Discrimination between surgical and nonsurgical nuclear cataracts based on ROC analysis.

PURPOSE: The aim of this article is to propose a quantitative methodology for determining a criterion to discriminate the nonsurgical nuclear cataract from the surgical one taking into account objective measures of intraocular scattering in patients with good visual acuity (>0.6). METHODS: Two groups of subjects were taken into account: a control group and a group with nuclear cataracts. At a first stage, eyes belonging to the cataract group were classified into "nonsurgical" and "surgical" cataracts by ophthalmologists at their clinical settings. At a second stage a double-pass instrument was also used to determine the objective scatter index (OSI) at the laboratory. Receiver operating characteristic (ROC) curves were used to analyze OSI values to determine a value able to separate between nonsurgical and surgical cataracts. RESULTS: We obtained statistically significant differences among the control and both nuclear cataract groups (p < 0.05). ROC curves determined an OSI criterion level (of 2.1) to suggest surgery in nuclear cataracts with an area under curve of 0.83, i.e. with 80% of sensitivity and 80% of specificity. CONCLUSIONS: ROC analysis allows separating both groups of nuclear cataract, and we determined a value of OSI in nuclear cataract quantification for surgery.

A Class I UV-blocking (senofilcon A) soft contact lens prevents UVA-induced yellow fluorescence and NADH loss in the rabbit lens nucleus in vivo.

It is known that fluorescence, much of it caused by UVA light excitation, increases in the aging human lens, resulting in loss of sharp vision. This study used an in vivo animal model to investigate UVA-excited fluorescence in the rabbit lens, which contains a high level of the UVA chromophore NADH, existing both free and bound to λ-crystallin. Also, the ability of a Class I (senofilcon A) soft contact lens to protect against UVA-induced effects on the rabbit lens was tested. Rabbit eyes were irradiated with UVA light in vivo (100 mW/cm(2) on the cornea) for 1 h using monochromatic 365 nm light. Irradiation was conducted in the presence of either a senofilcon A contact lens, a minimally UV-absorbing lotrafilcon A contact lens, or no contact lens at all. Eyes irradiated without a contact lens showed blue 365 nm-excited fluorescence initially, but this changed to intense yellow fluorescence after 1 h. Isolated, previously irradiated lenses exhibited yellow fluorescence originating from the lens nucleus when viewed under 365 nm light, but showed normal blue fluorescence arising from the cortex. Previously irradiated lenses also exhibited a faint yellow color when observed under visible light. The senofilcon A contact lens protected completely against the UVA-induced effects on fluorescence and lens yellowing, whereas the lotrafilcon A lens showed no protection. The UVA-exposure also produced a 53% loss of total NADH (free plus bound) in the lens nucleus, with only a 13% drop in the anterior cortex. NADH loss in the nucleus was completely prevented with use of a senofilcon A contact lens, but no significant protection was observed with a lotrafilcon A lens. Overall, the senofilcon A lens provided an average of 67% protection against UVA-induced loss of four pyridine nucleotides in four different regions of the lens. HPLC analysis with fluorescence detection indicated a nearly six-fold increase in 365 nm-excited yellow fluorescence arising from lens nuclear λ-crystallin after the in vivo UVA exposure. It is concluded that UVA-induced loss of free NADH (which fluoresces blue) may have allowed the natural yellow fluorescence of λ-crystallin and other proteins in the lens nucleus to become visible. Increased fluorescence exhibited by UVA-exposed λ-crystallin may have been the result of a UVA-induced change in the conformation of the protein occurring during the initial UVA-exposure in vivo. The results demonstrate the greater susceptibility of the lens nucleus to UVA-induced stress, and may relate to the formation of human nuclear cataract. The senofilcon A contact lens was shown to be beneficial in protecting the rabbit lens against effects of UVA light, including changes in fluorescence, increased yellowing and loss of pyridine nucleotides.

NASA study of cataract in astronauts (NASCA). Report 1: Cross-sectional study of the relationship of exposure to space radiation and risk of lens opacity.

