2023 Prentice Medal Award lecture: Ocular surface-related symptoms of discomfort and other stories.

ABSTRACT: I have been fortunate to spend portions of my career in each of private practice, industry, and academia. At some times, these occupations have dictated the research direction, whereas, at others, curiosity has been allowed to dominate. This has resulted in multiple avenues of inquiry (some might say, too many), along which I have traveled with a rich and varied cast of collaborators, who have all taught me a great deal. The privilege of being awarded the Charles F. Prentice medal provides me an opportunity to summarize some of these activities. Beginning with an attempt to use contact lenses to solve a problem for those affected by albinism, the story shifts to addressing some of the wider deficiencies of contact lenses, in particular the consequences of their oxygen permeability and tendency to induce discomfort toward the end of the day. After briefly considering some aspects of meibomian gland function, the narrative concludes with the latest investigations of neurological links between the cornea and migraine.

Diagnosing dry-eye: Which tests are most accurate?

PURPOSE: To demonstrate how the likelihood of making a correct diagnosis of dry eye disease varies according to the clinical test methods used. METHODS: The probability of a person having dry eye, given that they return a positive test, was calculated for a range of standard tests, using the Bayes-Price rule. Global specificity and sensitivity values for each test were estimated by employing the Beta distribution to combine all relevant data obtained from a literature review. RESULTS: At an assumed prevalence of 11.6%, the single test with the highest probability of a correct diagnosis was corneal staining (probability = 0.28) and the lowest was the ocular surface disease index - OSDI (0.14). The best combination of symptoms with a single test of tear film homeostasis was the 5-item dry eye questionnaire (DEQ-5) + corneal staining (0.42) while OSDI + tear film break up time (TBUT) was the worst (0.23). The simultaneous observation of conjunctival and corneal staining was associated with a probability of 0.49. The probability of a correct diagnosis increased with the number of positive tests, up to a maximum of 0.90 when all of DEQ-5, conjunctival and corneal staining, osmolarity and TBUT were positive. CONCLUSION: A significant risk of misdiagnosis is associated with using any single test for dry eye disease, or the minimum TFOS DEWS II criterion of symptoms plus any single test of tear film homeostasis. To minimize this risk, the maximum number of tests available should be performed and the results used to inform diagnosis. The simultaneous occurrence of conjunctival and corneal staining should be considered a key outcome and be specified in future guidelines.

Associations between Binocular Vision Disorders and Contact Lens Dissatisfaction.

SIGNIFICANCE: These data demonstrate that binocular vision disorders (BVDs) contribute to contact lens (CL) dissatisfaction independently of CL discomfort (CLD) in myopic, pre-presbyopic, adult, single-vision CL wearers. PURPOSE: This study aimed to determine whether BVDs contribute to CL dissatisfaction and whether this contribution is independent of CLD. METHODS: Participants attended one clinical visit while wearing their habitual CLs. Symptoms from CLD and BVDs were measured with the Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and Convergence Insufficiency Syndrome Survey (CISS), respectively. A comprehensive binocular vision (BV) assessment was performed. The Ocular Surface Disease Index (OSDI) was used to measure CL dissatisfaction from CLD and BVDs based on reported correlations between the CLDEQ-8 and the CISS with the OSDI. Participants were categorized according to their CL comfort status (CLD [≥12 on CLDEQ-8] or non-CLD [<12 on CLDEQ-8]) and BV status (BVD or non-BVD). RESULTS: Seventy-six participants completed the trial, and 19 (25%) were diagnosed with BVD. Those diagnosed with BVD scored higher than did those diagnosed with non-BVD for the OSDI (25.1 ± 12.7 vs. 10.7 ± 7.3, P < .001) and CISS (18.7 ± 7.7 vs. 11.9 ± 5.9, P = .001), but not the CLDEQ-8 (P = .25). Those categorized as having CLD scored higher than did those categorized as having non-CLD for the OSDI (19.0 ± 12.3 vs. 9.3 ± 5.9, P = .003) and CISS (16.1 ± 6.8 vs. 11.0 ± 6.2, P = .001). There were no significant interactions between BV status and CL comfort status for any questionnaire (P > .08). CONCLUSIONS: Higher scores for OSDI in those with CLD or BVD indicate that both conditions contribute to CL dissatisfaction. Higher scores for the CISS in those with CLD suggest a degree of overlap for some BVD symptoms. Nonsignificant differences between BVD and non-BVD for the CLDEQ-8 suggest that BVDs contribute to CL dissatisfaction independently of CLD.

