Associations of retinal oximetry in persons with diabetes.

BACKGROUND: There are limited data available on the variables that might affect retinal vessel oxygen saturation (SO2) in diabetes. Therefore, the aim of this study is to assess factors associated with retinal oximetry values in persons with diabetes. DESIGN: Clinic-based cross-sectional study. PARTICIPANTS: Fifty-eight persons with diabetes aged 18+ years, recruited from the University of Melbourne, the Royal Victorian Eye and Ear Hospital, and St. Vincent's Hospital (Melbourne), Australia. METHODS: Retinal oximetry was performed using the oximetry module of the Vesselmap system (Imedos UG, Jena, Germany) in 92 diabetic eyes. Generalized estimating equation models were used to estimate the associations between candidate variables (age; gender; retinal capillary flow; duration of diabetes; hypertension; smoking status; presence of diabetic retinopathy [DR]; glycated haemoglobin; triglyceride; total cholesterol; finger SO2 and ocular perfusion pressure) with retinal oximetry measures. MAIN OUTCOME MEASURE: Arteriolar SO2, venular SO2 and the arterio-venous (A-V) difference. RESULTS: Of the candidate factors assessed, only the presence of DR was significantly associated with increased venular SO2 and decreased A-V difference in unadjusted analyses. In models adjusting for age and gender and significant variables from unadjusted analyses, compared with no DR, the presence of DR was significantly associated with greater retinal venular SO2 values (ß = 3.65%, 95% confidence interval: 0.67-6.63%) and decreased A-V difference (ß = -2.00%, 95% confidence interval: -3.46 to -0.53%). CONCLUSION: In patients with diabetes, eyes with DR were associated with increased venular SO2 and decreased A-V difference compared with eyes without DR, suggesting an altered metabolic state in DR.

Flicker-induced retinal arteriole dilation is reduced by ambient lighting.

PURPOSE: To investigate the impact of ambient room lighting on the magnitude of flicker light-induced retinal vasodilations in healthy individuals. METHODS: Twenty healthy nonsmokers participated in a balanced 2 × 2 crossover study. Retinal vascular imaging was performed with the dynamic vessel analyzer under reduced or normal ambient lighting, then again after 20 minutes under the alternate condition. Baseline calibers of selected arteriole and venule segments were recorded in measurement units. Maximum percentage dilations from baseline during 20 seconds of luminance flicker were calculated from the mean of three measurement cycles. Within-subject differences were assessed by repeated measures analysis of variance with the assumption of no carryover effects and pairwise comparisons from the fitted model. RESULTS: Mean (SD) maximum arteriole dilations during flicker stimulation under reduced and normal ambient lighting were 4.8% (2.3%) and 4.1% (1.9%), respectively (P = 0.019). Maximum arteriole dilations were (mean ± 95% confidence interval) 0.7% ± 0.6% lower under normal ambient lighting compared with reduced lighting. Ambient lighting had no significant effect on maximum venular dilations during flicker stimulation or on the baseline calibers of arterioles or venules. CONCLUSIONS: Retinal arteriole dilation in response to luminance flicker stimulation is reduced under higher ambient lighting conditions. Reduced responses with higher ambient lighting may reflect reduced contrast between the ON and OFF flicker phases. Although it may not always be feasible to conduct studies under reduced lighting conditions, ambient lighting levels should be consistent to ensure that comparisons are valid.

Flicker light-induced retinal vasodilation is unaffected by inhibition of epoxyeicosatrienoic acids and prostaglandins in humans.

PURPOSE: To investigate the role of epoxyeicosatrienoic acids (EETs) and prostaglandins (PGs) in retinal blood vessel calibers and vasodilation during flicker light stimulation in humans. METHODS: Twelve healthy nonsmokers participated in a balanced crossover study. Oral fluconazole 400 mg and dispersible aspirin 600 mg were used to inhibit production of EETs and PGs, respectively. Retinal imaging was performed 1 hour after drug ingestion with the Dynamic Vessel Analyzer. Resting calibers of selected vessel segments were recorded in measurement units (MU). Maximum percentage dilations during flicker stimulation were calculated from baseline calibers. We then studied six participants each after fluconazole and aspirin ingestions at 30-minute intervals for 2 hours. Within-subject differences were assessed by ANOVA and Dunnett-adjusted pairwise comparisons with significance taken at P < 0.05. RESULTS: In crossover study participants, mean (SD) arteriole and venule dilations without drug administration were 4.4% (2.0%) and 4.6% (1.7%), respectively. Neither drug affected vasodilation during flicker stimulation. Mean (SD) resting arteriole and venule calibers on no-drug visits were 119.6 (10.6) MU and 145.7 (17.0) MU, respectively. Fluconazole reduced mean (±95% CI) resting venule calibers by 5.1 (4.3) MU. In repeated measures participants, neither drug affected vasodilations, but fluconazole reduced resting venule calibers over 2 hours (P < 0.001). CONCLUSIONS: Epoxyeicosatrienoic acids and prostaglandins are unlikely to be primary mediators of flicker light-induced retinal vasodilation in humans. However, EETs may play a role in the regulation of retinal vascular tone and blood flow under resting physiological conditions.

