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WINKLER, Schmut, Rieger, Muranov
[Diagnosis and therapy of dry eye syndrome]Horwath-Winter J, Nepp J, Rieger G, Schmut O. Ophthalmologe. 2006 Aug;103(8):724; author reply 725. German. [citation only]
Iodine brine-therapy from the ophthalmological and internal medicine viewpoint. 150th anniversary of Landeskuranstalten, 55th anniversary of Paracelsus-Institute, 50th anniversary of Department of Ophthalmology Bad HallSchmut O, Horwath-Winter J, Rieger G, Winkler R, Klieber M, Loos W, Griebenow S Spektrum Augenheilkd (2006) 20/3: 150-7. [article in German]
"In this review the history of the spa Bad Hall, the content of ions and chemical elements in the iodine brine, and the biological as well as the therapeutical effect of the water is discussed. Especially the effect of the iodine containing water for the therapy of different eye diseases is reported. Studies showing the improvement of visual acuity, the colour perception, the contrast sensitivity and the capability to delay cataract development by a therapy with iodine brine are discussed. Especially the therapies of the sicca syndrome by iontophoresis with iodine brine and with an oil-in-water emulsion spray are mentioned."
Sustainability of the increased watersoluble anti-oxitave status (ACW) in tear fluid taken without stimulation after iodide-iontophoresis in Bad HallGriebenow S, Rieger G, Horwath-Winter J, Schmut O Spektrum Augenheilkd (2006) 20/1:7-8. [article in German]
"Background. The tear fluid contains antioxidative protective mechanisms. By the attack of free radicals, arising by influence of ozone, UV light, smog, smoking, etc., these antioxidative protective mechanisms can be destroyed. The so-called environmental induced dry eye can arise by the damage of the tear-fluid compounds by oxidative stress.
In earlier studies, we pointed out that the antioxidative status can be positively influenced by the supply of the oxygen radical scavenger iodide taken up in the course of a cure in Bad Hall. The sustainability of the increased antioxidative capacity was examined after ophthalmo-iodine-iontophoresis-treatments had been carried out.
Method. For the investigation of sustainability, 21 patients after 6 months and 18 patients after 9 months were measured out of a group of 23 patients. The analysis of the ACW value was carried out by photochemoluminescence.
Results. It is evident that ACW values in the tear fluid were still increased significantly 6 months after therapy for patients with a three-week eye treatment duration.
Conclusion. The more than 6 month improvement of the antioxidative capacity in the tear liquid underlines the important value of this ophthalmo-iodide-iontophoresis treatment for patients with a dry eye condition."
Iodide iontophoresis as a treatment for dry eye syndrome.Horwath-Winter J, Schmut O, Haller-Schober EM, Gruber A, Rieger G. Br J Ophthalmol. 2005 Jan;89(1):40-4.
"BACKGROUND/AIMS: Among the causes related to the development or perpetuation and aggravation of dry eye disease, oxidative reactions may have a role in the pathogenesis of this disorder. Antioxidants, such as iodide, have shown a strong effect in preventing the oxidative damage to constituents of the anterior part of the eye. In this clinical trial the effectiveness of iodide iontophoresis and iodide application without current in moderate to severe dry eye patients was compared.
METHODS: 16 patients were treated with iodide iontophoresis and 12 patients with iodide application without current for 10 days. Subjective improvement, frequency of artificial tear application, tear function parameters (break up time, Schirmer test without local anaesthesia), vital staining (fluorescein and rose bengal staining) as well as impression cytology of the bulbar conjunctiva were evaluated before treatment, 1 week, 1 month, and 3 months after treatment.
RESULTS: A reduction in subjective symptoms, frequency of artificial tear substitute application, and an improvement in certain tear film and ocular surface factors could be observed in both groups. A stronger positive influence was seen after application of iodide with current (iontophoresis), as observed in a distinct improvement in break up time, fluorescein and rose bengal staining, and in a longer duration of this effect compared with the non-current group. No significant change in Schirmer test results and impression cytology were observed in both groups.
CONCLUSIONS: Iodide iontophoresis has been demonstrated to be a safe and well tolerated method of improving subjective and objective dry eye factors in patients with ocular surface disease."
Iodide protects hyaluronate from oxidative stressSchmut O, Rieger G, Winkler R, Griebenow S, Wachswender C, Horwath-Winter J Spektrum Augenheilkd (2004) 18/6: 294-7 [article in German]
"Background: H2O2 and free radicals are responsible for damaging reactions by oxidative stress. It was investigated whether iodide can destroy H2O2 and a protection against oxidative stress can be obtained by this reaction.
