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.

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.

Anterior segment optical coherence tomography imaging and ocular biometry in cataract patients with open angle glaucoma comorbidity.

BACKGROUND: Anterior chamber angle anatomy in perspective of ocular biometry may be the key element to intraocular pressure (IOP) reduction, especially in glaucoma patients. We aim to investigate anterior chamber angle and biometrical data prior to cataract surgery in patients with and without glaucoma comorbidity. MATERIALS AND METHODS: This prospective comparative case-control study included 62 subjects (38 with cataract only and 24 with cataract and glaucoma). A full ophthalmic examination including, Goldmann applanation tonometry, anterior chamber swept source optical coherence tomography (DRI OCT Triton plus (Ver.10.13)) and swept source optical biometry (IOL Master 700 v1.7) was performed on all participants. RESULTS: We found that ocular biometry parameters and anterior chamber parameters were not significantly different among groups. However, when we added cut-off values for narrow angles, we found that glaucoma group tended to have more narrow angles than control group. IOP was higher in glaucoma group despite all glaucoma patients having medically controlled IOP. In all subjects, anterior chamber parameters correlated well with lens position (LP), but less with relative lens position, while LP cut-off value of 5.1 mm could be used for predicting narrow anterior chamber angle parameters. CONCLUSIONS: Cataract patients tend to develop narrow anterior chamber angles. Anterior chamber angle parameters have a positive moderate to strong relationship with lens position. LP may be used predicting narrow angles.

Can the Treatment of Normal-Pressure Hydrocephalus Induce Normal-Tension Glaucoma? A Narrative Review of a Current Knowledge.

Ventriculoperitoneal shunt placement is the most commonly used treatment of normal-pressure hydrocephalus (NPH). It has been hypothesized that normal-tension glaucoma (NTG) is caused by the treatment of NPH by using the shunt to reduce intracranial pressure (ICP). The aim of this study is to review the literature published regarding this hypothesis and to emphasize the need for neuro-ophthalmic follow-up for the concerned patients. The source literature was selected from the results of an online PubMed search, using the keywords "hydrocephalus glaucoma" and "normal-tension glaucoma shunt". One prospective study on adults, one prospective study on children, two retrospective studies on adults and children, two case reports, three review papers including medical hypotheses, and one prospective study on monkeys were identified. Hypothesis about the association between the treatment of NPH using the shunt to reduce ICP and the development of NTG were supported in all reviewed papers. This suggests that a safe lower limit of ICP for neurological patients, especially shunt-treated NPH patients, should be kept. Thus, we proposed to modify the paradigm of safe upper ICP threshold recommended in neurosurgery and neurology into the paradigm of safe ICP corridor applicable in neurology and ophthalmology, especially for shunt-treated hydrocephalic and glaucoma patients.

Optic nerve head diurnal vessel density variations in glaucoma and ocular hypertension measured by optical coherence tomography angiography.

BACKGROUND/AIMS: To evaluate diurnal variations in optic nerve head (ONH) vessel density assessed by optical coherence tomography angiography (OCT-A) in healthy subjects, ocular hypertension (OHT), and open-angle glaucoma (OAG) patients. METHODS: Forty subjects (OAG, 21; OHT, 6; healthy, 13) were assessed for vessel density percentage (VD%) and flow index in the ONH (NH VD%, NH index), and in the radial peripapillary capillary layer (RPC VD%, RPC index) at 9:00, 11:00, 14:00, 16:00, and 18:00 on a single day. Repeated measures ANOVAs were used to test for changes in the parameters measured at multiple time points. RESULTS: All OCT-A parameters analyzed at the different time points were statistically lower in the OAG patients compared to both the OHT and healthy groups (p < 0.05). In the OAG group, the NH index, RPC index, NH VD%, and RPC VD% were statistically lower at 18:00 compared to 14:00, and the RPC VD% was statistically lower at 9:00 than 14:00. In the OHT group, the RPC index was statistically lower at 9:00 than 11:00. In the healthy group, the NH VD% and RPC VD% were statistically lower at 16:00 than 18:00, and the RPC index was statistically lower at 9:00 than 11:00. No other statistically significant difference was found in none of the three groups comparing any other time point (p > 0.05). CONCLUSION: In healthy subjects, OHT and OAG patients, the variations in the OCT-A derived parameters were relatively small. These results suggest that in the clinical practice the OCT-A assessment can be performed independently of the time of the day, contrasting IOP evaluation.

Regional Infoveillance of COVID-19 Case Rates: Analysis of Search-Engine Query Patterns.

