The fall and rise of tear albumin levels:a multifactorial phenomenon

Albumin in tears is used as a diagnostic marker of ocular insult and inflammation, but whether its presence in tears is responsive or part of an adaptive reaction remains unresolved. A review of the literature on tear albumin concentration emphasizes that variables such as collection method, stimulus, assay technique, and disease state influence the quoted values to different extents. Influence of assay technique is negligible in comparison to variation in sampling conditions. Ocular disease increases albumin concentrations but not in a specific manner. The literature review also highlighted that little systematic research has been carried out on the daily cycle of tear albumin levels. In order to remedy this shortcoming, we investigated variations in tear albumin concentration during the waking day. The concentration of albumin in 400 tear samples collected from 13 subjects was assessed at 2-hourly intervals throughout the waking day. Highest daytime albumin concentrations were obtained within 10 minutes of waking, with a mean concentration of >50 ± 22 µg/ml. Albumin levels were at their lowest, but most consistent, 2-6 hours post-waking. This pattern was followed by a progressive increase in albumin concentration during the latter part of the day. Although individual subject-to-subject concentration differences were observed, this distinctive pattern of diurnal variation was found in all subjects. The results presented suggest a regulated, not random, pattern of variation within the period of study. © 2013 Elsevier Inc. All rights reserved.

Predicting success with silicone-hydrogel contact lenses in new wearers

Purpose: to evaluate changes in tear metrics and ocular signs induced by six months of silicone-hydrogel contact lens wear and the difference in baseline characteristics between those who successfully continued in contact lens wear compared to those that did not. Methods: Non-invasive Keratograph, Tearscope and fluorescein tear break-up times (TBUTs), tear meniscus height, bulbar and limbal hyperaemia, lid-parallel conjunctival folds (LIPCOF), phenol red thread, fluorescein and lissamine-green staining, and lid wiper epitheliopathy were measured on 60 new contact lens wearers fitted with monthly silicone-hydrogels (average age 36 ± 14 years, 40 females). Symptoms were evaluated by the Ocular Surface Disease Index (OSDI). After six months full time contact lens wear the above metrics were re-measured on those patients still in contact lens wear (n= 33). The initial measurements were also compared between the group still wearing lenses after six months and those who had ceased lens wear (n= 27). Results: There were significant changes in tear meniscus height (p= 0.031), bulbar hyperaemia (p= 0.011), fluorescein TBUT (p= 0.027), corneal (p= 0.007) and conjunctival (p= 0.009) staining, LIPCOF (p= 0.011) and lid wiper epitheliopathy (p= 0.002) after six months of silicone-hydrogel wear. Successful wearers had a higher non-invasive (17.0 ± 8.2. s vs 12.0 ± 5.6. s; p= 0.001) and fluorescein (10.7 ± 6.4. s vs 7.5 ± 4.7. s; p= 0.001) TBUT than drop-outs, although OSDI (cut-off 4.2) was also a strong predictor of success. Conclusion: Silicone-hydrogel lenses induced significant changes in the tear film and ocular surface as well as lid margin staining. Wettability of the ocular surface is the main factor affecting contact lens drop-out. © 2013 British Contact Lens Association.

The predictive ability of clinical tests for contact lens induced dry eye

Approximately half of current contact lens wearers suffer from dryness and discomfort, particularly towards the end of the day. Contact lens practitioners have a number of dry eye tests available to help them to predict which of their patients may be at risk of contact lens drop out and advise them accordingly. This thesis set out to rationalize them to see if any are of more diagnostic significance than others. This doctorate has found: (1) The Keratograph, a device which permits an automated, examiner independent technique for measuring non invasive tear break up time (NITBUT) measured NITBUT consistently shorter than measurements recorded with the Tearscope. When measuring central corneal curvature the spherical equivalent power of the cornea was measured as being significantly flatter than with a validated automated keratometer. (2) Non-invasive and invasive tear break-up times significantly correlated to each other, but not the other tear metrics. Symptomology, assessed using the OSDI questionnaire, correlated more with those tests indicating possible damage to the ocular surface (including LWE, LIPCOF and conjunctival staining) than with tests of either tear volume or stability. Cluster analysis showed some statistically significant groups of patients with different sign and symptom profiles. The largest cluster demonstrated poor tear quality with both non-invasive and invasive tests, low tear volume and more symptoms. (3) Care should be taken in fitting patients new to contact lenses if they have a NITBUT less than 10s or an OSDI comfort rating greater than 4.2 as they are more likely to drop-out within the first 6 months. Cluster analysis was not found to be beneficial in predicting which patients will succeed with lenses and which will not. A combination of the OSDI questionnaire and a NITBUT measurement was most useful both in diagnosing dry eye and in predicting contact lens drop out.

