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The British Journal of Ophthalmology Jan 2000Diabetic patients often complain of dry eye symptoms, such as burning and/or foreign body sensation. The aim of the present study was to investigate whether diabetes...
BACKGROUND
Diabetic patients often complain of dry eye symptoms, such as burning and/or foreign body sensation. The aim of the present study was to investigate whether diabetes mellitus is correlated with tear film dysfunction and/or tear hyposecretion.
METHODS
In 86 consecutive insulin dependent diabetics with retinopathy and 84 non-diabetic controls (age and sex matched) we performed fluorophotometry of tear secretion, the Schirmer test, and impression cytology of the conjunctival epithelium and determined the tear film break up time.
RESULTS
When compared with the healthy control group diabetics showed decreased Schirmer test readings (-37%, p <0.001) and significantly more frequent and pronounced signs of conjunctival metaplasia. None of the other values differed between groups.
CONCLUSION
In insulin dependent diabetics, reflex tearing was demonstrated to be significantly decreased. In contrast, unstimulated basal tear flow and tear film break up time were found to be normal. However, a majority of insulin dependent diabetics shows distinct signs of conjunctival surface disease.
Topics: Aged; Case-Control Studies; Conjunctiva; Diabetes Mellitus, Type 1; Fluorophotometry; Humans; Metaplasia; Middle Aged; Reflex; Tears
PubMed: 10611093
DOI: 10.1136/bjo.84.1.19 -
The Ocular Surface Jan 2016Our aim was to quantitate day-to-day changes in the tear and meibum lipid profile of individual subjects in a pilot study of healthy humans. (Comparative Study)
Comparative Study
PURPOSE
Our aim was to quantitate day-to-day changes in the tear and meibum lipid profile of individual subjects in a pilot study of healthy humans.
METHODS
Matched tear and meibum samples were obtained from four subjects on three consecutive days. Quantitative lipid profiles of human basal tears and meibum were compared using multivariate analysis by principal components.
RESULTS
Substantial differences in the lipid profile between subjects were observed, while lipid profiles were steady across the three consecutive days of sampling. Multivariate principal component analysis demonstrated that lysophosphatidylcholine was the largest variant lipid class between subjects in tears, while wax esters comprised the most variation between subjects in meibum secretions.
CONCLUSION
Interday variability is shown to be much smaller than interpatient variability, suggesting that tears and meibum subjects both have unique profiles in humans.
Topics: Adult; Female; Humans; Lipids; Male; Meibomian Glands; Pilot Projects; Tears; Young Adult
PubMed: 26416436
DOI: 10.1016/j.jtos.2015.08.005 -
BMC Ophthalmology Jun 2017Physical cooling of the eye surface relieves ocular discomfort, but translating this event to drug treatment of dry eye discomfort not been studied. Here, we synthesized... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Physical cooling of the eye surface relieves ocular discomfort, but translating this event to drug treatment of dry eye discomfort not been studied. Here, we synthesized a water-soluble TRPM8 receptor agonist called cryosim-3 (C3, 1-diisopropylphosphorylnonane) which selectively activates TRPM8 (linked to cooling) but not TRPV1 or TRPA1 (linked to nociception) and tested C3 in subjects with mild forms of dry eye disease.
METHODS
A set of 1-dialkylphosphoryalkanes were tested for activation of TRPM8, TRPV1 and TRPA1 receptors in transfected cells. The bioactivity profiles were compared by perioral, topical, and intravenous delivery to anesthetized rats. The selected lead candidate C3 or vehicle (water) was applied with a cotton gauze pad to upper eyelids of patients with dry eye disease (n = 30). Cooling sensation, tear film break-up time (TBUT), basal tear secretion, and corneal staining were evaluated. C3 was then applied four times daily for 2 weeks to patients using a pre-loaded single unit applicator containing 2 mg/mL of C3 in water (n = 20) or water only. TBUT, basal tear secretion, and corneal staining, and three questionnaires surveys of ocular discomfort (VAS scale, OSDI, and CVS symptoms) were analyzed before and at 1 and 2 weeks thereafter.
RESULTS
C3 was a selective and potent TRPM8 agonist without TRPV1 or TRPA1 activity. In test animals, the absence of shaking behavior after C3 perioral administration made it the first choice for further study. C3 increased tear secretion in an animal model of dry eye disease and did not irritate when wiped on eyes of volunteers. C3 singly applied (2 mg/ml) produced significant cooling in <5 min, an effecting lasting 46 min with an increase in tear secretion for 60 min. C3 applied for 2 weeks also significantly increased basal tear secretion with questionnaire surveys of ocular discomfort indices clearly showing improvement of symptoms at 1 and 2 weeks. No complaints of irritation or pain were reported by any subject.
