Paul J. Murphy

Changes in the tear film and ocular surface from dry eye syndrome

Dry eye syndrome (DES) refers to a spectrum of ocular surface diseases with diverse and frequently multiple aetiologies. The common feature of the various manifestations of DES is an abnormal tear film. Tear film abnormalities associated with DES are tear deficiency, owing to insufficient supply or excessive loss, and anomalous tear composition. These categorizations are artificial, as in reality both often coexist. DES disrupts the homeostasis of the tear film with its adjacent structures, and adversely affects its ability to perform essential functions such as supporting the ocular surface epithelium and preventing microbial invasion. In addition, whatever the initial trigger, moderate and severe DES is characterized by ocular surface inflammation, which in turn becomes the cause and consequence of cell damage, creating a self-perpetuating cycle of deterioration. Progress has been made in our understanding of the aetiology and pathogenesis of DES, and these advances have encouraged a proliferation of therapeutic options. This article aims to amalgamate prevailing ideas of DES development, and to assist in that, relevant aspects of the structure, function, and production of the tear film are reviewed. Additionally, a synopsis of therapeutic strategies for DES is presented, detailing treatments currently available, and those in development.

The agreement and repeatability of tear meniscus height measurement methods

Purpose. This study investigated the agreement and repeatability of five techniques of measuring tear meniscus height (TMH). Methods. Pairs of TMH measurements were obtained from one eye of 25 normal subjects with five techniques: optical coherence tomography in cross-section (OCT) and optical pachymetry in cross-section (PACH), without fluorescein; and 5 minutes after the instillation of fluorescein, optical pachymetry en-face (SL-F) and in cross-section (SL-X), and video capture en-face (VC). These 10 measurements were taken on different days within a period of 21 days. Additionally, immediately successive replicates were taken at the first visit when VC was used, allowing for the separation of technique repeatability from true day-to-day variation in TMH. Results. Ninety-five percent confidence intervals for the mean TMH and 95% repeatability coefficients for repeated testing on separate occasions were: 0.25 to 0.29 mm, 0.14 mm—OCT, 0.30 to 0.36 mm, 0.13 mm—PACH, 0.27 to 0.34 mm, 0.092 mm—SL-F, 0.35 to 0.41 mm, 0.19 mm—SL-X, and 0.30 to 0.38 mm, 0.088 mm—VC. Reported repeatability coefficients are averages because, despite a relatively narrow experimental range, the measurements of low TMH were generally more repeatable than those of large TMH. Ninety-five percent limits of agreement were wide for all pairwise comparisons and included zero, indicating that the methods used in this study are interchangeable when taking single recordings, at least on subjects without dry eye. Conclusions. The average TMH of the five techniques was similar, although OCT and SL-X tended to record lower and higher values, respectively. However, their agreement for single recordings was poor, an inevitable consequence of the low intertest repeatability found for all methods. A much improved repeatability for immediate replicates indicated that this, in turn, was principally caused by a large day-to-day variation in TMH rather than measurement error.

The relationship between clinical signs and dry eye symptoms

PurposeTo evaluate (i) the relationship between traditional and new clinical tests (lid-wiper epitheliopathy (LWE), lid-parallel conjunctival folds (LIPCOF)) and dry eye symptoms in non-contact lens wearers, and (ii) that a combination of these tests can improve predictive ability for the development of dry eye symptoms.MethodsTear meniscus height (TMH), non-invasive break-up time (NIBUT), ocular hyperaemia, LIPCOF, phenol red thread test (PRTT), corneal and conjunctival staining, and LWE grades were observed in a cohort of 47 healthy, non-lens wearers (male=17, female=30, median age=35 years, range=19–70). Symptoms were assessed using the Ocular Surface Disease Index (OSDI).ResultsLWE was significantly correlated to both temporal and nasal LIPCOF (0.537<r<0.607, P<0.05). LIPCOF and LWE were significantly correlated to NIBUT and PRTT (r>−0.248, P<0.001). Significant correlations were found between NIBUT and TMH (r=0.461, P=0.001) and PRTT (r=0.640, P<0.001). OSDI scores were significant correlated to NIBUT, TMH, PRTT, LIPCOF, and LWE (r>∣0.31∣; P<0.05). Significant discriminators of OSDI+/− were NIBUT (area under the receiver operative characteristic curve (AUC)=0.895), TMH (0.715), PRTT (0.781), LIPCOF (temporal/nasal/Sum 0.748/0.828/0.816), and LWE (0.749). Best predictive ability was achieved by combining NIBUT with nasal LIPCOF (AUC=0.944).ConclusionsThe individual tests NIBUT, TMH, PRTT, LIPCOF, and LWE were significantly, but moderately, related to OSDI scores. The strongest relationship appeared by combining NIBUT with nasal LIPCOF.

