Comparison Between Ocular Biometric Parameters and Intraocular Pressure With and Without Contact Lenses.

OBJECTIVES: To compare the values of central corneal thickness, anterior chamber depth (ACD), lens thickness (LT), vitreous length (VL), axial length (AL), and corneal-compensated intraocular pressure performed with and without contact lenses (CL). METHODS: Forty volunteer participants (16 men and 24 women, 24.2±2.9 years) were recruited. In a single visit, participants underwent autorefraction, keratometry, biometry, topography, pachymetry, and tonometry with the naked eye (without CL). Then, biometry, pachymetry, and tonometry were repeated twice wearing two CL (somofilcon A and nesofilcon A) fitted in a random order. RESULTS: Many of the ocular biometric values were affected by the use of CL during measurements (paired t test; all P ≤0.003), except for LT and VL (Wilcoxon test; both P ≥0.272). Corneal-compensated intraocular pressure was also affected by contact lens wear during measurements, obtaining lower values when wearing them (Wilcoxon test; all P ≤0.001). CONCLUSIONS: Central corneal thickness, ACD, AL, and corneal-compensated intraocular pressure measurements cannot be performed while wearing CL. However, LT and VL measurements were not affected by any contact lens use. In addition, it was observed that ACD results from both devices are not interchangeable either when measured with the naked eye or using any contact lens.

Diurnal variations of tear film osmolarity on the ocular surface.

The measurement of tear film osmolarity has been suggested as a gold standard in the diagnosis of dry eye. Many tear film physiological variables oscillate during the day. This review summarises current clinical knowledge regarding diurnal osmolarity variation in the tear film. A critical analysis is presented in respect of of sample size and characteristics, differences in the diurnal osmolarity variation on healthy versus altered tear film conditions or environment, and time of day and number of measurements undertaken. A comparison of 21 studies was made for studies in which one of the main objectives was to analyse the variance of tear film osmolarity at different time-points in a day on human cohorts. Tear film osmolarity appeard to be somewhat influenced by the time of day in healthy subjects and patients with ocular surface disease, or altered by environmental conditions. Both healthy and non-physiological tear film cohorts showed variations in results depending on the study: no variations during the day or statistically different values at some point in the day. These differences could be in the middle of the day or between the beginning and the end of the day, with higher values in the morning than in the afternoon, or even the opposite situation. The possibility of diurnal variations in tear film osmolarity should be considered by the clinician since the time of day when the tear film measurements are made can be critical in making the right diagnosis. Future studies in the diurnal variation field may have to use a well-established range of measurement time-points and a larger group of healthy subjects and and subjects who have a tear film altered by pathological or environmental conditions.

Capability of the Inter-Eye Differences in Osmolarity, Break-Up Time and Corneal Staining on the Diagnostic of Dry Eye.

PURPOSE: Inter-eye variability is a recognized characteristic of Dry Eye Disease (DED) and has been proposed as a diagnostic indicator in clinical practice. This study aimed to assess the diagnostic potential of the absolute difference between eyes in three key diagnostic tests recommended by the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) Diagnostic Methodology report: tear film osmolarity, Fluorescein Break-Up Time (FBUT), and ocular surface staining. METHODS: A total of 180 participants were included in a cross-sectional study. Before a dry eye examination, participants completed an online self-administered OSDI questionnaire. The TFOS DEWS II diagnostic criteria for DED assessment were used: along with OSDI, osmolarity, FBUT and ocular surface staining were measured in all participants in both eyes following standardized methodology. Based on signs and symptoms, participants were diagnosed as having No DED or DED. After diagnosis, the parameters were computed as the right and left eyes' absolute inter-eye difference (|OD-OS|). RESULTS: Receiver Operating Characteristics analyses for computed parameters were used based on the previous diagnosis. ROC analyses showed that Osmolarity|OD-OS| have a diagnostic capability to differentiate between No DED and DED participants with a cut-off value of 9.5 mOsm/L (AUC = 0.745 ± 0.052, p < 0.003), whereas FBUT|OD-OS| and Corneal Stainning|OD-OS| have not (AUC, both p ≥ 0.160). CONCLUSION: The present study found that the Osmolarity|OD-OS| parameter could be used as a diagnostic indicator for DED assessment, while the FBUT|OD-OS| and the Corneal Staining|OD-OS| parameters do not have this capability.

