Retinal Changes Research Articles

Assessment of Retinal Microvascular Changes by Oct Angiography after use of Argon Micropulse Laser Versus Traditional Argon Laser for Treatment of Diabetic Macular Edema

Assessment of Retinal Microvascular Changes by Oct Angiography after use of Argon Micropulse Laser Versus Traditional Argon Laser for Treatment of Diabetic Macular Edema

Relationship between retinal volume changes and the prognosis of BRVO-ME treated with ranibizumab

BackgroundThis study aimed to evaluate the efficacy of ranibizumab for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO-ME), changes in retinal volume and central retinal thickness (CRT) before and after therapy, and the connection between visual prognosis and changes in retinal volume. MethodsThe 120 patients(121 eyes) of BRVO-ME were recruited from July 2020 to October 2022 at the Affiliated Hospital of Weifang Medical University. The clinical data of patients were retrospectively examined for changes in best-corrected visual acuity (BCVA), retinal volume, and CRT at 1 day, 1 week, 1 month, 3 months, 6 months and 1year after treatment. FindingsVisual acuity improved gradually and became steady approximately 1 months after treatment, whereas retinal volume decreased gradually in both the outer and full layers and stabilized around 6 month after treatment. The decline in retinal volume and CRT was more visible in the deeper layers than in the inner levels. A higher correlation was observed between retinal volume and BCVA than between CRT and BCVA. BCVA after one year of treatment had a high correlation with baseline outer retinal volume. InterpretationTreatment of BRVO-ME with ranibizumab is highly effective, and the recovery of visual function was depends more on early treatment. The outer retina is the major site of edema. Changes in retinal volume may serve as a better predictor of visual prognosis than changes in CRT. Baseline ourter retinal volume is correlated with long-term visual prognosis.

Age-Related Retinal Layer Thickness Changes Measured by OCT in APPNL-F/NL-F Mice: Implications for Alzheimer's Disease.

In Alzheimer's disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans.

Swept-source optical coherence tomography early findings in patients with carotid artery disease.

Ocular ischemic syndrome can be the first and only hint of life-threatening carotid artery disease. The early recognition of carotid stenosis-related retinal signs, as well as the comprehension of the pathophysiology behind retinal changes could become relevant for physicians to predict the risk of stroke. The aim of this study is to assess the carotid artery disease-induced early structural retinochoroidal changes by means of swept-source optical coherence tomography (SS-OCT). A prospective observational study was conducted in 72 eyes with carotid stenosis. According to the degree of stenosis, the participants were divided into a normal group (34 eyes), a mild-moderate stenosis group (22 eyes), a severe stenosis group (16 eyes). SS-OCT and OCTA were performed to scan macular fovea. Central macular thickness (CMT), subfoveal choroidal thickness (SCT) and foveal avascular zona (FAZ) area were the major measurements for our study. CMT was significantly thicker in group 3 when compared to group 2 and 1. SCT was significantly thinner in group 3 vs group 1, being thicker in group 2 when compared to group 1. No significant differences were obtained when comparing FAZ in the superficial and middle capillary plexus although it was significant when comparing the FAZ in the deep capillary plexus between group 1 and 3. internal carotid artery stenosis greater than 70% leads to a significant increase in CMT and a decrease in SCT prior the development of clinical findings of ocular ischemia syndrome.

Retinal Microstructural Changes Reflecting Treatment-Associated Cognitive Dysfunction in Patients with Lower-Grade Gliomas

