Retinal blood oxygen saturation and aqueous humour biomarkers in early diabetic retinopathy.

PURPOSE: The aim of this study was to assess the relationship between retinal blood oxygen saturation (SO2 ) and specific aqueous humour (AH) concentrations of proangiogenic biomarkers in diabetic patients with nonproliferative diabetic retinopathy (NPDR) and to compare them with those of matched control subjects. METHODS: The sample comprised 14 participants with mild-to-moderate NPDR (69.1 ± 6.6 years) and 17 age-matched healthy controls (69.7 ± 6.3 years); all participants were previously scheduled for routine cataract extraction with intraocular lens implantation. Multiplex cytokine analyses of specific biomarkers, including vascular endothelial growth factor A (VEGF-A), angiopoietin2 (Ang2), epidermal growth factor (EGF), hepatocyte growth factor (HGF) and interleukin-8 (IL-8) were performed by BioPlex 200 system. Six non-invasive hyperspectral retinal images were acquired. RESULTS: Mean SO2 was significantly higher in both arterioles (94.4 ± 1.9 versus 93.0 ± 1.6) and venules (64.4 ± 5.6 versus 55.9 ± 4.8) of NPDR than in the healthy controls (p < 0.001). AH levels of HGF (p = 0.018), Ang2 (p = 0.005) and IL-8 (p = 0.034) were significantly higher, and EGF (p = 0.030) was significantly lower in NPDR subjects. The study demonstrated a correlation between venular retinal blood oxygen saturation and proangiogenic factors HGF (r = 0.558, p = 0.038), Ang2 (r = 0.556, p = 0.039) and EGF (r = -0.554, p = 0.040), but did not find any correlation for IL-8 (r = 0.330, p = 0.249) even though this biomarker was significantly higher in the diabetic group. CONCLUSION: To our knowledge, the present study is the first report considering the association between SO2 and AH concentrations of protein biomarkers in diabetic retinopathy. The biomarkers of interest have been shown to participate in cell death, which may explain higher oxygen saturation in NPDR.

Aqueous humour concentrations of TGF-ß, PLGF and FGF-1 and total retinal blood flow in patients with early non-proliferative diabetic retinopathy.

PURPOSE: To correlate angiogenic cytokines in the aqueous humour with total retinal blood flow in subjects with type 2 diabetes with non-proliferative diabetic retinopathy (NPDR). METHODS: A total of 17 controls and 16 NPDR patients were recruited into the study. Aqueous humour was collected at the start of cataract surgery to assess the concentration of 14 angiogenic cytokines. Aqueous humour was analysed using the suspension array method. Six images were acquired to assess total retinal blood flow (TRBF) using the prototype RTVue™ Doppler Fourier domain optical coherence tomography (Doppler FD-OCT) (Optovue, Inc., Fremont, CA) using a double circular scan protocol, 1 month postsurgery. At the same visit, forearm blood was collected to determine glycosylated haemoglobin (A1c). RESULTS: Transforming growth factor beta (TGF-ß1, TGF-ß2) and PLGF were increased while FGF-1 was reduced in NPDR compared to controls (Bonferroni corrected, p < 0.003 for all). Total retinal blood flow (TRBF) was significantly reduced in the NPDR group compared to controls (33.1 ± 9.9 versus 43.3 ± 5.3 µl/min, p = 0.002). Aqueous FGF-1 significantly correlated with TRBF in the NPDR group (r = 0.71, p = 0.01; r2  = 0.51). In a multiple regression analysis, A1c was found to be a significant predictor of aqueous TGF-ß1 and FGF-1 (p = 0.018 and p = 0.020, respectively). CONCLUSION: Aqueous angiogenic cytokines (TGF-ß1, TGF-ß2 and PLGF) were elevated in conjunction with a reduction in TRBF in patients with NPDR compared to controls. Non-invasive measurement of TRBF may be useful for predicting aqueous FGF-1 levels and severity of vasculopathy in DR.

Retinal Blood Flow and Retinal Blood Oxygen Saturation in Mild to Moderate Diabetic Retinopathy.