The global prevalence of dry eye disease: A Bayesian view.

PURPOSE: To provide estimates for the prevalence of dry eye disease globally and in sub-groups defined by: diagnostic criterion, sex, geographic location and age, using a Bayesian approach. METHODS: Modelling prevalence as a Beta distribution, estimates were inferred from Bayesian posterior distributions obtained by combing an uninformed prior with likelihood functions generated from all relevant studies reporting dry eye prevalence between 1997 and 2021. RESULTS: Global prevalence of dry eye disease was estimated at 11.59% (standard deviation (SD) = 0.04). For symptomatic disease, the estimate was 9.12% (SD = 0.04), with women 9.5% (SD = 0.05) and men 6.8% (SD = 0.06); prevalence was lowest in North America, 4.6% (SD = 0.03) and highest in Africa, 47.9% (SD = 1.8). For signs, prevalence was 35.2% (SD = 0.3), with woman 34.7% (SD = 0.7) and men 37.6% (SD = 0.7); North America showed the lowest regional prevalence, 3.5%, (SD = 0.4) with Eastern Asia the highest, 42.8% (SD = 0.4). Using TFOS DEWS II diagnostic criteria resulted in a global prevalence of 29.5% (SD = 0.8), with women 28.1% (SD = 1.2) and men 24.9% (SD = 1.4). Prevalence was lowest during the fifth decade, increasing approximately linearly with age thereafter. Estimates for other categories are given in accompanying tables. CONCLUSION: A simple, flexible, yet powerful means of combining data from multiple sources to yield prevalence estimates across a range of circumstances is described, that is compatible with published guidelines for conducting meta-analysis. Estimates can be readily updated as new information emerges, or according to need. Understanding the specific characteristics of studies chosen for inclusion is critical to the validity of the outcome. Although dry eye disease is evidently common, affecting about one in 11 people world-wide, data are sparse for the young and all geographical locations except Eastern Asia.

Filaggrin Expression in the Lid Margin During Contact Lens Wear.

AIM: To investigate the expression of the keratinization-related protein, filaggrin, in the lid margin epithelium of contact lens (CL) wearers compared with nonwearers. METHODS: This was a cross-sectional study of 100 individuals with different exposures to CL wear: short, moderate, and long experience; previous CL wearers; and nonwearers as controls. Impression cytology samples were collected from the lid wiper (LW) area of the central upper lid margin. After fixing, an equal, random sample was selected from each group (n=13) for immunocytochemistry analysis using antihuman primary anybody (mouse filaggrin), then stained with secondary antibody (fluorescein isothiocyanate-conjugated donkey anti-mouse immunoglobulin G horseradish peroxidase) to detect filaggrin. Imaging was performed with the 3i-Vivo 2-photon microscope equipped with a Zeiss 20×-objective and SlideBook-reader software. RESULTS: Sixty-five samples from 65 participants (37 women; mean age±SD: 25.1±4.1 years) were collected. Filaggrin was detected in all 65 randomly selected immunostained marginal epithelium samples. All samples were similar in showing patchy areas of filaggrin immunostaining, regardless of CL wear, symptoms or epithelium morphology. Because the filaggrin immunostaining showed similar patterns across almost all the observed samples, comparison between subject groups was impractical. The presence of filaggrin in the healthy LW was additionally confirmed by an independent laboratory. CONCLUSION: Filaggrin expression seems to be a normal part of epithelial cell differentiation in the lid margin and may not be a useful keratinization/stress biomarker in the marginal epithelium. Investigating other keratinization biomarkers that are not detected in the normal mucocutaneous junction/LW may help to understand the keratinization nature of LW epithelium changes in CL wearers.