Impact of soft contact lens edge design and mid-peripheral lens shape on the epithelium and its indentation with lens mobility

Purpose. To evaluate the influence of soft contact lens midperipheral shape profile and edge design on the apparent epithelial thickness and indentation of the ocular surface with lens movement. Methods. Four soft contact lens designs comprising of two different plano midperipheral shape profiles and two edge designs (chiseled and knife edge) of silicone-hydrogel material were examined in 26 subjects aged 24.7 ± 4.6 years, each worn bilaterally in randomized order. Lens movement was imaged enface on insertion, at 2 and 4 hours with a high-speed, high-resolution camera simultaneous to the cross-section of the edge of the contact lens interaction with the ocular surface captured using optical coherence tomography (OCT) nasally, temporally, and inferiorly. Optical imaging distortions were individually corrected for by imaging the apparent distortion of a glass slide surface by the removed lens. Results. Apparent epithelial thickness varied with edge position (P < 0.001). When distortion was corrected for, epithelial indentation decreased with time after insertion (P = 0.010), changed after a blink (P < 0.001), and varied with position on the lens edge (P < 0.001), with the latter being affected by midperipheral lens shape profile and edge design. Horizontal and vertical lens movement did not change with time postinsertion. Vertical motion was affected by midperipheral lens shape profile (P < 0.001) and edge design (P < 0.001). Lens movement was associated with physiologic epithelium thickness for lens midperipheral shape profile and edge designs. Conclusions. Dynamic OCT coupled with high-resolution video demonstrated that soft contact lens movement and image-corrected ocular surface indentation were influenced by both lens edge design and midperipheral lens shape profiles. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Effectiveness of nonpharmacologic treatments for acute seasonal allergic conjunctivitis

Objective - To investigate whether artificial tears and cold compress alone or in combination provide a treatment benefit and whether they were as effective as or could enhance topical antiallergic medication. Design - Randomized, masked clinical trial. Participants - Eighteen subjects (mean age, 29.5±11.0 years) allergic to grass pollen. Intervention - Controlled exposure to grass pollen using an environmental chamber to stimulate an ocular allergic reaction followed by application of artificial tears (ATs), 5 minutes of cold compress (CC), ATs combined with CC, or no treatment applied at each separate visit in random order. A subset of 11 subjects also had epinastine hydrochloride (EH) applied alone and combined with CC in random order or instillation of a volume-matched saline control. Main Outcome Measures - Bulbar conjunctival hyperemia, ocular surface temperature, and ocular symptoms repeated before and every 10 minutes after treatment for 1 hour. Results - Bulbar conjunctival hyperemia and ocular symptoms decreased and temperature recovered to baseline faster with nonpharmaceutical treatments compared with no treatment (P?ocular surface temperature to less than the pre-exposure baseline. Artificial tear instillation alone or CC combined with ATs or EH significantly reduced the temperature (P??0.05). At all measurement intervals, symptoms were reduced for both EH and EH combined with CC than CC or ATs alone or in combination (P?

