Eric B. Papas

In vivo confocal microscopy of the human cornea

Aims: To describe the optics of in vivo confocal microscopy, its advantages over previous methods, and to summarise the literature that arose from its use for the observation of the human cornea. A critical review of the clinical usefulness of this new technology for the corneal examination is undertaken. Methods: Confocal microscopes obtain increased resolution by limiting the illumination and observation systems to a single point. Rapid scanning is used to reconstruct a full field of view and allows for “real time” viewing. Results: Coronal sections of the in situ epithelium, Bowman’s membrane, stroma, and endothelium can be visualised at a resolution of 1–2 μm. A backscattered light intensity curve allows objective measurements of sublayer thickness and corneal haze to be taken. In vivo confocal microscopy is therefore particularly useful in the areas of infective keratitis, corneal dystrophies, refractive surgery, and contact lens wear, where it aids in differential diagnosis and detection of subtle short and long term changes. Real time endothelial cell assessment can also be performed. Conclusion: Because of their ability to visualise living tissue at cellular levels, confocal microscopes have proved useful additions to the current clinical tools.

Global vision impairment due to uncorrected presbyopia.

OBJECTIVES To evaluate the personal and community burdens of uncorrected presbyopia. METHODS We used multiple population-based surveys to estimate the global presbyopia prevalence, the spectacle coverage rate for presbyopia, and the community perception of vision impairment caused by uncorrected presbyopia. For planning purposes, the data were extrapolated for the future using population projections extracted from the International Data Base of the US Census Bureau. RESULTS It is estimated that there were 1.04 billion people globally with presbyopia in 2005, 517 million of whom had no spectacles or inadequate spectacles. Of these, 410 million were prevented from performing near tasks in the way they required. Vision impairment from uncorrected presbyopia predominantly exists (94%) in the developing world. CONCLUSIONS Uncorrected presbyopia causes widespread, avoidable vision impairment throughout the world. Alleviation of this problem requires a substantial increase in the number of personnel trained to deliver appropriate eye care together with the establishment of sustainable, affordable spectacle delivery systems in developing countries. In addition, given that people with presbyopia are at higher risk for permanently sight-threatening conditions such as glaucoma and diabetic eye disease, primary eye care should include refraction services as well as detection and appropriate referral for these and other such conditions.

The international workshop on meibomian gland dysfunction: Report of the subcommittee on the epidemiology of, and associated risk factors for, MGD

Scientists have been interested in studying the secretions of the meibomian glands for many years, 1– 8 and diseases associated with the meibomian glands (e.g., cancers, posterior blepharitis) have been noted in the medical literature since at least the early part of the 20th Century. 9 –13 However, the term “meibomian gland dysfunction” (MGD) was only introduced by Korb and Henriquez in 1980. 14 The terminology “meibomian gland disease” was later introduced by Bron et al. 15 as an umbrella term to indicate any disease affecting the meibomian glands (see Definition and Classification). Although the etiology of MGD may differ from that of aqueous-deficient dry eye disease (which is due to insufficient lacrimal gland production), the two conditions share many clinical features, including symptoms of ocular surface irritation and visual fluctuation, altered tear film stability, and potential ocular surface compromise. When MGD is of sufficient degree, it may give rise to the second major subtype of dry eye disease, evaporative dry eye. 16 These subtypes are not mutually exclusive, as has been acknowledged. 16

Silicone Hydrogel Contact Lenses and the Ocular Surface

For 30 years, contact lens research focused on the need for highly oxygen-permeable (Dk) soft lens materials. High Dk silicone hydrogel contact lenses, made available in 1999, met this need. The purpose of this review is to examine how silicone hydrogel lens wear affects the ocular surfaces and to highlight areas in which further research is needed to improve biocompatibility. Silicone hydrogel lenses have eliminated lens-induced hypoxia for the majority of wearers and have a less pronounced effect on corneal homeostasis compared to other lens types; however, mechanical interaction with ocular tissue and the effects on tear film structure and physiology are similar to that found with soft lens wear in general. Although the ocular health benefits of silicone hydrogel lenses have increased the length of time lenses can be worn overnight, the risk of infection is similar to that found with other soft lens types, and overnight wear remains a higher risk factor for infection than daily wear, regardless of lens material. Future contact lens research will focus on gaining a better understanding of the way in which contact lenses interact with the corneal surface, upper eyelid, and the tear film, and the lens-related factors contributing to infection and inflammatory responses.

