Purpose To investigate ocular surface sensations, specifically ocular discomfort using psychophysical and clinical techniques. The measurement of discomfort on the ocular surface has been limited to the use of traditional rating scales until recently. This thesis focuses on the scaling of discomfort using a psychophysical approach and also investigates the less explored area of the influence of blur on ocular discomfort. The specific aims of each chapter are: Chapter 2: To evaluate the difference thresholds of the central cornea in lens and non-lens wearers. Chapter 3: To devise a novel scale for ocular discomfort, relating subjective estimation of discomfort arising from contact lens wear to discomfort produced by the pneumatic stimuli delivered by a modified Belmonte esthesiometer. Chapter 4: To evaluate the influence of blur on ocular comfort while systematically manipulating vision using habitual refractive correction, induced spatial and optical blur, and under the absence of visual structure. Chapter 5: To examine if subjects rate discomfort and intensity of suprathreshold pneumatic stimuli differently when viewing clear and defocused targets and to examine the suprathreshold scaling of stimuli under the same visual conditions. Methods Chapter 2: The mechanical sensitivity of the central cornea was determined in 12 lens wearers and 12 non-lens wearers using a modified Belmonte pneumatic esthesiometer. The mechanical threshold of the central cornea was first estimated using the method of limits. Then, a series of systematically increasing stimuli were presented, with the first stimuli being 25% less than the threshold. The subjects were asked to compare the intensity of each stimulus with the preceding one and report if any difference in intensity was detectable. The intensities at which the subjects perceived an increased intensity from the previous was recorded. The difference threshold (DL) was the differences between the stimulus intensities at which an increase was perceived and five DLs were measured for each subject. Weber’s constants that relate the size of the difference thresholds to the stimulus intensity were derived for each DL level and repeated measures ANOVA was used to compare the Weber’s constants in the lens and non-lens wearing groups. Chapter 3: Twenty seven participants were enrolled for this magnitude matching study. Soft (HEMA) contact lenses of eight different lens designs varying in base curve and diameter were fit on all participants. The study was conducted on two separate days with four lenses randomly assigned on each day. The assigned soft contact lens was placed on the chosen eye and the sensations were measured using a numerical rating scale. Following this, the subjects were asked to regulate the intensity of the pneumatic stimulus using the control dial in order to match the discomfort from the stimulus to the discomfort from contact lens wear. At the completion of magnitude matching, ratings of sensations were again recorded. Pearson product moment correlation was used to correlate the objective esthesiometer matches to the subjective ratings of discomfort reported by each participant. The method of least log squares was used to derive the power exponents as defined by Stevens’ power law and analyze the psychophysical functions. Repeated measures ANOVA was used to investigate the effect of lens sequence and session on ocular discomfort with contact lens wear. The impact of lens type and time on discomfort was studied using linear mixed modeling. Chapter 4: Twenty emmetropic subjects rated ocular comfort, vision and sensation attributes (burning, itching and warmth) under conditions of normal vision, spatial blur and dioptric defocus, each session lasting for five minutes. Subjects viewed digital targets projected from a distance of 3m, and ocular surface sensations, vision were rated using magnitude estimation. Dioptric defocus was produced using +6.00DS contact lenses and equivalent spatial blur was created by spatially blurring the targets. Clear target images were used during dioptric defocus and blurred images during spatial blur session. Comfort was also rated under the absence of visual structure in fifteen of the participants using a ganzfeld and black occluders. Repeated measures ANOVA was used to compare vision and comfort ratings between the different experimental conditions. Chapter 5: Twenty one participants were enrolled. Ocular discomfort was produced by delivering mechanical stimuli from a pneumatic esthesiometer, and participants were asked to rate the intensity of stimulus and the discomfort induced by it under clear and defocused visual conditions. Esthesiometry was performed on one eye while the fellow eye viewed either a clear or blurred 6/60 fixation target through a trial lens. For the clear visual condition, the trial lens contained +0.25DS over their distance refractive correction and for the defocused condition, an additional +4.00DS was used. Mechanical thresholds from the central cornea were estimated using ascending methods