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.

The Change in Corneal and Conjunctival Sensation Following Pterygium Surgery.

BACKGROUND: The cornea is one of the most densely innervated in the body. Pterygium surgery includes removal of the pterygium tissue from the cornea and conjunctiva followed by autologous conjunctival grafting. OBJECTIVES: To examine the change in corneal and conjunctival sensation post-pterygium surgery. METHODS: This prospective study included patients with primary pterygium. We collected and analyzed demographic data, visual acuity (VA), refraction, quantified sensation, and corneal tomography. Comparison in sensation in the cornea, conjunctiva, and conjunctival autograft was recorded the day of surgery and at least 6 months postoperatively. RESULTS: Nine patients participated in the study. Mean follow-up time was 9 months (9  3.3, 6-12.4). No complications were documented during or following surgery and no recurrences were found. Statistically significant increases in corneal sensation in the nasal corneal and in the nasal conjunctival areas were noted by the end of follow-up compared to before surgery (P = 0.05, paired samples t-test). There was a significant correlation between the increase in nasal corneal and conjunctival sensation with improved Schirmer testing outcomes and tear break-up time after surgery (P = 0.05, P = 0.01, Pearson correlation). There was a positive correlation between the changes in nasal corneal sensation after surgery and improved changes in VA (P = 0.02, Pearson correlation). CONCLUSIONS: We found improvement in sensation 9 months after pterygium surgery, which may be due to reinnervation of the cornea and conjunctival autograft from the neighboring non-injured nerve fibers. Larger studies with confocal microscopy should be conducted for further analysis.

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.

A modified pediatric ocular trauma score for predicting visual outcome post open globe injury.

PURPOSE: To construct a new pediatric ocular trauma score for predicting visual outcome after open globe injuries (OGI) and to compare it to the ocular trauma score (OTS) and pediatric ocular trauma score (POTS). METHODS: This is a retrospective chart review study. For each case, the following data were collected: demographics, mechanism of the injury, initial ophthalmologic findings, presented and last follow-up visual acuity (VA), ocular treatments, and final ocular findings. We then analyzed the risk factors for the poor visual outcome (VA ≤ 20/200), and a modified pediatric ocular trauma score (MPOTS) was constructed accordingly and compared to the OTS and POTS for predicting poor outcome. Finally, a different cohort of pediatric OGIs was used for score validation. RESULTS: Forty-five cases were included, significant predicting factors for poor visual outcome were initial VA ≤ 20/200, zone 2-3 locations of injury, presence of retinal detachment, vitreous hemorrhage, hyphema, and iris prolapse at initial presentation. The calculated Spearman correlation coefficients between each system score and poor visual outcome were OTS 0.56, POTS 0.57, and MPOTS 0.64 (P < 0.001 for all). A total of 71 new cases were used as validation cohort, and calculated Spearman correlation coefficients between each system score and poor visual outcome were: OTS 0.50, POTS 0.51, and MPOTS 0.53 (P < 0.001 for all). CONCLUSIONS: We suggest a new scoring system for predicting poor final visual outcomes after OGI's in children, which is simpler and more clinically suitable for this study population. It was found to be a better predictor of visual outcome in this scenario compared with existing scoring systems.

Agreement of Corneal Endothelial Cell Analysis Between Konan-Noncon Robo SP-6000 and Tomey EM-3000 Specular Microscopes in Healthy Subjects.