PurposeTo determine whether microstructural retinal changes, tumor features, and Apolipoprotein E (APOE) ε4 polymorphism are correlated with clinically detectable treatment-associated cognitive dysfunction (TACD) in patients with lower-grade gliomas. DesignCohort study. Participants and ControlsSixteen lower-grade glioma patients at a U.S. academic Ophthalmology department between January 2021 and November 2023. Normal controls were recruited from convenient sampling. MethodsMontreal Cognitive Assessment (MoCA) scores and retinal changes were assessed in 6-months intervals. APOE genotyping was performed, and tumor details were recorded. Partial least-squares discriminant (PLSD) model was established to evaluate the association between TACD with APOE genotype, ophthalmic, and tumor features. Main Outcome MeasuresThe main outcome measure was cognitive status as measured by the MoCA score and analyzed in relation to ophthalmic measurements, tumor features, and APOE genotype. ResultsMedian time to first eye exam was 34 months (2–266) from tumor diagnosis and 23 months (0–246) from radiation. Nine patients (56%) had abnormal cognition (MoCA <26/30). MoCA scores were significantly worse in patients with temporal (22±7.2) than frontal lobe tumors (26±3.1, p=0.02) and those with oligodendrogliomas (22±4.1) than astrocytomas (26±3.6, =0.02). Patients with TACD had significant radial peripapillary capillary density loss (45%±4.6) compared to those with normal cognition (49%±2.6, p=0.02). A PLSD model correlated MoCA scores with retinal nerve fiber thickness, intraocular pressure, foveal avascular zone, best-corrected visual acuity, months since first diagnosis, and tumor pathology (oligodendroglioma or not). Using these features, the model identified patients with TACD with 77% accuracy. APOE genotyping showed: two ε2/ε3 (13%), ten ε3/ε3 (63%), and one ε3/ε4 (6%). ConclusionRetinal microstructural changes may serve as biomarkers for TACD in patients with lower-grade gliomas. Temporal lobe tumors and oligodendrogliomas may increase susceptibility to TACD. Utilization of retinal markers may enhance TACD diagnosis, progression monitoring, and inform management of lower-grade glioma patients. A larger study with serial eye exams is warranted to evaluate the role of APOE ε4 and develop a predictive model.

Variation of retinal and choroidal microvascularization after an exercise stress test in patients with effort angina.

To describe retinal and choroidal vascular changes following an exercise stress test (ET) in patients with effort angina and to determine whether optical coherence tomography angiography (OCT-A) could play a role in the prediction of ischemic cardiac events. Prospective comparative study including patients with effort angina. All patients underwent OCT-A before and after an ET was performed. Blood flow, intercapillary spaces, and vessel density were analyzed in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Vessel density in the choriocapillaris and the parameters of the central avascular zone (CAZ) were also analyzed. Of the 38 eyes included in the study, a decrease in blood flow was found in 39.5% in the large SCP vessels, in 50% in the capillaris of the SCP, and in 81.6% in the DCP. An increase in intercapillary spaces was observed in the SCP in 68.4% of eyes and in the DCP in 55.3% of eyes. A statistically significant decrease in the DCP density was observed after an ET (p = 0.03). There were no significant modifications in the CAZ parameters, the SCP density, nor the choriocapillaris density. Patients with a positive ET had a decreased DCP density in 83.3%. Among patients with an increased DCP density, 92.85% had a negatif ET. This pilot study suggests that DCP density significantly decreases after an ET. The DCP appears to be most affected in patients with effort angina. A larger trial is needed to further investigate these hypotheses.

Hyperglycemia-independent neonatal streptozotocin-induced retinopathy (NSIR) in rats.

Introduction: Chemicals, such as MNU (N-methyl-N-nitrosourea) and NaIO3 (sodium iodate), are widely used to induce retinal degeneration in rodents. Streptozotocin (STZ) is an analog of N-acetyl glucosamine in which an MNU moiety is linked to a hexose and has a special toxic effect on insulin-producing pancreatic β-cells. It is commonly used to induce hyperglycemia to model diabetes. While intracerebroventricular injection of STZ can produce Alzheimer's disease independent of hyperglycemia, most retinal studies using STZ focus on the effects of hyperglycemia on the retina, but whether STZ has any impact on retinal cells independent of hyperglycemia is unknown. We aimed to investigate the role of cytotoxicity of STZ in rat retina. Methods: Intravitreal or subcutaneous injection of STZ was performed on newborn rats. Electroretinogram (ERG) and H&E staining investigated retinal function and morphological changes. Retinal cell types, cell death, proliferation, inflammation, and angiogenesis were studied by immunostaining. RNA sequencing was performed to examine the transcriptome changes of retinal cells after intravitreal injection of STZ. Results: Intravitreal (5μg or 10μg) or subcutaneous (30mg/kg) injection of STZ at the early stage of newborn rats couldn't induce hyperglycemia but caused NSIR (Neonatal STZ-induced retinopathy), including reduced ERG amplitudes, retinal rosettes and apoptosis, cell cycle arrest, microglial activation, and delayed retinal angiogenesis. STZ did not affect the early-born retinal cell types but significantly reduced the late-born ones. Short-term and long-term hyperglycemia had no significant effects on the NSIR phenotypes. RNA sequencing revealed that STZ induces oxidative stress and activates the p53 pathway of retinal cells. Locally or systemically, STZ injection after P8 couldn't induce SINR when all retinal progenitors exit the cell cycle. Conclusion: NSIR in rats is independent of hyperglycemia but due to STZ's direct cytotoxic effects on retinal progenitor cells. NSIR is a typical reaction to STZ-induced retinal oxidative stress and DNA damage. This significant finding suggests that NSIR may be a valuable model for studying retinal progenitor DNA damage-related diseases, potentially leading to new insights and treatments.