Effectiveness of nonpharmacologic treatments for acute seasonal allergic conjunctivitis

Objective To investigate whether artificial tears and cold compress alone or in combination provide a treatment benefit and whether they were as effective as or could enhance topical antiallergic medication. Design Randomized, masked clinical trial. Participants Eighteen subjects (mean age, 29.5±11.0 years) allergic to grass pollen. Intervention Controlled exposure to grass pollen using an environmental chamber to stimulate an ocular allergic reaction followed by application of artificial tears (ATs), 5 minutes of cold compress (CC), ATs combined with CC, or no treatment applied at each separate visit in random order. A subset of 11 subjects also had epinastine hydrochloride (EH) applied alone and combined with CC in random order or instillation of a volume-matched saline control. Main Outcome Measures Bulbar conjunctival hyperemia, ocular surface temperature, and ocular symptoms repeated before and every 10 minutes after treatment for 1 hour. Results Bulbar conjunctival hyperemia and ocular symptoms decreased and temperature recovered to baseline faster with nonpharmaceutical treatments compared with no treatment (P <0.05). Artificial tears combined with CC reduced hyperemia more than other treatments (P <0.05). The treatment effect of EH was enhanced by combining it with a CC (P <0.001). Cold compress combined with ATs or EH lowered the antigen-raised ocular surface temperature to less than the pre-exposure baseline. Artificial tear instillation alone or CC combined with ATs or EH significantly reduced the temperature (P <0.05). Cold compress combined with ATs or EH had a similar cooling effect (P > 0.05). At all measurement intervals, symptoms were reduced for both EH and EH combined with CC than CC or ATs alone or in combination (P <0.014). Conclusions After controlled exposure to grass pollen, CC and AT treatment showed a therapeutic effect on the signs and symptoms of allergic conjunctivitis. A CC enhanced the use of EH alone and was the only treatment to reduce symptoms to baseline within 1 hour of antigenic challenge. Signs of allergic conjunctivitis generally were reduced most by a combination of a CC in combination with ATs or EH. © 2014 by the American Academy of Ophthalmology.

Report of the inaugural meeting of the TFOS i2 = initiating innovation Series:targeting the unmet need for dry eye treatment

On March 21, 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i2 = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i2 meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i2 meeting.

What is the optimum artificial treament for dry eye?

Dry eye disease is a common clinical condition whose aetiology and management challenges clinicians and researchers alike. Practitioners have a number of dry eye tests available to clinically assess dry eye disease, in order to treat their patients effectively and successfully. This thesis set out to determine the most relevant and successful key tests for dry eye disease diagnosis/ management. There has been very little research on determining the most effective treatment options for these patients; therefore a randomised controlled study was conducted in order to see how different artificial treatments perform compared to each other, whether the preferred treatment could have been predicted from their ocular clinical assessment, and if the preferred treatment subjectively related to the greatest improvement in ocular physiology and tear film stability. This research has found: 1. From the plethora of ocular the tear tests available to utilise in clinical practice, the tear stability tests as measured by the non-invasive tear break (NITBUT) up time and invasive tear break up time (NaFL TBUT) are strongly correlated. The tear volume tests are also related as measured by the phenol red thread (PRT) and tear meniscus height (TMH). Lid Parallel Conjunctival Folds (LIPCOF) and conjunctival staining are significantly correlated to one another. Symptomology and osmolarity were also found to be important tests in order to assess for dry eye. 2. Artificial tear supplements do work for ocular comfort, as well as the ocular surface as observed by conjunctival staining and the reduction LIPCOF. There is no strong evidence of one type of artificial tear supplement being more effective than others, and the data suggest that these improvements are more due to the time than the specific drops. 3. When trying to predict patient preference for artificial tears from baseline measurements, the individual category of artificial tear supplements appeared to have an improvement in at least 1 tear metric. Undoubtedly, from the study the patients preferred artificial tear supplements’ were rated much higher than the other three drops used in the study and their subjective responses were statistically significant than the signs. 4. Patients are also willing to pay for a community dry eye service in their area of £17. In conclusion, the dry eye tests conducted in the study correlate with one another and with the symptoms reported by the patient. Artificial tears do make a difference objectively as well as subjectively. There is no optimum artificial treatment for dry eye, however regular consistent use of artificial eye drops will improve the ocular surface.