PURPOSE: The aim of this study was to evaluate the relationship between retinal blood flow (RBF) and retinal blood oxygen saturation (SO2) in mild to moderate nonproliferative diabetic retinopathy (NPDR) and in age-matched controls. METHODS: One eye of each of 15 healthy subjects (68 ± 6 years) and 13 subjects with mild to moderate NPDR (67 ± 10 years) was dilated. None of the patients with NPDR had received treatment for their retinopathic changes or had any evidence of sight-threatening characteristics. Doppler Fourier-domain optical coherence tomography blood flow was measured using the prototype RTVue system; six separate measurements each comprising an upper and a lower nasal pupil scan were acquired. Six hyperspectral retinal measurements were acquired using a noninvasive hyperspectral retinal camera (prototype H-8.5 HR Camera). RESULTS: Total RBF was significantly lower in NPDR when compared to controls (42.7 ± 7.5 vs. 33.0 ± 9.2 µL/min; P = 0.004). Mean retinal arterial and venular SO2 were higher in NPDR than in controls (94.7 ± 2.4% vs. 92.9 ± 1.6%, P = 0.02; 62.5 ± 5.7% vs. 56.3 ± 4.7%, P = 0.003). This study showed a correlation between RBF and arteriolar SO2 in both controls (r = 0.58, P = 0.02) and NPDR (r = 0.54, P = 0.05), but no correlation between venular RBF and venular SO2 in controls (r = 0.24, P = 0.83) or in NPDR (r = 0.23, P = 0.45). The arteriovenous difference (AV difference) was lower in the NPDR group when compared to controls (30.6 ± 6 vs. 36.7 ± 5.3, P = 0.008). CONCLUSIONS: This study found a lower total RBF and a lower AV difference in the NPDR group, suggesting a reduced oxygen uptake from the retina in people with relatively early diabetic retinopathy.

The impact of cataract on the quantitative, non-invasive assessment of retinal blood Flow.

PURPOSE: The aim of the study was to determine the impact of cataract on the quantitative, non-invasive assessment of retinal blood flow assessed by bidirectional laser Doppler flowmetry and simultaneous vessel densitometry. METHODOLOGY: Ten patients scheduled for extracapsular cataract extraction using phacoemulsification and intraocular lens implantation between the ages of 61 and 84 (mean age 73 years, SD ± 8) were prospectively recruited. Two visits were required to complete the study; one visit prior to extracapsular cataract extraction and one at least 6 weeks after the surgery to allow for sufficient postoperative recovery. The severity of cataract was documented using the Lens Opacity Classification System (LOCS, III) at the first visit. Retinal arteriolar hemodynamics were measured at both visits using the high-intensity setting of the Canon Laser Blood Flowmeter. RESULTS: All eyes showed no clinical signs of postoperative intraocular inflammation. The quantitative assessment of retinal arteriolar diameter and blood flow were reduced following extracapsular cataract extraction (Wilcoxon signed-rank test, p = 0.022 and p=0.028, respectively); however, centreline blood velocity was not significantly changed (Wilcoxon signed-rank test, p=0.074). Intraocular pressure was unchanged pre- and postcataract extraction. CONCLUSIONS: Retinal vessel densitometry assessment in the presence of cataract results in the erroneous elevation of the diameter measurement and thereby the calculation of blood flow. The bidirectional Doppler assessment of blood velocity appears to be more robust to light scatter induced by cataract. Care needs to be exercised in the interpretation of studies of retinal vessel diameter or blood flow that utilize similar densitometry techniques.

A 10-year population-based cohort analysis of cataract surgery rates in Ontario.

BACKGROUND: We studied the rates and distribution of cataract surgery throughout Ontario using population-based administrative data. METHODS: We identified patients who had had cataract surgery performed between April 1, 1994, and March 31, 2005. We calculated crude cataract surgery rates, overall and regional adjusted rates per 100,000 residents aged 65 and over, and age- and sex-specific rates. RESULTS: The number of cataract surgeries performed on patients over 65 more than doubled, from 43,818 to 90,183, over the 10-year period and accounted for approximately 81% of all cataract surgeries in Ontario. Age- and sex-adjusted rates varied considerably among health administrative geographic regions. For 2004-2005, rates including all cataract surgeries ranged from 4272 to 6563 cataract surgeries per 100,000 residents aged 65 or older. INTERPRETATION: There has been a significant increase in the number of cataract surgeries performed over the past decade in Ontario with considerable regional variation. Observed rates were higher than those reported for other countries.