Myopic shift and lens turbidity following hyperbaric oxygen therapy - a prospective, longitudinal, observational cohort study.

PURPOSE: To examine visual acuity, refraction and ocular status before, during and after hyperbaric oxygen therapy (HBOT). METHODS: Twenty-nine patients underwent 40 standard protocol HBOT treatments. In all subjects, refraction and best corrected visual acuity were measured at baseline and after ten, 20, 30 and 40 treatments, and at a 12-week follow-up. A subgroup (n = 19) were given additional examinations at baseline, after 40 treatments and at follow-up including measuring central corneal thickness (CCT), corneal curvature, anterior chamber depth, lens thickness, axial length, fundus morphology, blood pressure and intraocular pressure (IOP). Lens colour and opalescence were graded using the Lens Opacities Classification System III (LOCS III). RESULTS: Myopic shifts [≥0.5 dioptre (D) spherical equivalent (SE)] occurred in 45 (77.6%) eyes. Median refractive changes of -0.75 D SE (right eye; p < 0.001) and -0.66 D SE (left eye; p < 0.001) were observed between pretreatment and treatment end (Wilcoxon signed rank test). Refraction returned to baseline at follow-up, except for a small persisting change towards myopia, median -0.25 D SE (left eye; p = 0.01). Using the LOCS III, median increases in lens nuclear colour, of 0.6 (right eye; p < 0.001) and 0.7 (left eye; p < 0.001), and opalescence of 0.7 (both eyes; p = 0.01) were found at the last examination. Small reductions were noted in CCT of -6.00 µm (right eye; p = 0.03) and -4.00 µm (left eye; p = 0.03), and IOP of -1.50 mmHg (left eye; p = 0.01). CONCLUSIONS: The transient myopic shift may have been due to lenticular refractive index changes. Reduced lens transparency is a potential consequence of HBOT.

Protein Disulfide Levels and Lens Elasticity Modulation: Applications for Presbyopia.

PURPOSE: The purpose of the experiments described here was to determine the effects of lipoic acid (LA)-dependent disulfide reduction on mouse lens elasticity, to synthesize the choline ester of LA (LACE), and to characterize the effects of topical ocular doses of LACE on mouse lens elasticity. METHODS: Eight-month-old mouse lenses (C57BL/6J) were incubated for 12 hours in medium supplemented with selected levels (0-500 µM) of LA. Lens elasticity was measured using the coverslip method. After the elasticity measurements, P-SH and PSSP levels were determined in homogenates by differential alkylation before and after alkylation. Choline ester of LA was synthesized and characterized by mass spectrometry and HPLC. Eight-month-old C57BL/6J mice were treated with 2.5 µL of a formulation of 5% LACE three times per day at 8-hour intervals in the right eye (OD) for 5 weeks. After the final treatment, lenses were removed and placed in a cuvette containing buffer. Elasticity was determined with a computer-controlled instrument that provided Z-stage upward movements in 1-µm increments with concomitant force measurements with a Harvard Apparatus F10 isometric force transducer. The elasticity of lenses from 8-week-old C57BL/6J mice was determined for comparison. RESULTS: Lipoic acid treatment led to a concentration-dependent decrease in lens protein disulfides concurrent with an increase in lens elasticity. The structure and purity of newly synthesized LACE was confirmed. Aqueous humor concentrations of LA were higher in eyes of mice following topical ocular treatment with LACE than in mice following topical ocular treatment with LA. The lenses of the treated eyes of the old mice were more elastic than the lenses of untreated eyes (i.e., the relative force required for similar Z displacements was higher in the lenses of untreated eyes). In most instances, the lenses of the treated eyes were even more elastic than the lenses of the 8-week-old mice. CONCLUSIONS: As the elasticity of the human lens decreases with age, humans lose the ability to accommodate. The results, briefly described in this abstract, suggest a topical ocular treatment to increase lens elasticity through reduction of disulfides to restore accommodative amplitude.

Myopic Shift during Hyperbaric Oxygenation Attributed to Lens Index Changes.