CONCLUSIONS
C3 is a promising candidate for study of TRPM8 function on the eye surface and for relief of dry eye discomfort.
TRIAL REGISTRATION
ISRCTN24802609 and ISRCTN13359367 . Registered 23 March 2015 and 2 September 2015.
Topics: Animals; Cricetinae; Disease Models, Animal; Double-Blind Method; Dry Eye Syndromes; Female; Humans; Male; Mice; Mice, Inbred C57BL; Ophthalmic Solutions; TRPM Cation Channels; Tears
PubMed: 28651550
DOI: 10.1186/s12886-017-0495-2 -
Clinical Ophthalmology (Auckland, N.Z.) 2021To assess the impact of botulinum toxin type A (BTX-A) on signs and symptoms of dry eye (DE) in affected eye of hemifacial spasm (HFS) patients and to compare the...
PURPOSE
To assess the impact of botulinum toxin type A (BTX-A) on signs and symptoms of dry eye (DE) in affected eye of hemifacial spasm (HFS) patients and to compare the prevalence of DE between affected and non-affected eye in HFS patients.
PATIENTS AND METHODS
This prospective study included participants with unilateral HFS, who received BTX-A injection as a treatment. The eyes ipsilateral to the spasm side were used as studied eyes and the contralateral eyes were used as controls. The Ocular Surface Disease Index (OSDI) score, tear break-up time (TBUT), corneal fluorescein staining, and Schirmer I test were measured at baseline, 1 and 3 months after BTX-A injection. Fluorescein clearance test (FCT) was evaluated at baseline and at 1 month after BTX-A injection.
RESULTS
Thirty-one participants (6 males and 25 females; mean age 61±10 years) were included. The prevalence of DE according to the Asia Dry Eye Society was not significantly different between affected (37.93%) and non-affected eyes (27.6%); P=0.083. At baseline, there was no significant difference in TBUT, Schirmer test, basal tear secretion, presence of delayed tear clearance, and presence of reflex tear secretion between affected and non-affected eyes, while significant difference in Oxford scheme grade was observed (P=0.031). OSDI score, TBUT, Oxford scheme grade, and Schirmer test at 1 month (P=0.817, 0.796, 0.534, 0.556), and 3 months (P=0.803, 0.904, 0.936, 0.684) after BTX-A injection did not significantly change from baseline in affected eyes. FCT results were not significantly different between baseline and at 1-month follow-up in both groups. All findings were corresponding in both naïve and long-term botulinum toxin injection groups.
CONCLUSION
We found no significant effect of BTX-A on signs and symptoms of DE in patients with HFS. Moreover, there was no significant association between HFS and DE. However, we found significant corneal surface damage in the affected eyes, which emphasized importance of ocular surface evaluation and prompt treatment in HFS patients.
PubMed: 33953536
DOI: 10.2147/OPTH.S305817 -
Frontiers in Cell and Developmental... 2022The cornea is exposed daily to a number of mechanical stresses including shear stress from tear film and blinking. Over time, these stressors can lead to changes in the...
The cornea is exposed daily to a number of mechanical stresses including shear stress from tear film and blinking. Over time, these stressors can lead to changes in the extracellular matrix that alter corneal stiffness, cell-substrate structures, and the integrity of cell-cell junctions. We hypothesized that changes in tissue stiffness of the cornea with age may alter calcium signaling between cells after injury, and the downstream effects of this signaling on cellular motility and wound healing. Nanoindentation studies revealed that there were significant differences in the stiffness of the corneal epithelium and stroma between corneas of 9- and 27-week mice. These changes corresponded to differences in the timeline of wound healing and in cell signaling. Corneas from 9-week mice were fully healed within 24 h. However, the wounds on corneas from 27-week mice remained incompletely healed. Furthermore, in the 27-week cohort there was no detectable calcium signaling at the wound in either apical or basal corneal epithelial cells. This is in contrast to the young cohort, where there was elevated basal cell activity relative to background levels. Cell culture experiments were performed to assess the roles of P2Y2, P2X7, and pannexin-1 in cellular motility during wound healing. Inhibition of P2Y2, P2X7, or pannexin-1 all significantly reduce wound closure. However, the inhibitors all have different effects on the trajectories of individual migrating cells. Together, these findings suggest that there are several significant differences in the stiffness and signaling that underlie the decreased wound healing efficacy of the cornea in older mice.
PubMed: 35602595
DOI: 10.3389/fcell.2022.886721 -
Frontiers in Bioengineering and... 2022Sterilization of biodegradable, collagen-based implants is challenging as irradiation sterilization methods can alter their mechanical properties. Electron beam (EB)...
