Retinal Diseases: multifocal pupillographic objective perimetry, and epidemiology

Abstract

My thesis entitled Retinal diseases: multifocal pupillographic objective perimtery, and epidemiology comprises two parts. First, retinal function measured with multifocal pupillographic objective perimetry (mfPOP) in neovascular AMD (nAMD) and diabetic macular oedema (DMO), and second, epidemiology of vitreoretinal diseases (VRD) in Bhutan and Nepal. The epidemiological chapters cover 1905 new VRD patients in Nepal, and 2913 in Bhutan. Those studies identified the common, preventable VRDs including: diabetic retinopathy and macular oedema, nAMD, high myopia, hypertensive retinopathy, retinal vein occlusion, retinal breaks, retinal vasculitis, retinopathy of prematurity, etc. In Nepal, females presented later than males by 9 years (p<0.0001), age or disease duration for diabetic retinopathy did not correlate with severity, presenting visual acuity (VA) was asymmetric between eyes (p<0.0001), and patients often only reported once their right (dominant) eyes had VA of 6/18 or worse. In Bhutan, females presented earlier: (p=0.003). Myopia constituted 92.1% of refractive error with myopia prevalence (MP) of 12.3%, more common among females (p=0.01) and urbanites (p=0.02). MP was highest among urban females (20.9%), followed by urban males (11.9%), rural females (6.8%), and rural males (5.2%). Logistic regression revealed that the odds of having myopia were increased by being a student (4.96 x) or professional (1.96 x), and decreased by rural living (1.75 x), all p =/< 0.038. Those diseases are treatable with complete recovery if managed early. To improve management, we address the knowledge gap in developing countries by advancing a reliable objective diagnostic method: an FDA-cleared prototype of mfPOP, the ObjectiveFIELD Analyser (OFA) (Konan Medical USA, Irvine, CA). In nAMD, the per-region central OFA sensitivities decreased and delays increased with disease severity in patients tested monthly for up to 2 years. Central sensitivity of eyes needing anti-VEGF treatment was less sensitive than in the untreated eyes by -2.23+/-0.051 dB (p<0.0002). Based on the peripheral responses we have noticed 2 types of patients: positive with peripheral hypersensitivity and longer delays than normal, and negative with peripheral hyposensitivity and shorter delays. Among the positive eyes the peripheral sensitivity increased on average by 9.88+/-4.41 dB/month (p=0.042), and the delay increased at 3.49+/-1.75 ms/month (p=0.049) before the clinical decision to treat. For the negative eyes, the peripheral sensitivity dropped, and the delay was shorter a month before the treatment by 9.38+/-3.59 (p=0.013), and a month following treatment it improved (shorter by 8.50+/-2.71 ms, p=0.004). Treatment drove subsequent responses towards normality either from the positive or negative patient condition. Importantly, changes occurred 1-3 months before treatment was indicated clinically or by other diagnostic methods. We followed Type 2 diabetes patients for up to 2 years. Reduced mean sensitivities and longer delays were seen compared to normal. Peripheral hypersensitivity and shorter delays were associated with shorter diabetes duration. Principal curve analysis showed correlation between OFA and Matrix values. Outer macular thickness correlated significantly with inner and outer OFA sensitivity and delay, all p<0.0012 with DMO, and median p=0.001 without DMO, while the inner thickness was not correlated. A mixed-effects logistic regression determined that outer thickness and OFA sensitivity contributed independently to a clinical diagnosis of DMO. Outer thickness, number of visits and male gender increased the odds of having DMO. From a practical standpoint dilation with tropicamide 1% affected per-region sensitivities for more hours than either delays or signal-to-noise ratios (SNRs). So sensitivity measurements should be considered only after 48 hours, but delays or SNRs can be measured after 8-12 hours following mydriasis with tropicamide.