Temporal characteristics of sodium fluorescein in the tear meniscus

Purpose To observe the emission intensity profile of sodium fluorescein in the human tear film as a function of time and concentration. Methods Twenty-two participants with no dry eye signs or symptoms were randomly allocated to receive 1 μL of either a 2 or 10% concentration of fluorescein to one eye. Images of the inferior tear meniscus were captured at regular intervals over 30 minutes and the process repeated for the other eye with the alternate concentration. Fluorescence intensity was quantified on the basis of the grayscale pixel values in the tear meniscus images. The fluorescein-decay profile over time and between concentrations was determined. Results Peak fluorescence intensity was reached in 3.9 ± 3.0 and 8.7 ± 4.4 minutes after instillation for the 2 and 10% concentrations, respectively. The 10% concentration of fluorescein maintained its peak fluorescence intensity longer than the 2% concentration (about 9 and 2 minutes, respectively). The peak fluorescence intensity was not significantly different between the higher and lower concentrations (44 ± 37 vs. 38 ± 32 units, P = .22). For both concentrations, the observed intensity did not return to baseline levels by the end of the 30-minute observation time. Conclusions The fluorescence intensity of fluorescein in a clinical setting varies with time such that both the onset and duration of maximum brightness are concentration dependent. At low concentration (2%), maximum brightness occurs almost immediately after instillation and lasts about 2 minutes. With a higher concentration (10%), the effective working window is delayed for about 7 to 8 minutes. Irrespective of initial concentration, observable fluorescence remains in the tear film beyond 30 minutes post-instillation

Glycerol monolaurate inhibits lipase production by clinical ocular isolates without affecting bacterial cell viability

PURPOSE. We sought to determine the relative lipase production of a range of ocular bacterial isolates and to assess the efficacy of glycerol monolaurate (GML) in inhibiting this lipase production in high lipase-producing bacteria without affecting bacterial cell growth. METHODS. Staphylococcus aureus, Staphylococcus epidermidis, Propionibacterium acnes, and Corynebacterium spp. were inoculated at a density of 106/mL in varying concentrations of GML up to 25 μg/mL for 24 hours at 378C with constant shaking. Bacterial suspensions were centrifuged, bacterial cell density was determined, and production of bacterial lipase was quantified using a commercial lipase assay kit. RESULTS. Staphylococcus spp. produced high levels of lipase activity compared with P. acnes and Corynebacterium spp. GML inhibited lipase production by Staphylococcal spp. in a dosedependent manner, with S. epidermidis lipase production consistently more sensitive to GML than S. aureus. Glycerol monolaurate showed significant (P \u3c 0.05) lipase inhibition above concentrations of 15 μg /mL in S. aureus and was not cytotoxic up to 25 μg /mL. For S. epidermidis, GML showed significant (P \u3c 0.05) lipase inhibition above 7.5 μg /mL. CONCLUSIONS. Lipase activity varied between species and between strains. Staphylococcal spp. produced higher lipase activity compared with P. acnes and Corynebacterium spp. Glycerol monolaurate inhibited lipase production by S. aureus and S. epidermidis at concentrations that did not adversely affect bacterial cell growth. GML can be used to inhibit ocular bacterial lipase production without proving detrimental to commensal bacteria viability

A cross-sectional study of ocular surface discomfort and corneal nerve dysfunction after paclitaxel treatment for cancer