The NASA Study of Cataract in Astronauts (NASCA) is a 5-year longitudinal study of the effect of space radiation exposure on the severity/progression of nuclear, cortical and posterior subcapsular (PSC) lens opacities. Here we report on baseline data that will be used over the course of the longitudinal study. Participants include 171 consenting astronauts who flew at least one mission in space and a comparison group made up of three components: (a) 53 astronauts who had not flown in space, (b) 95 military aircrew personnel, and (c) 99 non-aircrew ground-based comparison subjects. Continuous measures of nuclear, cortical and PSC lens opacities were derived from Nidek EAS 1000 digitized images. Age, demographics, general health, nutritional intake and solar ocular exposure were measured at baseline. Astronauts who flew at least one mission were matched to comparison subjects using propensity scores based on demographic characteristics and medical history stratified by gender and smoking (ever/never). The cross-sectional data for matched subjects were analyzed by fitting customized non-normal regression models to examine the effect of space radiation on each measure of opacity. The variability and median of cortical cataracts were significantly higher for exposed astronauts than for nonexposed astronauts and comparison subjects with similar ages (P=0.015). Galactic cosmic space radiation (GCR) may be linked to increased PSC area (P=0.056) and the number of PSC centers (P=0.095). Within the astronaut group, PSC size was greater in subjects with higher space radiation doses (P=0.016). No association was found between space radiation and nuclear cataracts. Cross-sectional data analysis revealed a small deleterious effect of space radiation for cortical cataracts and possibly for PSC cataracts. These results suggest increased cataract risks at smaller radiation doses than have been reported previously.

Radiation cataracts: mechanisms involved in their long delayed occurrence but then rapid progression.

PURPOSE: This study was directed to assess the DNA damage and DNA repair response to X-ray inflicted lens oxidative damage and to investigate the subsequent changes in lens epithelial cell (LEC) behavior in vivo that led to long delayed but then rapidly developing cataracts. METHODS: Two-month-old C57Bl/6 female mice received 11 Grays (Gy) of soft x-irradiation to the head only. The animals' eyes were examined for cataract status in 30 day intervals by slit lamp over an 11 month period post-irradiation. LEC migration, DNA fragment, free DNA retention, and reactive oxygen species (ROS) presence were established in the living lenses with fluorescent dyes using laser scanning confocal microscopy (LSCM). The extent and removal of initial LEC DNA damage were determined by comet assay. Immunohistochemistry was used to determine the presence of oxidized DNA and the response of a DNA repair protein in the lenses. RESULTS: This treatment resulted in advanced cortical cataracts that developed 5-11 months post-irradiation but then appeared suddenly within a 30 day period. The initially incurred DNA strand breaks were repaired within 30 min, but DNA damage remained as shown 72 h post-irradiation by the presence of the DNA adduct, 8-hydroxyguanosine (8-OHG), and a DNA repair protein, XRCC1. This was followed months later by abnormal behavior by LEC descendant cells with abnormal differentiation and migration patterns as seen with LSCM and fluorescent dyes. CONCLUSIONS: The sudden development of cortical cataracts several months post-irradiation coupled with the above findings suggests an accumulation of damaged descendants from the initially x-irradiated LECs. As these cells migrate abnormally and leave acellular lens surface sites, eventually a crisis point may arrive for lens entry of environmental O(2) with resultant ROS formation that overwhelms protection by resident antioxidant enzymes and results in the coagulation of lens proteins. The events seen in this study indicate the retention and transmission of progenitor cell DNA damage in descendant LEC. The cellular and molecular events parallel those previously reported for LSCM observations in age-related cataracts.

Predicted light scattering from particles observed in human age-related nuclear cataracts using mie scattering theory.

