Retinal Vascular Signs as Screening and Prognostic Factors for Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Current Evidence

Background: The substantial burden of kidney disease fosters interest in new ways of screening for early disease diagnosis, especially by non-invasive imaging. Increasing evidence for an association between retinal microvascular signs and kidney disease prompted us to investigate the relevant current literature on such an association systematically by performing a meta-analysis of our findings. Methods: We scrutinized the current literature by searching PubMed and Embase databases from for clinical studies of the association between retinal microvascular signs and prevalent or incident kidney disease. After excluding cases that did not meet our criteria, we extracted relevant data from 42 published studies (9 prospective, 32 cross-sectional, and 1 retrospective). Results: Our investigation yielded significant associations between retinal vascular changes (including retinopathy and retinal vascular diameter) and kidney dysfunction (including chronic kidney disease (CKD), end-stage renal disease (ESRD), albuminuria, and estimated glomerular filtration rate (eGFR) decline). According to our meta-analysis, retinopathy was associated with ESRD (hazard ratio (HR) 2.12 (95% confidence interval CI; 1.39–3.22)) and with CKD prevalence in the general population (odds ratio (OR) 1.31 (95% CI; 1.14–1.50)), and specifically in type 2 diabetic patients (OR 1.68 (95% CI; 1.68–2.16)). CRAE was associated with prevalent CKD (OR 1.41 (95% CI; 1.09–1.82)). Conclusions: Our findings suggest that the retinal microvasculature can provide essential data about concurrent kidney disease status and predict future risk for kidney disease development and progression.

Retinal microvascular signs in COVID-19

Background/aimsTo explore if retinal findings are associated with COVID-19 infection.MethodsIn this prospective cross-sectional study, we recruited participants positive for COVID-19 by nasopharyngeal swab, with no medical history. Subjects underwent retinal imaging with an automated imaging device (3D OCT-1 Maestro, Topcon, Tokyo, Japan) to obtain colour fundus photographs (CFP) and optical coherence tomographic (OCT) scans of the macula. Data on personal biodata, medical history and vital signs were collected from electronic medical records.Results108 patients were recruited. Mean age was 36.0±5.4 years. 41 (38.0%) had symptoms of acute respiratory infection (ARI) at presentation. Of 216 eyes, 25 (11.6%) had retinal signs—eight (3.7%) with microhaemorrhages, six (2.8%) with retinal vascular tortuosity and two (0.93%) with cotton wool spots (CWS). 11 eyes (5.1%) had hyper-reflective plaques in the ganglion cell-inner plexiform layer layer on OCT, of which two also had retinal signs visible on CFP (CWS and microhaemorrhage, respectively). There was no significant difference in the prevalence of retinal signs in symptomatic versus asymptomatic patients (12 (15.0%) vs 13 (9.6%), p=0.227). Patients with retinal signs were significantly more likely to have transiently elevated blood pressure than those without (p=0.03).ConclusionOne in nine had retinal microvascular signs on ocular imaging. These signs were observed even in asymptomatic patients with normal vital signs. These retinal microvascular signs may be related to underlying cardiovascular and thrombotic alternations associated with COVID-19 infection.

Retinal microvascular signs and risk of diabetic kidney disease in asian and white populations

The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians (SEED) and 703 White (WESDR) adults with diabetes. Retinal microvascular signs at baseline included vascular caliber (arteriolar—CRAE, and venular—CRVE) and diabetic retinopathy (DR). Incident cases of DKD were identified after ~ 6-year. Incident cases were defined based on eGFR in SEED and proteinuria or history of renal dialysis in WESDR. The incidence of DKD were 11.8% in SEED and 14.0% in WESDR. Wider CRAE in SEED (OR = 1.58 [1.02, 2.45]) and wider CRVE (OR = 1.69 [1.02, 2.80)) in WESDR were associated with increased risk of DKD. Presence of DR was associated with an increased risk of DKD in both cohorts (SEED: OR = 1.91 [1.21, 3.01] in SEED, WESDR: OR = 1.99 [1.18, 3.35]). Adding DR and retinal vascular calibers in the model beyond traditional risk factors led to an improvement of predictive performance of DKD risk between 1.1 and 2.4%; and improved classification (NRI 3 between 9%). Microvascular changes in the retina are longitudinally associated with risk of DKD.

Differential associations between retinal signs and CMBs by location

ObjectiveTo test the hypothesis that age-related macular degeneration (AMD) and retinal microvascular signs are differentially associated with lobar and deep cerebral microbleeds (CMBs).MethodsCMBs in lobar regions indicate cerebral amyloid angiopathy (CAA). β-Amyloid deposits are implicated in both CAA and AMD. Deep CMBs are associated with hypertension, a major risk factor for retinal microvascular damage. This population-based cohort study included 2,502 participants in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who undertook binocular digital retinal photographs at baseline (2002–2006) to assess retinal microvascular signs and AMD and brain MRI scan at both baseline and follow-up (2007–2011) to assess CMBs. We assessed retinal microvascular lesion burden by counting the 3 retinal microvascular signs (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) concurrently present in the participant. We used multiple logistic models to examine the association of baseline retinal pathology to incident CMBs detected at follow-up.ResultsDuring an average 5.2 years of follow-up, 461 people (18.3%) developed new CMBs, including 293 in exclusively lobar regions and 168 in deep regions. Pure geographic atrophy was significantly associated with strictly lobar CMBs (multivariable-adjusted odds ratio 2.59, 95% confidence interval [CI] 1.01–6.65) but not with deep CMBs. Concurrently having ≥2 retinal microvascular signs was associated with a 3-fold (95% CI 1.73–5.20) increased likelihood for deep CMBs but not exclusively lobar CMBs.ConclusionsRetinal microvascular signs and pure geographic atrophy may be associated with deep and exclusively lobar CMBs, respectively, in older people. These results have implications for further research to define the role of small vessel disease in cognitive impairment.