Ophthalmology (Eye & Ear Hospital) - Theses
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ItemThe relationship between myopia and diabetic retinopathy: potential protective effects and underlying mechanisms( 2013)There is controversy over observations that myopia is protective of diabetic retinopathy (DR) due to the uncertainty over the contributory roles of ocular biometric parameters (i.e. axial length [AL], corneal curvature [CC], and anterior chamber depth [ACD]) all of which are closely associated with myopia. Moreover, theories on the mechanisms underpinning the supposed protective myopia-DR relationship are educated guesses inferred from observations of reduced retinal blood flow and/or oxygen (O2) consumption in myopic eyes. Therefore, this thesis has three main aims. The first is to investigate the associations of myopia and myopia-related ocular biometric parameters with DR (and diabetic macular edema [DME]). The second and third aims are to assess the respective roles of a reduction in retinal capillary blood flow (RCF) and O2 consumption as potential mechanisms underlying this protective myopia-DR relationship. Aim one included 609 patients with diabetes aged 18+ years. After multivariable adjustments, eyes with longer AL were less likely to have mild (odds ratio [OR]: 0.58, 95% confidence interval [CI]: 0.41- 0.83 per mm increase), moderate (OR: 0.73, 95% CI: 0.60-0.88), and severe DR (OR: 0.67, 95% CI: 0.53-0.85), and also had a lower risk of mild (OR: 0.70, 95% CI: 0.56- 0.86); and moderate DME (OR: 0.72, 95% CI: 0.56- 0.93). No associations were found for refractive error, CC or ACD with DR, suggesting that the myopia-DR association is likely due to a longer AL in myopic eyes. For aim two, I utilized 85 persons with diabetes aged 18+ years, independent of the sample used in aim one. Evaluating the relationship between AL, RCF and DR, I found no association between AL and RCF (per mm increase in AL, regression coefficient [β] -1.80, 95% CI: -13.50-9.50) or between RCF and the risk of DR (per unit increase in RCF, OR 1.00, 95% CI 0.99-1.00) after multivariable adjustments. These findings suggest that diminished RCF may not be a major mechanism underlying the protective association between axial elongation and DR. In aim three, I utilized the arterio-venous (A-V) difference in O2 saturation (SO2), as a surrogate marker of relative O2 consumption. A reliability and reproducibility study in 20 healthy individuals aged 18+ years found extremely high intra-class correlation coefficient (ICC) values for intra-observer reliability (0.99 for both arteriolar and venular SO2), inter-observer reliability (ICC of 0.94 for arteriolar SO2 and 0.96 for venular SO2) and intra-subject reproducibility (ICC of 0.98 for both arteriolar and venular SO2) for the retinal oximeter utilized in this doctoral thesis. Finally I explored the role of O2 consumption as one of the mechanisms underpinning the protective association between AL and DR. Due to the potential confounding effects of diabetes on retinal function, the relationship between AL, retinal function (assessed using multifocal electroretinogram [mfERG] P1 amplitude) and the A-V difference was conducted in 50 healthy subjects aged 18+ years. 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 (βp = -0.002), while the indirect effect of AL on A-V difference via changes in retinal function were substantial (βp = -0.51). 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. In conclusion, I have demonstrated that a longer AL is the main factor contributing to the protective association of myopia with risk of DR. Furthermore, I have established that the protective myopia-DR relationship may be partially due to the alleviation of hypoxia in diabetes, due to a reduction in retinal function as the eye elongates.