of limits and then stimuli that were 25%, 50%, 75% and 100 % above threshold were presented in random order. Participants rated intensity and discomfort of each stimulus using a 0-100 numerical scale where 0 indicated no sensation and 100 indicated highest imaginable intensity/discomfort. There were 3 sessions with clear visual conditions and 3 sessions with defocus, in random order. Results Chapter 2: The functions relating Weber’s constants to stimulus intensities were slightly different in lens and non-lens wearing groups, although the absolute thresholds were similar. Repeated measures ANOVA revealed a significant main effect of DL level on Weber’s constant (p<0.001), with the Weber’s fraction at the first DL being higher than the following DLs. A significant main effect of the group type was also observed, with the lens wearers showing higher Weber’s constants than the non-lens wearers (p=0.02) However, there was no interaction between DL level and lens wearing group on Weber’s constants (p=0.38). Chapter 3: The average and individual psychophysical functions appeared to follow Stevens’ power function, with mechanical and chemical stimuli giving rise to different power exponents. Examination of the individual transducer functions revealed that only about half of the subjects were able to match the contact lens sensations to the pneumatic stimulus discomfort, with both mechanical and chemical stimulation. The lens types did not have any impact (p=0.65) on the session or sequence in which the lens was presented, although an effect of session and sequence on discomfort was observed. The average discomfort ratings produced by the different lens types were similar. There appeared to be significant effects of time (p<0.001) on the reporting of discomfort with lens wear, with the discomfort upon lens insertion rated to be higher than after lenses settling. Chapter 4: Ratings of vision under spatial blur and dioptric defocus were significantly different (p<0.001) from normal vision condition. Vision with dioptric defocus was rated worse (p<0.001) than spatial blur. Significant differences in comfort were observed between normal vision and blur, including spatial blur (p=0.02) and dioptric defocus (p=0.001). However, there was no significant difference (p=0.99) in comfort between spatial blur and dioptric defocus. Comfort remained unchanged between normal vision, occluders and ganzfeld although vision was absent in the later two conditions. Chapter 5: There was no significant difference in mechanical thresholds under clear and defocused conditions with a paired t-test (p=0.66) and similar results were obtained with repeated measures ANOVA, with no significant difference in discomfort (p=0.10) and intensity (p=0.075) ratings between the two visual conditions. However, paired t-test between the derived exponents under clear and defocused conditions showed significant differences for discomfort (p=0.05) and no significant difference for the ratings of intensity (p=0.22). Comparison of exponents between discomfort and intensity showed a significant difference in both clear (p=0.02) and defocus conditions (p<0.001). Conclusions: Chapter 2: The differential sensitivity of the ocular surface can be successfully measured with a pneumatic esthesiometer and it appears that Weber’s law holds true for corneal nociceptive sensory processing. There are subtle differences in mechanical difference thresholds between lens and non-lens wearers suggesting the possibility of different neural activity levels in the two groups. Chapter 3: Subjective ratings of discomfort can be scaled by corneal esthesiometry in a selective group of people. In the subset of subjects with poorer correlations, perhaps the pneumatic mechanical stimulus was too localized and specific to match the complex sensations experienced while wearing contact lenses. However, there is also a group of subjects who are poor at making judgments about ocular comfort. Hence, the use of special sensory panels should be considered when ocular comfort is the primary outcome. Chapter 4: There does seem to be an association between clarity of vision and ocular comfort, although the pathways for pain and vision are perhaps exclusive. Interactions between vision and other senses have been reported, but a similar inter-sensory interaction between pain and vision is yet to be clearly demonstrated. The decreased comfort observed in this study might perhaps be due to nocebo or Hawthorne effects. Chapter 5: Suprathreshold scaling of pneumatic stimuli can vary with the viewing conditions, with defocus associated with higher exponents than clear visual conditions. However, the ratings of comfort appear to be similar under both the conditions. If defocus does affect comfort, it is subtle and does not affect the sensory components, but tiny effects through the affective aspect of pain can contribute to the differences in power exponents. The differences in the perception of comfort do not appear to be attributable to the differences in threshold or sensory intensity.

