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Purpose: Birdshot chorioretinopathy (BCR) is a potentially blinding ocular disorder involving the retinal vasculature and choroid without any systemic manifestations. The objective of the study was to describe vascular calibre changes in BCR and analyse the possibility of this optical biomarker for staging and monitoring disease activity in BCR., Methods: This retrospective case-control study at a tertiary referral eye centre in the UK included 33 eyes from 21 patients with BCR and equal number of eyes from control subjects. Diagnosis of BCR was confirmed on fundus fluorescein and indocyanine green angiography. Vascular calibres were measured using validated semiautomated software., Results: Patients with BCR had smaller retinal venular calibres central retinal venular equivalent (CRVE) than controls (211.3 versus 227.9 μm, p = 0.008). After adjusting for variables, the difference between the two groups for CRVE at baseline was statistically significant based on two different analysis methods. Central retinal venular equivalent (CRVE) was lower at the 6-month follow-up visit (206.2 versus 213.8 μm, p-value = 0.03), and arteriole-to-venule ratio was larger (0.74 versus 0.71, p = 0.04) in subjects with BCR. Arteriolar calibre (CRAE) remained the same., Conclusion: This study provides novel insight into the pattern of vascular involvement in BCR. There was significant difference in the CRVE in patients with BCR. More studies are needed to correlate this data with visual function and treatment outcome and to validate the findings., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Retinal vasculitis is a potentially sight-threatening inflammation of the retinal vessels, but little is known about the in vivo vascular changes, which occur in affected eyes. The authors therefore sought to measure vessel caliber in eyes with vasculitis., Methods: Retrospective case-control study. Vasculitis was confirmed using fluorescein angiography. Vessel calibers were measured using validated semiautomated software., Results: There were 21 eyes from 15 patients with vasculitis and 33 control eyes from 21 control subjects. Most cases were diagnosed with idiopathic vasculitis. All had periphlebitis, and one eye also had arteritis. After adjustment for age and gender, mean arteriolar caliber was 143 μm (95% confidence interval [CI], 134-152) in cases and 158 μm (95% CI, 151-165) in controls (P = 0.01). Venular caliber was similar in cases (229 μm; 95% CI, 215-243) and controls (228 μm; 95% CI, 217-234; P = 0.91), whereas arteriole-to-venule ratio was smaller in cases (0.63; 95% CI, 0.60-0.66) compared with controls (0.70; 95% CI, 0.02-0.11; P = 0.004)., Conclusion: Retinal vasculitis was associated with narrower arteriolar caliber, whereas venular caliber was similar to controls. This resulted in a smaller arteriole-to-venule ratio in eyes with vasculitis.

Purpose: Diabetic macular ischaemia (DMI) is an important cause of visual loss in patients with diabetes, but its relationship to the larger retinal vessels is unknown. We examined whether retinal vessel calibre is related to DMI., Methods: Clinic-based case-control study of patients with type 2 diabetes. The presence and severity of DMI was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) protocols from fundus fluorescein angiographic (FFA) images. Custom software was used to quantify the greatest linear dimension and area of the foveal avascular zone (FAZ). Retinal vessel calibre was measured using a semi-automated software on fundus fluorescein images., Results: Of 53 patients examined, 18 (34%), 18 (34%) and 17 (32%) had no/mild, moderate and severe DMI, respectively. Persons with moderate or severe DMI had narrower mean retinal arteriolar calibre than persons with no/mild DMI (140.6 μm 95% confidence interval (CI) 134.7, 146.4 versus 150.7 μm, 95% CI 142.5, 158, p = 0.04). The association remained after multivariate adjustment for age, gender, previous panretinal photocoagulation, neovascularization at the disc and elsewhere and diabetic retinopathy severity. Increased FAZ size was also associated with narrower arteriolar calibre. Retinal venular calibre and arteriole to venule ratio (AVR) were not associated with DMI., Conclusions: Retinal arteriolar narrowing was associated with moderate-to-severe macular ischaemia in eyes with diabetic retinopathy. This suggests that larger vessels other than capillaries may also be associated with DMI., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective: In the current study, we aimed to examine the associations of low birth weight with retinal vascular caliber and vascular fractal dimension during early adolescence., Methods: A population-based study of 12-year-old schoolchildren (2353/3144 [75.3%]) recruited from a random cluster sample of 21 schools. Birth weight, birth length and head circumference were obtained via parent report of the child's birth record. Retinal images were taken and vessel diameter and fractal dimension were quantified using validated computer-based methods., Results: After adjusting for age, sex, ethnicity, body mass index, iris color, axial length, mean arterial blood pressure, prematurity and fellow retinal vascular caliber, children in the lowest quartiles of birth weight had ∼2.5 μm narrower mean retinal arteriolar caliber than those in the highest quartiles (p for trend = 0.001). Associations were observed between shorter birth length and smaller head circumference with narrower retinal arterioles. Smaller head circumference was associated with decreased fractal dimension (p for trend = 0.03)., Conclusions: Children with lower birth weight were more likely to have narrower retinal arterioles, while those with smaller head circumference were more likely to have reduced complexity of their retinal microvasculature. These variations in microvascular structure in adolescence could reflect a susceptibility to cardiovascular disease during adulthood, resulting from a disadvantaged growth environment in utero., (© 2010 John Wiley & Sons Ltd.)