PURPOSE: To compare corneal endothelium parameters taken by two common noncontact specular microscopes in healthy subjects. METHODS: Healthy participants visiting the outpatient eye clinic at the Rabin Medical Center, Petah Tikva, Israel, were recruited prospectively. All participants underwent three consecutive corneal endothelial cell photographs with both the Konan-Noncon Robo SP-6000 and the Tomey EM-3000 specular microscopes. Endothelial cell density (ECD) was evaluated using the manual center technique in both machines. Bland-Altman graphs were used to assess the agreement between the devices, and intraclass correlation coefficient (ICC) served to assess intraobserver variability for each device. RESULTS: Recruited were 49 healthy subjects with a mean age of 48.9±15.6 years, 49 right eyes were included. The mean ECD was comparable between the Tomey EM-3000 and the Konan-Noncon Robo SP-6000 (2,713.2±242.4 vs. 2,700.8±300.5 cells/mm2, respectively, P=0.47) with a mean difference of 12.4 cells/mm2 (0.67%), a mean ECD absolute difference of 93.3 cells/mm2, and low 95% limits of agreement of -222.0 to +246.9 cells/mm2. A folded empirical distribution function curve showed that all differences fell within 525.4 cells/mm2, centered around a median of 13.3 cells/mm2. Intraclass correlation coefficient was high for both the Konan-Noncon Robo SP-6000 (0.93, 95% confidence interval [CI]: 0.89-0.95) and the Tomey EM-3000 (0.88, 95% CI: 0.82-0.93). CONCLUSIONS: The difference in endothelial cell measurements between the Konan SP-6000 and the Tomey EM-3000 specular microscopes through the center and the L-count analyzing techniques, respectively, is clinically small and not statistically significant. Nevertheless, caution should be taken when used interchangeably because ECD difference between the two machines can be as high as 525.4 cells/mm2.

The Effect of COVID-19 on Israeli Ophthalmology Departments: Directors' Perspectives.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic presented a major medical management challenge to ophthalmology departments throughout Israel. OBJECTIVES: To examine the managerial challenges, actions taken, and insights of directors of ophthalmology departments in Israel during the COVID-19 pandemic. METHODS: We conducted a cross sectional survey of directors of ophthalmology departments during the COVID-19 pandemic while the Israeli population was quarantined. RESULTS: All 21 directors answered the survey. The majority of the COVID-19 admissions were located in the center of Israel (53%) and Jerusalem (30%). E-communication took a central role in coping with the pandemic with 80% of the directors satisfied with this form of communication; 75% reported a reduction in clinical and surgery volume of at least 25%, and 40% reported reallocations of manpower. Most of the medical staff used gloves, a face shield, disposable robe, and a mask with no uniformity across departments. Cross satisfaction was noted regarding a hospital's ability to equip the departments. Lack of preparation for post-pandemic era was reported by all directors, but one (95%). Directors sought guidelines and uniformity regarding outpatient referral to the hospital (p = 0.035). CONCLUSIONS: Guidelines via safe digital platforms aid in management decisions and uniformity across departments. Advanced preparation is needed to prevent adverse clinical outcomes and to maintain treatment continuum. Our results can be used to guide and help improve the preparedness of ophthalmology departments during COVID-19 and for future pandemics.

The Incidence of Retinal Vein Occlusion in Patients with Pseudoexfoliation Glaucoma: A Retrospective Cohort Study.

PURPOSE: The aim of this study was to evaluate pseudoexfoliation (PXF) as an independent risk factor for the occurrence of retinal vein occlusion (RVO). METHODS: This is a retrospective cohort study on the records of 300 PXF glaucoma patients (PXF group), 300 non-PXF glaucoma patients, and 599 nonglaucoma non-PXF (nGnP group) patients. RESULTS: Multivariate analysis resulted in a significant probability for RVO in the PXF (p = 0.005; OR 2.29 [1.13-4.68]) and non-PXF glaucoma groups (p = 0.005; OR 3.03 [1.55-5.94]) compared to the nGnP group. There was a much higher probability for central RVO (CRVO) in the PXF (p = 0.013; OR 3.64 [1.39-9.49]) and non-PXF glaucoma groups (p = 0.013; OR 3.78 [1.48-9.65]) compared to the nGnP group. After matching and excluding neovascular glaucoma, no significant difference was found between the PXF and non-PXF glaucoma groups regarding RVO (p = 0.541), CRVO (p = 0.092), and branch RVO (p = 0.774). CONCLUSIONS: PXF and other types of glaucoma are associated with RVOs, mainly CRVO. PXF was not found to be an independent risk factor for CRVO.

The Epidemiological, Clinical, and Histopathological Characteristics of Lacrimal Gland Biopsies in a Tertiary Care Center in Israel.

