SARS-CoV-2 and COVID-19: A Narrative Review.

The World Health Organisation has reported that the viral disease known as COVID-19, caused by SARS-CoV-2, is the leading cause of death by a single infectious agent. This narrative review examines certain components of the pandemic: its origins, early clinical data, global and UK-focussed epidemiology, vaccination, variants, and long COVID.

Angiogenesis, Metabolism, Endothelial and Platelet Markers in Diabetes and Cardiovascular Disease.

Introduction: Diabetes is a leading risk factor for cardiovascular disease (CVD), the pathophysiology of both being linked to metabolic, endothelial, renal, angiogenic and platelet abnormalities. We hypothesised that abnormalities in these systems are more adverse in those whose CVD is compounded by diabetes, compared to those with diabetes or CVD alone. Materials and methods: Serum or plasma from 66 patients with diabetes alone, 76 with CVD alone, and 70 with both diabetes and CVD i.e. diabetic cardiovascular disease, was probed for markers of angiogenesis [angiopoietin 1 and 2, vascular endothelial growth factor (VEGF) and endoglin], metabolic [soluble receptor for advanced glycation products (sRAGE), leptin, lipocalin-2, interleukin-8, and cystatin-C], the endothelium (von Willebrand factor, endothelial microparticles and soluble E selectin)], and the platelet (platelet microparticles and soluble P selectin) by ELISA, Luminex or flow cytometry. Results: VEGF (p = 0.04), von Willebrand factor (p = 0.001) and endothelial microparticles (p = 0.042) were all higher in diabetic cardiovascular disease than in diabetes alone and cardiovascular disease alone. Soluble E selectin was higher in diabetic cardiovascular disease than in diabetes alone (p = 0.045), whilst cystatin-C (p = 0.004) and soluble P selectin (p < 0.001) were higher in diabetes and diabetic cardiovascular disease than in cardiovascular disease alone. There were no differences in angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, or interleukin-8. Conclusion: Angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, interleukin-8, and cystatin-c cannot differentiate diabetes from cardiovascular disease, or both conditions combined. Our data point to a more adverse endothelial (von Willebrand factor, endothelial microparticles), and angiogenic profile (VEGF) in those with diabetic cardiovascular disease, supporting the view that this group should be targeted more aggressively.

Oxygen saturation in retinal vessels and their correlation with endothelial microparticles in diabetes mellitus and/or cardiovascular disease.

PURPOSE: Retinal oxygen supply is a critical requirement in ocular function, and when inadequate can lead to retinopathy. Endothelial dysfunction is a leading pathophysiology in diabetes and cardiovascular disease and may be assessed by endothelial microparticles (EMPs). We hypothesised links between retinal vessel oxygenation and EMPs, expecting these indices to be more adverse in those with both DM and CVD. METHODS: Plasma from 34 patients with diabetes mellitus alone (DM), 40 with cardiovascular disease (CVD) alone and 36 with DM plus CVD was probed for EMPs by flow cytometry, but also for vascular markers soluble E-selectin (sEsel) and von Willebrand factor (vWf) (both ELISA). Retinal vessel fractal dimension, lacunarity, calibres and oxygen saturation were assessed from monochromatic and dual wavelength imaging respectively, intra-ocular pressure by was measured by rebound tonometry (I-CARE). RESULTS: There was no difference in oxygenation (arterial p = 0.725, venous p = 0.264, arterio-venous difference 0.375) between the groups, but there were differences in EMPs (p = 0.049), vWf (p = 0.004) and sEsel (p = 0.032). In the entire cohort, and in diabetes alone, EMPs correlated with venous oxygenation (r = 0.24, p = 0.009 and r = 0.43, p = 0.011 respectively), while in DM + CVD, sEsel correlated with venous oxygenation (r = 0.55, p = 0.002) and with the arterial-venous difference (r = -0.63, p = 0.001). In multivariate regression analysis of vascular markers against retinal oximetry indices in the entire group, EMPs were positively linked to venous oxygenation (p = 0.037). CONCLUSIONS: Despite differences in systemic markers of vascular function between DM, CVD and DM + CVD, there was no difference in arterial or venous retinal oxygenation, or their difference. However, EMPs were linked to venous oximetry, and may provide further insight into the mechanisms underlying diabetes and diabetic retinopathy.

Comparative quantification of focal and diffuse visual field loss by the SPARK Precision threshold algorithm and SITA.

PURPOSE: The aims of this paper were to examine focal and diffuse visual field loss in terms of threshold agreement between the widely used SITA Standard Humphrey Field Analyser (HFA) threshold algorithm with the SPARK Precision algorithm (Oculus Twinfield 2). METHODS: A total of 39 treated glaucoma patients (34 primary open angle and 5 primary angle closure glaucoma) and 31 cataract patients without glaucoma were tested in succession with the Oculus Twinfield 2 (Oculus Optikgeräte GmbH, Wetzlar, Germany) using the SPARK Precision algorithm and with the HFA 3 (Carl Zeiss Meditec, Dublin, CA) using the 30-2 SITA Standard algorithm. RESULTS: SPARK Precision required around half the testing time of SITA Standard. There was a good correlation between the MS of the two threshold algorithms but MD and PSD were significantly less severe with SPARK Precision in both glaucoma (focal field loss) and cataract (diffuse field loss) groups (p < 0.001). There was poor agreement for all global indices (MS, MD and PSD) between the two algorithms and there was a significant proportional bias of MD in the glaucoma group and PSD in both glaucoma and cataract groups. The pointwise sensitivity analysis yielded higher threshold estimates in SPARK Precision than in SITA Standard in the nasal field. Classification of glaucoma severity using AGIS was significantly lower with SPARK Precision compared to SITA Standard (p < 0.001). CONCLUSION: SITA renders deeper defects than SPARK. Compared to the SITA Standard threshold algorithm, SPARK Precision cannot quantify early glaucomatous field loss. This may be due to the mathematical linear interpolation of threshold sensitivity or deeper scotomas due to the plateau effect caused by the reduced dynamic range of the Twinfield 2 perimeter. Although not of clinical significance in early glaucoma, the plateau effect may hinder the long-term follow-up of patients during disease progression.