Purpose To investigate ocular surface sensations, specifically ocular discomfort using psychophysical and clinical techniques. The measurement of discomfort on the ocular surface has been limited to the use of traditional rating scales until recently. This thesis focuses on the scaling of discomfort using a psychophysical approach and also investigates the less explored area of the influence of blur on ocular discomfort. The specific aims of each chapter are: Chapter 2: To evaluate the difference thresholds of the central cornea in lens and non-lens wearers. Chapter 3: To devise a novel scale for ocular discomfort, relating subjective estimation of discomfort arising from contact lens wear to discomfort produced by the pneumatic stimuli delivered by a modified Belmonte esthesiometer. Chapter 4: To evaluate the influence of blur on ocular comfort while systematically manipulating vision using habitual refractive correction, induced spatial and optical blur, and under the absence of visual structure. Chapter 5: To examine if subjects rate discomfort and intensity of suprathreshold pneumatic stimuli differently when viewing clear and defocused targets and to examine the suprathreshold scaling of stimuli under the same visual conditions. Methods Chapter 2: The mechanical sensitivity of the central cornea was determined in 12 lens wearers and 12 non-lens wearers using a modified Belmonte pneumatic esthesiometer. The mechanical threshold of the central cornea was first estimated using the method of limits. Then, a series of systematically increasing stimuli were presented, with the first stimuli being 25% less than the threshold. The subjects were asked to compare the intensity of each stimulus with the preceding one and report if any difference in intensity was detectable. The intensities at which the subjects perceived an increased intensity from the previous was recorded. The difference threshold (DL) was the differences between the stimulus intensities at which an increase was perceived and five DLs were measured for each subject. Weber’s constants that relate the size of the difference thresholds to the stimulus intensity were derived for each DL level and repeated measures ANOVA was used to compare the Weber’s constants in the lens and non-lens wearing groups. Chapter 3: Twenty seven participants were enrolled for this magnitude matching study. Soft (HEMA) contact lenses of eight different lens designs varying in base curve and diameter were fit on all participants. The study was conducted on two separate days with four lenses randomly assigned on each day. The assigned soft contact lens was placed on the chosen eye and the sensations were measured using a numerical rating scale. Following this, the subjects were asked to regulate the intensity of the pneumatic stimulus using the control dial in order to match the discomfort from the stimulus to the discomfort from contact lens wear. At the completion of magnitude matching, ratings of sensations were again recorded. Pearson product moment correlation was used to correlate the objective esthesiometer matches to the subjective ratings of discomfort reported by each participant. The method of least log squares was used to derive the power exponents as defined by Stevens’ power law and analyze the psychophysical functions. Repeated measures ANOVA was used to investigate the effect of lens sequence and session on ocular discomfort with contact lens wear. The impact of lens type and time on discomfort was studied using linear mixed modeling. Chapter 4: Twenty emmetropic subjects rated ocular comfort, vision and sensation attributes (burning, itching and warmth) under conditions of normal vision, spatial blur and dioptric defocus, each session lasting for five minutes. Subjects viewed digital targets projected from a distance of 3m, and ocular surface sensations, vision were rated using magnitude estimation. Dioptric defocus was produced using +6.00DS contact lenses and equivalent spatial blur was created by spatially blurring the targets. Clear target images were used during dioptric defocus and blurred images during spatial blur session. Comfort was also rated under the absence of visual structure in fifteen of the participants using a ganzfeld and black occluders. Repeated measures ANOVA was used to compare vision and comfort ratings between the different experimental conditions. Chapter 5: Twenty one participants were enrolled. Ocular discomfort was produced by delivering mechanical stimuli from a pneumatic esthesiometer, and participants were asked to rate the intensity of stimulus and the discomfort induced by it under clear and defocused visual conditions. Esthesiometry was performed on one eye while the fellow eye viewed either a clear or blurred 6/60 fixation target through a trial lens. For the clear visual condition, the trial lens contained +0.25DS over their distance refractive correction and for the defocused condition, an additional +4.00DS was used. Mechanical thresholds from the central cornea were estimated using ascending methods of limits and then stimuli that were 25%, 50%, 75% and 100 % above threshold were presented in random order. Participants rated intensity and discomfort of each stimulus using a 0-100 numerical scale where 0 indicated no sensation and 100 indicated highest imaginable intensity/discomfort. There were 3 sessions with clear visual conditions and 3 sessions with defocus, in random order. Results Chapter 2: The functions relating Weber’s constants to stimulus intensities were slightly different in lens and non-lens wearing groups, although the absolute thresholds were similar. Repeated measures ANOVA revealed a significant main effect of DL level on Weber’s constant (p<0.001), with the Weber’s fraction at the first DL being higher than the following DLs. A significant main effect of the group type was also observed, with the lens wearers showing higher Weber’s constants than the non-lens wearers (p=0.02) However, there was no interaction between DL level and lens wearing group on Weber’s constants (p=0.38). Chapter 3: The average and individual psychophysical functions appeared to follow Stevens’ power function, with mechanical and chemical stimuli giving rise to different power exponents. Examination of the individual transducer functions revealed that only about half of the subjects were able to match the contact lens sensations