BACKGROUND: Timely allocation of medical resources for coronavirus disease (COVID-19) requires early detection of regional outbreaks. Internet browsing data may predict case outbreaks in local populations that are yet to be confirmed. OBJECTIVE: We investigated whether search-engine query patterns can help to predict COVID-19 case rates at the state and metropolitan area levels in the United States. METHODS: We used regional confirmed case data from the New York Times and Google Trends results from 50 states and 166 county-based designated market areas (DMA). We identified search terms whose activity precedes and correlates with confirmed case rates at the national level. We used univariate regression to construct a composite explanatory variable based on best-fitting search queries offset by temporal lags. We measured the raw and z-transformed Pearson correlation and root-mean-square error (RMSE) of the explanatory variable with out-of-sample case rate data at the state and DMA levels. RESULTS: Predictions were highly correlated with confirmed case rates at the state (mean r=0.69, 95% CI 0.51-0.81; median RMSE 1.27, IQR 1.48) and DMA levels (mean r=0.51, 95% CI 0.39-0.61; median RMSE 4.38, IQR 1.80), using search data available up to 10 days prior to confirmed case rates. They fit case-rate activity in 49 of 50 states and in 103 of 166 DMA at a significance level of .05. CONCLUSIONS: Identifiable patterns in search query activity may help to predict emerging regional outbreaks of COVID-19, although they remain vulnerable to stochastic changes in search intensity.

Tear film imager for dynamic mapping of the human tear film.

Dry eye (DE) disease is a multifactorial disease of the outer ocular surface characterized by several ocular symptoms and mainly by tear film instability. We have developed an optical imaging system, the tear film imager (TFI), which is the first instrument that can directly image the muco-aqueous tear layer physical dimension in vivo and evaluate its parameters in a noninvasive mode with nanometer axial resolution. This instrument provides quantified information about many attributes of the tear film, including muco-aqueous layer thickness, lipid layer thickness, thickness change rate, and the break-up time. The TFI performances are based on simultaneous acquisition of large field of view (FOV) imagery and fast spectrometric measurement of the interference from the thin tear film sublayers. Herein, after describing the instrument and the methodology of the measurements, we use a tear film mock-up to quantify device accuracy (2.2 nm) and repeatability (0.25 nm standard deviation). In conclusion, we present a new technology for the assessment of the tear film with an unprecedented axial resolution and excellent accuracy and reproducibility.

Lutein Complex Supplementation Increases Ocular Blood Flow Biomarkers in Healthy Subjects.

Introduction: To investigate the effects of a lutein complex supplementation on ocular blood flow in healthy subjects. Materials and Methods: Sixteen healthy female patients (mean age 36.8 ± 12.1 years) were enrolled in this randomized, placebo-controlled, double-blinded, two-period crossover study. Subjects received daily an oral dose of the lutein with synergistic phytochemicals complex (lutein (10 mg), ascorbic acid (500 mg), tocopherols (364 mg), carnosic acid (2.5 mg), zeaxanthin (2 mg), copper (2 mg), with synergistic effects in reducing pro-inflammatory mediators and cytokines when administered together in combination) and placebo during administration periods. Measurements were taken before and after three-week supplementation periods, with crossover visits separated by a three-week washout period. Data analysis included blood pressure, heart rate, intraocular pressure, visual acuity, contrast sensitivity detection, ocular perfusion pressure, confocal scanning laser Doppler imaging of retinal capillary blood flow, and Doppler imaging of the retrobulbar blood vessels. Results: Lutein complex supplementation produced a statistically significant increase in mean superior retinal capillary blood flow, measured in arbitrary units (60, p = 0.0466) and a decrease in the percentage of avascular area in the superior (-0.029, p = 0.0491) and inferior (-0.023, p = 0.0477) retina, as well as reduced systolic (-4.06, p = 0.0295) and diastolic (-3.69, p = 0.0441) blood pressure measured in mmHg from baseline. Data comparison between the two supplement groups revealed a significant decrease in systemic diastolic blood pressure (change from pre- to post-treatment with lutein supplement (mean (SE)): -3.69 (1.68); change from pre- to post-treatment with placebo: 0.31 (2.57); p = 0.0357) and a significant increase in the peak systolic velocity (measured in cm/sec) in the central retinal artery (change from pre- to post-treatment with lutein supplement: 0.36 (0.19); change from pre- to post-treatment with placebo: -0.33 (0.21); p = 0.0384) with lutein complex supplement; data analyses from the placebo group were all non-significant. Discussion: In healthy participants, oral administration of a lutein phytochemicals complex for three weeks produced increased ocular blood flow biomarkers within retinal vascular beds and reduced diastolic blood pressure compared to placebo.