Ocular surface dysfunction is common in patients receiving anti-cancer drug treatment. The effects of paclitaxel, a neurotoxic chemotherapeutic drug, on ocular surface discomfort associated with dry eye disease was investigated. Patients with cancer who had completed paclitaxel treatment between 3 and 24 months prior to assessment (n = 29) and age- and sex-matched healthy control subjects (n = 29) were recruited and assessed with the Ocular Surface Disease Index (OSDI) to measure ocular surface discomfort. In-vivo corneal confocal microscopy was used to evaluate corneal nerve parameters in the right eye. Peripheral neurotoxicity was assessed using patient-reported outcomes and clinical grading scales. The paclitaxel group had significantly worse OSDI total scores compared with controls (Median, Md = 19.3 and Md = 0, p = 0.007, respectively). Corneal nerve fiber and inferior whorl lengths were reduced in the paclitaxel group compared with controls (14.2 ± 4.0 and 14.4 ± 4.0 mm/mm2 vs. 16.4 ± 4.0 and 16.9 ± 4.9 mm/mm2, respectively, p = 0.04). When analyzed by presence of peripheral neuropathy, paclitaxel-treated patients with neuropathy showed worse OSDI total scores compared to those without peripheral neuropathy post-treatment (p = 0.001) and healthy controls (p < 0.001). More severe ocular discomfort and worse visual function was associated with greater peripheral neurotoxicity symptoms (r = 0.60, p = 0.001) and neuropathy severity (r = 0.49, p = 0.008), respectively. Patients who have been treated with paclitaxel have a higher risk of ocular surface discomfort associated with dry eye disease, particularly those with peripheral neuropathy. Future longitudinal studies should investigate the clinical impact of corneal nerve reduction in dry eye disease

BCLA CLEAR Presbyopia: Definitions

Presbyopia is often the first sign of ageing experienced by humans. Standardising terminology and adopting it across the BCLA CLEAR Presbyopia reports, improves consistency in the communication of the evidence-based understanding of this universal physiological process. Presbyopia can be functionally and psychologically debilitating, especially for those with poor access to eyecare. Presbyopia was defined as occurring when the physiologically normal age-related reduction in the eye's focusing range reaches a point that, when optimally corrected for far vision, the clarity of vision at near is insufficient to satisfy an individual's requirements. Accommodation is the change in optical power of the eye due to a change in crystalline lens shape and position, whereas pseudo-accommodation is the attainment of functional near vision in an emmetropic or far-corrected eye without changing the refractive power of the eye. Other definitions specific to vision and lenses for presbyopia were also defined. It is recommended that these definitions be consistently adopted in order to standardise future research, clinical evaluations and education

BCLA CLEAR Presbyopia:Epidemiology and impact

The global all-ages prevalence of epidemiologically-measured 'functional' presbyopia was estimated at 24.9% in 2015, affecting 1.8 billion people. This prevalence was projected to stabilise at 24.1% in 2030 due to increasing myopia, but to affect more people (2.1 billion) due to population dynamics. Factors affecting the prevalence of presbyopia include age, geographic location, urban versus rural location, sex, and, to a lesser extent, socioeconomic status, literacy and education, health literacy and inequality. Risk factors for early onset of presbyopia included environmental factors, nutrition, near demands, refractive error, accommodative dysfunction, medications, certain health conditions and sleep. Presbyopia was found to impact on quality-of-life, in particular quality of vision, labour force participation, work productivity and financial burden, mental health, social wellbeing and physical health. Current understanding makes it clear that presbyopia is a very common age-related condition that has significant impacts on both patient-reported outcome measures and economics. However, there are complexities in defining presbyopia for epidemiological and impact studies. Standardisation of definitions will assist future synthesis, pattern analysis and sense-making between studies

Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm 2) compared to healthy controls (Md = 10.1 cells/mm 2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm 2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research

BCLA CLEAR Presbyopia: Management with contact lenses and spectacles

This paper seeks to outline the history, market situation, clinical management and product performance related to the correction of presbyopia with both contact lenses and spectacles. The history of the development of various optical forms of presbyopic correction are reviewed, and an overview is presented of the current market status of contact lenses and spectacles. Clinical considerations in the fitting and aftercare of presbyopic contact lens and spectacle lens wearers are presented, with general recommendations for best practice. Current options for contact lens correction of presbyopia include soft simultaneous, rigid translating and rigid simultaneous designs, in addition to monovision. Spectacle options include single vision lenses, bifocal lenses and a range of progressive addition lenses. The comparative performance of both contact lens and spectacle lens options is presented. With a significant proportion of the global population now being presbyopic, this overview is particularly timely and is designed to act as a guide for researchers, industry and eyecare practitioners alike

