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To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24–48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 µm, p = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients. [ABSTRACT FROM AUTHOR]

Primary blast injury (caused by the initial rapid increase in pressure following an explosive blast) to the retina and optic nerve (ON) causes progressive visual loss and neurodegeneration. Military personnel are exposed to multiple low-overpressure blast waves, which may be in quick succession, such as during breacher training or in combat. We investigated the necroptotic cell death pathway in the retina in a mouse repeated primary ocular blast injury (rPBI) model using immunohistochemistry. We further evaluated whether intravitreal injections of a potent necroptosis inhibitor, Necrostatin-1s (Nec-1s), protects the retina and ON axons by retinal ganglion cells (RGC) counts, ON axonal counting and optical coherence tomography (OCT) analysis of vitreous haze. Receptor interacting protein kinase (RIPK) 3, increased in the inner plexiform layer 2 days post injury (dpi) and persisted until 14 dpi, whilst RIPK1 protein expression did not change after injury. The number of degenerating ON axons was increased at 28 dpi but there was no evidence of a reduction in the number of intact ON axons or RNA-binding protein with multiple splicing (RBPMS)+ RGC in the retina by 28 dpi in animals not receiving any intravitreal injections. But, when intravitreal injections (vehicle or Nec-1s) were given there was a significant reduction in RBPMS+ RGC numbers, suggesting that rPBI with intraocular injections is damaging to RGC. There were fewer RGC lost after Nec-1s than vehicle injection, but there was no effect of Nec-1s or vehicle treatment on the number of degenerating axons. OCT analysis demonstrated no effect of rPBI on vitreous haze, but intravitreal injection combined with rPBI increased vitreous haze (P = 0.004). Whilst necroptosis may be an active cell death signalling pathway after rPBI, its inhibition did not prevent cell death, and intravitreal injections in combination with rPBI increased vitreous inflammation and reduced RBPMS+ RGC numbers, implying intravitreal injection is not an ideal method for drug delivery after rPBI. • The retina and optic nerve can be injured after repeated primary blast injury (rPBI). • Retinal necroptosis protein RIPK3 increased after rPBI. • Intravitreal injections and rPBI can cause additive injury with increased cell death and inflammation. • Treatment with pharmacological necroptosis inhibitor, Necrostatin-1s, may provide some retinal ganglion cell neuroprotection. [ABSTRACT FROM AUTHOR]

Purpose: Investigate the association between the optical coherence tomography angiography (OCTA) metrics derived from different analysis programs to understand the comparability of studies using these different approaches., Methods: Secondary analysis of a prospective observational study (March 2018-September 2021). Forty-four right eyes and 42 left eyes from 44 patients were included. Patients were either undergoing upper gastrointestinal surgery with a critical care stay planned or were already in the critical care unit with sepsis. OCTA scans were obtained in an ophthalmology department or critical care setting. Fourteen OCTA metrics were compared within and between the programs, and agreement was measured by Pearson's R coefficient and intraclass correlation coefficient., Results: Correlation was highest between all Heidelberg metrics and Fractalyse (all >0.84), and lowest between Matlab skeletonized or foveal avascular zone metrics and all other measures (e.g., skeletal fractal dimension and vessel density at -0.02). Agreement between eyes was moderate to excellent in all metrics (0.60-0.90)., Conclusions: The significant variability between metrics and programs used for OCTA analysis demonstrates that they are not interchangeable and supports a recommendation for perfusion density metrics to be reported as standard., Translational Relevance: Agreement between different OCTA analyses is variable and not interchangeable. The high agreement between non-skeletonized vessel density metrics suggests that these should be routinely reported.

Purpose: Traumatic brain injury (TBI) causes structural damage and functional impairment in the visual system, often with retinal ganglion cell (RGC) degeneration occurring without visual symptoms. RGC degeneration is associated with reduced retinal blood-flow, however, it is not known whether reductions in perfusion precede or are secondary to neurodegeneration., Methods: We conducted a prospective observational single-center case series. Patients were included if they were admitted to the hospital after acute TBI and underwent ophthalmic clinical examination, including optical coherence tomography (OCT) and OCT angiography (OCTA) acutely and at follow-up. Ganglion cell layer thickness (GCL) thickness, vascular density in the superficial vascular plexus (SVP), and intermediate capillary plexus (ICP) were quantified., Results: Twenty-one patients aged 20 to 65 years (mean = 38 years) including 16 men and 5 women were examined less than 14 days after moderate to severe TBI, and again after 2 to 6 months. Macular structure and perfusion were normal at baseline in all patients. Visual function was abnormal at baseline in three patients and subsequent neurodegeneration and loss of perfusion corresponded to baseline visual function abnormalities. Nine patients (43%) had reduced macular GCL thickness at follow up. Perfusion in the SVP strongly associated with local GCL thickness. The strongest association of the SVP metrics was the sum of vessel density (P < 0.0001)., Conclusions: In cases of reduced visual function after TBI, macular perfusion remained normal until reductions in GCL thickness occurred, indicating that perfusion changes were secondary to local GCL loss.

Sepsis is a severe illness which results in alterations in the end organ microvascular haemodynamics and is associated with a high risk of mortality. There is currently no real-time method of monitoring microcirculatory perfusion during sepsis. Retinal microcirculation is closely linked to cerebral perfusion and may reflect systemic vascular alterations. Retinal perfusion can be assessed using the non-invasive imaging technique of optical coherence tomography angiography (OCTA). This narrative review aims to discuss the utility of using retinal imaging and OCTA in systemic illness and sepsis. OCTA can be used as a functional, non-invasive and real-time biomarker along with other haemodynamic parameters for assessing and managing patients with sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Courtie, Gilani, Veenith and Blanch.)