Background: Lacunar stroke accounts for a quarter of cases of acute ischaemic stroke; however, its underlying pathophysiology remains unclear. Our aim was to establish whether there is an association between changes in the retinal microvasculature and lacunar stroke that might provide clues to the pathology of cerebral small vessel disease., Methods: In this cross-sectional study, we recruited patients who presented with acute stroke at three centres in two countries (Sydney and Melbourne, Australia, and Singapore). Each patient had standardised clinical assessments, retinal photography, and CT or MRI of the brain. Changes in the retinal microvasculature were assessed from retinal photographs by graders who were masked to the patients' clinical details. Lacunar stroke was diagnosed according to a modified version of the TOAST criteria (Treatment of Acute Stroke Trial) or the OCSP criteria (Oxfordshire Community Stroke Project) and by MRI findings., Findings: We recruited 1321 patients aged 19 to 94 years with acute ischaemic stroke; 410 (31%) had lacunar stroke. Patients with acute lacunar stroke were no more likely to have hypertension (p=0.12), diabetes (p=0.51), or hypercholesterolaemia (p=0.91) than were patients with other types of ischaemic stroke. However, patients with lacunar stroke were more likely to have retinal microvessel signs, particularly when stroke subtype was confirmed using diffusion-weighted MRI, than were patients with other stroke subtypes. After adjustment for age, sex, study site, smoking history, hypertension, and diabetes, the patients with lacunar stroke were more likely than those with other stroke subtypes to have microvessel signs, and when stroke subtype was confirmed by diffusion-weighted MRI the odds ratios were: 3.55 (95% CI 1.77-7.12) for focal arteriolar narrowing; 1.96 (1.19-3.24) for arteriovenous nipping; 2.32 (1.42-3.79) for enhanced light reflex of the arteriolar wall; 1.33 (0.74-2.41) for generalised retinal arteriolar narrowing; 1.45 (0.84-2.51) for small retinal arteriole:venule ratio; and 1.35 (0.80-2.26) for retinal venular widening., Interpretation: Our findings suggest that acute lacunar stroke is a manifestation of non-atherothrombotic occlusive small vessel disease, which might have implications for the prevention and treatment of this stroke subtype., Funding: National Health and Medical Research Council of Australia; National Medical Research Council of Singapore; Scottish Funding Council; New South Wales Health.

Objective: Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes., Research Design and Methods: We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12-20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol., Results: In this study, 137 patients (18.8%) had diabetic retinopathy signs; of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023-1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02-7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21-1.56]). This association remained after additional adjustment for retinal vascular caliber., Conclusions: Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.

Objective: To examine the relative contributions of systemic cardiovascular factors to retinal arteriolar and venular caliber in men and women and in whites and African Americans., Methods: In the Atherosclerosis Risk in Communities study, retinal arteriolar caliber (central retinal arteriolar equivalent), and venular caliber (central retinal venular equivalent) were measured from digitized retinal photographs of 8794 participants., Results: The main systemic determinants of narrower central retinal arteriolar equivalent were, in order of relative decreasing contribution, higher current mean arterial blood pressure, lower serum albumin level, current alcohol consumption, and higher body mass index (calculated as weight in kilograms divided by height in meters squared). The main systemic determinants of wider central retinal venular equivalent were current cigarette smoking and higher current mean arterial blood pressure, followed by higher white blood cell count, body mass index, and plasma low-density lipoprotein cholesterol levels. These associations were generally similar in whites and African Americans and in men and women., Conclusions: The major systemic determinant of narrower retinal arteriolar caliber is higher blood pressure, while those of wider retinal venular caliber are cigarette smoking, higher blood pressure, systemic inflammation, and obesity. These data offer further insights into the systemic processes influencing arteriolar and venular characteristics and may help explain the observed associations of retinal vascular caliber and the risk of clinical cardiovascular disease.