Materials and methods: The decrease of H2O2 concentrations in physiological buffer solutions by addition of iodide was determined by titration with KMnO4. By viscometry the protecting activity of iodide on hyaluronate solutions against oxidative degradation by H2O2 was measured.
Results: Micromolar amounts of iodide can decrease the H2O2 concentration in physiological solutions within a short time. Iodide has the capability to protect hyaluronate from depolymerization by H2O2.
Conclusions: The protecting activity of iodide from H2O2-induced oxidative stress may be responsible for the positive effect on the anterior part of the eye by sprays and iontophoresis with iodide brine as performed in Bad Hall (Upper Austria)."
Protection by iodide of lens from selenite-induced cataract.Muranov K, Poliansky N, Winkler R, Rieger G, Schmut O, Horwath-Winter J. Graefes Arch Clin Exp Ophthalmol. 2004 Feb;242(2):146-51.
"BACKGROUND: Iodide has been used empirically against different age-related eye diseases, including cataract. The purpose of the present study was to investigate the effect of iodide on selenite-induced cataract in rat lens.
METHODS: Young white rats received subcutaneously sodium selenite (20 and 30 nmol/g b.w.) on day 13 post partum (p.p.). Cataract development was measured by expert estimation and image data analysis. Potassium iodide (1.5 nmol/g b.w.) was given (1-5 times) i.p. at different times with respect to the selenite administration. Lens opacification was analyzed in selenite, selenite-iodide, iodide and control groups on day 7 after selenite administration.
RESULTS: Iodide showed a significant protective effect against selenite cataract when injected 2 days (2 times) before selenite injection, i.e., on days 11 and 12 p.p. No significant effects on lens opacity were found: (1) after only one iodide injection (on day 12 p.p.), (2) after an initial iodide administration 1 h before selenite and (3) after injections of iodide once a day for 5 consecutive days. The protective effect of iodide was the same (about 50%) for both selenite doses used.
CONCLUSIONS: There is a time-dependent protective influence of iodide against selenite cataract development. It is supposed that the anticataract effect of iodide could be based on direct or indirect antioxidant mechanisms."
Iodide protection from UVB irradiation-induced degradation of hyaluronate and against UVB-damage of human conjunctival fibroblasts.Schmut O, Horwath-Winter J, Rieger G, Winkler R, Trummer G, Spitzenberger H, Wachswender C. Graefes Arch Clin Exp Ophthalmol. 2004 Apr;242(4):279-83. Epub 2003 Dec 16.
"BACKGROUND: To determine whether iodide protects from UVB irradiation-induced destruction of hyaluronate and against UVB injury of cultured human conjunctival fibroblasts.
METHODS: Hyaluronate and primary cultured human conjunctival fibroblasts were incubated with various concentrations of iodide and then exposed to UV light irradiation of 312 nm. Hyaluronate destruction was determined by viscosity measurements. Cell viability was assessed with MTT assay.
RESULTS: Iodide protects hyaluronate from UVB light-induced degradation of this macromolecule in a concentration-dependent manner. Incubation of human conjunctival fibroblasts with iodide inhibited cells from damage by UVB light.
CONCLUSION: Iodide protects hyaluronate, a component of tear fluid and tissues of the anterior part of the eye, against UVB light-induced degradation. Also, injury of human conjunctival cells can be prevented by incubation with iodide before UVB irradiation. The mechanism of protection is likely to include an antioxidative reaction. To support the natural defence mechanisms of the eyes, the administration of an antioxidant such as iodide to artificial tears, for example, may help to prevent the damage of the eye provoked by oxidative stress.
Evaluation of the clinical course of dry eye syndrome.Horwath-Winter J, Berghold A, Schmut O, Floegel I, Solhdju V, Bodner E, Schwantzer G, Haller-Schober EM. Arch Ophthalmol. 2003 Oct;121(10):1364-8. [abstract only]
"OBJECTIVE: To assess subjective symptoms, tear function factors, and ocular surface morphology in the clinical course of patients with dry eye syndrome under treatment within an observation period of up to 8 years.