PURPOSE: To employ Mie scattering theory to predict the light-scattering from micrometer-sized particles surrounded by lipid shells, called multilamellar bodies (MLBs), reported in human age-related nuclear cataracts. METHODS: Mie scattering theory is applicable to randomly distributed spherical and globular particles separated by distances much greater than the wavelength of incident light. With an assumed refractive index of 1.40 for nuclear cytoplasm, particle refractive indices from 1.33 to 1.58 were used to calculate scattering efficiencies for particle radii 0.05 to 3 microm and incident light with wavelengths (in vacuo) of 400, 550, and 700 nm. RESULTS: Surface plots of scattering efficiency versus particle radius and refractive index were calculated for coated spherical particles. Pronounced peaks and valleys identified combinations of particle parameters that produce high and low scattering efficiencies. Small particles (<0.3 microm radius) had low scattering efficiency over a wide range of particle refractive indices. Particles with radii 0.6 to 3 microm and refractive indices 0.08 to 0.10 greater (or less) than the surrounding cytoplasm had very high scattering efficiencies. This size range corresponds well to MLBs in cataractous nuclei (average MLB radius, 1.4 microm) and, at an estimated 4000 particles/mm(3) of tissue, up to 18% of the incident light was scattered primarily within a 20 degrees forward cone. CONCLUSIONS: The calculated size of spherical particles that scatter efficiently was close to the observed dimensions of MLBs in cataractous nuclei. Particle refractive indices only 0.02 units different from the surrounding cytoplasm scatter a significant amount of light. These results suggest that the MLBs observed in human age-related nuclear cataracts may be major sources of forward light scattering that reduces contrast of fine details, particularly under dim light.

Cosmic radiation increases the risk of nuclear cataract in airline pilots: a population-based case-control study.

BACKGROUND: Aviation involves exposure to ionizing radiation of cosmic origin. The association between lesions of the ocular lens and ionizing radiation is well-known. OBJECTIVE: To investigate whether employment as a commercial airline pilot and the resulting exposure to cosmic radiation is associated with lens opacification. METHODS: This is a population-based case-control study of 445 men. Lens opacification was classified into 4 types using the World Health Organization simplified grading system. These 4 types, serving as cases, included 71 persons with nuclear cataracts, 102 with cortical lens opacification, 69 with central optical zone involvement, and 32 with posterior subcapsular lens opacification. Control subjects are those with a different type of lens opacification or without lens opacification. Exposure was assessed based on employment time as pilots, annual number of hours flown on each aircraft type, time tables, flight profiles, and individual cumulative radiation doses (in millisieverts) calculated by a software program. Odds ratios were calculated using logistic regression. RESULTS: The odds ratio for nuclear cataract risk among cases and controls was 3.02 (95% confidence interval, 1.44-6.35) for pilots compared with nonpilots, adjusted for age, smoking status, and sunbathing habits. The odds ratio for nuclear cataract associated with estimation of cumulative radiation dose (in millisieverts) to the age of 40 years was 1.06 (95% confidence interval, 1.02-1.10), adjusted for age, smoking status, and sunbathing habits. CONCLUSION: The association between the cosmic radiation exposure of pilots and the risk of nuclear cataracts, adjusted for age, smoking status, and sunbathing habits, indicates that cosmic radiation may be a causative factor in nuclear cataracts among commercial airline pilots.

Age-related nuclear cataract: a lens transport problem.

Age-related nuclear cataract is a major cause of blindness. It is characterised by opacification and colouration in the centre of the lens and is accompanied by extensive protein oxidation. The reason for the onset of nuclear cataract is not known, but it is proposed here that the underlying cause is the development, with age, of a barrier to the transport of metabolites within the lens. Such a barrier may result in an increase in the half-lives of reactive molecules, such as UV filters, thus promoting posttranslational modification of proteins in the nucleus and may also act to prevent an adequate flux of antioxidants from reaching the lens interior and, as a consequence, allow oxidation of nuclear components. Further, this oxidation may take place even if the lens outer cortex and epithelium remain perfectly functional.

Impact of aging and hyperbaric oxygen in vivo on guinea pig lens lipids and nuclear light scatter.