Purpose: To describe the relationship of retinal vascular caliber with cardiovascular risk factors in an Asian population., Methods: The Singapore Malay Eye Study is a population-based, cross-sectional survey that included 3280 (78.7% response) persons aged 40 to 80 years. Retinal vascular caliber was measured from digital retinal photographs using a validated standardized protocol. Data on major cardiovascular risk factors were collected from all participants., Results: Of the 3019 participants with retinal vascular caliber data available, the mean retinal arteriolar caliber (CRAE) was 139.5 +/- 15.7 microm (SD), and mean venular caliber (CRVE) was 219.3 +/- 22.2 microm (SD). Smaller retinal arteriolar caliber was associated with higher current mean blood pressure and male sex (P < 0.001 for both). Larger retinal venular caliber was associated with younger age, current cigarette smoking, greater body mass index, higher glycosylated hemoglobin level, and lower HDL cholesterol (P = 0.012 for glycosylated hemoglobin level and P < 0.001 for other risk factors). The association of retinal arteriolar narrowing and blood pressure was stronger in younger people than in older people and in men than in women (P for interaction < 0.001 for both)., Conclusions: In this Asian population, smaller retinal arteriolar caliber was associated with hypertension and larger retinal venular caliber with cigarette smoking, dyslipidemia, hyperglycemia, and higher body mass index. The pattern of these associations is similar to that in white populations.

Objective: Microvascular disease may contribute to hearing loss. We tested this hypothesis by examining the relation of retinal microvascular abnormalities and hearing loss., Methods: This was a cross-sectional, population-based study. We performed retinal photography and pure-tone audiometry on 1511 older individuals (ages 54+ years) from the Blue Mountains Eye Study population. Examination of the retinal microvasculature provides a noninvasive means of assessing systemic microvascular changes associated with cardiovascular disease, especially since reliable methods of quantifying retinal microvascular abnormalities from retinal photographs have recently been developed. Trained graders masked to audiometry data assessed retinal photographs for signs of retinal microvascular damage, for example, focal arteriolar narrowing, arteriovenous nicking, and retinopathy (microaneurysms, retinal hemorrhages), and used a computer-assisted method to measure arteriolar and venular calibers. We defined moderate or profound hearing loss as pure-tone average air-conducted hearing thresholds in the better ear worse than 40 dB at 0.5, 1, 2, and 4 kHz. We used odds ratios (OR), 95% confidence intervals (CI), and probability values to present the associations between retinal microvascular abnormalities and hearing loss; an OR >1 indicates that persons with the microvascular abnormality are more likely to have hearing loss, a CI that includes 1.00 (e.g., 0.85 to 2.34) indicates no statistically significant association (i.e., the association may have occurred due to chance), whereas a value of p < 0.05 indicates that an association is unlikely to have occurred due to chance., Results: The proportion of women and men with moderate or profound hearing loss was 10.4% (90/862) and 15.4% (100/649), respectively. After adjustment for age, sex, blood pressure, and other risk factors for hearing loss, retinopathy in women was associated with hearing loss (adjusted OR, 2.10; 95% CI, 1.09 to 4.06, p = 0.002) but not in men. Associations were stronger for moderate or worse low-frequency (0.25 to 1.0 kHz) hearing loss in women (adjusted OR, 3.00; 95% CI, 1.25 to 7.19, p = 0.0005) but were absent for high-frequency hearing loss. In men, no retinal microvascular abnormalities were associated with hearing loss at either low or high frequencies., Conclusions: Retinopathy, a sign of retinal microvascular damage, was associated with hearing loss in women but not in men. Our results provide modest support to the hypothesis that microvascular disease may play a role in age-related hearing loss in women, particularly low-frequency losses.