A new non-contact corneal aesthesiometer (NCCA).

A novel method for testing the corneal nerve function, through non-invasive measurement of corneal sensitivity, is presented. The method of using a controlled pulse of air to stimulate the corneal surface is described. Technical information of the aesthesiometers construction is given. Examples of the ability of the instrument to accurately locate the corneal sensitivity threshold using either a method of constant stimuli, or a method of limits, is described for 14 normal, non-lens wearing eyes. Measurements are made in millibars of air pressure required. Mean normal values found were 0.342 +/- 0.068 millibars. Discussion is made of the instruments mode of action, its advantages over other invasive instruments, and potential clinical application.

Mucins and ocular signs in symptomatic and asymptomatic contact lens wear.

Purpose. Lid wiper epitheliopathy (LWE) and lid parallel conjunctival folds (LIPCOF) are related to dry eye symptoms in contact lens wearers. Both clinical signs are assumed to be related to mechanical forces during blinking. As the mucus layer is a protector of the ocular surface tissue, this study investigates whether any alterations of mucins are detectable comparing symptomatic and asymptomatic soft contact lens wearers. Methods. Comfort was evaluated using the Contact Lens Dry Eye Questionnaire. Corneal staining, LWE, and LIPCOF were assessed in the right eyes of 50 (19 men, 31 women; mean age, 32.1 ± 11.4 years) experienced lens wearers. The tear film was sampled using Schirmer strips pressed onto the temporal conjunctiva and from harvested contact lenses. Mucins were assessed in dot-blots and Western blots after electrophoresis on 1% agarose or 4 to 12% NuPAGE Gels. Non-parametric analyses were used to study differences between groups and correlations between objective tests, mucins, and symptoms. Results. Thirty-one subjects were classified asymptomatic and 19 symptomatic by the questionnaire. LWE and LIPCOF were significantly increased in the symptomatic group (p < 0.035). MUC5AC reactivity was significantly decreased in symptomatics (p = 0.050). MUC4 was correlated to temporal LIPCOF and LWE, (r = −0.47 and −0.46; p < 0.01). MUC16 and MUC5AC correlated with corneal staining (0.36 < r < 0.53; p < 0.04). Conclusions. Symptomatic contact lens wearers exhibit significantly more LWE and LIPCOF, and decreased MUC5AC reactivity. LWE and LIPCOF are significantly correlated; this may reflect their common frictional origin. Increased friction might follow from insufficient mucins, or an altered composition of the resident mucins at the ocular surface. In this study, we show that decreased mucin production is associated with the severity of LWE and LIPCOF.

Incidence and severity of keratoconus in Asir province, Saudi Arabia

Aim: To assess the incidence and associated signs and symptoms of patients with keratoconus in Asir Province, Saudi Arabia. Methods: 125 new keratoconus patients (51 male, 74 female; mean age 18.5 (SD 3.8) years; range 8–28 years) were recruited from referrals to the department of ophthalmology, Asir Central Hospital, over a 1 year period. Age, visual acuity, and keratometry were recorded along with clinical signs and symptoms. Results: The incidence of keratoconus in Asir Province is 20 cases per 100 000 population. Also, the disease severity is high, as indicated by an early mean age (17.7 (3.6) years) with advanced stage keratoconus. Visual acuity, with either spectacles or rigid contact lenses, was 6/12 or better in 98% of eyes measured. Just over half (56%) of patients had atopic ocular disease. 16% of patients had a positive family history of the disease and 16% had atopic dermatitis (eczema and/or vitiligo). Conclusion: The incidence and severity of keratoconus in Asir Province, Saudi Arabia, is high with an early onset and more rapid progress to the severe disease stage at a young age. This might reflect the influence of genetic and/or environmental factor(s) in the aetiology of keratoconus.