Photobiomodulation (low-level light therapy) and dry eye disease.

Dry eye disease is one of the most common, chief-complaints presenting in clinical practice, with a prevalence of up to 50%. Evaporative dry eye, as a result of meibomian gland dysfunction, is thought to be the biggest component factor. Treatments for meibomian gland dysfunction aim to restore tear film homoeostasis and include warm compress therapy, eyelid hygiene, in-office meibomian gland expression and lipid-containing, artificial tears. A recent introduction to the in-office treatments available for meibomian gland dysfunction has been low-level light therapy, also known as photobiomodulation. The technique involves applying red, or near infra-red, radiation using low-power light sources and is suggested to promote tissue repair, decrease inflammation, and relieve pain. This work aims to review the available literature on the efficacy and safety of photobiomodulation in meibomian gland dysfunction and dry eye disease, as well as what is currently known about its mechanism of action.

Temporal considerations in contact lens discomfort.

PURPOSE: To determine the relative contributions to perceived discomfort during contact lens wear of contact time with the lens and the time of day at which wear begins, using a wearing framework similar to that of regular users. METHODS: Twenty-three participants reported ocular discomfort using a 1-100 visual analogue rating scale, when prompted by email, during one day without contact lenses and on three other days while wearing soft contact lenses for twelve hours. Contact lens wear began at a different time on each day. The effect of start time on the change in discomfort during the wearing period was evaluated. RESULTS: The average (± 95 % CI) change in discomfort over 12 h without contact lenses was -0.3 ± 3.5. The corresponding values during contact lens wear were 23.5 ± 14.6 when starting wear before 8am, 16.8 ± 11.0 when starting between 8am & 10am and 22.7 ± 8.4 when starting after 10am. While the increased discomfort was significant irrespective of start time (p < 0.01), there were no statistically significant differences between start times (p = 0.98). CONCLUSION: Discomfort during contact lens wear is associated with the length of time lenses are on-eye but not with the time of day when lenses are placed on-eye. This relationship is variable in the population and does not, of itself, explain why contact lenses become uncomfortable during wear. Active monitoring of participant compliance should be a consideration in all studies involving time critical responses.

Changes in the tarsal conjunctiva viewed by in vivo confocal microscopy are associated with ocular symptoms and contact lens wear.

PURPOSE: To investigate the effect of soft contact lens (CL) wear on the morphology of the epithelial-lamina propria junction as well as the possible association with symptoms of discomfort. METHODS: Ninety-two subjects were recruited, including 60 soft CL wearers, 16 previous wearers, and 16 non-wearers. Additionally, subjects were classified as symptomatic or asymptomatic using the Contact Lens Dry Eye Questionnaire 8 for the CL wearers (a score ≥ 12 was considered symptomatic) and the Dry Eye Questionnaire 5 for the previous wearers and non-wearers (a score ≥ 5 was considered symptomatic). In vivo confocal microscopy of the tarsal conjunctiva was performed on a single occasion. Papillae density, shortest diameter, longest diameter, area, circularity, lumen/wall brightness ratio, irregularity, reflectivity, inhomogeneous appearance of wall and inhomogeneous appearance of rete ridges were evaluated. Effects of CL wear, symptoms and their interaction were analysed using two-way analysis of variance. Correlations were investigated using Spearman's coefficient. Data are presented as mean (standard deviation) or median [interquartile range]. RESULTS: Contact lens wearers, compared to previous wearers and non-wearers, showed higher circularity [0.65 (0.08) vs 0.59 (0.10) vs 0.57 (0.11), p = 0.003]. Subjects with symptoms, compared to asymptomatic participants, showed higher circularity [0.64 (0.08) vs 0.61 (0.10), p < 0.001] and lower irregularity (1.0 [0.7-2.0] vs 1.3 [1.0-2.3], p = 0.009). For previous wearers, those with symptoms showed greater density (135.4 [107.3-183.3] vs 87.5 [85.4-116.7], p = 0.013) and circularity [0.64 (0.07) vs 0.54 (0.10), p = 0.016]. For non-wearers, those with symptoms showed higher circularity [0.65 (0.08) vs 0.50 (0.08), p < 0.001]. DEQ-5 correlated with circularity (ρ = 0.55, p = 0.001). CONCLUSIONS: Soft CL wear modifies papillae of the epithelial-lamina propria junction into a more rounded shape; however, CL cessation appears to resolve this alteration. Additionally, a more rounded papillae shape is associated with ocular symptoms in subjects not actively wearing CLs.