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems, Part II: Long-Term Stability and Clinical Ocular Biopermanence.

BACKGROUND: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed. METHODS: Long-term stability at -20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters. RESULTS: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time. CONCLUSIONS: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at -20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.

Categorization of the Aqueous Deficient Dry Eye by a Cut-Off Criterion of TMH Measured with Tearscope.

A decrease of the Tear Meniscus Height (TMH) has been proposed as a useful indicator for Aqueous Deficient Dry Eye (ADDE) categorization. The present study aimed to calculate a TMH cut-off criterion for the categorization or severity assessment of ADDE with the Tearscope. 200 participants with a previous Dry Eye Disease (DED) diagnosis according to TFOS DEWS-II criteria were recruited. TMH by slit-lamp illumination and Lipid Layer Pattern (LLP) with Tearscope were assessed to categorise the participants into the ADDE or the Evaporative Dry Eye (EDE) group. The ADDE group was also subdivided into Mild-moderate ADDE and Moderate-severe ADDE based on TMH with slit-lamp. Additionally, the TMH was measured by Tearscope (TMH-Tc). Receiver Operating Characteristics showed that the TMH-Tc have a diagnostic capability to differentiate between ADDE and EDE participants, and between Mild-moderate or Moderate-severe ADDE, with a cut-off value of 0.159 mm (AUC = 0.843 ± 0.035, p < 0.001; sensitivity: 86.4%; specificity: 75.4%) and 0.105 mm (AUC = 0.953 ± 0.025, p < 0.001; sensitivity: 98.1%; specificity: 80.0%), respectively. The present study proposed a cut-off criterion to differentiate between ADDE and EDE participants, or between ADDE severities through TMH assessed by Tearscope.

Inter-week variation of meibometry and tear break-up time in healthy subjects.

CLINICAL RELEVANCE: Variation with time in the tear film parameters should be considered by the clinician since the time when measurements are made can influence proper diagnosis. BACKGROUND: A hallmark of dry eye is an unstable tear film associated with variability in objective daily measures. The purpose of the present study was to evaluate the inter-week repeatability of meibometry, break-up time (BUT) and maximum blink interval (MBI) in healthy subjects. METHODS: Forty healthy subjects were recruited for the study. Meibometry, BUT and MBI were performed twice in two sessions, one-week apart. Meibum from the lower eyelid was collected and quantified with the Meibometer MB550. Five meibomian curves were generated by tape and each peak value was averaged as a mean value per session. BUT and MBI were determined three times after fluorescein instillation and recorded by a DV-3 camera attached to the slit lamp. BUT and MBI videos were analysed by a second masked observer. Both BUT and MBI values were calculated by averaging the two most similar measurements of the three evaluated. RESULTS: No statistical difference between inter-week sessions was obtained for the meibometry (p > 0.340; Wilcoxon test), BUT (p > 0.326; Wilcoxon test) and MBI values (p ≥ 0.248; Wilcoxon test). Inter-week differences were low for BUT and MBI when time intervals were no longer than 15 seconds (both p ≥ 0.586; Wilcoxon test). A correlation between BUT and MBI was found (r ≥ 0.668, p < 0.001; Spearman Rho), while a no statistical correlation was obtained between meibometry results and BUT or MBI (all p ≥ 0.194; Spearman Rho). CONCLUSION: Meibum secretion and the tear film stability present good intersession repeatability, and are stable along with sessions in healthy patients.

Clinical assessment of the lower tear meniscus height.