Crossover evaluation of silicone hydrogel daily disposable contact lenses

PURPOSE: To assess the surface tear breakup time and clinical performance of three daily disposable silicone hydrogel contact lenses over 16 hours of wear. METHODS: Thirty-nine patients (mean [±SD] age, 22.1 [±3.5] years) bilaterally wore (narafilcon A, filcon II-3, and delefilcon A) contact lenses in a prospective, randomized, masked, 1-week crossover clinical trial. Tear film was assessed by the tear meniscus height (TMH), ocular/contact lens surface temperature dynamics, and lens surface noninvasive breakup time at 8, 12, and 16 hours of wear. Clinical performance and ocular physiology were assessed by subjective questionnaire, by high-/low-contrast logMAR (logarithm of the minimum angle of resolution) acuity, and through bulbar and limbal hyperemia grading. Corneal and conjunctival staining were assessed after lens removal. RESULTS: Delefilcon A demonstrated a longer noninvasive breakup time (13.4 [±4.4] seconds) than filcon II-3 (11.6 [±3.7] seconds; p < 0.001) and narafilcon A (12.3 [±3.7] seconds; p < 0.001). A greater TMH (0.35 [±0.11] mm) was shown by delefilcon A than filcon II-3 (0.32 [±0.10] seconds; p = 0.016). Delefilcon A showed less corneal staining after 16 hours of lens wear (0.7 [±0.6] Efron grade) than filcon II-3 (1.1 [±0.7]; p < 0.001) and narafilcon A (0.9 [±0.7]; p = 0.031). Time was not a significant factor for prelens tear film stability (F = 0.594, p = 0.555) or TMH (F = 0.632, p = 0.534). Lens brand did not affect temperature (F = 1.220, p = 0.308), but it decreased toward the end of the day (F = 19.497, p < 0.001). Comfort, quality of vision, visual acuity and contrast acuity, and limbal grading were similar between the lens brands but decreased with time during the day (p < 0.05). CONCLUSIONS: The tear breakup time over the contact lens surface differed between lens types and may have a role in protecting the ocular surface.

Gravidade do olho seco em pacientes internados em unidade de terapia intensiva: análise de conceito e construção de definições

Dry eye syndrome is a multifactorial disease of the tear film, resulting from the instability of the lacrimal functional unit that produces volume change, up or tear distribution. In patients in intensive care the cause is enhanced due to various risk factors, such as mechanical ventilation, sedation, lagophthalmos, low temperatures, among others. The study's purpose is to build an assessment tool of Dry Eye Severity in patients in intensive care units based on the systematization of nursing care and their classification systems. The aim of this study is to build an assessment tool of Dry Eye Severity in hospitalized patients in Care Unit Intensiva.Trata is a methodological study conducted in three stages, namely: context analysis, concept analysis, construction of operational definitions and magnitudes of nursing outcome. For the first step we used the methodological framework for Hinds, Chaves and Cypress (1992). For the second step we used the model of Walker and Avant and an integrative review Whitemore seconds, Knalf (2005). This step enabled the identification of the concept of attributes, background and consequent ground and the construction of the settings for the result of nursing severity of dry eye. For the construction of settings and operational magnitudes, it was used Psicometria proposed by Pasquali (1999). As a result of context analysis, visualized from the reflection that the matter should be discussed and that nursing needs to pay attention to the problem of eye injury, so minimizing strategies are created this event with a high prevalence. With the integrative review were located from the crosses 19 853 titles, selected 215, and from the abstracts 96 articles were read in full. From reading 10 were excluded culminating in the sample of 86 articles that were used to analyze the concept and construction of settings. Selected articles were found in greater numbers in the Scopus database (55.82%), performed in the United States (39.53%), and published mainly in the last five years (48.82). Regarding the concept of analysis were identified as antecedents: age, lagophthalmos, environmental factors, medication use, systemic diseases, mechanical ventilation and ophthalmic surgery. As attributes: TBUT <10s, Schimer I test <5 mm in Schimer II test <10mm, reduced osmolarity. As consequential: the ocular surface damage, ocular discomfort, visual instability. The settings were built and added indicators such as: decreased blink mechanism and eyestrain.

