IOP increase in the case of elevated trabecular meshwork resistance, and (iii) support the use of the model as a quantitative tool to complement in vivo studies and help design and optimize medications for ocular diseases.

Aging Effects on Optic Nerve Neurodegeneration.

Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding the mechanisms of age-related changes can facilitate targeted treatments for ocular pathologies that arise at any point in life. In this review, we examine these age-related, neurodegenerative changes in the optic nerve, contextualize these changes from the anatomic to the molecular level, and appreciate their relationship with ocular pathophysiology. From simple structural and mechanical changes at the optic nerve head (ONH), to epigenetic and biochemical alterations of tissue and the environment, multiple age-dependent mechanisms drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, and lowered regenerative ability of respective axons. In conjunction, aging decreases the ability of myelin to preserve maximal conductivity, even with "successfully" regenerated axons. Glial cells, however, regeneratively overcompensate and result in a microenvironment that promotes RGC axonal death. Better elucidating optic nerve neurodegeneration remains of interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, and astrocytes; clarifying the exact processes of aged ocular connective tissue alterations and their ultrastructural impacts; and developing novel technologies and pharmacotherapies that target known genetic, biochemical, matrisome, and neuroinflammatory markers. Management models should account for age-related changes when addressing glaucoma, diabetic retinopathy, and other blinding diseases.

Heterogeneity of Ocular Hemodynamic Biomarkers among Open Angle Glaucoma Patients of African and European Descent.

This study investigated the heterogeneity of ocular hemodynamic biomarkers in early open angle glaucoma (OAG) patients and healthy controls of African (AD) and European descent (ED). Sixty OAG patients (38 ED, 22 AD) and 65 healthy controls (47 ED, 18 AD) participated in a prospective, cross-sectional study assessing: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), visual field (VF) and vascular densities (VD) via optical coherence tomography angiography (OCTA). Comparisons between outcomes were adjusted for age, diabetes status and BP. VF, IOP, BP and OPP were not significantly different between OAG subgroups or controls. Multiple VD biomarkers were significantly lower in OAG patients of ED (p < 0.05) while central macular VD was lower in OAG patients of AD vs. OAG patients of ED (p = 0.024). Macular and parafoveal thickness were significantly lower in AD OAG patients compared to those of ED (p = 0.006-0.049). OAG patients of AD had a negative correlation between IOP and VF index (r = -0.86) while ED patients had a slightly positive relationship (r = 0.26); difference between groups (p < 0.001). Age-adjusted OCTA biomarkers exhibit significant variation in early OAG patients of AD and ED.

Metabolic blood flow regulation in a hybrid model of the human retinal microcirculation.

The retinal vascular network supplies perfusion to vital visual structures, including retinal ganglion cells responsible for vision. Impairments in retinal blood flow and oxygenation are involved in the progression of many ocular diseases, including glaucoma. In this study, an established theoretical hybrid model of a retinal microvascular network is extended to include the effects of local blood flow regulation on oxygenation. A heterogeneous representation of the arterioles based on confocal microscopy images is combined with a compartmental description of the downstream capillaries and venules. A Green's function method is used to simulate oxygen transport in the arterioles, and a Krogh cylinder model is applied to the capillary and venular compartments. Acute blood flow regulation is simulated in response to changes in pressure, shear stress, and metabolism. Model results predict that both increased intraocular pressure and impairment of blood flow regulation can cause decreased tissue oxygenation, indicating that both mechanisms represent factors that could lead to impaired oxygenation characteristic of ocular disease. Results also indicate that the metabolic response mechanism reduces the fraction of poorly oxygenated tissue but that the pressure- and shear stress-dependent response mechanisms may hinder the vascular response to changes in oxygenation. Importantly, the heterogeneity of the vascular network demonstrates that traditionally reported average values of tissue oxygen levels hide significant localized defects in tissue oxygenation that may be involved in disease processes, including glaucoma. Ultimately, the model framework presented in this study will facilitate future comparisons to sectorial-specific clinical data to better assess the role of impaired blood flow regulation in ocular disease.

The Relationship between Intracranial Pressure and Visual Field Zones in Normal-Tension Glaucoma Patients.

Growing evidence suggests that intracranial pressure (ICP) plays an important role in the pathophysiology of glaucoma, especially in normal-tension glaucoma (NTG) patients. Controversial results exist about ICP's relationship to visual field (VF) changes. With the aim to assess the relationship between ICP and VF zones in NTG patients, 80 NTG patients (age 59.5 (11.6) years) with early-stage glaucoma were included in this prospective study. Intraocular pressure (IOP) (Goldmann), visual perimetry (Humphrey) and non-invasive ICP (via a two-depth Transcranial Doppler, Vittamed UAB, Lithuania) were evaluated. Translaminar pressure difference (TPD) was calculated according to the formula TPD = IOP − ICP. The VFs of each patient were divided into five zones: nasal, temporal, peripheral, central, and paracentral. The average pattern deviation (PD) scores were calculated in each zone. The level of significance p < 0.05 was considered significant. NTG patients had a mean ICP of 8.5 (2.4) mmHg. Higher TPD was related with lower mean deviation (MD) (p = 0.01) and higher pattern standard deviation (PSD) (p = 0.01). ICP was significantly associated with the lowest averaged PD scores in the nasal VF zone (p < 0.001). There were no significant correlations between ICP and other VF zones with the most negative mean PD value. (p > 0.05). Further studies are needed to analyze the involvement of ICP in NTG management.

