Blanka Golebiowski

The role of corneal innervation in LASIK-induced neuropathic dry eye.

Almost half the patients who undergo laser in situ keratomileusis (LASIK) experience dry eye following the procedure. However, the etiology of LASIK-induced dry eye is unclear. The purpose of this review is to examine and summarize the current evidence for the etiology of LASIK-induced dry eye, with a focus on ocular surface sensitivity and corneal innervation. Evidence suggests that the alteration of corneal nerves after LASIK is the most likely cause of the subjective symptoms of LASIK-induced dry eye, even though corneal sensitivity and the clinical indicators of dry eye return to apparently normal values within a year due to the partial recovery of the corneal nerve plexus. The hypothesis is explored that dry eye symptoms following LASIK may result from abnormal sensation due to LASIK-induced corneal neuropathy. Other factors, such as alterations in conjunctival goblet cell density, might also contribute to the symptoms and signs of LASIK-induced dry eye. Inter-relationships between nerve morphology, tear neuropeptide levels and dry eye require further investigation. A better understanding of this phenomenon may result in improved management of post-LASIK dry eye.

Assessing the sensory function of the ocular surface: implications of use of a non-contact air jet aesthesiometer versus the Cochet-Bonnet aesthesiometer.

Assessment of corneal sensory function is commonly carried out using the Cochet-Bonnet aesthesiometer. The limitations of this instrument have lead to development of newer instruments, such as the CRCERT-Belmonte aesthesiometer, which utilise a jet of air as their stimulus. Recent work, however, has demonstrated contradictory effects on ocular surface sensitivity when measured with different types of aesthesiometer. The purpose of the present study was to compare clinical measurements of corneal sensitivity obtained with the CRCERT-Belmonte and the Cochet-Bonnet aesthesiometers and to examine their stimulus characteristics in terms of force exerted. No association was found between central corneal sensitivity measured with the two aesthesiometers in a group of normal subjects. Sensitivity was measured to be lower with the Cochet-Bonnet aesthesiometer than with the CRCERT-Belmonte. Over half of the subjects could not be assessed with the standard Cochet-Bonnet filament and 11% could not be assessed with either filament, as their corneal sensitivity was outside of the range of the instrument. In contrast, all subjects were within the stimulus range of the CRCERT-Belmonte aesthesiometer. Corneal sensitivity measurements made with the non-contact CRCERT-Belmonte aesthesiometer and the Cochet-Bonnet aesthesiometer are not comparable. Due to dissimilarities in the composition of their stimuli, and thus mode of stimulation, it is possible that the two instruments measure different aspects of the neural response. The underestimation of corneal sensitivity by the Cochet-Bonnet aesthesiometer and its inability to measure sensitivity of some subjects at all are important considerations in the assessment of sensitivity loss. Subtle changes are unlikely to be detected with this instrument, particularly at higher sensitivity levels. The Cochet-Bonnet should therefore be used with caution and the 0.08 mm diameter used as the filament of choice. Adoption of a non-contact aesthesiometer as standard for ocular sensitivity measurement should be considered. The non-contact instrument allows superior stimulus reproducibility and better control over stimulus characteristics, in addition to the ability for exploration of the response of all three types of neuro-receptors on the ocular surface.

The TFOS International Workshop on Contact Lens Discomfort: Report of the Subcommittee on Neurobiology

This report characterizes the neurobiology of the ocular surface and highlights relevant mechanisms that may underpin contact lens-related discomfort. While there is limited evidence for the mechanisms involved in contact lens-related discomfort, neurobiological mechanisms in dry eye disease, the inflammatory pathway, the effect of hyperosmolarity on ocular surface nociceptors, and subsequent sensory processing of ocular pain and discomfort have been at least partly elucidated and are presented herein to provide insight in this new arena. The stimulus to the ocular surface from a contact lens is likely to be complex and multifactorial, including components of osmolarity, solution effects, desiccation, thermal effects, inflammation, friction, and mechanical stimulation. Sensory input will arise from stimulation of the lid margin, palpebral and bulbar conjunctiva, and the cornea.