Solution toxicity in soft contact lens daily wear is associated with corneal inflammation

Purpose. Contact lens-associated solution toxicity manifests as generalized, mild punctate epithelial fluorescein staining and usually is widely reported as asymptomatic, with no substantial clinical sequelae. This study examined the relationship between solution toxicity and corneal infiltrative events (CIEs) in soft contact lens daily wear. Methods. Several nonrandomized interventional clinical trials conducted between May and November 2005 were analyzed retrospectively. Subjects wore commercially available soft contact lenses bilaterally, on a daily schedule, disinfected overnight using marketed lens care solutions for 3 months with monthly disposal. Solution toxicity was defined as diffuse punctate staining in at least four of five areas of the cornea after instillation of sodium fluorescein. First events of corneal staining or corneal infiltrates were used to calculate incidence (per 100 eye months). Results. Toxic staining was detected in 77 of 609 subjects and all CIEs were mild and symptomatic or asymptomatic. The incidence of CIEs in eyes with a predisposition to toxic staining was 6.7% and in unaffected eyes was 2.3%. CIEs were 3-times more likely to occur in eyes that exhibited solution toxicity compared to unaffected eyes (odds ratio = 3.08, p = 0.008, 95% CI 1.40 to 6.76). Previous events of limbal redness (≥grade 2.0) were not associated with CIEs (odds ratio = 1.53, p = 0.364, 95% CI 0.63 to 3.70). The rate of CIEs increased as the rate of toxic staining increased for specific lens type-solution combinations (Spearman’s rho = 0.558, p = 0.025, n = 16), and peroxide-based solutions consistently resulted in the lowest rates of toxic staining and corneal inflammation. Conclusions. Eyes that experience solution toxicity are more likely to experience a CIE. Daily wear soft lens wearers should be routinely examined with sodium fluorescein soon after lenses are inserted and alternative solution/lens type combinations should be investigated if toxic staining is detected.

Contact Lens–Related Adverse Events and the Silicone Hydrogel Lenses and Daily Wear Care System Used

OBJECTIVE To investigate the incidence of adverse events related to the use of varying silicone hydrogel contact lens and lens solution combinations. METHODS Individuals with myopia (N = 558) participated in 1 or more of approximately 40-participant trials in a matrix of 20 silicone hydrogel contact lens and lens-solution combinations. Visits were at baseline, 2 weeks, 1 month, and 3 months. The mean study completion rate was 90% of the expected participant-months (final data set: 840 lens-solution combinations and 2271 participant-months). Adverse events were reported as the first occurrence of each type per 100 participant-months for each lens-solution combination. RESULTS The rate of all corneal infiltrative events (CIEs) was 3.1 per 100 participant-months (range, 0-10.5), and the rate of symptomatic CIEs was 1.7 per 100 participant-months (range, 0-10.5), including 1 case of microbial keratitis (0.04 per 100 participant-months). Rates for CIEs differed substantially among solution groups, with hydrogen peroxide having the lowest rate (0.6 per 100 participant-months; range, 0-0.9). The rate was 0.8 per 100 participant-months (range, 0-8.0) for superior epithelial arcuate lesions, which varied by lens type, 0.04 per 100 participant-months (1 case only) for corneal erosion, and 0.4 per 100 participant-months (range, 0-2.0) for contact lens papillary conjunctivitis, which was modified by type of solution. The rate of solution-induced corneal staining for all lens-solution combinations was 4.7 per 100 participant-months (range, 0-23) and varied significantly based on lens-solution combination (P < .001). CONCLUSIONS The frequency of adverse events varied with silicone hydrogel contact lens and lens solution combinations, with hydrogen peroxide having the lowest incidence of CIEs and solution-induced corneal staining, indicating that lens material and design, type of solution, and solution-lens interactions are likely contributing factors in this mode of lens wear.

Comparison of reverse-geometry lens designs for overnight orthokeratology.