Changes in Macular Thickness after Cataract Surgery in Patients with Open Angle Glaucoma.

BACKGROUND: The purpose of this study was to examine the changes in IOP, total macular and RNFL, ganglion cell layer (GCL) thickness, and aqueous humour flare in open angle glaucoma (OAG) patients before and 6 months after cataract surgery. METHODS: This was a prospective observational case-control age- and gender-matched study. Groups: 40 subjects in a controlled OAG (OAGc) group, 20 subjects in an uncontrolled OAG (OAGu) group, and 60 control group subjects. EXAMINATION: complete ophthalmic evaluation, IOP measurement, anterior and posterior segment Optical Coherence Tomography (OCT), and laser flare photometry before and 6 months postoperatively. RESULTS: Six months postoperatively IOP decreased in all groups. An increase in macular thickness was found postoperatively in all groups. Preoperative aqueous humour flare was higher in the OAGc group than in the control group. After cataract surgery, aqueous humour flare was higher in the control group compared to the preoperative result. CONCLUSIONS: Changes in IOP following cataract surgery were strongly negatively correlated with preoperative IOP. An increase in macular thickness was observed 6 months postoperatively in all groups. Aqueous humour flare did not differ in OAGc and OAGu groups pre- and postoperatively but significantly increased in the control group postoperatively.

Association of Brain Volume and Retinal Thickness in the Early Stages of Alzheimer's Disease.

BACKGROUND: The eye has been considered a 'window to the brain,' and several neurological diseases including neurodegenerative conditions like Alzheimer's disease (AD) also show changes in the retina. OBJECTIVE: To investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline. METHODS: 75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD). Differences in demographics, thickness of RNFL, and brain volume were assessed using ANCOVA, while partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary RNFL with brain volumes, with p < 0.05 considered statistically significant. RESULTS: Mean RNFL thickness was significantly correlated with brain volumes, including global volume (right eye r = 0.235 p = 0.046, left eye r = 0.244, p = 0.037), temporal lobe (right eye r = 0.242 p = 0.039, left eye r = 0.290, p = 0.013), hippocampal (right eye r = 0.320 p = 0.005, left eye r = 0.306, p = 0.008), amygdala (left eye r = 0.332, p = 0.004), and occipital lobe (right eye r = 0.264 p = 0.024) volumes. CONCLUSION: RNFL thickness in both eyes was positively associated with brain volumes in subjects with subjective and objective cognitive decline. The RNFL, however, did not correlate with the disease, but the small sample number makes it important to conduct larger studies. RNFL thickness may be a useful non-invasive and inexpensive tool for detection of brain neurodegeneration and may assist with diagnosis and monitoring of progression and treatment in AD.

Anatomic Biomarkers of Macular Edema Associated with Retinal Vein Occlusion.

PURPOSE: To assess the relationship between best-corrected visual acuity (BCVA) and anatomic features in patients with macular edema (ME) related to retinal vein occlusion (RVO). DESIGN: Post hoc analysis of 3 clinical trials, which included verified diagnoses, protocol refractions, and the assessment of OCT and fluorescein angiography (FA) images at a masked reading center. PARTICIPANTS: Patients diagnosed with RVO-ME. METHODS: Correlation analyses were performed to determine the correlation between BCVA and macular anatomy at baseline and at 12 and 24 weeks and between changes from baseline to 12 and 24 weeks. MAIN OUTCOME MEASURES: The correlations between BCVA and central subfield thickness (CST), ellipsoid zone (EZ) integrity, intraretinal fluid (IRF), subretinal fluid, central leakage, and ischemia were assessed. RESULTS: In a total of 828 eyes with RVO-ME, the mean age, BCVA, and CST at baseline was 64.7 years, 51.1 letters, and 656.9 µm, respectively. At baseline, a moderate negative correlation was observed between BCVA and CST (r = - 0.56, P < 0.001). At weeks 12 and 24, the mean BCVA of eyes with definitely abnormal (absent) EZ was statistically significantly worse than that of eyes with normal EZ. At week 12, a moderate negative correlation was observed between changes in BCVA and changes in CST (r = - 0.35, P < 0.001), with a similar degree of association noted at week 24 (r = - 0.35, P < 0.001). At weeks 12 and 24, eyes that showed any improvement in central IRF showed a greater improvement in BCVA than eyes that showed no improvement worsening (week 12: 463 eyes, 18.3 letters vs. 177 eyes, 13.0 letters, respectively, P < 0.001) and (week 24: 332 eyes, 20.2 letters vs. 131 eyes, 13.3 letters, respectively, P < 0.001). With respect to the correlation between baseline BCVA and fluorescein leakage or capillary nonperfusion, the Pearson correlation coefficients were - 0.41 (P < 0.001) and - 0.16 (P = 0.060), respectively. CONCLUSIONS: In addition to CST, there are important clinically relevant relationships between BCVA and both OCT and FA anatomic features in patients with RVO-ME.