Decreased retinal capillary flow is not a mediator of the protective myopia-diabetic retinopathy relationship.

PURPOSE: The mechanisms supporting the protective relationship between a longer axial length (AL) and a decreased risk of diabetic retinopathy (DR) remain unclear. Previous studies have demonstrated reduced retinal blood flow in axial myopia, and it has been suggested that the compromised retinal capillaries in diabetes are less likely to leak and rupture as a result of this decreased flow. In this study, we therefore investigated if reduced retinal capillary flow (RCF) is a potential mechanism underpinning this protective relationship. METHODS: Retinal capillary flow was assessed using the Heidelberg Retinal Flowmeter in 150 eyes of 85 patients with diabetes aged 18+ years from the Royal Victorian Eye and Ear Hospital and St. Vincent's Hospital (Melbourne), Australia. Axial length was measured using the Intraocular Lens Master. Diabetic retinopathy was graded from two-field retinal photographs into none, mild, moderate, and severe DR using the modified Airlie House classification system. RESULTS: A total of 74 out of 150 eyes (49.3%) had DR. A longer AL was associated with decreased odds of DR presence (per mm increase in AL, odds ratio [OR] 0.61, 95% confidence interval [CI] 0.41-0.91) and DR severity (OR: 0.65; 95% CI: 0.44-0.95). However, no association was found between AL and RCF (per mm increase in AL, regression coefficient [ß] -1.80, 95% CI -13.50 to 9.50) or between RCF and DR (per unit increase in RCF, OR 1.00; 95% CI 0.99-1.00). CONCLUSIONS: Our finding suggests that diminished RCF may not be a major factor underlying the protective association between axial elongation and DR.

Retinal arteriolar dilation to flicker light is reduced on short-term retesting.

PURPOSE: To investigate the impact of retesting frequency over a short period on flicker light-induced retinal vasodilation. METHODS: Twenty healthy participants were included. The retinal vascular response to flicker light stimulation was assessed three times (at baseline and after 5 and 30 minutes of rest [tests 1, 2, and 3, respectively]) in each participant using the Dynamic Vessel Analyzer. Relative dilations of selected arteriole and venule segments during flicker stimulation and resting diameters were measured automatically. The mean vessel dilations and resting diameters were compared using repeated-measures analysis of variance. RESULTS: Participants were young (mean [SD] age, 33.1 [5.7] years) and mostly female (70%). The mean (SD) maximum arteriolar dilations during flicker stimulation were 3.23% (2.06%), 2.44% (1.62%), and 3.36% (2.11%) in tests 1, 2, and 3, respectively. The mean (SD) venular dilations were 4.26% (1.28%), 3.81% (1.61%), and 4.43% (1.73%) in tests 1, 2, and 3, respectively. The mean arteriolar dilations were significantly different across the three tests (P < 0.001). Compared with test 1, arteriolar dilations were significantly reduced after 5 minutes (P = 0.008) but not 30 minutes (P = 0.437) of rest. No significant differences were found over time for the mean venular dilations (P = 0.128). Resting diameters of selected vessels were not significantly different between tests. CONCLUSIONS: Retinal arteriolar dilation during flicker stimulation is reduced on short-term retesting, without a significant change in baseline vessel diameter, indicating decreased responsiveness to the flicker stimulus. Researchers should allow at least 30 minutes between consecutive tests to minimize suppression of the flicker response.

Axial length, retinal function, and oxygen consumption: a potential mechanism for a lower risk of diabetic retinopathy in longer eyes.

PURPOSE: To determine the relationship between axial length (AL), retinal function, and relative oxygen (O2) consumption to better understand the protective effect of axial elongation on diabetic retinopathy development. METHODS: Measurements of AL, multifocal electroretinogram (mfERG), and relative O2 consumption (difference between arteriolar and venular O2 saturation levels or A-V difference) were performed on 50 healthy individuals. The relationships between AL, mfERG amplitude, and A-V difference were analyzed using linear regression models. Path analysis was performed to determine the direct and indirect effects (via mfERG amplitude) of AL on A-V difference. RESULTS: mfERG P1 amplitude was positively associated with A-V difference (ß = 0.33; 95% confidence interval [CI]: 0.23-0.42). Increased AL was significantly associated with a decrease in A-V difference (ß = -1.08; 95% CI: -1.52 to -0.65) as well as a decrease in retinal function (ß = -3.14, 95% CI: -4.07 to -2.20). Path analysis models including AL (study factor), retinal function (intermediate variable), and A-V difference (outcome variable) showed that AL had little direct association with A-V difference (ß(p) = -0.002), while the indirect effect of AL on A-V difference via changes in retinal function were substantial (ß(p) = -0.51). CONCLUSIONS: In eyes with longer AL, the reduction in A-V difference is explained by the parallel reduction in retinal function. These findings suggest that longer eyes have decreased retinal function and O2 consumption, and thus are relatively less hypoxic in the presence of diabetes, which may partly explain the reduced risk of DR in these eyes.