Substance P in flush tears and Schirmer strips of healthy participants

PURPOSE: To determine the repeatability of the flush tear collection technique and the Schirmer strip for Substance P tear analysis. METHODS: The tears of 10 healthy non-contact-lens wearers were collected via Schirmer strip and microcapillary following instillation of either 20 &mu;L (F-20) or 60 &mu;L (F-60) of saline. Each technique was conducted on two occasions and in a randomized order. Total protein content (TPC) and Substance P concentrations were determined. The overall protein separation profile of each type of tears was examined using one-dimensional gel electrophoresis (1DGE). RESULTS: Collection rates were significantly faster for the F-60 compared to F-20 (17.3 &plusmn; 6.9 &mu;L/min and 11.9 &plusmn; 5.3 &mu;L/min, respectively, P &lt; .001), with an average Schirmer strip length of 1.5 &plusmn; 2.1 mm/min. The coefficient of repeatability between days and eyes was greatest for the Schirmer strip, with eyes and days being significantly different (P = .03 and P = .03, respectively) for Schirmer strip Substance P. TPC was 3.8 &plusmn; 2.6 mg/mL, 3.3 &plusmn; 1.8 mg/mL, and 3.6 &plusmn; 3.0 mg/mL for F-20, F-60, and Schirmer strip techniques, respectively, with no significant difference between techniques (P = .85). Substance P concentration was 13.1 &plusmn; 14.8 ng/mL, 9.1 &plusmn; 6.1 ng/mL, and 14.9 &plusmn; 10.6 ng/mL for F-20, F-60, and Schirmer strip tears, respectively, with no significant difference between techniques (P = .57). 1DGE profile showed similar electrophoresis patterns among F-20, F-60, and basal tears. CONCLUSIONS: The F-60 method allows faster collection than F-20, but the latter results in better repeatability than both the F-60 and Schirmer sampling techniques. All three techniques return the same concentrations of TPC and Substance P. This indicates that tear collection using the F-20 may be more appropriate when conducting comparative analysis, whereas the F-60 may be more appropriate when more volume is required

The relationship between corneal nerve morphology and inflammatory mediators and neuropeptides in healthy individuals

SIGNIFICANCE This study set out to explore the relationship between the ocular surface immune and nervous systems by exploring corneal nerve structure and the presence of inflammatory mediators and neuropeptides in the tear film. PURPOSE The purpose of this study was to determine the association between corneal nerve morphology and tear film inflammatory mediators and a neuropeptide in healthy individuals. METHODS Flush tears were collected from both eyes of 21 healthy participants aged 39.7 ± 9.9 years (10 females, 11 males) and analyzed for substance P, matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), tumor necrosis factor and interleukin 6. In vivo central corneal confocal microscopy was performed on the right eye, and eight images were captured. Variables measured were corneal nerve fiber length (CNFL), corneal nerve density (CNFD), corneal nerve branch density, fiber total branch density, corneal nerve fiber area, corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrac). For each eye, the average across the images and the maximum and minimum values were determined for each variable. Pearson correlation analysis was performed to test for associations. RESULTS Substance P correlated with CNFrac (max) (r = -0.48, P =.03) and CNFW (min) (r = -0.52, P =.02). TIMP-1 correlated with CNFD (average) (r = -0.53, P =.03), CNFL (average) (r = -0.49, P =.05), CNFrac (max) (r = -0.49, P =.05), and CNFD (min) (r = -0.55, P =.02). Interleukin 6 correlated with CNFW (average) (r = -0.49, P =.05), the standard deviation of CNFL (r = -0.51, P =.04), CNFL (max) (r = -0.50, P =.04), CNFrac (max) (r = -0.50, P =.04), and CNFW (min) (r = -0.55, P =.02). Tumor necrosis factor matrix metalloproteinase-9, and its ratio with TIMP-1 did not correlate with any corneal nerve parameters. CONCLUSIONS Both inflammatory mediators and neuropeptides correlated with measures of corneal nerve morphology, supporting the link between the inflammatory and nervous systems.</p