Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha2, a functional neurturin receptor.
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Glial cell line-derived neurotrophic factor (GDNF) and a related protein, neurturin (NTN), require a GPI-linked coreceptor, either GFR alpha1 or GFR alpha2, for signaling via the transmembrane Ret tyrosine kinase. We show that mice lacking functional GFR alpha2 coreceptor (Gfra2-/-) are viable and fertile but have dry eyes and grow poorly after weaning, presumably due to malnutrition. While the sympathetic innervation appeared normal, the parasympathetic cholinergic innervation was almost absent in the lacrimal and salivary glands and severely reduced in the small bowel. Neurite outgrowth and trophic effects of NTN at low concentrations were lacking in Gfra2-/- trigeminal neurons in vitro, whereas responses to GDNF were similar between the genotypes. Thus, GFR alpha2 is a physiological NTN receptor, essential for the development of specific postganglionic parasympathetic neurons. (+info)
Diseases associated with ocular surface abnormalities: the importance of reflex tearing.
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AIM: To investigate the correlation between tear function tests and ocular surface integrity in patients with dry eye. METHODS: 297 dry eye patients (55 Sjogren's syndrome, two male and 53 female, average age 52.4 (SD 15.0) years, and 242 non-Sjogren's syndrome, 41 male and 201 female, average age 53.5 (14.1) years) were examined. The following tear function tests were performed: (1) cotton thread test, (2) Schirmer test with topical anaesthesia, (3) Schirmer test without anaesthesia, (4) Schirmer test with nasal stimulation, (5) tear clearance test, and (6) tear break up time (BUT). The ocular surface was evaluated by rose bengal and fluorescein staining. Correlation analysis was performed between each tear function index and vital staining scores. RESULTS: Among the six tear function tests, the Schirmer test with nasal stimulation correlated most with both of the vital stains (rho = 0.530 for rose bengal and 0.393 for fluorescein). The Schirmer test with or without anaesthesia correlated slightly with rose bengal staining, whereas tear clearance test and tear break up time slightly correlated with fluorescein staining. CONCLUSION: Vital staining of the ocular surface correlates most with reflex tearing measured by the Schirmer test with nasal stimulation. (+info)
Decreased tear lactoferrin concentration in patients with chronic hepatitis C.
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BACKGROUND/AIMS: Decreased tear volume in patients with chronic hepatitis C has been reported in the literature. Lactoferrin is abundantly present in human tears, the main source of which is the acini of the lacrimal glands. In this study tear lactoferrin levels were measured to investigate the dry eye condition of patients with chronic hepatitis C. METHODS: Lactoferrin in tears/fluid was measured by a radial immunodiffusion assay in 42 patients with chronic hepatitis C. The rate of lacrimal secretion was determined by the cotton thread test. Rose bengal staining of the ocular surface was also performed. RESULTS: Only three patients out of 42 complained of dry eye sensation and, in 31 patients, six showed positive results on the rose bengal staining test of the ocular surface. The lactoferrin concentration of tear fluid in the chronic hepatitis C group (1.42 (SD 0.56) mg/ml) was significantly lower than in the control group (1.90 (0.62) mg/ml; p <0.00048). The cotton thread test results in the chronic hepatitis C group (12.9 (5. 5) mm) were significantly lower than in the control group (17.9 (5. 3) mm; p<0.00048). Also, in the chronic hepatitis C group, tear lactoferrin concentration correlated with the results of the cotton thread test (r = 0.35, p<0.05). CONCLUSION: Chronic hepatitis C patients showed both decreased tear volume, and decreased tear lactoferrin concentration. These findings suggest that there may be dysfunction of the lacrimal glands in patients with chronic hepatitis C, which may account for the mild dry eye. (+info)
Abnormal tear dynamics and symptoms of eyestrain in operators of visual display terminals.
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OBJECTIVES: To clarify the relation between the prevalence of dry eye syndrome and subjective symptoms of asthenopia in visual display terminal (VDT) operators. METHOD: 722 VDT workers (242 subject workers with symptoms of asthenopia and 480 controls without such symptoms) without obvious organic ocular diseases received an ophthalmological examination consisting of refractometry and a tear function (phenol red thread) test. RESULTS: More than 30% of symptomatic workers were found to meet the criteria of dry eye, and the odds ratio compared with the controls was 4.61 (p < 0.001). This odds ratio was significantly greater than that obtained for refractive errors (2.31). CONCLUSIONS: Although this cross sectional study could not prove that dry eyes are the cause of asthenopia, the profound association of dry eyes with symptoms of asthenopia could be verified. It would be useful to carry out tear function tests in workers with symptoms of asthenopia. (+info)
New treatment of dry eye: the effect of calcium ointment through eyelid skin delivery.