PURPOSE: To measure lipid compositional and structural changes in lenses as a result of hyperbaric oxygen (HBO) treatment in vivo. HBO treatment in vivo has been shown to produce increased lens nuclear light scattering. METHODS: Guinea pigs, approximately 650 days old at death, were given 30 and 50 HBO treatments over 10- and 17-week periods, respectively, and the lenses were sectioned into equatorial, cortical, and nuclear regions. Lipid oxidation, composition, and structure were measured using infrared spectroscopy. Phospholipid composition was measured using (31)P-NMR spectroscopy. Data were compared with those obtained from lenses of 29- and 644-day-old untreated guinea pigs. RESULTS: The percentage of sphingolipid approximately doubled with increasing age (29-544 days old). Concomitant with an increase in sphingolipid was an increase in hydrocarbon chain saturation. The extent of normal lens lipid hydrocarbon chain order increased with age from the equatorial and cortical regions to the nucleus. These order data support the hypothesis that the degree of lipid hydrocarbon order is determined by the amount of lipid saturation, as regulated by the content of saturated sphingolipid. Products of lipid oxidation (including lipid hydroxyl, hydroperoxyl, and aldehydes) and lipid disorder increased only in the nuclear region of lenses after 30 HBO treatments, compared with control lenses. Enhanced oxidation correlated with the observed loss of transparency in the central region. HBO treatment in vivo appeared to accelerate age-related changes in lens lipid oxidation, particularly in the nucleus, which possesses less antioxidant capability. CONCLUSIONS: Oxidation could account for the lipid compositional changes that are observed to occur in the lens with age and cataract. Increased lipid oxidation and hydrocarbon chain disorder correlate with increased lens nuclear opacity in the in vivo HBO model.

Light exposure and the risk of cortical, nuclear, and posterior subcapsular cataracts: the Pathologies Oculaires Liées à l'Age (POLA) study.

BACKGROUND: Exposure to light may be an important risk factor for the development of cataracts. OBJECTIVE: To present the relation of ambient solar radiation and professional and leisure exposures to light with the different types of cataracts. METHODS: Pathologies Oculaires Liées a l'Age (POLA) is a population-based study on cataract and age-related macular degeneration and their risk factors in 2584 residents of Sète (southern France). Cataract classification was based on lens examination at slitlamp according to Lens Opacities Classification System III. A questionnaire about light exposure was administered. RESULTS: After multivariate adjustment, participants who had higher ambient solar radiation had a 2.5-fold (95% confidence interval [CI], 1.2-5.0), 4.0-fold (95% CI, 2.0-8.0), and 2.9-fold (95% CI, 1.5-5.3) increased risk of cortical and mixed cataract and cataract surgery, respectively. Solar ambient radiation was not significantly associated with posterior subcapsular and nuclear cataracts. By contrast, posterior subcapsular cataracts were significantly associated with professional exposure to sunlight (odds ratio [OR], 1.63; 95% CI, 1.01-2.63) and frequent use of sunglasses (OR, 0.62; 95% CI, 0.43-0.90). Mixed cataract was also associated with professional exposure to artificial light (OR, 3.02; 95% CI, 1.03-8.82). CONCLUSION: Our study further confirms the role of sunlight exposure in the pathogenesis of cataract, in particular in its cortical localization.

Comparison of various calpain inhibitors in reduction of light scattering, protein precipitation and nuclear cataract in vitro.