Prevalence of Primary Glaucoma as Diagnosed by Study Optometrists of L. V. Prasad eye Institute - Glaucoma Epidemiology and Molecular Genetics Study.

PURPOSE: To report the prevalence of primary glaucoma as identified by study optometrists of the L. V. Prasad Eye Institute - Glaucoma Epidemiology and Molecular Genetics Study (LVPEI-GLEAMS). METHODS: Two study optometrists and a total number of 3833 individuals participated in the LVPEI-GLEAMS. All subjects underwent a complete medical history and comprehensive eye examination including slit lamp photography, imaging of anterior and posterior segment, frequency doubling technology and standard automated perimetry including gonioscopy with a Sussman 4 mirror goniolens, post dilated evaluation of the optic disc and fundus was done with a 90 D lens by the study optometrist. A diagnosis of primary open angle glaucoma (POAG), primary angle closure suspect (PACS), primary angle closure (PAC), primary angle closure glaucoma (PACG), normal tension glaucoma (NTG), glaucoma/disc suspect or no glaucoma was made based on the clinical examination. RESULTS: Estimated prevalence of OAG (POAG and NTG) was 1.07% (0.74-1.39), PACS 2.03% (1.58-2.48), PAC 1.77% (1.35-2.19), PACG 0.21% (0.06-0.35) as identified by the study optometrists on site. CONCLUSIONS: Prevalence of all the categories of primary glaucoma, as reported by the study optometrists of LVPEI-GLEAMS was comparable to previous findings of other regions in South India.

Measuring Daily Disposable Contact Lenses against Nonwearer Benchmarks.

SIGNIFICANCE: Since becoming a popular form of refractive error correction, contact lenses have aspired to replicate the nonwearer experience. This study assessed how well currently available daily disposable soft lenses have achieved that goal, using a graphical representation to show individual lens behavior relative to benchmarks. PURPOSE: The purpose of this study was to assess comfort, vision, and adverse events during daily disposable contact lens wear, relative to emmetropes and spectacle wearers. METHOD: Three-month clinical studies, where participants either wore one of five daily disposable contact lenses (n = 201), were full-time spectacle wearers with no history of contact lens wear (n = 34), or emmetropic non-contact lens wearers (n = 40). Vision quality and comfort were assessed at the beginning and end of the day (1 to 10). Corneal infiltrative events were recorded. Between-group comparisons were made using a linear mixed model and literature estimates of clinical significance. RESULTS: Initial comfort among emmetropes (mean ± 95% confidence interval, 8.0 ± 0.5) was not significantly different from any of the lens types (range, 7.2 ± 0.4 to 8.0 ± 0.4, all P > .06) or spectacle wearers (7.3 ± 0.5, P = .45). Comfort deteriorated during the day in all groups (P < .05). End-of-day comfort for emmetropes (7.3 ± 0.6) was significantly better, only than lenses B (5.7 ± 0.6, P < .001) and D (6.2 ± 0.5, P = .01). Vision quality for emmetropes (8.6 ± 0.5) was better than spectacle wearers (7.8 ± 0.5, P = .04) and lenses A (7.6 ± 0.4, P = .003) and B (7.5 ± 0.4, P < .001). Corneal infiltrative events occurred in 0% of emmetropes and 2.9% of spectacle wearers and ranged from 2.4 to 7.5% in lens wearers. CONCLUSIONS: Under the conditions of this study, comfort and vision with some contemporary daily disposable contact lenses were indistinguishable from nonwearing emmetropes. Although the contact lens-wearing groups had rates of corneal infiltrative events that were not statistically different from the nonwearers, the study had insufficient power to permit robust conclusions in this respect.