A novel method to predict the dry eye symptoms in new contact lens wearers

Purpose. Lid wiper epitheliopathy (LWE) and lid parallel conjunctival folds (LIPCOF) give moderate prediction levels for dryness symptoms in experienced contact lens (CL) wearers. This study investigated whether a combination of LWE and LIPCOF plus other tear film tests and subjective evaluation before contact lens fitting was better able to predict CL-induced dry eye (CLIDE) symptoms. Methods. Tear meniscus height, non-invasive break-up time (NIBUT), ocular hyperaemia, LIPCOF, phenol red thread test, corneal and conjunctival staining, and LWE of the right eye of 33 new soft CL wearers (12 males, 21 females, median age = 30.5 years; range = 19 to 44) were assessed in a prospective 2-mo longitudinal study. Symptoms were evaluated by the Ocular Surface Disease Index (OSDI) and subjects were grouped according to their response in the Contact Lens Dry Eye Questionnaire (CLDEQ) during the study (20 symptomatic and 13 asymptomatic). The subjects were fitted with vifilcon A and senofilcon A lenses for a 2-week period, consecutively. Results. Limbal hyperaemia (repeated measures analysis of variance; p < 0.05) and LWE (Friedman; p < 0.004) increased significantly during the study but not LIPCOF (p ≥ 0.318; temporal, nasal, and Sum), bulbar hyperaemia (p = 0.432), staining (p ≥ 0.060), OSDI (p = 0.126), or CLDEQ (p = 0.317, &kgr; = 0.279). Limbal hyperaemia significantly decreased in senofilcon A lenses. Wearing comfort among symptomatics was significantly better with senofilcon A (p = 0.005). At the enrolment visit, the subjects who became symptomatic exhibited significantly decreased NIBUT and increased LIPCOF and OSDI (range, p < 0.027). The best test combination to predict CLIDE (logistic regression analyses) was LIPCOF Sum plus NIBUT and OSDI, (positive predictive value = 87% and accuracy = 91%). Conclusions. LIPCOF, NIBUT, and OSDI are significant discriminators for CLIDE in new CL wearers compared with hyperaemia, tear meniscus height, phenol red thread test, staining, and LWE. The best test combination is NIBUT plus LIPCOF Sum and OSDI (named the Contact-Lens-Predicting-Test).

How red is a white eye? Clinical grading of normal conjunctival hyperaemia

PurposeTo quantify the level of normal bulbar conjunctival hyperaemia using the Cornea and Contact Lens Research Unit (CCLRU) grading scale, and to investigate inter-observer agreement.MethodsBulbar conjunctival hyperaemia was assessed by two trained observers, using the CCLRU grading scale (zero to four units) interpolated into 0.1 increments, on the right eye of 121 healthy, non-contact lens-wearing subjects (male=58, female=63, median age=28 years, range 16–77). The eye was observed using a slit-lamp bio-microscope (× 10 magnification) under diffuse, white illumination. The subjects position of gaze was directed to allow grading of four quadrants: superior, nasal, inferior, and temporal conjunctiva. Bulbar redness was defined as the average of those four grades of conjunctival hyperaemia. A further twenty subjects were recruited to assess inter-observer agreement (male=8, female=12, median age=23 years).ResultsThe average bulbar redness was 1.93 (±0.32 SD) units. The nasal (2.3±0.4) and temporal (2.1±0.4) quadrants were significantly redder than the superior (1.6±0.4) and inferior (1.7±0.4) quadrants (P<0.0001). Males had redder eyes than females by 0.2 units. Inter-observer 95% limits of agreement for bulbar redness was 0.38 units.ConclusionsThe average bulbar redness of 1.9 units was higher than expected, reflecting the design of the grading scale. A bulbar redness of greater than 2.6 units may be considered abnormal, and a change in bulbar redness of ≥0.4 units may be significant.

Effect of a liposomal spray on the pre-ocular tear film

PURPOSE With the potential to address evaporative dry eye, a novel spray has been developed in which phospholipid liposomes are delivered to the tear film via the surface of the closed eyelid. This study evaluated the short-term effects of liposomal spray application on the lipid and stability characteristics of the pre-ocular tear film in normal eyes. METHODS Twenty-two subjects (12M, 10F) aged 35.1+/-7.1 years participated in this prospective, randomised, double-masked investigation in which the liposomal spray was applied to one eye, and an equal volume of saline spray (control) applied to the contralateral eye. Lipid layer grade (LLG), non-invasive tear film stability (NIBUT) and tear meniscus height (TMH) were evaluated at baseline, and at 30, 60, 90 and 135min post-application. Subjective reports of comfort were also compared. RESULTS Treated and control eyes were not significantly different at baseline (p>0.05). Post-application, LLG increased significantly, at 30 and 60min, only in the treated eyes (p=0.005). NIBUT also increased significantly in the treated eyes only (p<0.001), at 30, 60 and 90min. TMH did not alter significantly (p>0.05). Comfort improved relative to baseline in 46% of treated and 18% of control eyes, at 30min post-application. Of those expressing a preference in comfort between the eyes, 68% preferred the liposomal spray. CONCLUSIONS Consistent with subjective reports of improved comfort, statistically and clinically significant improvements in lipid layer thickness and tear film stability are observed in normal eyes for > or =1h after a single application of a phospholipid liposomal spray.

Reliability of the Non‐Contact Corneal Aesthesiometer and its comparison with the Cochet–Bonnet aesthesiometer

Aims‐: To determine the repeatability of measurement of the corneal sensation threshold using the Non‐Contact Corneal Aesthesiometer (NCCA); to evaluate the effect of the air‐jet diameter and stimulus duration on the threshold; and to compare the sensation thresholds found with the NCCA and with the Cochet–Bonnet Aesthesiometer (C–BA), on the same group of normal, human subjects.