Deformations and Ruptures in Human Lenses With Cortical Cataract Subjected to Ex Vivo Simulated Accommodation.

Purpose: Human cortical opacities are most commonly accompanied by changes in lens fiber structure in the equatorial region at the lens nucleus-cortex interface. Cortex and nucleus have different elastic properties, which change with age. We therefore subjected ex vivo lenses to simulated accommodation and studied the internal deformations to better understand the mechanism of cortical cataract formation. Methods: Nine human donor lenses (33-88 years old) were tested using a bespoke radial stretching device for anterior eye segments. Seven of the lenses exhibited cortical cataracts. The other two lenses, without cataract, were used as controls. Frontal and cross-sectional images of the lens obtained during stretching facilitated measurements on equatorial lens diameter and central lens thickness in the stretched and unstretched states. Results: Stretching caused the lens equatorial diameter to increase in all cases. Conversely, the lens central thickness showed no systematic variation during stretching. For four of the lenses with cortical cataract, ruptures were observed during stretching at the nucleus-cortex boundary adjacent to the cortical cataracts. Ruptures were not observed in the control lenses or in the three other lenses with cortical cataract. Conclusions: Internal ruptures can occur in aged ex vivo lenses subjected to simulated disaccommodation. These ruptures occur at the nucleus-cortex interface; at this location, a significant stiffness discontinuity is expected to develop with age. It is hypothesized that ruptures occur in in vivo lenses during accommodation-or attempted accommodation.

Morphology of age-related cuneiform cortical cataracts: the case for mechanical stress.

We evaluated the gross morphology, location, and fiber cell architecture of equatorial cortical opacities in the aging human lens. Using dark-field stereomicroscopy, we photographed donor lenses in toto and as thick slices. In addition, we investigated the details of the fiber cell architecture using fluorescent staining for membranes and by scanning electron microscopy. We then combined our data with data from recent studies on lens viscoelasticity. We found that small cortical and cuneiform opacities are accompanied by changes in fiber structure and architecture mainly in the equatorial border zone between the lens nucleus and cortex. Because the lens cortex and nucleus have different viscoelastic properties in young and old lenses, we hypothesize that external forces during accommodation cause shear stress predominantly in this border zone. The location of the described changes suggests that these mechanical forces may cause fiber disorganization, small cortical opacities, and ultimately, cuneiform cataracts.

Higher-order aberrations of age-related cataract.

PURPOSE: To analyze higher-order aberrations induced by different types of lenticular opacities. SETTING: Federal University of São Paulo, São Paulo, Brazil. METHODS: One hundred thirty-eyes of 65 patients with bilateral cataract, classified according to the Lens Opacities Classification System III (LOCS III), had complete ophthalmic examinations, corneal topography (EyeSys Technologies), and wavefront analysis (LADARWave, Alcon Laboratories). Patients with cataracts that could not be measured by a Hartmann-Shack sensor or those with coexisting ocular disease were excluded. Higher-order aberrations were compared between the nuclear, cortical, and posterior subcapsular groups for statistical significance. RESULTS: One hundred five eyes of 65 patients were assessed. Twenty-eight eyes (23.33%) had predominantly nuclear opacification (NO1-NO6 and C1-2), and 13 (10.83%) had mainly cortical opacification (C1-4). Sixty-four eyes (65.83%) had a mixed pattern of LOCS III classification, which hindered the establishment of a correlation between the aberrometry and cataract type. Eighteen eyes that presented with dense posterior subcapsular cataract (P4-5) and 7 eyes with cortical C5 LOCS III classification were excluded. In eyes with nuclear opacification, the mean spherical aberration with a 6.0 mm pupil was 0.45 microm +/- 0.17 (SD) and the mean coma was 0.29 +/- 0.13 microm. In eyes with predominantly cortical cataract, the mean spherical aberration was 0.12 +/- 0.10 microm and the mean coma was 0.49 +/- 0.23 microm. The cortical cataract group had statistically significantly higher coma than the other groups (P<.001). The nuclear cataract group had statistically significantly higher spherical aberrations than the other groups (P<.001). CONCLUSIONS: Different types of early lenticular opacities induced different wavefront aberration profiles. Coma predominated in the cortical cataract group, and spherical aberration predominated in the nuclear cataract group.