PURPOSE: To compare effects of calpain inhibitors on in vitro light-scattering in rat lens soluble protein and calcium-ionophore (A23187)-induced cataract formation in cultured rat lenses. METHODS: Rat lens soluble protein was hydrolyzed for 24 hours by activation of endogenous lens calpain. Ten calpain inhibitors were tested in this model at 10 and 25 microM concentration. As an index of protein precipitation, light scattering was measured daily at 405 nm for 8 days. Lens proteins were analyzed by isoelectric-focussing. Subsequently, rat lenses were cultured for 5 days with 10 microM A23187. Calpain inhibitors (SJA6017, MDL28170, AK295 and PD150606), which inhibited light-scattering were tested at 100 microM concentration in this model. Cataract evaluation, isoelectric-focussing and calcium determinations were performed. RESULTS: At 25 microM concentration AK295, SJA6017, E-64, PD-150606 and MDL28170 produced greater than 25% inhibition of light-scattering. Isoelectric-focussing revealed that addition of Ca(2+) produced characteristic crystallin proteolysis and aggregation patterns. AK295, SJA6017, MDL28170 and E64c prevented these changes. Lenses cultured in A23187 exhibited nuclear cataract, elevated calcium and proteolysis and aggregation of crystallins. Co-culture with SJA6017, MDL28170 and E64c reduced A23187-induced nuclear opacities, proteolysis and aggregation of crystallins without affecting increased total calcium. CONCLUSIONS: Endogenous calpain-activation model and A23187-induced cataract model can be used sequentially to screen calpain inhibitors for potential anti-cataract activity. Proteolytic changes in lens cortex after exposure to A23187 are also due to calpain activation. AK295, SJA6017 and MDL28170 possess efficacy against calcium-induced models of rodent cataracts. Use of calpain inhibitors represents a promising approach to cataract therapy.

In vivo light scattering intensity in the lens versus in vitro spectral transmission in the nuclear region.

In order to understand the correlation between nuclear opacity and spectral light transmission factor, the in vivo light scattering intensity of Scheimpflug lens images and the light transmission through slices of surgically removed nucleus were examined densitometrically as well as spectrophotometrically respectively, using both human and Brown Norway rat lenses. The experiments using rat lenses showed that the increase of the light scattering intensity in the nuclear regions is correlated with a decrease of the spectral transmission factor. The transparent anterior cortical region did not influence the light transmission (T%) through the nucleus. No significant influence was seen from the application of freezing and thawing procedures to measure light transmission. The examinations of the human subjects which were based on the rat study showed that the light transmission of nuclear cataracts objectively evaluated as grade I was almost the same as that observed in noncataractous nuclei. The light transmission of nuclear cataracts graded II or above, however, showed around 50% of the spectral light transmission of noncataractous nuclei.

UV-B and early cortical and nuclear changes in the human lens.

Experimental studies in mice and rats have shown that UV (B) irradiation leads to specific lens changes, viz. yellowing of the nucleus and a multilayered epithelium in the anterior pole with disrupted cortical fibres underneath. Biomicroscopic and ultrastructural studies on ageing human lenses revealed yellowing of the lens nucleus and locally ruptured membranes and small opacities in the equatorial cortex. No changes in the anterior pole were ever observed. This discrepancy between the human and animal lens, contraindicating UV as an important risk factor for human cataract, is discussed and may be due to several factors: (1) a difference between the high level acute and low level chronic irradiation; (2) species differences: nocturnal animals may be unable to cope with bright light exposure; (3) differences in scavenger and other defense mechanisms between humans and animals.

Effect of chronic near-ultraviolet radiation on the gray squirrel lens in vivo.

The effects of ambient exposure to near-ultraviolet (near-UV) radiation (300-400 nm) on the ocular lens of the diurnal squirrel (Sciurus carolinensis) are reported. Gray squirrels lived in cages illuminated for 12 hr a day with near-UV light (6 mW/cm2, 365 nm) for 1 yr. The non-UV-exposed controls were housed separately. In the lenses of UV-exposed animals, anterior pole changes occurred. Central epithelial cells swelled, disappeared, or underwent proliferation. A band of disoriented degenerating fiber cells was seen in the midcortex, with a degree of liquefaction. When lens protein compartments were separated by centrifugation, water-insoluble but urea-soluble fractions were enhanced in the outer and inner cortex and the nucleus. Both high-performance liquid chromatography and polyacrylamide gel electrophoresis revealed that proteins mainly in the midcortex and nucleus were altered considerably. Evidence of a loss of sulfhydryl compounds (by chemical and Raman spectroscopic analyses) and an increase of protein-thiol mixed disulfides (chemically) was also observed. These data prove that repetitive ambient exposure of diurnal animals to near-UV radiation at subsolar levels damages the lens by interfering with the maintenance of epithelial cells and altering the structural proteins; some of this may be due to the conversion of sulfhydryls to mixed disulfides.