METHODS: In 97 patients (78 women and 19 men) with ocular discomfort, a clinical diagnosis of dry eye syndrome was made based on typical symptoms and a reduced tear film breakup time of less than 10 seconds. Subsequent evaluations revealed a diagnosis of aqueous tear deficiency in 9 patients, meibomian gland dysfunction in 32 patients, and aqueous tear deficiency combined with meibomian gland dysfunction in 30 patients, aqueous tear deficiency associated with Sjogren syndrome in 12 patients, and aqueous tear deficiency and meibomian gland dysfunction associated with Sjogren syndrome in 14 patients. Follow-up assessments were performed 12 to 94 months (mean follow-up, 40 months) after the initial diagnosis.
MAIN OUTCOME MEASURES: In different subgroups of dry eye tear film breakup time, Schirmer test without local anesthesia (Schirmer I), fluorescein and rose bengal staining, impression cytology, as well as subjective dry eye symptoms and frequency of tear substitute application were compared at baseline and after a follow-up of 1 to 8 years (mean, 3.3 years).
RESULTS: At baseline, tear film function and ocular surface test results found more pathologic abnormalities and more severe subjective symptoms in patients with aqueous tear deficiency associated with Sjogren syndrome and aqueous tear deficiency and meibomian gland dysfunction associated with Sjogren syndrome compared with the other groups who had dry eye syndrome. No differences in frequency of tear substitute application were observed. At follow-up, tear breakup time, Schirmer I test results, and corneal fluorescein staining improved compared with baseline values, whereas rose bengal staining and impression cytology of the conjunctival surface remained almost unchanged. Subjective symptoms and frequency of artificial tear application were reduced.
CONCLUSIONS: Within the observation period of up to 8 years, the dry eye syndrome improved or stabilized under appropriate treatment. Although no patient was completely cured, subjective reports as well as frequency of artificial tear application were reduced."
Dual method for the determination of peroxidase activity and total peroxides-iodide leads to a significant increase of peroxidase activity in human sera.Tatzber F, Griebenow S, Wonisch W, Winkler R. Anal Biochem. 2003 May 15;316(2):147-53. [abstract only]
"Peroxidases are very important enzymes, e.g., as preventive antioxidants by removing noxious peroxides from the blood. For this reason we evaluated a colorimetric method which detects the activity of endogenous peroxidases by their reaction with hydrogen peroxide, using tetramethylbenzidine as the chromogenic substrate. This assay design can be easily reversed by change of the variable compound to measure also total peroxides in plasma or serum. An increased total antioxidant status was reported previously by the addition of iodide to human serum. In this study iodide activated the endogenous peroxidases significantly in comparison to control sera and isomolar NaCl as well as horseradish peroxidase. Corresponding to the increased peroxidase activity a concomitant decrease of total peroxides occurred in the same samples. This exchangeable assay design is a beneficial opportunity to screen total peroxide levels as well as peroxidase activity in human sera without time-consuming preparations. The method proved to be simple and is favorable due to its specificity, reproducibility, and low costs. Moreover, we were able to find an explanation for the increased total antioxidant status in the presence of iodide, which is presumably an indirect protective effect via an enhanced activity of enzymatic antioxidants, thereby reducing endogenous peroxides."
Anti-oxidative capacity of various artificial tear preparations.Rieger G. Graefes Arch Clin Exp Ophthalmol. 2001 Mar;239(3):222-6.
"BACKGROUND: Increased UV radiation and ozone exposure may cause "dry eyes of environmental origin", if the normal anti-oxidative capacity of the tear film can no longer cope with the oxidative stress. The use of artificial tears with an adequate anti-oxidative effect may be beneficial in the treatment of dry eyes caused by environmental factors.
METHODS: The anti-oxidative capacity of various commercial artificial tear preparations was determined with a modified TRAP procedure. The two preparations with the strongest anti-oxidative effect were then examined for their protective effects against UV or ozone exposure in a hyaluronate model.
RESULTS: Of 19 artificial tear preparations tested, only 6 showed strong to moderate anti-oxidative effects. All others were at best weakly anti-oxidative or had no anti-oxidative effect at all. Some of them even acted as oxidants. Although the two most strongly anti-oxidative preparations performed somewhat differently on UV and ozone exposure, they were both found to be highly protective against these important oxidative stress factors.
CONCLUSIONS: The anti-oxidative capacity of artificial tear preparations varies widely. While some are strong anti-oxidants, others are less active or even act as oxidants. If the carefully elicited history of patients with dry eyes suggests that noxious environmental factors may be causally involved, artificial tears which are not just lubricants or contain wetting agents, but act as anti-oxidants, should be chosen for treatment from the many commercially available preparations. Such an etiology-oriented concept would probably improve the success rate of treatment for dry eyes."
