title: Choroidal Structure and Function in Chronic Retinal Diseases
Creators: name: Boonarpha, N
Publisher: name: University of Liverpool Repository
Year: 2016

description: Introduction: The choroid plays an important role in maintaining retinal homeostasis. Changes in choroidal structure and a failure of choroidal autoregulation (the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure) may have a great consequence in the pathogenesis of several chronic chorioretinal diseases including diabetic retinopathy (DR) and central serous chorioretinopathy (CSCR). Aim: The main aim of this thesis is to study the structure and function of the choroid and determine its role in the pathogenesis of DR and CSCR using enhanced depth imaging optical coherence tomography (EDI OCT) and laser Doppler flowmetry (LDF). Methods: A protocol for standardising the choroidal thickness (ChT) measurement using topographical appearances of the choroidal posterior boundary was developed and validated on EDI OCT images from healthy volunteers and patients with DR. Extensive experiments were performed in order to validate the hardware and software of the LDF device. Two controlled prospective studies were designed and performed; 1) Diabetic Retinopathy: Functional and Structural Study (DREFUS Study), and 2) Liverpool Central Serous Chorioretinopathy study (Liverpool CSCR Study). The DREFUS study involved diabetic patients with/without DR and healthy volunteers. DR patients were grouped using the presence or absence of clinically significant macular oedema (CSMO). The Liverpool CSCR study included patients presented with CSCR and healthy volunteers. For both of the studies the ChT was measured using a single horizontal EDI OCT scan while the choroidal blood flow (ChBFlow) parameters (choroidal blood volume [ChBVolume] and velocity [ChBVelocity]) were measured by using LDF. Isometric exercise was used to test choroidal autoregulation function. Mean arterial BP (MAP), ocular perfusion pressure (OPP) and change in choroidal vascular resistance were calculated to evaluate the choroidal autoregulation. In addition, best corrected visual acuity (BCVA), blood pressure (BP), colour fundus photography, fluorescein angiography (FA), and OCT were performed. Other tests including indocyanine green angiography (ICG), volumetric EDI OCT scans, microperimetry, intraocular pressure, and axial length were only performed by the CSCR study. Statistical analyses (correlation, t-test, ANOVA, ANCOVA, intraclass correlation coefficient [ICC], Fisher exact test, Mann-Whitney test) were performed as appropriate. Results: The standardised protocol for ChT measurement was produced. ICC for interobserver and intraobserver agreements on ChT measurements using of the protocol were 0.96 and 0.99 respectively for healthy eyes (n = 12) and 0.97 and 0.99 respectively for eyes with DR (n = 46). The mean subfoveal ChT (SfChT) was 304 µm (95% confidence interval (CI): 282 – 326) for patients with DR (N = 61). There were no significant differences in ChT between healthy eyes (N = 41; 351 µm (95% CI: 321 – 381)), diabetic eyes (N = 12; 299.9 µm (95% CI: 248.7 - 351.2) and eyes with DR (P &gt;0.05). A statistically significant increase in ChBVelocity by 8% was observed following an increase of MAP by 18% in DR with CSMO. The mean SfChT of CSCR patients (N = 45) was 468.5 µm (95% CI: 437.1 – 499.9), approximately 30% thicker than in healthy eyes (N = 25; 361.4 µm (95% CI: 319.8 – 402.2) (P &lt;0.05). Hypertension was identified as the main risk factor affecting ChT in CSCR, particularly during the active stage of CSCR (normotensive CSCR: SfChT = 431 µm (95% CI: 378 – 485) vs hypertensive CSCR: SfChT = 521 µm (95% CI: 468 – 574): P &lt;0.05). An increase in OPP by 40% caused the ChT to increase significantly in CSCR patient (435.3 µm (95% CI: 378.2 - 492.4) at baseline vs 446.3 µm (95% CI: 393.4 - 499.2) at the end of exercise; P &lt;0.05). An increase of OPP by 31% caused significant change in ChBVolume in CSCR patients compared to healthy eyes (P = 0.03). Changes in ChBVolume in CSCR patients were negatively correlated with changes in choroidal vascular resistance (r = -0.83, P &lt;0.05). Conclusions: In patients with diabetes, no significant changes in the ChT were observed in any group of DR patients. ChBVelocity regulation was impaired in patients with severe DR. These findings suggest that functional changes of the choroid may occur well before the structural changes in patients with DR. In CSCR patients, increases in ChT and choroidal volume were observed in all CSCR phenotypes and also related with hypertension and the area of choroidal vascular hyperpermeability seen on ICG. The disruption of the regulation of choroidal structure and function was observed during isometric exercise in CSCR patients. These findings highlight the significance of choroidal regulation in the pathogenesis of DR and CSCR.