Corneal and conjunctival sensitivity to air stimuli.

Aims: To determine the repeatability of ocular surface sensitivity to mechanical stimulation using air stimuli and the effect of contact lens (CL) wear on sensitivity. Methods: Repeatability: 14 subjects (24–39 years) participated. Mechanical sensitivity to warmed (34°C) and ambient (20°C) air was measured for the central cornea (CC), inferior cornea (IC), and inferior conjunctiva (ICON). Measurements were taken on 12 days; six morning and six afternoon measurements. Differences between sites, time of day, and stimulus temperature were evaluated. CL wear: 10 subjects (22–30 years) participated. Measurements were taken at the same time of day, either following no wear, wear of a CL of oxygen permeability [Dk] of 28×10−9 [cm/s][ml O2/ml mm Hg] or wear of a CL of Dk 140×10−9 [cm/s][ml O2/ml mm Hg]. Differences between sites and wear conditions were evaluated. Results: Repeatability: Sensitivity varied between sites (p<0.01), time of day (p<0.05), and stimulus temperatures (p<0.01). There were no significant differences between days. Mean thresholds for eye temperature stimuli were; CC 64.4 (SD 28.6) ml/min; IC 84.6 (40.0) ml/min; ICON 120.6 (40.4) ml/min and for ambient temperature stimuli were CC 53.9 (16.0) ml/min, IC 59.0 (20.0) ml/min; ICON 72.6 (43.7) ml/min. CL wear: Sensitivity varied between sites and wear conditions (p<0.05). Conjunctival sensitivity was increased after wear of highly oxygen permeable CLs but unaffected by wear of low oxygen permeable CLs. Conclusions: The prototype gas aesthesiometer is able to repeatably measure ocular surface sensitivity and measurements are consistent with previously reported techniques.

Sex hormones and the dry eye

The greater prevalence of dry eye in women compared to men suggests that sex hormones may have a role in this condition. This review aims to present evidence for how sex hormones may affect the ocular structures involved in the production, regulation and maintenance of the normal tear film. It is hypothesised that hormone changes alter the homeostasis of the ocular surface and contribute to dry eye. Androgens impact on the structure and function of the meibomian and lacrimal glands and therefore androgen deficiency is, at least in part, associated with the aetiology of dry eye. In contrast, reports of the effects of oestrogen and progesterone on these ocular structures and on the conjunctiva are contradictory and the mechanisms of action of these female‐specific sex hormones in the eye are not well understood. The uncertainty of the effects of oestrogen and progesterone on dry eye symptoms is reflected in the controversial relationship between hormone replacement therapy and the signs and symptoms of dry eye. Current understanding of sex hormone influences on the immune system suggests that oestrogen may modulate a cascade of inflammatory events, which underlie dry eye.

Estimating a just-noticeable difference for ocular comfort in contact lens wearers.

PURPOSE To estimate the just-noticeable difference (JND) in ocular comfort rating by human, contact lens-wearing subjects using 1 to 100 numerical scales. METHODS Ostensibly identical, new contact lenses were worn simultaneously in both eyes by 40 subjects who made individual comfort ratings for each eye using a 100-point numerical ratings scale (NRS). Concurrently, interocular preference was indicated on a five-point Likert scale (1 to 5: strongly prefer right, slightly prefer right, no preference, slightly prefer left, strongly prefer left, respectively). Differences in NRS comfort score (ΔC) between the right and left eyes were determined for each Likert scale preference criteria. The distribution of group ΔC scores was examined relative to alternative definitions of JND as a means of estimating its value. RESULTS For Likert scores indicating the presence of a slight interocular preference, absolute ΔC ranged from 1 to 30 units with a mean of 7.4 ± 1.3 (95% confidence interval) across all lenses and trials. When there was no Likert scale preference expressed between the eyes, absolute ΔC did not exceed 5 units. CONCLUSIONS For ratings of comfort using a 100-point numerical rating scale, the inter-ocular JND is unlikely to be less than 5 units. The estimate for the average value in the population was approximately 7 to 8 units. These numbers indicate the lowest level at which changes in comfort measured with such scales are likely to be clinically significant.