BACKGROUND: The distribution of pathology and clinical characteristics of lacrimal gland diseases are different in different areas of the world. OBJECTIVES: To evaluate the incidence rate, patient characteristics, and indications for surgical intervention of lacrimal gland lesions in a tertiary care center in Israel. METHODS: All biopsied or surgically removed lacrimal gland lesions at the Goldschleger Eye Institute from 2009 to 2015 were identified. The following data were collected: age, gender, indications for surgical intervention, diagnosis, treatment, and prognosis. RESULTS: We evaluated 28 lacrimal gland biopsies from 26 patients (11 men, 15 women). Mean age at biopsy was 47.5 years old. The most common presenting symptoms were: eyelid swollenness (57.14%), ptosis (32.14%), and proptosis (10.71%). All patients underwent computed tomography and magnetic resonance imaging. In 28 cases, infiltrations of the lacrimal gland were found. In nine cases infiltration of muscles or orbital extension were found. The most common pathologies were non-specified inflammation (44.82%), lymphoma (20.68%), and immunoglobulin G4-related disease (10.34%). The treatment was diverse according to the patient diagnosis. Prognosis of lacrimal gland disease was good; however, in five patients the systemic disease progressed. CONCLUSIONS: Lesions of the lacrimal gland comprise a wide variety of pathological findings that require different treatment strategies. Lacrimal gland biopsies enable physicians to precisely recognize the pathology; therefore, it is important to consider this surgical method in any patient with lesions in the lacrimal gland.

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.

Diagnostic Capability of OCTA-Derived Macular Biomarkers for Early to Moderate Primary Open Angle Glaucoma.

Background/Objectives: To investigate macular vascular biomarkers for the detection of primary open-angle glaucoma (POAG). Methods: A total of 56 POAG patients and 94 non-glaucomatous controls underwent optical coherence tomography angiography (OCTA) assessment of macular vessel density (VD) in the superficial (SCP), and deep (DCP) capillary plexus, foveal avascular zone (FAZ) area, perimeter, VD, choriocapillaris and outer retina flow area. POAG patients were classified for severity based on the Glaucoma Staging System 2 of Brusini. ANCOVA comparisons adjusted for age, sex, race, hypertension, diabetes, and areas under the receiver operating characteristic curves (AUCs) for POAG/control differentiation were compared using the DeLong method. Results: Global, hemispheric, and quadrant SCP VD was significantly lower in POAG patients in the whole image, parafovea, and perifovea (p < 0.001). No significant differences were found between POAG and controls for DCP VD, FAZ parameters, and the retinal and choriocapillaris flow area (p > 0.05). SCP VD in the whole image and perifovea were significantly lower in POAG patients in stage 2 than stage 0 (p < 0.001). The AUCs of SCP VD in the whole image (0.86) and perifovea (0.84) were significantly higher than the AUCs of all DCP VD (p < 0.05), FAZ parameters (p < 0.001), and retinal (p < 0.001) and choriocapillaris flow areas (p < 0.05). Whole image SCP VD was similar to the AUC of the global retinal nerve fiber layer (RNFL) (AUC = 0.89, p = 0.53) and ganglion cell complex (GCC) thickness (AUC = 0.83, p = 0.42). Conclusions: SCP VD is lower with increasing functional damage in POAG patients. The AUC for SCP VD was similar to RNFL and GCC using clinical diagnosis as the reference standard.

Using Multi-Layer Perceptron Driven Diagnosis to Compare Biomarkers for Primary Open Angle Glaucoma.