PURPOSE: To examine ocular lens parameters and structural changes to elucidate mechanisms underlying the myopic shift and cataract-related changes that occur in some patients during hyperbaric oxygen (HBO) therapy. METHODS: Scheimpflug images (Nidek EAS-1000) of the crystalline lens, measurements of scattered light, objective refraction, keratometry, tonometry, and axial length of the eye were obtained after the first day of HBO therapy and repeated when patients had completed 19 days of the treatment. RESULTS: Significant reduction in mean (± SD) optical density was found in the lens nucleus, -2.8 (± 4.3) units (p = 0.009) and -2.2 (± 4.1) units (p = 0.027) within circular and oval areas, respectively. Significant decrease in mean (± SD) backward scattered light was measured, -0.4 (± 0.8) units (p = 0.022). Mean (± SD) myopic shift was -0.58 (± 0.39) diopters (p < 0.001), whereas cortical optical density, forward scattered light, lenticular parameters, keratometry, tonometry, anterior chamber depth, and axial length of the eye appeared unchanged. CONCLUSIONS: Transient myopic shift reported in patients during HBO therapy is attributed to changes in the refractive index of the lens. No changes in lens curvatures or thickness were found after treatment.

Dietary vitamin C and E modulates oxidative stress induced-kidney and lens injury in diabetic aged male rats through modulating glucose homeostasis and antioxidant systems.

Diabetes induces oxidative stress in aged human and rat, although daily supplementation of vitamins C and E (VCE) can be beneficial to aged diabetic rats by reducing free radical production. The aim of the present study was to evaluate whether dietary VCE supplementation relieves oxidative stress in streptozotocin (STZ)-induced diabetic in aged rats. Thirty aged rats were randomly divided into three groups. The first group was used as a control. The second group was made diabetic using a single dose of intraperitoneal STZ. VCE-supplemented feed was given to aged diabetic rats constituting the third group. On the 21st day of the experiment, blood, lens and kidney samples were taken from all animals. Glutathione peroxidase (GSH-Px) activity in lens and kidney, reduced glutathione (GSH), vitamin E and ß-carotene concentrations in kidney were lower in the diabetic group than in the control whereas plasma glucose, urea and creatinine, and kidney and lens peroxidation (LP) levels were higher in the diabetic group than in the control. However, kidney and lens LP levels, and plasma glucose, urea and creatinine values were decreased by VCE supplementation. Lens and kidney GSH-Px activity, kidney GSH, vitamin E and ß-carotene concentrations and erythrocyte counts were increased by VCE treatment. Kidney weights, vitamin A, haemoglobin, hematocrit, leukocyte and platelets values were not changed by diabetes and/or VCE supplementation. VCE ameliorated also diabetes-induced histopathological changes in kidney. In conclusion, we observed that VCE supplementation is beneficial towards kidney and lens of aged diabetic rats by modulating oxidative and antioxidant systems.

Evaluation of actual vs expected photodynamic therapy spot size.

PURPOSE: To determine the accuracy of the photodynamic therapy (PDT) laser spot size on the retina as generated by 2 Food and Drug Administration (FDA)-approved lasers. DESIGN: Prospective observational case series. METHODS: Fundus photographs were taken of 1 eye of each of 10 subjects with the WinStation 4000 fundus photography system (OIS; Ophthalmic Imaging Systems, Sacramento, California, USA); disc size was calculated using OIS software. Slit-lamp photographs were taken of the PDT laser spot focused on the retina adjacent to the optic disc, using various spot sizes in combination with 3 different contact lenses and 2 different lasers. Spot size at the retina was determined by measuring the ratio of disc diameter to spot diameter in Adobe Photoshop (San Jose, California, USA) and applying this ratio to the OIS disc measurements. RESULTS: Spot size at the retina averaged 87% of expected spot size for the Coherent Opal laser (Coherent Inc, Santa Clara, California, USA) and 104% of expected spot size for the Zeiss Visulas laser (Carl Zeiss Meditec Inc, Dublin, California, USA)(P = .002). Multivariate analysis demonstrated that percentage of expected spot size decreased with larger spot diameter (P = .01 for Coherent laser; P = .02 for Zeiss laser). CONCLUSIONS: PDT spot size at the retina appears to be consistently smaller than expected for the Coherent laser while the spot size was consistently within 10% of expected size for the Zeiss laser. The deviation from expected size increased with larger spot size using the Coherent laser.