Consequences of wear interruption for discomfort with contact lenses.

Purpose To establish whether increased end-of-day discomfort during soft contact lens wear is associated with short-term changes occurring to the lens itself. Methods Twenty-seven subjects wore hydrogel lenses (Focus Dailies; Alcon) bilaterally for 10 hours on two separate days. Comfort was reported using 1–100 numerical rating scales (1 = intolerable discomfort, 100 = lens cannot be felt). Day 1 ratings were taken before lens insertion and at 0.05, 5, and 10 hours post-insertion. Day 2 ratings occurred at similar times, but lenses were removed after the 5-hour assessment and either reinserted (n = 14) or newly replaced (n = 12). An additional rating was taken 5 minutes after re-insertion. Wear then continued to the 10-hour point. In a separate study, 24 different subjects repeated these procedures using a silicone hydrogel lens (AirOptix Aqua; Alcon) with wear taking place on 3 days to permit lens replacement to be with existing as well as new lenses in all subjects. Results For hydrogel lenses, comfort scores (mean ± 95% CI) reported after 10 hours were 79.4 ± 8.3 when lenses were worn un-replaced, compared with 73.2 ± 9.2 for replacement with the existing lens. When replacement was with a brand new lens, the corresponding values were 72.9 ± 10.9 (un-replaced) versus 69.2 ± 12.8 (new lens replacement). For silicone hydrogel lenses, 10-hour comfort was 90.3 ± 3.2 (un-replaced) versus 92.2 ± 2.9 (replacement with existing lens) versus 90.0 ± 3.3 (replacement with new lens). Differences between replacement conditions were not significant in any case (analysis of variance, p > 0.05). Conclusions Final comfort was not influenced by replacing lenses midway through the wearing period. Comfort decrements experienced by users of these daily contact lenses towards the later part of the wearing period are not caused by changes occurring to the lenses on this time scale. Possible alternative etiological factors include a fatigue-like response in one or more ocular tissues or stimulation of ocular surface nociceptors induced by the presence of the contact lens.

Corneal and Conjunctival Sensory Function: The Impact on Ocular Surface Sensitivity of Change from Low to High Oxygen Transmissibility Contact Lenses

PURPOSE Deprivation of oxygen to the ocular surface during contact lens wear has been implicated in the alteration of sensory function. This study investigates whether increasing oxygen availability through discontinuation of contact lens wear or transfer into highly oxygen transmissible (high Dk/t) lenses leads to a change in corneal or conjunctival sensitivity. METHODS Twenty-seven long-term extended wearers of low Dk/t soft contact lenses ceased lens wear for 1 week and were refitted with high Dk/t silicone hydrogel lenses. A control group of 25 nonwearers matched for age and sex was also recruited. Central corneal and inferior conjunctival sensitivity were measured using an air-jet aesthesiometer. Threshold was determined using a staircase technique. Measurements were taken during low Dk/t lens wear; after 1 week of no wear; and after 1, 3, 6, and 12 months of high Dk/t lens wear. Measurements were carried out on one occasion on the nonwearers. RESULTS Corneal sensitivity decreased 1 week after discontinuation of low Dk/t lenses and no further change in sensitivity occurred with high Dk/t lens wear. Conjunctival sensitivity did not change over the same time frame. Ocular surface sensitivity in long-term low Dk/t soft lens wearers was similar to that of nonwearers. Sensitivity was higher in females than males in the nonwearers, but not in the lens-wearing group. An interaction of sex on change in conjunctival threshold was found in the lens wearers. CONCLUSIONS These findings indicate that factors other than oxygen availability alone determine sensitivity of the ocular surface. Silicone hydrogel contact lenses appear to have only a minor impact on ocular surface sensitivity in previous lens wearers.