Diadenosine polyphosphates in the tears of aniridia patients

Purpose To quantify diadenosine polyphosphate levels in tears of congenital aniridia patients to estimate the ocular surface changes associated with congenital aniridia compared to normal individuals. Methods Fifteen patients diagnosed with congenital aniridia and a control group of forty volunteers were studied. Tears were collected to quantify the levels of diadenosine polyphosphates Ap4A and Ap5A by high-performance liquid chromatography (H.P.L.C). Break-up time (BUT), corneal staining, McMonnies questionnaire and the Schirmer I test were applied to both groups. Results Dinucleotides in congenital aniridia patients were higher than in control subjects. For the congenital aniridia group, under 15 years old, the values were 0.77 ± 0.01 μm and 0.17 ± 0.02 μm for Ap4A and Ap5A, respectively. The group aged from 15 to 40 years old provided concentrations of 4.37 ± 0.97 μm and 0.46 ± 0.05 μm for Ap4A and Ap5A, the group over 40 gave concentrations of 11.17 ± 5.53 μm and 0.68 ± 0.17 μm for Ap4A and Ap5A. Dinucleotide concentrations increased with age, being statistically significant different among the three age groups (p < 0.05). Congenital aniridia patients showed a normal tear secretion and no dry eye McMonnies scores, except for the group over 40 years old. BUT values decreased and corneal staining increased with age and correlated with the levels of diadenosine polyphosphates (p < 0.05). Conclusions The levels of dinucleotides in tears increase in aniridia patients compared with healthy subjects, and they seem to be related with the progression of corneal disorders in aniridia patients, both of which increase with ageing.

Diadenosine polyphosphates after laser in situ keratomileusis and photorefractive keratectomy refractive techniques

Purpose:  To study the concentrations of diadenosine polyphosphates in the ocular surface after PRK and LASIK. Methods:  Sixty-one patients (30 males and 31 females) with ages ranging from 20 to 63 (34.04 ± 9.13 years) were recruited in Balear Institute of Ophthalmology, Palma de Mallorca, Spain. LASIK was performed in 92 eyes of 46 patients and PRK in 25 eyes of 15 patients. Variations in the levels of diadenosine polyphosphate (Ap4A and Ap5A), Schirmer I (Jones test), TBUT, corneal staining together with the Dry Eye Questionnaire to evaluate discomfort and dryness were studied. All tests were performed at the preoperative visit and at 1-day, 2-week, 1-month and 3-month postoperative visits. Results:  Ap4A showed a 5 and 3.5 fold increase at the 1-day visit for LASIK and PRK, respectively. LASIK patients continued having higher statistically significant concentrations (p = 0.01) all over the follow-up. Ap5A showed no significant differences at any visit. Tear volume decreased during the 3 months in LASIK. The PRK cases had a normal volume at 1 month. TBUT in LASIK increased at the 1-day visit (p = 0,002) and decreased from the 2 weeks onwards and for the PRK, decreased by a 35% at the 1-day visit and kept reduced for a month. Discomfort only increased at the 1-day visit (p = 0.007). Dryness frequency was similar in all visits. Conclusions:  Ap4A levels only are increased in refractive surgery patients during the first day after the surgery. This increasing suggests that Ap4A may help accelerating the healing process.

Effect of Melatonin and Analogues on Corneal Wound Healing: Involvement of Mt2 Melatonin Receptor

Purpose: We have investigated the effect of melatonin and its analogues on rabbit corneal epithelial wound healing. Methods: New Zealand rabbits were anaesthetised and wounds were made by placing Whatman paper discs soaked in n-heptanol on the cornea. Melatonin and analogues (all 10 nmol) were instilled. Wound diameter was measured every 2 hours by means of fluorescein application with a Topcon SL-8Z slit lamp. Melatonin antagonists (all 10 nmol) were applied 2 hours before the application of the n-heptanol-soaked disc and then every 6 hours together with melatonin. To confirm the presence of MT2 receptors in corneal epithelial cells immunohistochemistry, Western blot and RT-PCR assays in native tissue and in rabbit corneal epithelial cells were performed. The tear components were extracted then processed by HPLC to quantify melatonin in tears. Results: Migration assays revealed that melatonin and particularly the treatment with the MT2 agonist IIK7, accelerated the rate of healing (p < 0.001). The application of the non-selective melatonin receptor antagonist luzindole and the MT2 antagonist DH97 (but not prazosin), prevented the effect of melatonin on wound healing (both p < 0.001). Immunohistochemistry, Western blot and RT-PCR assays showed the presence of MT2 melatonin receptor in corneal epithelial cells. In addition, we have identified melatonin in tears and determined its daily variations. Conclusions: These data suggest that MT2 receptors are implicated in the effect of melatonin on corneal wound healing regulating migration rate. This suggests the potential use of melatonin and its analogues to enhance epithelial wound healing in ocular surface disease.