Vitex negundo attenuates calpain activation and cataractogenesis in selenite models.

Recent investigations have shown that phytochemical antioxidants can scavenge free radicals and prevent various diseases. Cataract is the leading cause of blindness and is associated with oxidative damage of the lens. Selenite-induced cataract in rat pups is an excellent mimic of oxidative stress-induced cataract. Selenite cataract is associated with oxidative stress, loss of calcium homeostasis, calpain activation and protein insolubilization in the lens. Our present study focuses on the isolation of flavonoids from Vitex negundo and to assess its efficacy in preventing these changes in the lens of selenite-induced cataract models. Eight-day-old Sprague-Dawley rat pups were used for the study and divided into four groups: Control (G I), Sodium selenite-induced (G II), Sodium selenite+quercetin treated (G III), Sodium selenite+flavonoids from Vitex negundo (FVN) (G IV). Cataract was induced by a single subcutaneous injection of Sodium selenite (4 mg/Kg body weight) on the 10th day. Treatment groups received quercetin (1.0mg/Kg body weight) and FVN (1.0mg/Kg body weight) intraperitoneally from 8th to 15th day. Cataract was visualized from the 16th day. Morphological examination of the rat lenses revealed no opacification in G I and mild opacification in G III and G IV (stage 1) whereas dense opacification in G II (stage 4-6). The activities of superoxide dismutase (SOD), catalase, Ca(2+)ATPase, concentration of reduced glutathione (GSH) and protein sulfhydryl content were significantly increased in G III and G IV compared to G II, while decreased activities of calpains, lower concentration of calcium and thiobarbituric acid reactive substances (TBARS) were observed in G III and IV as compared to G II. Lens protein profile of water soluble proteins showed normal levels of expression in treated groups compared to that of selenite-induced rats. These results indicate good antioxidant and therapeutic potential of FVN in modulating biochemical parameters against selenite-induced cataract, which have been reported in this paper for the first time.

Intratissue refractive index shaping (IRIS) of the cornea and lens using a low-pulse-energy femtosecond laser oscillator.

PURPOSE: To assess the optical effect of high-repetition-rate, low-energy femtosecond laser pulses on lightly fixed corneas and lenses. METHODS: Eight corneas and eight lenses were extracted postmortem from normal, adult cats. They were lightly fixed and stored in a solution that minimized swelling and opacification. An 800-nm Ti:Sapphire femtosecond laser oscillator with a 27-fs pulse duration and 93-MHz repetition rate was used to inscribe gratings consisting of 20 to 40 lines, each 1-microm wide, 100-microm long, and 5-microm apart, 100 mum below the tissue surface. Refractive index changes in the micromachined regions were calculated immediately and after 1 month of storage by measuring the intensity distribution of diffracted light when the gratings were irradiated with a 632.8-nm He-Ne laser. RESULTS: Periodic gratings were created in the stromal layer of the corneas and the cortex of the lenses by adjusting the laser pulse energy until visible plasma luminescence and bubbles were no longer generated. The gratings had low scattering loss and could only be visualized using phase microscopy. Refractive index changes measured 0.005 +/- 0.001 to 0.01 +/- 0.001 in corneal tissue and 0.015 +/- 0.001 to 0.021 +/- 0.001 in the lenses. The gratings and refractive index changes were preserved after storing the micromachined corneas and lenses for 1 month. CONCLUSIONS: These pilot experiments demonstrate a novel application of low-pulse-energy, MHz femtosecond lasers in modifying the refractive index of transparent ocular tissues without apparent tissue destruction. Although it remains to be verified in living tissues, the stability of this effect suggests that the observed modifications are due to long-term molecular and/or structural changes.