The Effect of Contact Lens Wear on the Cellular Morphology of the Lid Wiper Area.

SIGNIFICANCE: This cross-sectional study presented a link between contact lens wear and changes on the cellular morphology characteristics of the lid wiper (LW) epithelium, which was not visible by LW staining. PURPOSE: The aim of this study was to establish if the duration of contact lens (CL) wear affects the cellular morphology of the LW epithelium. METHODS: This was a cross-sectional study of 100 individuals with different exposures to CL wear: short, moderate, and long experience of CL wear; previous CL wearers; and nonwearers (NWs) as controls. Impression cytology samples were collected from the central upper lid margin (LW area). After fixing, samples were stained with periodic acid-Schiff and haematoxylin for cell morphology analysis and subsequently graded according to the Nelson 0- to 3-point scale. Lid wiper staining was assessed with the aid of lissamine green and graded using the Korb (0- to 3-point) scale. One-way Kruskal-Wallis analysis followed by the Dunn multiple-comparisons test was used for statistical comparison. RESULTS: The Nelson grade for LW epithelium morphology was significantly different between groups (P = .003). Abnormal epithelial morphology as defined by grade 2 or 3 was evident in 66.7% of CL wearers with short experience and 76.5% of CL wearers with moderate experience. This was significantly higher than NWs of whom only 21.5% showed greater than grade 1 (P = .02 and .005, respectively). There was no significant difference between NWs and other groups. Lid wiper staining did not significantly differ between groups (P = .50) or correlate with the Nelson grade (Spearman r = 0.02, P = .08). CONCLUSIONS: Metaplasia of the LW epithelium was significantly greater in the early to moderate stages of CL. This supports the view that mechanical irritation is responsible for LW changes in CL wear. Ceasing CL wear seems to lead to recovery. Lid wiper staining did not reflect the underlying morphological changes.

Treatment Practices and Outcomes of Meibomian Gland Dysfunction at a Tertiary Center in Southern India.

OBJECTIVE: To describe the current treatment practices for meibomian gland dysfunction (MGD) at a tertiary eye center, together with the subjective outcomes and compliance behaviors of patients. METHODS: This retrospective cohort study reviewed medical records for MGD severity grading, treatment prescribed, and follow-up schedule. In addition, participants were surveyed to gauge subjective outcomes and treatment adherence. RESULTS: Eight hundred ten patients were diagnosed with "MGD" or "meibomitis" and had a total of 14 different treatment combinations prescribed. In 3.0% of cases, there was no treatment specified. As MGD severity increased, it became more likely that management would be applied and this was also associated with significantly longer treatment durations (P=0.02) and shorter follow-up periods (P<0.001). Posttreatment subjective outcomes and treatment adherence surveys had a response rate of 36.7% and 24.1% respectively. Overall, 53.5% reported sustained improvement, 40.7% no improvement, and 5.7% experienced temporary relief. Although no treatment regimen seemed to be more efficacious than others, patients showed greater adherence when using topical reagents compared with lid hygiene measures (P≤0.002). CONCLUSION: Clinicians, in this large tertiary eye center, use a wide range of treatment regimens to manage MGD. This suggests the need for development of standard management protocols. Whether alone, or in combination, no MGD treatment significantly improved subjective symptoms, a result that may be influenced by compliance behaviors. Use of topical reagents (eye drops or ointment) seemed to be associated with the best compliance. Future focus on more effective MGD treatments is needed to improve practical outcomes.

