AbstractPurposeTo investigate differences in key clinical parameters between asymptomatic and highly symptomatic soft contact lens (CL) wearers after 14 h of wear.MethodsIn this pilot investigation, Phase 1 identified asymptomatic (CLDEQ‐8 score ≤ 7) and highly symptomatic (CLDEQ‐8 score ≥ 20) subjects after fitting with nelfilcon A CLs. Phase 2 investigated the following over a single nelfilcon A CL‐wearing day (14 ± 2 h): blinking characteristics, tear meniscus height (TMH), non‐invasive tear break‐up time (NIBUT), tear film osmolarity and eyelid margin staining. Parameters for the two groups were compared using linear mixed models and post‐hoc testing. The relationship between comfort scores and the clinical parameters was also investigated.ResultsOverall, 161 and 42 subjects were enrolled into Phase 1 and 2, respectively. Twenty‐five asymptomatic and 17 symptomatic subjects completed Phase 2. Lower eyelid TMH was decreased after 14 h in symptomatic compared with asymptomatic subjects (least square mean [LSM] difference −0.04 mm, 95% CI: −0.07, −0.01). Osmolarity was lower in symptomatic than in asymptomatic subjects at fitting (LSM difference −9.89, 95% CI: −18.91, −0.86). Upper eyelid margin staining was greater after 14 h in symptomatic than in asymptomatic subjects (LSM difference 0.53, 95% CI: 0.01, 1.05) and greater after 14 h than baseline in the symptomatic group (LSM difference 0.61, 95% CI: 0.16, 1.07). There was a significant relationship between comfort and upper eyelid margin staining (r = −0.40, 95% CI: −0.63, −0.11) and blink rate (r = −0.31, 95% CI: −0.57, −0.003).ConclusionThe potential parameters most effective in differentiating asymptomatic from symptomatic wearers were upper eyelid margin staining and lower TMH. The parameter with the strongest relationship to comfort was upper eyelid margin staining, where higher comfort scores were associated with lower levels of staining.