Changes of individual retinal layer thickness post-uneventful cataract surgery determined by spectral-domain optical coherence tomography over a 3-months period

PurposeTo evaluate retinal thickness changes of individual retinal layers using spectral-domain optical coherence tomography (SD-OCT) after uneventful cataract surgery over a 3-months period. DesignProspective cohort study. Methods41 patients who underwent uneventful cataract surgery were included. Retinal SD-OCT images of both eyes were acquired preoperatively, 1 day after surgery as well as 1 month and 3 months postoperatively. Changes of retinal layer thickness were estimated after semi-automated segmentation for the following individual layers in the central subfield (CS, 1 mm) and inner ring (IR, 1–3 mm) of the early treatment diabetic retinopathy study (ETDRS) grid: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), RNFL-GCL-IPL complex, inner nuclear layer (INL), outer plexiform layer (OPL), INL-OPL complex, outer nuclear layer (ONL), inner retina layer (IRL) and the total retina (TR). Furthermore, a sub-analysis with exclusion of patients devoid CME and an analysis in regard of patient age, lens status of the fellow eye, best corrected visual acuity and duration of surgery was conducted. ResultsThis study found significant alterations in all analysed retinal layers except for the RNFL (p = 0.33) and the GCL (p = 0.06) in the central subfield and the INL-OPL complex (p = 0.07) in the inner ring over the 3-months period (all p < 0.05). Retinal thickness decreases on the first postoperative day, followed by a significant increase 1 month after surgery and subsequent reduction at 3 months following uneventful cataract surgery could be observed. ConclusionThese results assume the hypothesis that the apex of inflammatory response, characterized by an augmentation in the thickness of individual retinal layers, occurs around 1 month after uneventful cataract surgery, and subsequently experience a reduction in activity. Therefore, we suggest that additional therapy for cystoid macular edema does not have to be initiated as early as the first month in mild cases.

Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment.

This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Ocular Inflammation and Oxidative Stress as a Result of Chronic Intermittent Hypoxia: A Rat Model of Sleep Apnea.

Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent complete or partial occlusion of the airway. Despite a recognized association between OSA and glaucoma, the nature of the underlying link remains unclear. In this study, we investigated whether mild OSA induces morphological, inflammatory, and metabolic changes in the retina resembling those seen in glaucoma using a rat model of OSA known as chronic intermittent hypoxia (CIH). Rats were randomly assigned to either normoxic or CIH groups. The CIH group was exposed to periodic hypoxia during its sleep phase with oxygen reduction from 21% to 10% and reoxygenation in 6 min cycles over 8 h/day. The eyes were subsequently enucleated, and then the retinas were evaluated for retinal ganglion cell number, oxidative stress, inflammatory markers, metabolic changes, and hypoxic response modulation using immunohistochemistry, multiplex assays, and capillary electrophoresis. Statistically significant differences were observed between normoxic and CIH groups for oxidative stress and inflammation, with CIH resulting in increased HIF-1α protein levels, higher oxidative stress marker 8-OHdG, and increased TNF-α. Pyruvate dehydrogenase kinase-1 protein was significantly reduced with CIH. No significant differences were found in retinal ganglion cell number. Our findings suggest that CIH induces oxidative stress, inflammation, and upregulation of HIF-1α in the retina, akin to early-stage glaucoma.