Signs and Symptoms of Dry Eye in Keratoconus Patients: A Pilot Study

Purpose: To compare signs and symptoms of dry eye in keratoconus (KC) patients versus healthy subjects. Methods: A total of 15 KC patients (KC group, n = 15 eyes) and 16 healthy subjects (control group, 16 eyes) were enrolled in this study. The Schirmer I test with no anesthetic, tear break-up time (TBUT), corneal staining characteristics, and ocular surface disease index (OSDI) scores were evaluated for both groups. Impression cytology, combined with/scanning laser confocal microscopy (LCM), was performed to evaluate goblet cell density, mucin cloud height (MCH), and goblet cell layer thickness (CLT). Finally, tear concentrations of di-adenosine tetraphosphate (Ap4A) were assessed. Results were statistically analyzed using Shapiro–Wilk and non-parametric Wilcoxon rank sum tests. Statistical significance was set at p < 0.05. Results: KC patients had lower tear volumes and greater corneal staining than did healthy subjects (p < 0.05). OSDI scores were 44.96 ± 8.65 and 17.78 ± 6.50 for the KC and control groups, respectively (p < 0.05). We found no statistically significant differences in TBUT between groups. Impression cytology revealed lower goblet cell densities in KC group patients versus control group subjects (84.88 ± 32.98 and 128.88 ± 50.60 cells/mm,2 respectively, p < 0.05). There was a statistically significant reduction in MCH and CLT in KC group patients compared with control group subjects. Ap4A tear concentrations were higher in KC group patients than in control group subjects (2.56 ± 1.10 and 0.15 ± 0.12 µM, respectively, p < 0.05). Conclusions: The parameters evaluated in this study indicate that KC patients suffer greater symptoms of dry eye and greater tear instability, primarily due to the decreased mucin production in their tears, than do healthy patients with no KC.

Effect of overnight orthokeratology on conjunctival goblet cells

Objective: To evaluate the differences between goblet cell density (GCD) and symptomatology after one month of orthokeratology lens wear. Methods: A pilot, short-term study was conducted. Twenty-two subjects (29.7. ±. 7.0 years old) participated voluntarily in the study. Subjects were divided into two groups: habitual silicone hydrogel contact lens wearers (SiHCLW) and new contact lens wearers (NCLW). Schirmer test, tear break up time (TBUT), Ocular Surface Disease Index (OSDI) questionnaire and conjunctival impression cytology. GCD, mucin cloud height (MCH) and cell layer thickness (CLT) were measured. All measurements were performed before orthokeratology fitting and one month after fitting to assess the evolution of the changes throughout this time. Results: No differences in tear volume and TBUT between groups were found (p>0.05). However, the OSDI score was statistically better after one month of orthokeratology lens wear than the baseline for the SiHCLW group (p=0.03). Regarding the goblet cell analysis, no differences were found in CLT and MCH from the baseline visit to the one month visit for the SiHCLW compared with NCLW groups (p>0.05). At baseline, the GCD in the SiHCLW group were statistically lower than NCLW group (p<0.001). There was a significant increase in GCD after orthokeratology fitting from 121±140cell/mm2 to 254±130cell/mm2 (p<0.001) in the SiHCLW group. Conclusion: Orthokeratology improves the dry eye subject symptoms and GCD after one month of wearing in SiHCLW. These results suggest that orthokeratology could be considered a good alternative for silicone hydrogel contact lens discomfort and dryness. © 2016 British Contact Lens Association.