This thesis aimed to assess the effect of exogenous lipid supplements on ocular comfort during contact lens wear and the biology underpinning those effects. A reliable device to measure the tear evaporation rate was developed and validated. Tear collection methods were optimised to characterise the tear lipidome. Electro spray tandem mass spectrometry was used to analyse individual lipid components. A pilot study demonstrated that the tear film stability during short-term contact lens wear was associated with ocular comfort, the activity of phospholipase A2 enzyme (sPLA2) and the concentrations of a lipid aldehyde, malondialdehyde (MDA). After 6-8 hours of lens wear, as the tear film stability increased so did the mole% of wax esters in the total lipidome whereas the mole% of cholesterol esters decreased. Higher tear evaporation rates were associated with reduced levels of phospholipids. The study also provided preliminary evidence for the effectiveness of an exogenous lipid supplement in improving ocular comfort and tear film stability during short-term contact lens wear. In the light of these preliminary findings, a double-masked, randomised crossover placebo controlled intervention study was conducted among habitual contact lens wearers to investigate various aspects of the lipid layer following the administration of two formulations of tear lipid supplements and their respective vehicle placebo. A transient improvement in tear film stability with the two lipid supplements was observed in symptomatic contact lens wearers. However, the improvement did not persist by the end of 2-week long lens wear. Between the two supplements, the anionic phospholipid emulsion drop showed a superior effect in ocular comfort, lipid layer appearance and tear evaporation rate in symptomatic wearers compared to the zwitterionic phospholipid spray. Improved contact lens wear comfort was related to increased tear film stability and lipid layer thickness, and a reduced tear evaporation rate, sPLA2 concentration and activity in tears. Increased concentration of sPLA2 was also associated with higher concentrations of degraded phospholipids and reduced levels of (O-acyl)-ω-hydroxy fatty acids in tears. The study found significant associations between various aspects of the lipid layer and comfort of the eye. These associations suggests that alterations in lipid biochemistry might be modulating changes in clinical and functional aspects of lipid layer which triggers changes in lens wear comfort. The learnings may help to inform development of topical preparations to improve comfort. Thus, the thesis provided an evidence based assessment of the effect of topical lipid preparations on ocular comfort by a comprehensive exploration of the clinical, functional and biochemical aspects of tear lipid layer.