The retinal vasculature is a unique site where the microcirculation can be noninvasively imaged in vivo. This presents an opportunity to study otherwise inaccessible structural features of the microcirculation. Recently, a number of population-based studies have developed quantitative methods of measuring these retinal signs, and investigated how these signs relate to metabolic disorders such as diabetes, hypertension, obesity, and metabolic syndrome. These studies have reported fairly consistent associations of retinopathy lesions, arteriolar narrowing and venular dilation with these metabolic disorders, suggesting a microvascular component in either the pathogenesis or manifestation of these disorders. Further, several of these signs have been associated with future risk of cardiovascular outcomes, such as coronary heart disease and stroke, independently of traditional risk factors. This review will examine in detail the evidence linking retinal vascular signs with metabolic disorders and discuss their implications for research and clinical practice.

Purpose: The arteriole to venule ratio (AVR) is widely used in studies of the associations of retinal microvascular disease with systemic and ocular outcomes. This is a discussion of the limitations of AVR; a comparison of its predictive information with that of its components, arteriolar and venular caliber; and a description of a suggested alternative method of modeling arteriolar and venular calibers directly., Methods: Data from the population-based Blue Mountains Eye Study were used to compare the predictive information in models using AVR with models using arteriolar and venular calibers directly. Determination was made of how the apparent relationship between vessel caliber and two systemic outcomes (blood pressure [BP] and white blood cell count [WBC]) was influenced by the choice of regression model. These findings were interpreted with reference to the known biological relationship among vessel calibers, BP, and WBC., Results: Models using arteriolar and venular calibers directly had more predictive information than models using AVR. The apparent relationship of vessel caliber to BP and WBC differed substantially, depending on the model chosen. For example, after adjustment for age, sex, and other covariates, decreasing venular caliber was associated with higher systolic BP when modeled separately, but was associated with lower systolic BP when modeled simultaneously with arteriolar caliber., Conclusions: The findings suggest AVR provides less information with regards to predicting systemic outcomes than its two components. Modeling arteriolar and venular calibers separately could be biased by confounding, while modeling both simultaneously appears to provide unbiased, biologically plausible results. The use of this approach is recommended in future research relating retinal vascular caliber to systemic or ocular outcomes.

Objective: To examine whether retinal vessel signs are independent predictors of the long-term development of age-related maculopathy (ARM)., Design: Prospective population-based cohort study., Participants: Blue Mountains Eye Study participants aged > or =49 years (n = 3654) were examined during 1992 through 1994; 2335 (75% of survivors) were reexamined after 5 years and 1952 (76% of survivors) were reexamined after 10 years., Methods: Baseline focal arteriolar narrowing and arteriovenous (AV) nicking were assessed and vessel calibers were measured from retinal photographs. A side-by-side grading method was used to assess ARM incidence. Eye-specific data were analyzed using generalized estimating equation models, adjusting for age, gender, smoking, and blood pressure., Main Outcome Measures: Incident early ARM (soft indistinct or reticular drusen or combined soft distinct drusen and retinal pigment abnormality) was defined in eyes free of both early and late ARM at baseline. Incident late ARM (either geographic atrophy or neovascular macular degeneration) was defined in eyes free of these 2 lesions at baseline., Results: Over a 10-year period, incident late ARM developed in 106/4745 eyes at risk of late ARM (2.2%). Eyes with mild (2.7%) or severe (4.6 %) AV nicking were more likely to develop late ARM than eyes without this sign (1.5%). The adjusted odds ratio (OR) was 1.4, 95% confidence interval (CI) 0.8 to 2.4 for mild and OR 2.6, 95% CI 1.2 to 5.5 for severe AV nicking. Eyes with focal narrowing were also more likely to develop late ARM (7.6% vs. 1.8%), adjusted OR 2.2, 95% CI 1.1 to 4.1. Incident early ARM developed in 398/4490 eyes at risk of early ARM (8.9%). Severe AV nicking, but not focal arteriolar narrowing, was associated with an increased long-term risk of early ARM (13.6% vs. 8.2%; OR 1.5; 95% CI 1.0-2.3). Neither arteriolar nor venular caliber was significantly associated with the incidence of either early or late ARM., Conclusions: These 10-year incidence data confirm our previous observation that structural retinal arteriolar changes may either contribute to ARM progression or share common pathologic pathways with ARM, independent of traditional vascular risk factors.