Effect of iodide on total antioxidant status of human serum.Winkler R, Griebenow S, Wonisch W. Cell Biochem Funct. 2000 Jun;18(2):143-6.
"Free radicals and subsequent lipid peroxidation have been implicated in the pathogenesis of several degenerative and chronic diseases which are also treated frequently in spas. There are some data arising from previous studies which support an antioxidant or scavenging effect of iodide, being the essential ingredient of a therapeutically used local brine. The aim of the study was to test the antioxidant capacity of iodide in human serum. For this reason we measured the so-called Total Antioxidant Status determined by a colorimetric method, which reflects the protection against the attack of reactive oxygen species, including enzymic and non-enzymic antioxidants. Exogenous iodide applied as NaI, shows a significantly increased antioxidant capacity in comparison with NaCl at a concentration of 15 microM, which is quite comparable to the upper range of serum iodide levels achieved through balneo-therapeutical intervention. This result is in accordance with previous results from in vitro depolymerization experiments with hyaluronic acid. The antioxidant effect of 15 microM NaI has been found to be approaching the physiologically relevant concentration of ascorbic acid (50 microM)."
The influence of environmental factors on the development of dry eye.Horwath J, Schmut O Contactologica 22:21-29. French [French abstract only]
Iodine distribution in a porcine eye model following iontophoresis.Rieger G, Winkler R, Buchberger W, Moser M. Ophthalmologica. 1995;209(2):84-7.
"Iodine distribution was studied in isolated porcine eyes after iontophoresis using 131I-labelled solutions and chemical methods. After a 15-min treatment with a therapeutically used iodine brine, the iodine content in the ocular tissues showed the following rank order: cornea > retina > vitreous body > anterior chamber fluid > lens. Replacement of the brine by 0.15 M NaI increased the uptake values in a different way, but the same rank order was maintained. The increase was highest in the cornea (5.6-fold) and only about 2-fold in the lens, nevertheless approaching now the level of 10(-4) M, a concentration which was regarded as being optimal for the antioxidant effect of I-. Among the other eye components, the relatively high iodine enrichment of the retina was remarkable. The data are discussed with respect to a possible protective, antioxidative and OH-scavenging efficacy of I- and to previous results in the literature concerning iodine uptake in ocular tissues."
Destruction of human tear proteins by ozone.Schmut O, Gruber E, el-Shabrawi Y, Faulborn J. Free Radic Biol Med. 1994 Aug;17(2):165-9. [abstract only]
"By an in vitro system human tears from healthy donors were exposed in a sealed vessel to a single dose of ozone. A marked destruction of tear proteins by ozone was observed as indicated by the disappearance of the protein pattern in polyacrylamide gel electrophoresis compared with the control. Lysozyme, a significant protein in tears, was demonstrated to be susceptible to degradation by O3. The destruction of tear proteins by ozone can be determined quantitatively by radial immunodiffusion as shown for human tear albumin. Variations of ozone concentrations and reaction time showed that destruction of tear proteins by ozone depended on the ozone concentration and occurred within a few minutes of exposure of tears to ozone."
Degradation of hyaluronate by the concerted action of ozone and sunlight.Schmut O, Ansari AN, Faulborn J. Ophthalmic Res. 1994;26(6):340-3. [abstract only]
"The influence of ozone and sunlight in a concerted reaction on hyaluronate solutions was investigated. The kinematic viscosity of hyaluronate solutions is decreased by ozone-air mixtures and simultaneous radiation with sun rays within a few minutes, indicating a depolymerization of the hyaluronate molecule. The reaction is dependent on the concentration of ozone and on the time of exposure to ozone and sunlight. The concerted degradation of hyaluronate is more effective than the reaction with each component, ozone and sun rays, alone. We conclude that hyaluronate depolymerization by ozone and sunlight may be one factor for irritations of the eye by photochemical smog and increased exposure to sun rays."