Sterilization of biodegradable, collagen-based implants is challenging as irradiation sterilization methods can alter their mechanical properties. Electron beam (EB) irradiation is a terminal sterilization method that has been used for biologically-derived implants. Here, recombinant human collagen type III-phosphorylcholine (RHCIII-MPC) hydrogels were irradiated with EB doses of 17, 19, or 21 kGy and their subsequent biocompatibility and ability to promote regeneration in rabbit corneas was evaluated. Unirradiated hydrogels stored in 1% chloroform in phosphate-buffered saline (C-PBS) were the controls. There were no significant differences between irradiated and non-irradiated samples in optical or physical properties (tensile strength, modulus, elasticity), or the ability to support cell growth. However, irradiated implants were more sensitive to high levels of collagenase than unirradiated controls and the C-PBS implants had increased cell growth compared to EB and controls at 72 h. Corneal implants e-beamed at 17 kGy or e-beamed and subsequently frozen (EB-F) to increase shelf-life showed no adverse biological effects of the irradiation. EB, EB-F, and C-PBS implanted corneas all rapidly re-epithelialized but showed mild neovascularization that resolved over 6 months. The regenerated neo-corneas were transparent at 6 months post-operation. confocal microscopy confirmed normal morphology for the epithelium, stroma, sub-basal nerves and unoperated endothelium. Histology showed that all the regenerated corneas were morphologically similar to the normal. Immunohistochemistry indicated the presence of a differentiated corneal epithelium and functional tear film. In conclusion, the e-beamed corneal implants performed as well as non-irradiated control implants, resulting in fully regenerated neo-corneas with new nerves and without blood vessels or inflammation that may impede vision or corneal function. Therefore, a complete validation study to establish EB irradiation as an effective means for corneal implant sterilization prior to clinical application is necessary as a next step.
PubMed: 35769102
DOI: 10.3389/fbioe.2022.883977 -
The British Journal of Ophthalmology Apr 1995The purpose of this study was to assess whether the preservative benzalkonium chloride (BAC 0.01%) present in timolol induced a decrease in basal tear turnover and a... (Comparative Study)
Comparative Study
AIMS
The purpose of this study was to assess whether the preservative benzalkonium chloride (BAC 0.01%) present in timolol induced a decrease in basal tear turnover and a deterioration of precorneal tear film in patients with glaucoma and ocular hypertension using topical timolol.
METHODS
The basal tear turnover of 20 patients with open angle glaucoma or ocular hypertension was measured by computerised objective fluorophotometry when using topical timolol preserved with BAC and 2 weeks after changing to topical timolol containing no preservative. Evaluation of the precorneal tear film was done by measuring the break up time (BUT) before and 2 weeks after changing medication.
RESULTS
The tear turnover of the patients before the change was 32% lower than that of healthy controls (mean tear turnover values (SD) (%/min): 10.7 (3.0) and 15.6 (5.4), respectively, p < 0.0001). A mean increase of 28% (47%) in the individual tear turnover values was found after the change to the preservative-free timolol (p = 0.04). The BUT values before the change of medication did not differ significantly from those after the change (p = 0.5) but both values were significantly lower than the values of healthy controls (p = 0.009 and p = 0.003, respectively).
CONCLUSION
Preservative-free timolol solution has a favourable effect on the tear turnover of patients with glaucoma and ocular hypertension in comparison with timolol containing BAC. The integrity of the precorneal tear film persisted to be affected when using timolol without BAC. Timolol without preservative can be recommended in those patients who have keratoconjunctivitis sicca or a borderline tear production since BAC may exacerbate a dry eye state.
Topics: Benzalkonium Compounds; Fluorophotometry; Glaucoma, Open-Angle; Humans; Middle Aged; Ocular Hypertension; Preservatives, Pharmaceutical; Secretory Rate; Tears; Timolol
PubMed: 7742279
DOI: 10.1136/bjo.79.4.339 -
Purinergic Signalling Mar 2015The purpose of this study is to investigate if the cholinergic stimulation by carbachol on tear secretion is a direct process or if it is also mediated by purinergic...