The relationship of systemic markers of haemostasis with retinal blood vessel responses in cardiovascular disease and/or diabetes.

Background Hypercoagulability is a leading factor in diabetes and cardiovascular disease. Retinal vessel responses to flickering light are an important tool for assessing ocular function. We hypothesised a significant relationship between systemic markers of haemostasis and retinal vessel function. Methods Intra-ocular pressure and retinal microcirculation function were measured in 116 patients with diabetes and/or cardiovascular disease using unstimulated and stimulated arterial and venous retinal vessel responses to flickering light. Haemostasis was evaluated by platelet microparticles, soluble P selectin, and five functional markers of fibrin clot formation and lysis, hyperglycaemia by HbA1c. Results Intra-ocular pressure was linked to the rates of clot formation (p = 0.006) and clot dissolution (p = 0.013) whilst central retinal vein equivalent was linked to HbA1c (p = 0.017). In the first of three flickering light cycles only, arterial baseline diameter fluctuation was linked to the lag time to clot formation (p = 0.017), whilst maximum venous dilatation was linked to HbA1c (p = 0.001) and clot density (p = 0.011). HbA1c was linked to venous dilatation amplitude (p = 0.003). There were no significant links between any ocular index and any platelet index. Conclusions In addition to glycaemia, several haemostasis measures, but no measures of platelet activity, are linked to ocular and retinal blood vessel indices in patients with diabetes and/or cardiovascular disease. These associations may have pathophysiological significance.

Retinal vessel diameters and reactivity in diabetes mellitus and/or cardiovascular disease.

BACKGROUND: Retinal vessel calibre and vascular dilation/constriction in response to flicker light provocation may provide a measure distinguishing patients suffering from diabetes mellitus and/or cardiovascular disease. METHODS: One hundred and sixteen age and sex matched patients with diabetes mellitus (DM), cardiovascular disease (CVD) and both DM and CVD (DM + CVD) underwent systemic and intraocular pressure measurements. Retinal vessel calibres were assessed using a validated computer-based program to compute central retinal artery and vein equivalents (CRVE) from monochromatic retinal images. Vessel dilation and constriction responses to flicker light provocation were assessed by continuous retinal vessel diameter recordings. Plasma endothelial markers von Willebrand factor (vWf) and soluble E selectin (sEsel) were measured by ELISA. RESULTS: Retinal vessel calibres were comparable across groups but CRVE correlated significantly with disease duration in DM patients (r = 0.57, p < 0.001). Patients suffering DM only exhibited reduced arterial vasomotion at rest and reduced arterial constriction following flicker light induced vessel dilation compared to patients with CVD and those suffering both CVD + DM (p = 0.030). Patients suffering from CVD + DM exhibited significant differences between each flicker cycle in regards to arterial maximum constriction (p = 0.006) and time needed to reach arterial maximum dilation (p = 0.004), whereas the other two groups did not show such inconsistencies between individual flicker cycles. vWf was raised in CVD + DM compared to the other two groups (p ≤ 0.02), whilst sEsel was raised in CVD + DM compared to DM alone (p = 0.044). CONCLUSIONS: Dynamic retinal vascular calibres as obtained by continuous diameter measurements using flicker light provocation can reveal subtle differences between groups suffering from CVD with and without DM. This difference in reaction pattern and lack of arterial constriction in DM may provide a suitable marker to monitor progression.

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses.

PURPOSE: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease. METHODS: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index. RESULTS: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p < 0.05). Arterial reaction time was linked to serum creatinine (p = 0.036) and eGFR (p = 0.039); venous reaction time was linked to creatinine clearance (p = 0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p < 0.001 and p = 0.003, respectively) and the dilatation amplitude (p = 0.038 and p = 0.048, respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p = 0.004) and dilatation amplitude (p = 0.017), vWf was linked to the maximum constriction response (p = 0.016), and creatinine clearance to the baseline diameter fluctuation (p = 0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p = 0.022). CONCLUSIONS: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.

Abnormal retinal vascular function and lipid levels in a sample of healthy UK South Asians.

BACKGROUND/AIMS: To investigate ethnic differences in retinal vascular function and their relationship to traditional risk indicators for cardiovascular disease (CVD). METHODS: A total of 90 normoglycaemic subjects (45 South Asian (SA) and 45 age- and gender-matched white Europeans (WEs)) were recruited for the present study. Retinal vessel reactivity to flickering light was assessed by means of the dynamic retinal vessel analyser according to a modified protocol. Fasting plasma glucose, triglycerides (TG), total, LDL and HDL cholesterol were also measured in all individuals. RESULTS: SA individuals showed higher fasting triglyceride (p=0.001) and lower HDL levels (p=0.007), leading to a higher TG:HDL-C ratio (p=0.001) than age-matched WE subjects. Additionally, in SAs, the retinal arterial reaction time in response to flicker stimulation was significantly longer in the last flicker cycle than in the WEs (p=0.039), and this change correlated positively with measured plasma TG levels (r=0.60; p=0.01). No such relationship was observed in the WEs (p>0.05). CONCLUSION: Even in the absence of overt vascular disease, in otherwise healthy SAs there are potential signs of retinal vascular function impairment that correlates with established plasma markers for CVD risk.