Purpose: To use neural network machine learning (ML) models to identify the most relevant ocular biomarkers for the diagnosis of primary open-angle glaucoma (POAG). Methods: Neural network models, also known as multi-layer perceptrons (MLPs), were trained on a prospectively collected observational dataset comprised of 93 glaucoma patients confirmed by a glaucoma specialist and 113 control subjects. The base model used only intraocular pressure, blood pressure, heart rate, and visual field (VF) parameters to diagnose glaucoma. The following models were given the base parameters in addition to one of the following biomarkers: structural features (optic nerve parameters, retinal nerve fiber layer [RNFL], ganglion cell complex [GCC] and macular thickness), choroidal thickness, and RNFL and GCC thickness only, by optical coherence tomography (OCT); and vascular features by OCT angiography (OCTA). Results: MLPs of three different structures were evaluated with tenfold cross validation. The testing area under the receiver operating characteristic curve (AUC) of the models were compared with independent samples t-tests. The vascular and structural models both had significantly higher accuracies than the base model, with the hemodynamic AUC (0.819) insignificantly outperforming the structural set AUC (0.816). The GCC + RNFL model and the model containing all structural and vascular features were also significantly more accurate than the base model. Conclusions: Neural network models indicate that OCTA optic nerve head vascular biomarkers are equally useful for ML diagnosis of POAG when compared to OCT structural biomarker features alone.

The Short-term Effects of Artificial Tears on the Tear Film Assessed by a Novel High-Resolution Tear Film Imager: A Pilot Study.

PURPOSE: The purpose of this study was to investigate the effects of artificial tears (AT) on the sublayers of the tear film assessed by a novel tear film imaging (TFI) device. METHODS: The mucoaqueous layer thickness (MALT) and lipid layer thickness (LLT) of 198 images from 11 healthy participants, 9 of whom had meibomian gland disease, were prospectively measured before and after exposure to 3 different AT preparations (Refresh Plus; Retaine [RTA]; Systane Complete PF [SYS]), using a novel nanometer resolution TFI device (AdOM, Israel). Participants were assessed at baseline and at 1, 5, 10, 30, and 60 minutes after instilling 1 drop of AT during 3 sessions on separate days. Repeated-measures analysis of variances were used for comparisons with P < 0.05 considered significant. RESULTS: For all ATs, the mean MALT was greatest 1 minute after drop instillation, with an increase of 67%, 55%, and 11% above the baseline for SYS, Refresh Plus, and RTA, respectively. The SYS formulation demonstrated the highest percentage increases in mean MALT and LLT at most postdrop time points. The MALT differences were significantly higher in the SYS than in the RTA (P = 0.014). After 60 minutes, no AT group demonstrated statistically significant changes in MALT or LLT compared with baseline. CONCLUSIONS: We report, for the first time, the effects of AT on MALT and LLT using a high-resolution TFI. A substantial acute mean MALT increase occurs 1 minute after AT instillation with all agents tested, but there were clear differences in response and durability, suggesting the benefits of choosing specific AT according to the needs of each patient.

The Short-term Effects of Artificial Tears on the Tear Film Assessed by a Novel High-Resolution Tear Film Imager: A Pilot Study.

PURPOSE: The purpose of this study was to investigate the effects of artificial tears (AT) on the sublayers of the tear film assessed by a novel tear film imaging (TFI) device. METHODS: The mucoaqueous layer thickness (MALT) and lipid layer thickness (LLT) of 198 images from 11 healthy participants, 9 of whom had meibomian gland disease, were prospectively measured before and after exposure to 3 different AT preparations (Refresh Plus; Retaine [RTA]; Systane Complete PF [SYS]), using a novel nanometer resolution TFI device (AdOM, Israel). Participants were assessed at baseline and at 1, 5, 10, 30, and 60 minutes after instilling 1 drop of AT during 3 sessions on separate days. Repeated-measures analysis of variances were used for comparisons with P < 0.05 considered significant. RESULTS: For all ATs, the mean MALT was greatest 1 minute after drop instillation, with an increase of 67%, 55%, and 11% above the baseline for SYS, Refresh Plus, and RTA, respectively. The SYS formulation demonstrated the highest percentage increases in mean MALT and LLT at most postdrop time points. The MALT differences were significantly higher in the SYS than in the RTA ( P = 0.014). After 60 minutes, no AT group demonstrated statistically significant changes in MALT or LLT compared with baseline. CONCLUSIONS: We report, for the first time, the effects of AT on MALT and LLT using a high-resolution TFI. A substantial acute mean MALT increase occurs 1 minute after AT instillation with all agents tested, but there were clear differences in response and durability, suggesting the benefits of choosing specific AT according to the needs of each patient.

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.

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.

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.

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.

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.