Discrimination of subjective responses between contact lenses with a novel questionnaire.

PURPOSE: To describe a ranked symptoms scale (RSS) discriminating subjective responses in contact lens (CL) wear in various situations. METHOD: Forty experienced clinical trial participants were interviewed for their perceptions of ocular comfort scales, resulting in a numerical RSS. For further evaluation, 20 CL wearers enrolled into a prospective, randomised, crossover trial. Two silicone-hydrogel CLs and a lens care solution (LCS) [Combinations A & B] were selected based on prior performance identifying best/worst combinations for end-of-day comfort. The RSS and a numerical rating scale (NRS) were administered at two time-points (insertion/removal) on alternating days for 6 days. RESULTS: Both NRS and RSS showed acceptable internal consistency for comfort, vision and handling (Cronbach alpha=0.71 for both scales) and similar repeatability for comfort and handling (coefficients-of-repeatability within 0.1 and 0.2 units, respectively, for each scale). The NRS and RSS discriminated differences between combinations for comfort (p≤0.031) and vision (p≤0.026) at both time-points. Additionally, the RSS showed lens/edge awareness influenced discomfort the most, ranking higher at insertion (p=0.038) and higher for Combination-B at both time-points (p≤0.002). Symptoms of dryness and tired eyes increased for both combinations at removal (p<0.02). The RSS also showed haziness and blurred distance vision influenced vision dissatisfaction with Combination-B at lens removal (p≤0.038) while eye strain/headache increased for both combinations by time of removal (p≤0.013). CONCLUSIONS: The RSS is able to discriminate subjective responses between combinations and time-of-day. The RSS's ability to rank symptoms may be a useful tool in understanding perceptions of discomfort or dissatisfaction with CL wear.

Contact lens technology to 2020 and beyond: a review of recent patent literature.

Contact lenses have been a common means of vision correction for more than half a century. Recent developments raise the possibility that the next several years will see the range of applications in which they are used broaden considerably, with an associated expansion in both the number and type of individuals who consider them to be a valuable option. To describe this new landscape, a review of recent patent submissions covering the period 1 January 2014 to 1 February 2017 was undertaken. The results show that in the main, areas where contact lenses will be applied include drug delivery, visual augmentation and biosensing.

TFOS DEWS II Tear Film Report.

The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.

Temporal Characteristics of Sodium Fluorescein in the Tear Meniscus.

PURPOSE: To observe the emission intensity profile of sodium fluorescein in the human tear film as a function of time and concentration. METHODS: Twenty-two participants with no dry eye signs or symptoms were randomly allocated to receive 1 µL of either a 2 or 10% concentration of fluorescein to one eye. Images of the inferior tear meniscus were captured at regular intervals over 30 minutes and the process repeated for the other eye with the alternate concentration. Fluorescence intensity was quantified on the basis of the grayscale pixel values in the tear meniscus images. The fluorescein-decay profile over time and between concentrations was determined. RESULTS: Peak fluorescence intensity was reached in 3.9 ± 3.0 and 8.7 ± 4.4 minutes after instillation for the 2 and 10% concentrations, respectively. The 10% concentration of fluorescein maintained its peak fluorescence intensity longer than the 2% concentration (about 9 and 2 minutes, respectively). The peak fluorescence intensity was not significantly different between the higher and lower concentrations (44 ± 37 vs. 38 ± 32 units, P = .22). For both concentrations, the observed intensity did not return to baseline levels by the end of the 30-minute observation time. CONCLUSIONS: The fluorescence intensity of fluorescein in a clinical setting varies with time such that both the onset and duration of maximum brightness are concentration dependent. At low concentration (2%), maximum brightness occurs almost immediately after instillation and lasts about 2 minutes. With a higher concentration (10%), the effective working window is delayed for about 7 to 8 minutes. Irrespective of initial concentration, observable fluorescence remains in the tear film beyond 30 minutes post-instillation.

