title: Early detection of diabetic macular oedema
Creators: name: Ku, Jae Yee
Publisher: name: University of Liverpool Repository
Year: 2022

description: Background Diabetic retinopathy (DR) is the second leading cause of visual loss in working-age adults in the United Kingdom (UK) after inherited eye disease, and is asymptomatic in its early stages. Visual loss from DR is commonly due to diabetic macular oedema (DMO) which current screening methods cannot detect directly. The handheld radial shape discrimination (hRSD) test, has been approved by the US Food and Drug Administration (FDA) as a means of detecting metamorphopsia, and therefore maculopathy. There is also emerging evidence that DR is a neurodegenerative disease resulting in thinning of the ganglion cell complex detected by optical coherence tomography (OCT) in early DR. This thesis describes studies of people with diabetes (PWD) and healthy controls (HC) investigating two emerging approaches, namely hRSD and OCT in the early detection of DMO. Methods Macular function was measured using hRSD, distance and near visual acuity (VA) and macular structure was assessed using Heidelberg Spectralis OCT. Retinal layers segmentation and mean thicknesses were measured across all Early Treatment Diabetic Retinopathy Study (ETDRS) subfields using the Heidelberg auto-segmentation software with manual adjustment as needed. One eye from each participant was randomly selected for analysis. Results 292 PWD (mean±SD 54±14 years, 175 males) referred from the local screening programme to hospital clinics as being at risk of DMO were recruited. 229 healthy participants (age 44±18 years; 94 males) were also recruited, of whom 50 (55±14 years, 26 males) were used as age-matched controls for the PWD. Compared to HC, hRSD performance and distance VA were progressively worse in PWD with no or minimal DR, (hRSD logMAR: HC -0.77±0.11, no DR -0.68±0.18, minimal DR -0.61±0.25, ANOVA p&lt;0.001; distance VA logMAR: HC -0.08±0.12, no DR 0.03±0.15, minimal DR 0.06±0.16, ANOVA p&lt;0.001). Compared to HC there was a reduction in full retinal thickness across most subfields in PWD with no or minimal DR. This reduction was driven by thinning in the outer nuclear layer (ONL) in the central subfield (CSF), ganglion cell layer (GCL) and inner plexiform layer (IPL) in the inner subfields and retinal nerve fibre layer (RNFL) in the outer subfields compared to HC. In the outer subfields, there was also thinning in the retinal pigment epithelium (RPE) in PWD with no DR and thinning in the GCL and IPL in PWD with minimal DR. Longitudinal data were available for 159 PWD (54±15 years, 97 males) who attended for a second visit after 191±86 days. In PWD with no or minimal DR, there was a significant decrease in GCL (visit 1 37.73±3.56µm, visit 2 37.27±3.84µm, t=2.523, p=0.020), IPL (visit 1 31.98±2.48µm, visit 2 31.61±2.69µm, t=2.517, p=0.020) and inner nuclear layer (INL) (visit 1 33.89±1.92µm, visit 2 32.96±1.11µm, t=3.129, p=0.005) between visits. Conclusions Functional and structural changes are detectable in the early pathogenesis of DR, consistent with neuroretinal thinning developing before microvascular abnormalities. Functional changes detected by the hRSD test in PWD with early DR have not been previously demonstrated. Findings from the Early Detection of Diabetic Macular Oedema (EDDMO) study add further support to the concept of pre-clinical retinopathy.