Metabolic plasticity in a Pde6bSTOP/STOP retinitis pigmentosa mouse model following rescue

ObjectiveRetinitis pigmentosa (RP) is a hereditary retinal disease characterized by progressive photoreceptor degeneration, leading to vision loss. The best hope for a cure for RP lies in gene therapy. However, given that RP patients are most often diagnosed in the midst of ongoing photoreceptor degeneration, it is unknown how the retinal proteome changes as RP disease progresses, and which changes can be prevented, halted, or reversed by gene therapy. MethodsHere, we used a Pde6b-deficient RP gene therapy mouse model and performed untargeted proteomic analysis to identify changes in protein expression during degeneration and after treatment. ResultsWe demonstrated that Pde6b gene restoration led to a novel form of homeostatic plasticity in rod phototransduction which functionally compensates for the decreased number of rods. By profiling protein levels of metabolic genes and measuring metabolites, we observed an upregulation of proteins associated with oxidative phosphorylation in mutant and treated photoreceptors. ConclusionIn conclusion, the metabolic demands of the retina differ in our Pde6b-deficient RP mouse model and are not rescued by gene therapy treatment. These findings provide novel insights into features of both RP disease progression and long-term rescue with gene therapy.

Histomorphology and Histomorphometrics of the retina in Juvenile and Adult African Giant Rats (Cricetomys gambianus)

Aging is accompanied with various forms of functional ultrastructural and morphological changes in the eye, including the retina, leading to vision deterioration. However, age related retinal degenerative changes requires further elucidation especially as all previous studies on age-related change of the retina were done in mutant mouse strain models of hereditary retinal degenerations. The potential of using African giant rats (AGRs) as models for ageing in the eye, especially retina, was explored in this study. A total of 14 AGRs divided into two age groups (juvenile and adult) were used to study the histomorphology and histomorphometrics of the retina as well as retinal astrocyte morphology and heterogeneity. Histological findings included retinal atrophy and hypoplasia, with cellular swellings of neuronal cell populations and astrocytes soma and ramifications in the retina of adult compared to juvenile AGR. We suggest that AGR be used as animal model for translational research into normal aging process of the retina, as well as to elucidate the process of age-related neuronal cells loss.

Retinal changes in anemia - A comparative cross sectional study using SD-OCT

Retinal changes in anemia - A comparative cross sectional study using SD-OCT

OCTA-based research on changes of retinal microcirculation in digestive tract malignancy

PurposeThis cross-sectional study measured retinal vessel density (VD) in patients with digestive tract malignancy by optical coherence tomography angiography (OCTA), and compared them with healthy controls to explore the retinal microcirculation changes in patients with digestive tract malignancy. Methods106 eligible participants were divided into three groups: gastric cancer (GC) group (36 individuals), colorectal cancer (CRC) group (34 individuals), and healthy control group (36 individuals). Angio 6 × 6 512 × 512 R4 and ONH Angio 6 × 6 512 × 512 R4 modes were performed to collect retinal vessel density data centered on fovea and papillary, respectively. The retina was automatically segmented into different layers (superficial vascular plexus (SVP), the inner retinal layer, radial peripapillary capillary plexus (RPCP), deep vascular plexus (DVP)) and areas to analyze. ResultsAt the optic nerve head (ONH) region, the VD of the inner retinal layer increased in both GC and CRC groups in all quadrants and areas. In the papillary area, VD in the inner retinal layer, SVP, and RPCP increased in the GC and CRC groups. In the parapapillary area, VD in the inner retinal layer increased in the GC and the CRC groups. Significant increase in the global VD were found in the GC group of the RPCP and SVP. Regarding the macular region, no statistical differences were observed in each layer. ConclusionsThe study suggested that retinal vessel density changed in patients with digestive tract malignancy, especially in the inner retinal layer of the ONH region, revealing the potential relevance of the relation between gastrointestinal cancer and retinal microcirculation.

Retinal Vascular and Structural Changes in the Murine Alzheimer's APPNL-F/NL-F Model from 6 to 20 Months.

Alzheimer's disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models.