Factors affecting corneal and conjunctival sensitivity measurement.

Purpose. Measurement of sensitivity provides important clues about sensation on the ocular surface. This study aimed to evaluate whether measurements of threshold of sensation to an air stimulus are affected by corneal/conjunctival location, gender, age, time of day, ambient temperature or humidity. Methods. A retrospective analysis is reported of ocular surface threshold measurements made by one examiner using the CRCERT-Belmonte esthesiometer. Multiple corneal measurements for 49 normal subjects (24M:25F) and conjunctival measurements for 33 subjects (16M:17F) were included in the analysis. Threshold was measured at the corneal apex and at the inferior conjunctiva 2 mm from the limbus. Measurements were made between 9 am and 6 pm, at ambient temperature 20 to 26°C and humidity 52 to 87%. Mixed model analysis of variance, paired-t-test and Pearson’s correlation were used to examine effects of various factors on threshold. Results. Mean group corneal threshold was 76.2 ± 26.8 mL/min and conjunctival threshold 123.7 ± 49.1 mL/min (n = 33, p < 0.001). Corneal and conjunctival threshold were well correlated (r = 0.66, p < 0.001). Thresholds were significantly higher for male than female subjects at both the cornea (M 82.2 ± 23.5 mL/min, F 67.6 ± 24.1 mL/min, p = 0.04) and conjunctiva (M 144.1 ± 40.7 mL/min, F 105.8 ± 50.2 mL/min, p = 0.02). A significant reduction in corneal threshold with age was apparent for females (n = 25, r = −0.49 p = 0.01) but not males. A similar effect on conjunctival sensitivity was not shown. No effect of time of day, ambient humidity or temperature was found on threshold at either site. Conclusions. Corneal and conjunctival sensitivity were found to be associated. Corneal and conjunctival sensitivity is higher in female subjects, who also show an age-related increase in corneal sensitivity. No change in sensitivity of either tissue is apparent within normal levels of ambient temperature or humidity or over the course of a working day.

Lid margins: sensitivity, staining, meibomian gland dysfunction, and symptoms.

Purpose. Ocular surface sensitivity plays a role in dry eye and ocular comfort through its probable influence on the neural feedback loop that regulates tear secretion, but little is known specifically about the role of lid or lid margin sensitivity in ocular surface health. The aim of this study was to characterize the eyelid margin and explore the relationships between lid margin sensitivity and staining, meibomian gland dysfunction, tear osmolarity, and ocular symptoms. A secondary aim was to look for differences and associations between lower- and upper-lid characteristics. Methods. Pilot study involving 27 healthy subjects (7 men, 20 women; mean age: 31 ± 14 years). Measurements included ocular symptoms (Ocular Surface Disease Index, Dry Eye Questionnaire), tear osmolarity, lid margin staining (fluorescein and lissamine green), meibomian gland dysfunction, and mechanical sensitivity of lower and upper lids. Results. Lower-lid margins were more sensitive (45.0 ± 13.2 vs. 40.0 ± 14.7 mm; p = 0.02) and displayed more staining (1.5 ± 1.0 vs. 0.2 ± 0.6, p < 0.001), but less evidence of meibomian gland dysfunction (2.0 ± 2.8 vs. 7.3 ± 6.2, p < 0.001), than upper-lid margins. Lid margin staining was more frequent in lower than upper lids (78% vs. 15% of subjects). Tear osmolarity correlated with upper-lid staining (r = 0.41, p = 0.04) and lower-lid sensitivity (r = 0.46, p = 0.02). Lid sensitivity was also inversely correlated with meibomian gland dysfunction at the lower lid (r = −0.51, p = 0.01). Surprisingly, there were no associations between symptoms and lid staining. Conclusions. Our study highlighted clear clinical differences between the lower and upper lids and demonstrated, for the first time, significant relationships between tear osmolarity and lid characteristics, including lid sensitivity.