Effect of the pyridoindole antioxidant stobadine on development of experimental diabetic cataract and on lens protein oxidation in rats: comparison with vitamin E and BHT.

PURPOSE: The aim of this study was to investigate the effect of dietary supplementation with the pyridoindole antioxidant stobadine on the development of diabetic cataract in rats. The findings were compared with the effect of the natural antioxidant vitamin E and the well known phenolic synthetic antioxidant butylated hydroxytoluene. METHODS: Streptozotocin induced diabetic male Wistars rats were fed for 18 weeks a standard diet or a diet supplemented with stobadine (0.05% w/w), vitamin E (0.1% w/w), butylated hydroxytoluene (BHT, 0.4% w/w), or a mixture of stobadine (0.05% w/w) and vitamin E (0.1% w/w). The progress of cataract was monitored biweekly by ophthalmoscopic inspection. Plasma glucose and body weight were recorded regularly. At the end of the experiment, the content of free sulfhydryl and carbonyl was determined in total lens proteins and in the stobadine group plasma levels of malondialdehyde were also measured. RESULTS: Long term treatment of diabetic animals with stobadine (STB), vitamin E, or BHT led to a marked delay in the development of advanced stages of cataract. At the end of the experiment, the visual cataract score was significantly decreased in the diabetic groups treated with stobadine or BHT, while vitamin E had no significant effect. Unexpectedly, combined treatment with STB+vitamin E advanced the progression of the higher stages of cataract, though without affecting the overall visual cataract score. Neither of the antioxidants exerted an effect on the glycemic state or body weight of the animals. Biochemical analyses of eye lens proteins showed significant diminution of sulfhydryl groups and elevation of carbonyl groups in diabetic animals in comparison to healthy controls. Dietary supplementation with any of the antioxidants studied did not influence the levels of these biomarkers significantly. Nevertheless, in diabetic animals, stobadine supplementation significantly attenuated plasma levels of malondialdehyde, an index of systemic oxidative damage. CONCLUSIONS: The results are in accordance with the postulated pro-oxidant role of chronic hyperglycemia, however, the direct oxidative free radical damage of eye lens proteins does not seem to be the key mechanism effective in the development of diabetic cataract. Sugar cataractogenesis appears to be a complex process, in which multiple mechanisms may be involved, including consequences of the overt oxidative stress in diabetes (e.g., protein modifying potential of toxic aldehydes generated as byproducts of carbohydrate autoxidation and lipid peroxidation). The ability of stobadine to attenuate lipoxidation reactions in diabetes may account, at least partly, for its observed anticataract action. Mechanisms involving reduction of mitochondrial damage by stobadine are also discussed.

Effect of hyperbaric oxygen on guinea pig lens optical quality and on the refractive state of the eye.

The main objective of this study was to investigate the effect of in vivo hyperbaric oxygen (HBO) treatment of albino guinea pigs on ocular refractive state and optical properties of the lens in vitro, as well as on the integrity of the mitochondria of the lens. The animals were treated 30-35 times (2.5-3 months) or 70 times (6 months) with HBO. An increased level of lens nuclear light scattering was evident by slit-lamp at 30 treatments, and this increased at 70 treatments. After 30-35 HBO treatments a myopic shift in refractive state of the eye was seen in two separate studies with two different refractionists. Also, the average back vertex distance of the lens was significantly shorter after 35 HBO treatments while spherical aberration (focal variability) increased after 70 treatments. No difference in refractive state was noted after 70 HBO treatments (a reversal of the initial myopic effect). The mitochondrial distribution and morphology of the lens epithelium and the superficial cortical fibre cells were normal after both 35 and 70 HBO treatments, highlighting that HBO treatment does not affect the superficial cortex of the lens. The results of the in vitro lens optical analysis carried out in this study correlate with the myopia observed after 30-35 HBO in vivo treatments. A similar reversible myopia and increase in lens nuclear light scattering is known to occur in humans treated with HBO for extended periods and the results suggest that the myopia was caused by a change in the refractive index of the lens. The significant loss of sharp focus after 70 HBO treatments can be correlated with previous reports of biochemical and morphological changes associated with HBO-induced loss of lens nuclear transparency in mature guinea pigs. The guinea pig HBO model may be a useful approach for the study of lens development and refractive error.