Comparative analysis of changes in retinal layer thickness following femtosecond laser-assisted cataract surgery and conventional cataract surgery

BackgroundTo investigate the influence of femtosecond laser-assisted cataract surgery (FLACS) on macula by examining changes in retinal layers after FLACS and to compare these changes with those after conventional cataract surgery (CCS).MethodsThis study included 113 unrelated Korean patients with age-related cataract who underwent CCS or FLACS in Severance Hospital between September 2019 and July 2021. Optical coherence tomography was performed before and 1 month after surgery. The total retinal layer (TRL) was separated into the inner retinal layer (IRL) and outer retinal layer (ORL); moreover, the IRL was subdivided into the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer (INL), outer plexiform layer, and outer nuclear layer. We performed between-group comparisons of the postoperative thickness in each retinal layer and the postoperative differences in retinal thickness. The average retinal thickness of the four inner macular ring quadrants was used for comparative analysis.ResultsCompared with the CCS group, the FLACS group exhibited a thicker ORL (P = 0.004) and a thinner INL (P = 0.007) after surgery. All retinal layer thickness values showed significant postoperative changes regardless of the type of surgery (P < 0.05). The postoperative increase in TRL and IRL thickness was significantly smaller in the FLACS group than in the CCS group (P = 0.027, P = 0.012).ConclusionsThe 1-month postoperative retinal changes were less pronounced in the FLACS group than in the CCS group.

Ophthalmic assessment of an intensive care ward patients in the first and last wave of the COVID-19. Do they have a difference?

BACKGROUND: The new coronavirus infection (COVID-19) gained the pandemic status in 2020, and despite the fact that since then the virus has become less pathogenic, its virulence has increased by 2023. Well-vascularized organs and tissues, including the retina, represent the target for coronavirus. The etiopathogenesis of COVID-associated retinopathy, first described in 2021, still remains poorly understood, and its forms and occurrence frequency during different periods of the infectious process vary greatly. AIM: To identify the main characteristics of the COVID-associated retinopathy in patients with moderate and severe COVID-19 course during the acute period of the disease. MATERIALS AND METHODS: The study, conducted in 2021 (group 1) and 2023 (group 2), included patients with confirmed COVID-19 of moderate to severe course during the first 7 days from the onset of symptoms. Group 1 included 46 people, mean age 65.5 years, and group 2 included 55 people, mean age 69.3 years. The ophthalmologic examination was carried out in the “red zone” and intensive care unit, and included examination of the anterior segment of the eye, indirect ophthalmoscopy, and fundus photography using a portable hand-held digital fundus camera (Smartscope M5, Optomed, Finland). Hypertension, diabetes mellitus, volume of lung damage, invasive mechanical ventilation, and anticoagulant therapy were considered as conditions affecting retinal microcirculation. RESULTS: The observation groups were homogeneous in terms of gender, age, and concomitant diseases. The incidence of ophthalmoscopic findings in group 1 was 17.3%, and in group 2 — 12.7%. Most often, during the first 7 days of the disease, signs of angiopathy were observed: dilatation of blood vessels, irregularity of their diameter and tortuosity. Among focal changes, there were multiple retinal hemorrhages (6.5% and 3.6%) and cotton wool spots (4.3% and 5.4%). In patients with fundus changes, diabetes mellitus was significantly less common (in group 1, 25% vs. 39%, p 0.001; in group 2, 28% vs. 44%, p 0.001), as well as arterial hypertension (in group 1, 55% vs. 66%, p = 0.003; in group 2 28% vs. 83%, p 0.001). In group 1, there was a higher proportion of patients treated in intensive care unit, as in group 2 (37% vs. 17%, p 0.001), but in group 2, patients with identified retinal changes were more likely to receive therapeutic doses of anticoagulants (33% vs. 12%, p 0.001). CONCLUSION: The main characteristics of COVID-associated retinopathy in patients with moderate to severe COVID-19 during the acute period of the disease are dilatation and pathological tortuosity of the retinal arteries and veins, intraretinal hemorrhages and cotton wool spots. The connection between COVID-associated retinopathy and concomitant to the infectious process cardiovascular conditions has not been established. Retinopathy associated with coronavirus infection, with absolute similarity of clinical manifestations, was significantly more common in 2021 than in 2023.

