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Table 2 Studies of retinal and cerebral blood flow changes in sepsis, other haemodynamic disturbances, and other inflammatory disorders

From: Retinal blood flow in critical illness and systemic disease: a review

Sepsis studies Species Imaging modality Pathology Metrics measured Findings
Taccone et al. [10] Animal (ovine) SDF videomicroscopy of the cerebral cortex—Microscan; MicroVision Medical Septic model Total perfused vessel density
Functional capillary density
Small perfused vessels
Perfused capillaries
Septic animals showed progressive reduction in all metrics compared to control group, suggesting cerebral microcirculatory impairment
Crippa et al. [12] Human Transcranial Doppler of the middle cerebral artery—Compumedics DWL, Dresden, Germany SABD Cerebral autoregulation by blood flow velocity and mean flow index Cerebral autoregulation impaired, cerebral blood flow increased and SABD in at least 50% of septic patients
No difference in mean flow index between survivors and non-survivors
Simkiene et al. [34] Human Portable IDF of conjunctival microcirculation—Cytocam®, Braedius Medical, Huizen, The Netherlands
Fundus imaging—Optomed Aurora (Optomed Oy, Oulu, Finland)
Sepsis or septic shock MFI
Retinal arteriolar and venular calibre
Lower MFI, TVD and PVD in all septic patients than healthy controls
Lower MFI in non-survivors than survivors
TVD and PVD and arteriolar calibre associated
De Backer and Creteur [107] Human OPS imaging of sublingual mucosa—Cytoscan ARII; Cytometrics Sepsis, pre-cardiac surgery patients, ICU controls Vascular density Septic patients had decreased vascular density compared with all other groups
Kanoore Edul et al. [108] Human SDF microscopy imaging of sublingual mucosa—Microscan; MicroVision Medical Septic shock MFI
Perfused capillary density
Hypoperfusion and microcirculatory abnormalities in septic patients compared with healthy controls, which were more severe in non-survivors
Hessler et al. [112] Ovine Portable IDF of sublingual and conjunctival microcirculation—Cytocam®, Braedius Medical, Huizen, The Netherlands Sepsis and haemorrhagic shock MFI
Lower PVD, PPV and MFI in haemorrhagic and septic shock in mouth and conjunctiva than control group
No change in TVD
Pranskunas et al. [113] Pig SDF videomicroscopy of sublingual, conjunctival, jejunal and rectal microcirculation—Microscan; Microvision Medical, Amsterdam, The Netherlands Sepsis MFI
Lower MFI and PPV observed in all locations in the sepsis group than control group, with the lowest MFI in sublingual region
No change in TVD
Sublingual associates with conjunctival MFI
Taccone et al. [55] Animal (ovine) SDF videomicroscopy of cerebral cortex—MicroScan (MicroVisionMedical, Amsterdam, The Netherlands) Sepsis Mean flow index
Proportion of small perfused vessels
Functional capillary density
Lactate/pyruvate ratio (tissue hypoxia)
Cerebral functional capillary density and proportion of small perfused vessels decreased significantly from baseline to shock onset, compared with control group
Brain oxygen levels reduced while lactate/pyruvate ratio increased in septic animals
Suggests impaired cerebral microcirculation in septic animals
Alnawaiseh et al. [123] Animal (ovine) OCTA—RTVue XR Avanti with Angiovue, Optovue Inc Haemorrhagic shock Flow density Reduced flow density of the superficial retina after shock induction, which recovered after resuscitation
Park [124] Animal (rat) OCTA (manufacturer not specified) Haemorrhagic shock and sepsis BFI against MAP and lactate As MAP decreased in the haemorrhagic shock model, BFI of the choroid but not retinal artery decreased and was associated with increased lactate concentration in sepsis
Erikson et al. [125] Human FFA—HRA 2–00153; Heidelberg Engineering, Heidelberg Sepsis RAFT
Inflammatory markers
Retinal abnormalities observed in half of the patients with sepsis, being more common in those showing PRAFT
Patients with PRAFT had lower levels of CRP and IL-6 compared with patients who had SRAFT, suggesting impaired inflammatory response
Simkiene et al. [126] Human Fundus imaging—Optomed Aurora (Optomed Oy, Finland) Sepsis Retinal arteriolar and venular calibre
Retinal vascular length density
Retinal arteriolar calibre higher in septic than healthy control patients, but venular calibre did not differ
Septic patients had lower retinal vascular length density
Other haemodynamic disturbances studies Species Imaging modality Pathology Metrics measured Findings
Chua et al. [15] Human OCTA—AngioVue; Optovue, Inc Systemic hypertension Retinal vessel density Vessel density was reduced in patients with poorly controlled blood pressure compared with those with well controlled blood pressure
Terheyden [114] Human OCTA—PLEX Elite 9000, Carl Zeiss Meditec Inc Systemic hypertensive crisis Retinal vessel density
Skeletal density
Vessel density index
Reduced skeletal density in the S-RL and D-RL and reduced vessel density in the D-RL in hypertensive patients compared with healthy controls
Alnawaiseh [115] Human OCTA—RTVue XR Avanti with AngioVue, Optovue, Inc AF FAZ area
Flow density
No difference found in FAZ area between groups
Flow density in the superficial retina and ONH were lower in the AF group
Arnould and Guenancia [116] Human/ OCTA—Cirrus HD-OCT, model 5000, Carl Zeiss Meditec ACS Retinal vascular density of SCP Vascular density of SCP negatively associated with cardiovascular risk factors and left ventricular ejection fraction at admission
Wang et al. [117] Human OCTA—AngioVue, Optovue, Inc Coronary heart disease Retinal vessel density
Flow area
Some early stage coronary heart disease patients showed reduced vessel density, and reduced choroidal vessel density and blood flow
Lin [120] Human OCTA (manufacturer not specified) High-risk pregnancies Retinal vessel perfusion density/vessel length density of SVP, ICP and DCP Reduced SVP perfusion density and vessel length density in high-risk pregnancy individuals compared with low-risk pregnancy individuals
Other inflammatory disorders studies Species Imaging modality Pathology Metrics measured Findings
Kılınç Hekimsoy et al. [118] Human OCTA—XR Avanti AngioVue Systemic sclerosis FAZ area and perimeter
Vessel density
Patients with systemic sclerosis showed significantly decreased vessel density compared with controls, but there was no difference in FAZ area or perimeter
Nakayama [16] Human OCT/OCTA—Topcon Triton, Topcon IBD FAZ area Patients with active disease showed decreased FAZ area compared with patients in remission
  1. Summary of studies investigating retinal and cerebral blood flow and microvascular changes in sepsis, other haemodynamic disturbances and other inflammatory disorders.
  2. SDF, sidestream dark field; SABD, sepsis-associated brain dysfunction; ICU, intensive care unit; OPS, orthogonal polarisation spectral; ICU, intensive care unit; OCTA, optical coherence tomography angiography; S-RL, superficial retinal layer; D-RL, deep retinal layer; AF, atrial fibrillation; FAZ, foveal avascular zone; IDF, incident dark field; MFI, microvascular flow index; TVD, total vessel density; PVD, perfused vessel density; PPV, proportion of perfused vessels; ONH, optic nerve head; ACS, acute coronary syndrome; SCP, superficial capillary plexus; OCT, optical coherence tomography; IBD, inflammatory bowel disease; SVP, superficial vascular plexus; ICP, intermediate capillary plexus; DCP, deep capillary plexus; BFI, blood flow index; MAP, mean arterial pressure; FFA, fundus fluorescein angiography; RAFT, retinal arterial filling time; PRAFT, prolonged RAFT; SRAFT, short RAFT