PURPOSE: Different values of the lower tear meniscus height (TMH) can be obtained depending on the method and technique of measurement employed. This study aimed to assess (1) differences between the absolute (TMH-A), reflex (TMH-R) and fluorescein (TMH-F) lower tear meniscus heights, (2) differences between the central (TMH-R), nasal (TMH-RN) and temporal (TMH-RT) reflex lower tear meniscus heights and (3) the amount of fluorescein present in the lower tear meniscus, 5 min after fluorescein instillation (TMH-FV). METHODS: Thirty four young healthy subjects were included in the study. The lower tear meniscus height (TMH) was measured using an eye piece graticule inserted into a slit-lamp. RESULTS: Mean +/- S.D. values of TMH-A, TMH-R, TMH-RN, TMH-RT, TMH-F and TMH-FV of 0.25 +/- 0.08, 0.13 +/- 0.05, 0.23 +/- 0.06, 0.21 +/- 0.05, 0.27 +/- 0.11 and 0.004 +/- 0.001 mm, respectively were found. The TMH-R was significantly lower than the TMH-A and the TMH-F (p < 0.0001). The TMH-RN and TMH-RT were significantly higher than the TMH-R (p < 0.0001). The TMH-F was significant higher than the TMH-FV (p < 0.0001). No significant differences were found between the TMH-A and TMH-F (p = 0.2), and between the TMH-RN and TMH-RT (p = 0.36). CONCLUSION: Careful instillation of fluorescein does not affect normal TMH values. Fluorescein is washed out from the lower tear meniscus 5 min after instillation. Higher values of the TMH can be found at nasal and temporal locations compared to the center of the lower eye lid.

Clinical relationship of meibometry with ocular symptoms and tear film stability.

PURPOSE: To evaluate the relationship between meibometry with both ocular symptoms and tear film stability by: (1) to find out whether meibometry is able to differentiate between dry eye symptomatic and asymptomatic subjects classified by standardized dry eye questionnaires (OSDI and McMonnies), and (2) to assess the clinical relationship between meibometry with both tear break-up time (BUT) and maximum blink interval (MBI). METHODS: 140 Patients were recruited for the study. Using Meibometer MB550, five curves were generated for each patient. Subjects performed OSDI and McMonnies questionnaires and were stratified following a two- and a three-subgroup stratification for each questionnaire. BUT/MBI were repeated three times (by video recordings), and they were determined by counting their frames. RESULTS: Subjects grouped by OSDI showed a trend to present lower meibometry values as the OSDI score were higher (ANOVA, p≤0.044). For McMonnies questionnaire this was only true for the two-subgroup stratification (ANOVA, p=0.04), but not for three-subgroup stratification (one-way ANOVA, p=0.30). On the other hand, meibometry values showed a statistical correlation with both BUT (r=0.305, p<0.001) and MBI (r=0.265, p<0.001). When the sample was divided in three groups regarding BUT value (≤5s, between 5 and 10s and≥10s), significant differences of meibometry values were found between BUT subgroups (p=0.008). CONCLUSION: Meibometer MB550 can discriminate asymptomatic from dry eye symptomatic patients. Furthermore, there is a relationship between meibometry and the tear film stability.

Corneal epithelial wound healing and bactericidal effect of conditioned medium from human uterine cervical stem cells.