Purpose. The efficacy of overnight wear of four types of reverse-geometry lenses was compared. The length of time needed to achieve correction and any adverse events that occurred during the course of the study were recorded. Methods. In this prospective, randomized study, 60 subjects (18 to 35 years old) with refractive error between −1.00 to −4.00 D (cyl ≤ −1.50) wore reverse-geometry lenses overnight only. All subjects were assigned a Rinehart Reeves lens in one eye, and subsets of 20 subjects were randomly assigned a Mountford BE, DreimLens, or Contex D Series 4 lens for the contralateral eye. Visits included baseline, dispensing, 1 day, 1 week, and 1 month. Biomicroscopy, unaided visual acuity, subjective refraction, best-corrected visual acuity at high and low contrast and high and low illumination, corneal topography, and subjective rating data were collected. Results. Forty-six subjects completed the study. At 1 month, there were no significant differences between lens types in their effect on unaided visual acuity, subjective sphere, subjective cylinder, best-corrected visual acuity at high and low contrast at high illumination and low contrast at low illumination, apical corneal radius, corneal eccentricity, and subjective ratings. Between 1 week and 1 month, there was a significant improvement in subjective ratings of quality of day and night vision (p < 0.05) but no significant change in the objective measures. No significant ocular adverse events were observed during the trial. Conclusions. The lens types tested were all similarly effective in the reduction of myopic refractive error. Subjective ratings continued to improve after objective measures stabilized at 1 week. Overnight lens wear proceeded for 1 month without significant adverse reactions.

Interactions of lens care with silicone hydrogel lenses and effect on comfort.

Purpose. The purpose of this study was to investigate the effect of lens care products on short-term subjective and physiological performance silicone hydrogel lenses. Methods. Ten subjects wore either lotrafilcon B or galyfilcon A silicone hydrogel contact lenses soaked in a lens care product containing either Polyquad/Aldox or PHMB or control lenses inserted directly from the pack. Subjects wore the lenses for 6 h. Ocular comfort (graded on a 1 to 10 scale) and ocular physiology were assessed. Unworn but soaked lenses were analyzed for metrological changes, release of excipients into phosphate buffered saline, and changes to their surface chemical composition. Results. None of the lens metrology measures or clinically observed conjunctival or limbal redness changed. Corneal staining was significantly (p < 0.008) raised, albeit to low levels, after 6 h wear for either lens type when soaked in the PHMB solution compared with the control lens (lotrafilcon B 0.4 to 0.9 ± 0.7 to 0.4 vs. 0.1 to 0.4 ± 0.3 to 0.5; galyfilcon A 0.2 to 0.3 ± 0.2 to 0.4 vs. 0.0 ± 0.0). For lotrafilcon B lenses, there were decreases in comfort (p = 0.002), increases in burning/stinging (p = 0.002) after 1 h of wear, and increases in lens awareness on lens insertion (p = 0.0001) when soaked in PHMB. However, lotrafilcon B lenses soaked in Polyquad/Aldox showed increases in burning/stinging after 1 and 6 h (p < 0.008) of lens wear. For galyfilcon A lenses, most significant (p ≤ 0.002) changes to symptomatology occurred after soaking in Polyquad/Aldox solution. More PHMB was released from lotrafilcon B lenses, and more MPDS material was released from galyfilcon A lenses. The surface of galyfilcon A lenses changed but irrespective of lens solution type, whereas the changes to the lens surface was dependent on solution type for lotrafilcon B lenses. Conclusions. Lens care products can change corneal staining and comfort responses during wear. These changes may be associated with release of material soaked into lenses or changes to the lens surface composition.

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.

A Comparison of Patient Matched Meibum and Tear Lipidomes

PURPOSE To quantify the molecular lipid composition of patient-matched tear and meibum samples and compare tear and meibum lipid molecular profiles. METHODS Lipids were extracted from tears and meibum by bi-phasic methods using 10:3 tert-butyl methyl ether:methanol, washed with aqueous ammonium acetate, and analyzed by chip-based nanoelectrospray ionization tandem mass spectrometry. Targeted precursor ion and neutral loss scans identified individual molecular lipids and quantification was obtained by comparison to internal standards in each lipid class. RESULTS Two hundred and thirty-six lipid species were identified and quantified from nine lipid classes comprised of cholesterol esters, wax esters, (O-acyl)-ω-hydroxy fatty acids, triacylglycerols, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylserine. With the exception of phospholipids, lipid molecular profiles were strikingly similar between tears and meibum. CONCLUSIONS Comparisons between tears and meibum indicate that meibum is likely to supply the majority of lipids in the tear film lipid layer. However, the observed higher mole ratio of phospholipid in tears shows that analysis of meibum alone does not provide a complete understanding of the tear film lipid composition.