to the pneumatic stimulus discomfort, with both mechanical and chemical stimulation. The lens types did not have any impact (p=0.65) on the session or sequence in which the lens was presented, although an effect of session and sequence on discomfort was observed. The average discomfort ratings produced by the different lens types were similar. There appeared to be significant effects of time (p<0.001) on the reporting of discomfort with lens wear, with the discomfort upon lens insertion rated to be higher than after lenses settling. Chapter 4: Ratings of vision under spatial blur and dioptric defocus were significantly different (p<0.001) from normal vision condition. Vision with dioptric defocus was rated worse (p<0.001) than spatial blur. Significant differences in comfort were observed between normal vision and blur, including spatial blur (p=0.02) and dioptric defocus (p=0.001). However, there was no significant difference (p=0.99) in comfort between spatial blur and dioptric defocus. Comfort remained unchanged between normal vision, occluders and ganzfeld although vision was absent in the later two conditions. Chapter 5: There was no significant difference in mechanical thresholds under clear and defocused conditions with a paired t-test (p=0.66) and similar results were obtained with repeated measures ANOVA, with no significant difference in discomfort (p=0.10) and intensity (p=0.075) ratings between the two visual conditions. However, paired t-test between the derived exponents under clear and defocused conditions showed significant differences for discomfort (p=0.05) and no significant difference for the ratings of intensity (p=0.22). Comparison of exponents between discomfort and intensity showed a significant difference in both clear (p=0.02) and defocus conditions (p<0.001). Conclusions: Chapter 2: The differential sensitivity of the ocular surface can be successfully measured with a pneumatic esthesiometer and it appears that Weber’s law holds true for corneal nociceptive sensory processing. There are subtle differences in mechanical difference thresholds between lens and non-lens wearers suggesting the possibility of different neural activity levels in the two groups. Chapter 3: Subjective ratings of discomfort can be scaled by corneal esthesiometry in a selective group of people. In the subset of subjects with poorer correlations, perhaps the pneumatic mechanical stimulus was too localized and specific to match the complex sensations experienced while wearing contact lenses. However, there is also a group of subjects who are poor at making judgments about ocular comfort. Hence, the use of special sensory panels should be considered when ocular comfort is the primary outcome. Chapter 4: There does seem to be an association between clarity of vision and ocular comfort, although the pathways for pain and vision are perhaps exclusive. Interactions between vision and other senses have been reported, but a similar inter-sensory interaction between pain and vision is yet to be clearly demonstrated. The decreased comfort observed in this study might perhaps be due to nocebo or Hawthorne effects. Chapter 5: Suprathreshold scaling of pneumatic stimuli can vary with the viewing conditions, with defocus associated with higher exponents than clear visual conditions. However, the ratings of comfort appear to be similar under both the conditions. If defocus does affect comfort, it is subtle and does not affect the sensory components, but tiny effects through the affective aspect of pain can contribute to the differences in power exponents. The differences in the perception of comfort do not appear to be attributable to the differences in threshold or sensory intensity.

<b>Purpose:</b> Assess the relationship between tear film drying and sensation between blinks. <b>Methods:</b> MATLAB sampled a slitlamp video camera, a potentiometer and a microphone while subjects kept one eye open for as long as possible. 23 subjects rated the intensity of the ocular sensation while video and voice data were collected simultaneously. The tear drying on the cornea was measured. <b>Results:</b> The sensation was triphasic. Two linear functions described the latter 2 parts of the data (r &#8805; 0. 95). The correlation between TBUT and the elbow in the time-discomfort function was 0. 72. Extent of tear film drying was linearly correlated to time (median correlation = 0. 88). The correlation between the discomfort elbow and image elbow was 0. 93 with single data pair for each subject. Analysis of sensation characteristics showed significant differences between itching and burning for both intensity and time (p = 0. 03 and p = 0. 02 respectively). <b>Conclusions:</b> Simultaneous recording of ocular surface appearance, discomfort intensity and attributes of sensation provide novel information about the development of discomfort during ocular surface drying. The rapid increase in discomfort proceeding blinking has been quantified and the relationship between the time course of drying and discomfort is elucidated.

<b>Purpose:</b> Assess the relationship between tear film drying and sensation between blinks. <b>Methods:</b> MATLAB sampled a slitlamp video camera, a potentiometer and a microphone while subjects kept one eye open for as long as possible. 23 subjects rated the intensity of the ocular sensation while video and voice data were collected simultaneously. The tear drying on the cornea was measured. <b>Results:</b> The sensation was triphasic. Two linear functions described the latter 2 parts of the data (r &#8805; 0. 95). The correlation between TBUT and the elbow in the time-discomfort function was 0. 72. Extent of tear film drying was linearly correlated to time (median correlation = 0. 88). The correlation between the discomfort elbow and image elbow was 0. 93 with single data pair for each subject. Analysis of sensation characteristics showed significant differences between itching and burning for both intensity and time (p = 0. 03 and p = 0. 02 respectively). <b>Conclusions:</b> Simultaneous recording of ocular surface appearance, discomfort intensity and attributes of sensation provide novel information about the development of discomfort during ocular surface drying. The rapid increase in discomfort proceeding blinking has been quantified and the relationship between the time course of drying and discomfort is elucidated.