Retinal vascular reactivity in carriers of X-linked inherited retinal disease - a study using optical coherence tomography angiography.

Female carriers of X-linked inherited retinal diseases (IRDs) can show highly variable phenotypes and disease progression. Vascular reactivity, a potential disease biomarker, has not been investigated in female IRD carriers. In this study, functional optical coherence tomography angiography (OCT-A) was used to dynamically assess the retinal microvasculature of X-linked IRD carriers. Genetically confirmed female carriers of IRDs (choroideremia or X-linked retinitis pigmentosa), and healthy women were recruited. Macular angiograms (3x3mm, Zeiss Plex Elite 9000) were obtained in 36 eyes of 15 X-linked IRD female carriers and 21 age-matched control women. Two tests were applied to test vascular reactivity: (i) mild hypoxia and (ii) handgrip test, to induce a vasodilatory or vasoconstrictive response, respectively. Changes to vessel density (VD) and vessel length density (VLD) were independently evaluated during each of the tests for both the superficial and deep capillary plexuses. In the control group, the superficial and deep VD decreased during the handgrip test (p<0.001 and p=0.037, respectively). Mean superficial VLD also decreased during the handgrip test (p=0.025), while the deep plexus did not change significantly (p=0.108). During hypoxia, VD and VLD increased in the deep plexus (p=0.027 and p=0.052, respectively) but not in the superficial plexus. In carriers, the physiologic vascular responses seen in controls were not observed in either plexus during either test, with no difference in VD or VLD noted (all p>0.05). Functional OCT-A is a useful tool to assess dynamic retinal microvascular changes. Subclinical impairment of the physiological vascular responses seen in carriers of X-linked IRDs may serve as a valuable clinical biomarker.

Wide-Field Optical Coherence Tomography Imaging Improves Rate of Change Detection in Progressing Glaucomatous Eyes Compared With Standard-Field Imaging.

To compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images. Forty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included. Thirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27). In this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.

Assessment of Blood Flow Velocity in Retinal Vasculitis Using the Retinal Function Imager-A Pilot Study.

Background: This pilot study aimed to evaluate the Retinal Function Imager (RFI) for visualizing retinal vasculature and assessment of blood flow characteristics in patients with retinal vasculitis. The RFI is a non-invasive imaging device measuring the blood flow velocity (BFV) in secondary and tertiary retinal vessels using hemoglobin as an intrinsic motion-contrast agent. Methods: To test the feasibility of the RFI for patients with retinal vasculitis, capillary perfusion maps (nCPMs) were generated from 15 eyes of eight patients (five females; mean age: 49 ± 12 years) with a mean uveitis duration of 74 ± 85 months. Five of these patients had birdshot chorioretinopathy, and three had primarily non-occlusive venous retinal vasculitis of unknown origin. To reflect that the BFV may be more reduced in patients with prolonged disease, patients were classified into a short-term (uveitis duration: 8-15 months) and a long-term uveitis group (uveitis duration: 60-264 months). Data were compared with healthy controls (16 eyes of 11 patients; mean age 45 ± 12 years; 8 females). Results: The mean BFV in the controls was 3.79 ± 0.50 mm/s in the retinal arteries and 2.35 ± 0.44 mm/s in the retinal veins, which was significantly higher compared to the retinal vasculitis group. Patients revealed an arterial BFV of 2.75 ± 0.74 mm/s (p < 0.001) and a venous BFV of 1.75 ± 0.51 mm/s (p = 0.016). In the short-term group, a trend towards a decreased venular and arteriolar BFV was seen, while a significant reduction was observed in the long-term group. The patients' microvasculature anatomy revealed by the nCPMs appeared unevenly distributed and a lower number of blood vessels were seen, along with a lower degree of complexity of their branching patterns, when compared with controls. Conclusions: This study demonstrated a reduction in venular and arteriolar BFVs in patients with retinal vasculitis. BFV alterations were already observed in early disease stages and became more pronounced in progressed disease. Additionally, we showed that retinal microvasculature changes may be observed by nCPMs. Retinal imaging with the RFI may serve as a diagnostic and quantifying tool in retinal vasculitis.