Vitamin E supplementation and cataract: randomized controlled trial.

OBJECTIVE: To determine whether treatment with vitamin E (500 IU daily) reduces either the incidence or rate of progression of age-related cataracts. DESIGN: A prospective, randomized, double-masked, placebo-controlled clinical trial entitled the Vitamin E, Cataract and Age-Related Maculopathy Trial. PARTICIPANTS: Of 1906 screened volunteers, 1193 eligible subjects with early or no cataract, aged 55 to 80 years, were enrolled and followed up for 4 years. INTERVENTION: Subjects were assigned randomly to receive either 500 IU of natural vitamin E in soybean oil encapsulated in gelatin or a placebo with an identical appearance. MAIN OUTCOME MEASURES: The incidence and progression rates of age-related cataract were assessed annually with both clinical lens opacity gradings and computerized analysis of Scheimpflug and retroillumination digital lens images obtained with a Nidek EAS-1000 lens camera. The analysis was undertaken using data from the eye with the more advanced opacity for each type of cataract separately and for any cataract changes in each individual. RESULTS: Overall, 87% of the study population completed the 4 years of follow-up, with 74% of the vitamin E group and 76% of the placebo group continuing on their randomized treatment allocation throughout this time. For cortical cataract, the 4-year cumulative incidence rate was 4.5% among those randomized to vitamin E and 4.8% among those randomized to placebo (P = 0.87). For nuclear cataract, the corresponding rates were 12.9% and 12.1% (P = 0.77). For posterior subcapsular cataract, the rates were 1.7% and 3.5% (P = 0.08), whereas for any of these forms of cataract, they were 17.1% and 16.7%, respectively. Progression of cortical cataract was seen in 16.7% of the vitamin E group and 18.4% of the placebo group (P = 0.76). Corresponding rates for nuclear cataract were 11.4% and 11.9% (P = 0.84), whereas those of any cataract were 16.5% and 16.7%, respectively. There was no difference in the rate of cataract extraction between the 2 groups (P = 0.87). Lens characteristics of the participants withdrawn from the randomized medications were not different from those who continued. CONCLUSIONS: Vitamin E given for 4 years at a dose of 500 IU daily did not reduce the incidence of or progression of nuclear, cortical, or posterior subcapsular cataracts. These findings do not support the use of vitamin E to prevent the development or to slow the progression of age-related cataracts.

Removal of intralenticular magnetic foreign bodies with intraocular magnet.

PURPOSE: To investigate the possibility of conservation of the lens after removal of intralenticular magnetic foreign bodies with intraocular magnet. METHODS: Intralenticular magnetic foreign bodies of 15 patients were removed by using an intraocular magnet. The lens of each injury eye was conserved. Follow-up observation of these cases ranged from one to four years. RESULTS: The intralenticular magnetic foreign bodies of 15 patients were successfully removed. The lens of each injury eye was conserved and the transparence of the lens was properly maintained. Sizes of these foreign bodies were measured, ranging from 0.3 mm to 3 mm in diameter. The follow-up observation showed that the corrected visual acuity of 14 cases was not changed after operation. CONCLUSIONS: The intraocular magnet is very helpful for removal of magnetic foreign bodies from the transparent lens. This magnet allows removing of the foreign body by the surgeon and no damage to the lens was induced during the operation. Thus, maintenance of visual acuity of most of the patients can be achieved.

[Is a cataract avoidable? Current status with special emphasis on the pathophysiology of oxidative lens damage, nutritional factors, and the ARED study]. / Ist die Katarakt vermeidbar? Eine aktuelle Bestandsaufnahme unter besonderer Berücksichtigung der Pathophysiologie oxidativer Linsenschäden, nutritiver Einflussfaktoren und der ARED-Studie.