Interpreting the corneal response to oxygen: Is there a basis for re-evaluating data from gas-goggle studies?

When anoxia (0% oxygen) is created within a gas-tight goggle, ocular physiological responses, including corneal swelling, limbal hyperaemia and pH change, are known to vary, depending on the presence or absence of a low, oxygen transmissibility contact lens. A new theory is proposed to account for this discrepancy based on the concept of lid derived oxygen, whereby oxygen originating from the vascular plexus of the palpebral conjunctiva supplements that available to the ocular surface in an open, normally blinking eye, even when the surrounding gaseous atmosphere is anoxic. The effect of a lid derived contribution to corneal oxygenation was assessed by using existing experimental data to model open-eye, corneal swelling behavior as a function of atmospheric oxygen content, both with and without the presence of a contact lens. These models predict that under atmospheric anoxia, contact lens wear results in 13.2% corneal swelling compared with only 5.4% when the lens was absent. Lid derived oxygen acts to provide the ocular surface in the non-contact lens wearing, normally blinking, open-eye with up to 4.7% equivalent oxygen concentration, even within the anoxic environment of a nitrogen filled goggle. Correcting for lid derived oxygen eliminates previously observed discrepancies in corneal swelling behavior and harmonizes the models for the contact lens wearing and gas-goggle cases. On this basis it is proposed that true anoxia at the ocular surface cannot be achieved by atmospheric manipulation (i.e. a gas-goggle) alone but requires an additional presence, e.g. a low, oxygen transmissibility contact lens, to prevent access to oxygen from the eyelids. Data from previously conducted experiments in which the gas-goggle paradigm was used, may have been founded on underestimates of the real oxygen concentration acting on the ocular surface at the time and if so, will require re-interpretation. Future work in this area should consider if a correction for lid derived oxygen is necessary.

Functional and Morphologic Changes of Meibomian Glands in an Asymptomatic Adult Population.

PURPOSE: The aim of the study was to understand natural changes of meibomian glands (MG) that occur with aging in the absence of any ocular pathology or ocular discomfort symptoms, to differentiate between "age normal" and pathologic or dysfunctional changes of the MG. METHODS: A total of 185 subjects (109 females) with no pre-existing ocular and systemic abnormalities were recruited and divided into four age groups: 25 to 34, 35 to 44, 45 to 54, and 55 to 66 years. At a single visit, the following MG measures were collected: meibum quality (MQ) and MG expressibility (MGE) of the lower lid, and MG drop-out score (meiboscale) using infrared meibography of the upper and lower lids. Assessments of anterior eye, tear function variables, noninvasive and invasive tear breakup time (TBUT), corneal integrity, and lid wiper epitheliopathy were also performed during the visit. An Ocular Surface Disease Index (OSDI) questionnaire was used to record dry eye symptoms. Meibum lipids samples were collected and analyzed. RESULTS: A majority of the study population (61%) was asymptomatic. There was a significant worsening in the MQ (P< 0.048), MGE (P < 0.03), and meiboscale (P < 0.01) with increasing age. Significant increase was observed in anterior blepharitis (P < 0.001) and telangiectasia (P< 0.02) with aging. Interestingly, tear osmolarity decreased significantly (P < 0.001), while tear meniscus height (P < 0.001) and invasive TBUT (P = 0.02) increased with increase in age. There was no significant association between MG variables and sex, ocular discomfort symptoms, or meibum lipids classes. CONCLUSIONS: Progressive MG loss occurs normally with age accompanied by reduced quality and quantity of the meibum produced. However, clinical presentation of ocular discomfort symptoms is stalled without corresponding disruption to tear function.