Quantitative photoacoustic spectroscopy of cataractous human lenses.

Quantitative photoacoustic spectra of the nuclei of cataractous human lenses with various degrees of colouration and opacification were measured in the spectral range 250-600 nm. The lens nuclei were obtained from 20 cataractous patients through extracapsular cataract extraction. These measurements yield the light loss per unit path length in the nucleus of cataractous lenses.

Nd:YAG laser photodisruption of the lens nucleus before phacoemulsification.

We studied the use of Q-switched Nd:YAG laser pulses to soften sclerotic lens nuclei before phacoemulsification. We obtained 105 lens nuclei from extracapsular cataract extractions, graded them for degree of sclerosis, and randomized them into laser treatment (53 lenses) or control groups (52 lenses). The treated lenses received laser pulses until confluent pits and clefts were visible. All lenses were phacoemulsified and the times recorded. Nd:YAG laser pretreatment decreased phacoemulsification time in all grades. In moderately sclerotic nuclei, average phacoemulsification time was reduced from 40.1 to 23.9 seconds (40.4%). The nuclei of ten lenses obtained from intracapsular cataract extractions were treated intracapsularly, and the posterior capsule was inadvertently ruptured in five.

Morphological and cell volume changes in the rat lens during the formation of radiation cataracts.

Earlier studies in our laboratory showed that 24 hr after X-irradiation, epithelial cells of early postnatal rat lenses increased in volume. Three days after X-irradiation, the underlying lens fibers increased in volume. This finding suggested a correlation between damage to epithelial cell volume regulation and subsequent fiber cell swelling. To test this hypothesis 4-week-old rat lenses were three-dimensionally reconstructed to determine average cell volumes of specific lens regions and wet weights of whole lenses were measured during radiation cataract formation. In addition, the differentiation of epithelial cells into lens fibers was monitored by autoradiography. Four-week-old Sprague-Dawley rats were injected with [3H]-thymidine and, 24 hr later, their eyes were irradiated with either 400 or 1200 rad. Lenses were examined with a slit lamp and cataracts were graded on a scale of 1+ to 4+. Animals were killed 24 hr and 3, 5, 15 and 30 weeks after exposure. Lenses were serially sectioned at 0.75 micron and epithelial, equatorial and cortical fiber cell volumes were determined. Rats exposed to 400 or 1200 rad developed 0.5-1.5+ or 2.5-3.0+ cataracts, respectively, 10-16 weeks after X-irradiation. Epithelial and equatorial cells of both groups did not significantly increase in volume during this period. Three weeks after irradiation with 1200 rad cortical fibers were disorganized and had increased volume. By 5 and 15 weeks, cortical fibers had more normal cell volumes, although their morphology remained grossly altered. Cortical fiber volume of lenses irradiated with 400 rad were not significantly different from control lenses throughout the experimental period. By 15 weeks lenses irradiated with 400 rad showed subtle changes in morphology. Wet weight determinations indicated that the localized increase in cortical fiber volume did not result in an increase in the wet weight of the entire lens. Autoradiography showed that affected fibers had been epithelial cells at the time of X-irradiation. These results provide additional evidence that disturbances in fiber differentiation are involved with cataract formation, but do not support the initial hypothesis that a disturbance in epithelial cell volume regulation leads to fiber cell swelling. Earlier results suggesting defects in lens epithelial volume regulation in radiation cataract formation may have been complicated by ocular inflammation.

Singlet oxygen as a possible factor in human senile nuclear cataract development.

The effects of photodynamically generated singlet oxygen on lens crystallins were investigated. This highly reactive oxidant can produce in crystallins in vitro the oxidative modifications characteristic of proteins from aging and cataractous lens. Additionally species capable of producing singlet oxygen in the presence of near UV radiation are shown to be present in human lenses. These findings are discussed with respect to a possible role of singlet oxygen in the etiology of human senile nuclear cataracts.