The benefit of long-term nutrient intake to reduce the risk of age-related ocular disease such as cataract or macular degeneration is subject to controversy. Conclusions about the benefits and risks of antioxidant supplements can be expected after reviewing the current literature concerning oxidative-induced lens damage and nutritional effects. Identification of influenceable risk factors for senile cataracts could achieve immense economical relevance. In contrast to former longitudinal epidemiological studies, the AREDS report failed to verify protective properties of highly concentrated vitamin supplements on cataract formation. Although there are enough epidemiological indications for reducing the risk of cataracts by the intake of antioxidants, a general recommendation for the use of supplements is untimely or even wrong until stringent evidence of efficacy is provided. The usefulness of cataract prevention is discussed.

A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9.

BACKGROUND: Experimental and observational data suggest that micronutrients with antioxidant capabilities may retard the development of age-related cataract. OBJECTIVE: To evaluate the effect of a high-dose antioxidant formulation on the development and progression of age-related lens opacities and visual acuity loss. DESIGN: The 11-center Age-Related Eye Disease Study (AREDS) was a double-masked clinical trial. Participants were randomly assigned to receive daily oral tablets containing either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no antioxidants. Participants with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial. Baseline and annual (starting at year 2) lens photographs were graded at a reading center for the severity of lens opacities using the AREDS cataract grading scale. MAIN OUTCOME MEASURES: Primary outcomes were (1) an increase from baseline in nuclear, cortical, or posterior subcapsular opacity grades or cataract surgery, and (2) at least moderate visual acuity loss from baseline (>/=15 letters). Primary analyses used repeated-measures logistic regression with a statistical significance level of P =.01. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. RESULTS: Of 4757 participants enrolled, 4629 who were aged from 55 to 80 years had at least 1 natural lens present and were followed up for an average of 6.3 years. No statistically significant effect of the antioxidant formulation was seen on the development or progression of age-related lens opacities (odds ratio = 0.97, P =.55). There was also no statistically significant effect of treatment in reducing the risk of progression for any of the 3 lens opacity types or for cataract surgery. For the 1117 participants with no age-related macular degeneration at baseline, no statistically significant difference was noted between treatment groups for at least moderate visual acuity loss. No statistically significant serious adverse effect was associated with treatment. CONCLUSION: Use of a high-dose formulation of vitamin C, vitamin E, and beta carotene in a relatively well-nourished older adult cohort had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss.

Lens transmission by fluorophotometry after brachytherapy and thermotherapy of choroidal melanoma.

We studied the effect of transpupillary thermotherapy (TTT) by a diode laser at 810 nm combined with episcleral ruthenium-106 plaque treatment (106Ru) on lens transparency in patients with choroidal melanoma. Lens transmission of blue-green light was measured by fluorophotometry in 17 patients treated with 106Ru treatment and TTT (measured 0.36 years after treatment), 12 patients treated with 106Ru alone (measured 19 years after treatment) and 25 age-matched healthy controls. Differences in lens transmission were not significant between treated and untreated fellow eyes (p > 0.15) nor between patient and control eyes (p > 0.25). TTT of choroidal melanoma combined with 106Ru plaque irradiation did not have a significant effect on the lens transparency up to 6 years after treatment.

Selenium-induced cataract--a correlation of dry mass content and light scattering.

Selenium-induced cataracts in young rats were used to compare light scattering and dry mass concentration along the lens axis. Selenium-treated rats and control rats were examined 1, 2, 4 and 6 days after subcutaneous injection of selenium or 0.9% NaCl. The development of nuclear cataract was followed with a Scheimpflug slit-lamp camera. Light-scattering was determined by densitometry of the negatives taken by the Scheimpflug camera. Dry mass concentration was determined by quantitative microradiography of the extracted lenses. Increasing light scatter was seen from day 2 to day 6. The dry mass concentration, however, was not changed until day 6. Two distinct zones were found surrounding the center of the nucleus, one with increased and one with decreased dry mass. The rapid changes in dry mass concentration were probably caused by shifts in water distribution within the lens. Similar zones of hydration have also been found in human senile nuclear cataract. Selenium-induced cataract in the rat is discussed in relation to human nuclear cataract.