[Changes of Glutathione Peroxidase Activity in Eye Tissues of Emory Mice in Relation to Cataract Status and Age]Rieger G, Winkler R. Ophthalmologica. 1994;208(1):5-9. German. [abstract only]
"The relationship between the activity of the antioxidant defense enzyme glutathione peroxidase (GSH-PX) and the degree of cataract (lens opacity) was examined in 14 Emory mice at the age of 2, 7 and 10 months. Significant decreases in specific GSH-PX activity (mU/mg wet tissue) in the lens as well as in the residual eye tissue were found between 2 and 10 months of age, showing a highly significant correlation of this decrease (r = 0.590, p approximately 0.001) with the increasing degree of turbidity of the lenses. The results are discussed with regard to the changes of antioxidant mechanisms during cataractogenesis and aging. The role of the maintenance of an optimal level of GSH-PX and other well-known antioxidants (enzymes, vitamins, trace elements including iodide) for a delay of cataractogenesis is pointed out."
[Changes in Contrast Sensitivity after Iodine Treatment in Bad Hall in Patients with Age-Related Maculopathy]Rieger G. Ophthalmologica. 1992;205(2):100-4. German. [abstract only]
"After a cure with iodine in Bad Hall (Upper Austria), patients with age-related maculopathy repeatedly reported improvement in visual power: the picture seen seems to be clearer on the whole or more distinct. These statements were checked in 50 patients with beginning age-related macula degeneration ('dry form') using the 'Vision Contrast test system (VCTS 6500)'. The analysis of the results showed that there is indeed a statistically highly significant improvement in contrast sensitivity after the cure (p < 0.0001). The spontaneous observations of the patients were therefore confirmed by the study."
Alterations of antioxidant tissue defense enzymes and related metabolic parameters in streptozotocin-diabetic rats--effects of iodine treatment.Winkler R, Moser M. Wien Klin Wochenschr. 1992;104(14):409-13.
"This study reports on the effect of streptozotocin (STZ) induced diabetes on water soluble-SH and -SS, as well as on hepatic glutathione peroxidase (GSH-Px), catalase and superoxide dismutase (SOD) activity and on malondialdehyde (MDA) content. In addition, we determined serum concentrations of glucose, cholesterol, triglycerides and thyroxine, and thyroid weight. To elucidate the possible impact of exogenous iodine on impaired free radical tissue defense mechanisms STZ-diabetic rats were exposed to iodine brine providing for a daily iodide uptake of about 300 micrograms/kg body weight. STZ-exposure caused a decline in thyroid weight (p less than 0.01) and in total serum thyroxine (p less than 0.001), as well as a fall in hepatic catalase (CAT) activity (p less than 0.01) versus control group. Impairment of catalase activity was related to serum glucose level (r = -0.569, p less than 0.01), while hepatic MDA was positively related to serum glucose (r = + 0.5, p less than 0.01). No protective effects of iodine brine were seen with regard to impairment by STZ of antioxidant enzyme status. We conclude that impairment by STZ of antioxidant enzymes may contribute to STZ-dependent experimental diabetes."
Influence of iodide on cataractogenesis in Emory mice.Buchberger W, Winkler R, Moser M, Rieger G. Ophthalmic Res. 1991;23(6):303-8. [abstract only]
"Cataract development was studied in two groups of Emory mice by periodical biomicroscopic examinations (beginning at 5 weeks of age) and by a final evaluation of water-soluble SH groups in the lenses. The experimental group was given 256 micrograms iodide/kg body weight with the drinking water throughout the study. The untreated control group received tap water. Iodide treatment induced a delay of cataract formation, resulting in a significant reduction of the time to progress from cataract degree 1 to degree 2 (iodide-treated group 12.8 +/- 1.7 weeks, untreated group 9.9 +/- 1.0 weeks; p less than 0.025). A still significant difference in the degree of cataract was also found between the two groups at week 47 of age. No difference was found in the content of water-soluble SH groups. The results are discussed in relation to the known antioxidant and .OH-scavenging effect of iodide and to the oxidative changes in the lens occurring during progression of cataract development."
[The effect of combined iodine treatment in Bad Hall on the color perception of patients]Rieger G. Klin Monatsbl Augenheilkd. 1988 Oct;193(4):416-9. German. [abstract only]
"After taking a cure with iodine treatments in Bad Hall (Upper Austria), patients with eye diseases repeatedly report improvements in their color vision. They state that colors are once again "more saturated, richer, and more distinct." These statements were checked using the Farnsworth Panel D-15 dicotomous test and the Lanthony desaturated 15 Hue test. The analysis of the results showed that there is indeed a statistically significant improvement in color vision after the cure. The spontaneous observations of the patients were therefore confirmed by the study."
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