The purpose of this study is to investigate if the cholinergic stimulation by carbachol on tear secretion is a direct process or if it is also mediated by purinergic mechanisms. Experiments were performed in New Zealand male rabbits. The amount of tear secretion was measured with Schirmer's test and then analyzed by a HPLC protocol in order to study the nucleotide levels. Animal eyes were instilled with carbachol (a cholinergic agonist), pirenzepine, gallamine and 4-DAMP (muscarinic antagonists), PPADS, suramin and reactive blue 2 (purinergic antagonists), and a P2Y2 receptor small interfering RNA (siRNA). Tear secretion increased with the instillation of carbachol, approximately 84 % over control values 20 min after the instillation and so did Ap4A and ATP release. When we applied carbachol in the presence of muscarinic antagonists, tear volume only increased to 4 % with atropine, 12 % in the case of pirenzepine, 3 % with gallamine, and 8 % with 4-DAMP. In the presence of carbachol and purinergic antagonists, tear secretion was increased to 12 % (all values compared to basal tear secretion). By analyzing tear secretion induced with carbachol in presence of a P2Y2 receptor siRNA, we found that tear secretion was diminished to 60 %. The inhibition of tear secretion in the presence of carbachol and purinergic antagonists or P2Y2 siRNA occurred with no apparent change in the tear amount of Ap4A. These experiments demonstrated the participation of Ap4A in lacrimal secretion process.
Topics: Animals; Atropine; Carbachol; Cholinergic Agonists; Dinucleoside Phosphates; Male; Muscarinic Antagonists; Rabbits; Tears
PubMed: 25398705
DOI: 10.1007/s11302-014-9434-3 -
Computational and Mathematical Methods... 2022The expression and clinical significance of tumor necrosis factor- (INF-) and interleukin 1- (IL-1) in retinal cells of patients with type 2 diabetes (T2DM) retinopathy...
AIMS
The expression and clinical significance of tumor necrosis factor- (INF-) and interleukin 1- (IL-1) in retinal cells of patients with type 2 diabetes (T2DM) retinopathy were detected by flow cytometry.
MATERIALS AND METHODS
Fifty patients with T2DM who attended our ophthalmology clinic between May 2021 and May 2022 were selected as the observation group. Another 50 healthy individuals who were examined at our hospital during the same period were selected as the comparison group. Tear film rupture time (BUT), fluorescein staining (FL), basal tear secretion (Schirmer I) test, and conjunctival impression cytology (CIC) were detected in both groups, and the expression of TNF- and IL-1 in retinal cells was observed by immunohistochemical staining.
RESULTS
The levels of IL13 and TNF- in the two groups were not exactly the same. The serum levels of IL13 and TNF- in the observation group were significantly higher than those in the control group, and there was a statistically significant difference ( < 0.05). TNF- and IL-1B expressions in the observation group were positively correlated with the fluorescence staining, and the expression of TNF- and IL-1 in the observation group was significantly negatively correlated with the BUT test and Schirmer I test.
CONCLUSION
Serums TNF- and IL-1 are significantly elevated in patients with T2DM retinopathy and gradually increase with disease progression. Combined detection of serums TNF- and IL-1 can help determine the severity of the disease and assess the prognosis.
Topics: Diabetes Mellitus, Type 2; Humans; Interleukin-13; Interleukin-1beta; Retinal Diseases; Tears; Tumor Necrosis Factor-alpha
PubMed: 35979044
DOI: 10.1155/2022/9073372 -
Eye (London, England) Jan 2017PurposeTo explore the morphological characteristics of toxic keratopathy (TK), which clinically presented as superficial punctate keratopathy (SPK), with the application...
PurposeTo explore the morphological characteristics of toxic keratopathy (TK), which clinically presented as superficial punctate keratopathy (SPK), with the application of in vivo laser-scanning confocal microscopy (LSCM), and evaluate its potential in the early diagnosis of TK.Patients and methodsThis was a cross-sectional study involving 16 patients with TK and 16 patients with dry eye (DE), demonstrating SPK under slit-lamp observation, and 10 normal eyes were enrolled in the study. All participants underwent history interviews, fluorescein staining, tear film break-up time (BUT) tests, Schirmer tests, and in vivo LSCM.ResultsThe area grading of corneal fluorescein punctate staining was higher in the TK group than the DE group. Measured by in vivo LSCM, superficial epithelial cell density was lower in the TK group than that of DE group. The sub-basal nerve presented lower density and tortuosity in the TK group than the DE group. Most notably, deposits with a snow-like appearance were observed in the epithelium in 12/16 (75.0%) of the TK cases, but none in the DE group (P<0.05).ConclusionThe SPK in TK patients was characterized by more widespread punctate staining, a lower density of superficial epithelial cells and sub-basal nerves, and a typical snow-like pattern of deposits in the epithelium by LSCM. These features might facilitate early diagnosis of TK from other disorders manifested as SPK.
Topics: Adolescent; Adult; Aged; Analysis of Variance; Cornea; Corneal Diseases; Cross-Sectional Studies; Dry Eye Syndromes; Epithelium, Corneal; Female; Fluorescein; Humans; Male; Microscopy, Confocal; Middle Aged; Tears; Young Adult
PubMed: 27740620
DOI: 10.1038/eye.2016.213