PURPOSE: To evaluate the effect of conditioned medium from human uterine cervical stem cells (CM-hUCESCs) on corneal epithelial healing in a rat model of dry eye after alkaline corneal epithelial ulcer. We also tested the bactericidal effect of CM-hUCESCs. METHODS: Dry eye was induced in rats by extraocular lacrimal gland excision, and corneal ulcers were produced using NaOH. Corneal histologic evaluation was made with hematoxylin-eosin (H&E) staining. Real-time PCR was used to evaluate mRNA expression levels of proinflammatory cytokines. We also studied the bactericidal effect of CM-hUCESCs in vitro and on infected corneal contact lenses (CLs) using Escherichia coli and Staphylococcus epidermidis bacteria. In addition, in order to investigate proteins from CM-hUCESCs that could mediate these effects, we carried out a human cytokine antibody array. RESULTS: After injury, dry eyes treated with CM-hUCESCs significantly improved epithelial regeneration and showed reduced corneal macrophage inflammatory protein-1 alpha (MIP-1α) and TNF-α mRNA expression as compared to untreated eyes and eyes treated with culture medium or sodium hyaluronate ophthalmic drops. In addition, we found in CM-hUCESCs high levels of proteins, such as tissue inhibitors of metalloproteinases 1 and 2, fibroblast growth factor 6 and 7, urokinase receptor, and hepatocyte growth factor, that could mediate these effects. In vitro, CM-hUCESCs showed a clear bactericidal effect on both E. coli and S. epidermidis and CLs infected with S. epidermidis. Analyses of CM-hUCESCs showed elevated levels of proteins that could be involved in the bactericidal effect, such as the chemokine (C-X-C motif) ligands 1, 6, 8, 10, and the chemokine (C-C motif) ligands 5 and 20. CONCLUSIONS: Treatment with CM-hUCESCs improved wound healing of alkali-injured corneas and showed a strong bactericidal effect on CLs. Patients using CLs and suffering from dry eye, allergies induced by commercial solutions, or small corneal injuries could benefit from this treatment.

Interobserver and intraobserver repeatability of lipid layer pattern evaluation by two experienced observers.

PURPOSE: The lipid layer plays a major role in limiting evaporation of the tear film. Based on interference phenomena, there is a test directed to lipid layer pattern (LLP) evaluation, but is affected by subjective interpretation of the patterns. The aim of this study is to compare the LLP evaluation between two experienced observers on a group of healthy patients. Furthermore, observers re-evaluated the same images to check their individual repeatability. MATERIALS AND METHODS: LLP was examined using a Tearscope-plus (Keeler, Windsor, UK) attached to a slit lamp. Tear film was recorded by a Topcon DV-3 digital camera video and LLP images were captured. This yielded 124 LLP images that were categorized (based on Guillon's scheme) by two expert observers in two sessions separated by one month. Interobserver repeatability and intraobserver repeatability between both sessions were studied by using Cohen's kappa coefficient. RESULTS: Comparing LLP categorization between both observers, Cohen's kappa coefficient was 0.615 and 0.633 for first and second session, respectively. When comparing LLP categorization by the same observer between both sessions, Cohen's kappa coefficient was 0.770 and 0.812 for Observer 1 and Observer 2, respectively. These results indicate substantial correlation in all cases. The most frequent misinterpretations were between open and closed meshwork and Wave and closed meshwork patterns. CONCLUSION: Although substantial correlation was found between categorizations of experienced observers, misinterpretation of the patterns may appear even in the same observer. Some misinterpretations between adjacent patterns could be palliated by including intermediate patterns between those categories.

A preliminary investigation into the relationship between ocular surface temperature and lipid layer thickness.

The aim of this study was to establish the relationship between OST, tear film stability as assessed by NIBUT and subjective evaluation of the lipid layer thickness in a young, asymptomatic, sample group (N=29). Non-invasive tear break-up time (NIBUT) and tear lipid layer structure were evaluated through a slit-lamp mounted Tearscope Plus. A self-calibrating infrared thermography camera was used to record two OST values (one immediately post-blink and one immediately pre the subsequent blink). The most common lipid layer pattern observed was the amorphous pattern (48.3%). Differences between post- and pre-blink OST values were observed (paired t-test; p<0.001). Significant differences of pre-blink OST values were observed between the closed marmoreal group with that from the amorphous and flow groups (Tukey post hoc test, p<0.05). There were no differences of NIBUT values between each lipid layer thickness (Kruskal-Wallis test; p=0.152). A no significant tendency for higher OST in eyes with increased NIBUT was observed. This study suggests that higher OST values could be associated with thicker tear lipid layer in normal subjects. The lack of significant results in relation with tear film stability may be due to only normal subjects were included.