RANIBIZUMAB FOR DIABETIC MACULAR EDEMA REFRACTORY TO MULTIPLE PRIOR TREATMENTS.

PURPOSE: Diabetic macular edema can be refractory to multiple treatment modalities. Although there have been anecdotal reports of ranibizumab showing efficacy when other modalities provided limited benefit, little has been published on treatment for refractory diabetic macular edema. This study sought to investigate this observation further. METHODS: Retrospective chart review. RESULTS: Thirty-three eyes of 22 patients with refractory diabetic macular edema were treated with 0.3 mg intravitreal ranibizumab. This group of eyes received an average of 5.1 prior treatments (macular laser, intravitreal bevacizumab, triamcinolone acetonide, or dexamethasone implant). The mean best corrected visual acuity before the initial ranibizumab injection was 20/110 and the mean central subfield thickness was 384 µm. After 7 visits over an average of 48 weeks, during which an average of 6 ranibizumab injections were administered, the mean visual acuity improved to 20/90 and the mean central subfield thickness improved to 335 µm. Both central subfield thickness and best corrected visual acuity improved with number of days of follow-up in a statistically significant fashion (P < 0.01). Similarly, both central subfield thickness and visual acuity improved with number of ranibizumab injections in a linear fashion, but this was not statistically significant. CONCLUSION: Ranibizumab can improve diabetic macular edema refractory to prior treatments of laser photocoagulation, intravitreal triamcinolone acetonide, and bevacizumab.

Surface measurements by white light spatial-phase-shift imaging interferometry.

A novel method of common-path imaging interferometry, the White Light Spatial-Phase-Shift (WLSPS) for object surface measurements, is discussed here. Compared to standard White Light Interferometry (WLI), which uses a reference mirror, the interferometry of WLSPS is obtained by creating manipulations to the light wavefront reflected from an object's surface. Using this approach, surface measurements can be obtained from any real object image, and do not need to be taken directly from the object itself. This creates the ability for a surface measurement tool to be attached to any optical system that generates a real image of an object. Further, as this method does not require a reference beam, the surface measurement system contains inherent vibration cancelation.

Spatial-phase-shift imaging interferometry using a spectrally modulated white light source.

An extension of the white light spatial-phase-shift (WLSPS) for object surface measurements is described. Using WLSPS, surface measurements can be obtained from any real object image without the need of a reference beam, thus achieving inherent vibration cancellation. The surface topography is obtained by acquiring multiple images of an object illuminated by a spectrally modulated white light source and using an appropriate algorithm. The modulation of the light source obviates the need for the continuous phase delay to obtain the interferograms.

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.

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 effect of nebulized dorzolamide/timolol fixed combination mist versus drops on retrobulbar blood flow and intraocular pressure in glaucoma patients.

OBJECTIVE: The aim of this study was to evaluate intraocular pressure (IOP), retrobulbar blood flow (RBF), and ocular side effects after the application of topical dorzolamide/timolol fixed combination (DTFC) drops vs topical nebulized DTFC mist in patients with primary open-angle glaucoma. MATERIAL AND METHODS: A total of 15 POAG patients were enrolled in a prospective study. Retrobulbar blood flow was measured in the ophthalmic (OA) and central retinal (CRA) arteries using color Doppler imaging. DTFC mist or drops were applied to the experimental eye, and it was examined after 15 and 60 minutes. DTFC mist was applied 6 times for 30 seconds using a misting device. RESULTS: DTFC mist significantly increased peak-systolic (PSV) and end-diastolic (EDV) velocities after 15 and 60 minutes in both the arteries (OA: increase of 12.5% and 9.6% in PSV, P=0.01; increase of 25.8% and 23.1% in EDV, P=0.03; CRA: increase of 11.5% and 8.7% in PSV, increase of 32% and 21.6% in EDV, respectively, P<0.05). DTFC drops had a similar effect on PSV and EDV in the CRA after 15 and 60 minutes (increase of 8.1% and 9.6% in PSV; increase of 17.1% and 23% in EDV, respectively, P=0.03), but a significant effect on PSV and EDV in the OA was documented only after 15 minutes (increase of 9% and 21.4%, respectively, P=0.02). DTFC mist reduced the resistance index in the CRA after 15 and 60 minutes (decrease of 8.5% and 10.2%, respectively, P=0.04). Both methodologies showed a significant decrease in IOP after 15 and 60 minutes (P<0.05). All patients complained of ocular irritation after drop application, and 1 patient complained of general weakness after mist treatment. CONCLUSIONS: Nebulized DTFC mist significantly reduced IOP and increased blood flow in the OA and the CRA, causing no ocular irritation as compared with traditional DTFC drop methodology.

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.

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.

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.