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AIM: To demonstrate the efficacy of a petrolatum based calcium ointment applied to the lower lid skin in the management of dry eye. METHODS: In a controlled double masked study, the effects of water free petrolatum ointment containing calcium carbonate (10% w/w) on tear functional factors and ocular surface vital staining in dry eye patients were observed. Petrolatum without calcium carbonate served as control. Patients were instructed to place ointment to the lower lid skin twice a day. Evaluation of subjective complaints, fluorescein and rose bengal staining patterns, blink rate, tear evaporation and tear break up time (BUT) were performed before and 3 months after treatment. In order to demonstrate the movement of petrolatum from the skin to the tear film, petrolatum containing 1% sodium fluorescein was placed on the lower lid of four healthy volunteers, and the concentration of fluorescein in the tear film was followed up to 6 hours using an anterior fluorometer. RESULTS: Subjective symptoms significantly improved in both the calcium group (p=0.001) and control (p=0.012), while only the calcium group demonstrated a significant improvement in fluorescein (p=0.043), rose bengal (p=0.021) scores, and blink rate (p=0.004). Tear evaporation also significantly decreased in both the calcium group (p=0.0004) and control (0.043). BUT did not improve in either group. CONCLUSION: Petrolatum based calcium ointment significantly improved symptoms, tear dynamics, and ocular surface staining in dry eye patients. However, some of the therapeutic effects may be due to lipids in the petrolatum vehicle. Petrolatum applied to the lower lid skin is an effective drug delivery system for slowly releasing drugs to the ocular surface. (+info)
Treatment of dry eye by autologous serum application in Sjogren's syndrome.
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AIM: To evaluate the efficacy of autologous serum application for the treatment of dry eye in Sjogren's syndrome. METHODS: The stability of essential components (EGF, vitamin A, and TGF-beta) in preserved serum were examined following preservation at 4 degrees C and -20 degrees C. In a primary clinical trial, 12 patients with Sjogren's syndrome were treated with autologous serum (diluted to 20% with sterile saline) for 4 weeks, and vital staining of the ocular surface was compared before and after treatment. The effects of serum on mucin (MUC-1) expression were observed in cultured conjunctival epithelial cells in vitro. RESULTS: EGF, vitamin A, and TGF-beta were well preserved for up to 1 month in the refrigerator at 4 degrees C and up to 3 months in the freezer at -20 degrees C. Rose bengal and fluorescein scores improved significantly from the initial scores of 5.3 and 5.6 to 1.7 and 2.5 after 4 weeks, respectively. The additive effect of human serum for cultured conjunctival epithelial cells showed significant MUC-1 upregulation on the cell surface. CONCLUSION: Autologous serum application is a safe and efficient way to provide essential components to the ocular surface in the treatment of dry eye associated with Sjogren's syndrome. (+info)
Double blind, randomised, placebo controlled, crossover, multicentre study to determine the efficacy of a 0.1% (w/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome.
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BACKGROUND/AIMS: Hyaluronan (sodium hyaluronate) has been shown to confer objective and subjective improvement in patients with dry eye syndrome. This study compared the efficacy and safety of a 0.1% solution of hyaluronan with 0.9% saline, when administered topically to the eye, in the treatment of symptoms of severe dry eye syndrome. METHODS: A randomised, double blind, crossover clinical trial in which subjects were randomised to receive either hyaluronan or saline, applied as one or two drops to the eye, three or four times a day or as required. After 28 days' treatment, subjects crossed over to the other study medication for a further 28 days' treatment. RESULTS: 70 subjects were included in the analyses of efficacy and significant improvements in Schirmer's score (p=0.0006) and rose bengal staining score (p=0.0001) were observed during treatment with hyaluronan. In a subjective assessment of the effectiveness of two treatments, a majority of subjects felt that hyaluronan was more effective than saline in alleviating the symptoms of burning and grittiness (p<0.001). No adverse events attributable to hyaluronan treatment were reported. CONCLUSION: The study demonstrates a clear benefit of hyaluronan over saline, in both subjective and objective assessments of dry eye syndrome. Hyaluronan was shown to be well tolerated. (+info)
Dry eye after haematopoietic stem cell transplantation.
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AIMS: To determine the incidence, natural course, and severity of dry eye occurring or worsening after haematopoietic stem cell transplantation (SCT). METHODS: At a tertiary care hospital, 53 patients undergoing allogeneic or autologous SCT followed by at least 180 days of follow up were studied prospectively. Examination included grading of symptoms of dry eye, evaluation of ocular surface, tear break up time, and Schirmer tests with and without nasal stimulation. Meibomian gland secretion was also examined using a slit lamp while applying steady digital pressure. RESULTS: Of the 53 patients, 44 received allografts. Half of these patients (22) developed dry eye or their pre-existing dry eye worsened after SCT, while none of nine autograft recipients did. Onset of dry eye was 171 (SD 59) days after SCT. Two types of dry eye occurred. One (n=10) was severe with ocular surface findings resembling Sjogren's syndrome and reduction of reflex tearing soon after onset. A mild type (n=12) had unimpaired reflex tearing. Meibomian gland dysfunction (MGD) was more frequent and severe in patients with dry eye and chronic graft versus host disease (GVHD), and overall severity of dry eye was greater in patients with MGD and chronic GVHD. CONCLUSIONS: Dry eye after SCT occurred only in allograft recipients, and was not evident in autograft recipients. The severe form of dry eye had a tendency to develop rapidly. Further study on the prediction and treatment of severe dry eye after SCT is necessary. (+info)