Influence of type and severity of pure forms of age-related cataract on visual acuity and contrast sensitivity. Italian American Cataract Study Group.

PURPOSE: To compare the relationship between logMAR visual acuity (VA) and cataract severity and between contrast sensitivity (CS) and cataract severity in pure types of age-related lens opacities. METHODS: Analysis included patients followed in the ongoing Italian-American Study of the Natural History of Age-Related Cataract. Lens opacities were classified and graded according to the Lens Opacities Classification System II (LOCS II). Visual acuity was measured with the Early Treatment Diabetic Retinopathy Study Chart. Contrast sensitivity was measured with the Pelli-Robson chart. RESULTS: Data from 1,076 eyes were used for the analysis (366 clear lenses; 550, 124, and 36 eyes with cortical, nuclear and posterior subcapsular cataract, respectively). In age-adjusted analyses, increasing severity of all three cataract types was associated with progressively higher logMAR VA, which translates into poorer acuity, and lower CS scores. For both VA and CS, the effect of increasing severity was greatest for nuclear and least for cortical opacities. After adjusting for age and VA, CS scores were no longer associated with cataract type and severity, with the exception of advanced cortical opacities. CONCLUSIONS: Increased cataract severity, as determined by LOCS II grading, is strongly associated with both VA and CS scores. Contrast sensitivity scores obtained from testing at low spatial frequency do not seem to offer additional information over standard VA testing in early cortical and posterior subcapsular opacities nor in nuclear cataracts.

Cl- influx into rat cortical lens fiber cells is mediated by a Cl- conductance that is not ClC-2 or -3.

PURPOSE: Exposure of organ-cultured lenses to Cl(-) channel blockers under isotonic conditions induces a localized cortical zone of extracellular space dilations. The purpose of this study was to investigate whether elongated lens fiber cells from this zone contain an anion conductance that mediates Cl(-) influx and whether two chloride channel isoforms known to be expressed in the lens (ClC-2 and -3) are responsible. METHODS: Fiber cells were isolated by enzymatic dissociation in the presence of Gd(3+) and Co(2+) and their electrical properties analyzed by whole-cell patch clamping. Cells from the zone of extracellular space dilations were selected for analysis on the basis of cell length. RT-PCR and immunocytochemistry were used to determine whether ClC-2 or -3 channel isoforms are expressed in fiber cells located in the zone of extracellular space dilations. RESULTS: Cells from the zone of extracellular space dilations were typically >120 microm in length and exhibited an outwardly rectifying Cl(-) conductance that was blocked by DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) and displayed an anion selectivity sequence of I(-) > Cl(-) >> gluconate. ClC-2 and -3 were found to be expressed at the transcript and protein level in lens fiber cells, but subsequent immunocytochemical studies indicated that expressed proteins did not colocalize with cell membranes in the zone of extracellular space dilations, being predominately cytoplasmic in nature. CONCLUSIONS: Taken together, the data indicate that extracellular space dilations are due to the inhibition of a Cl(-) channel(s) that normally mediates Cl(-) influx into cortical lens fiber cells under isotonic conditions. The molecular identity of this channel remains to be determined.

The role of prostaglandins E2 and F2 alpha in ultraviolet radiation-induced cortical cataracts in vivo.

PURPOSE: Previous work has shown that exposure of lens epithelial cells or rabbit eyes in vivo to ultraviolet B (UVB) radiation enhanced prostaglandin (PG)E2 synthesis. Such enhanced PGE2 synthesis was related to the increased DNA synthesis that followed UVB exposure. The current study examined the relationship between enhanced prostaglandin synthesis and UVB-induced cataract formation. METHODS: Seventy albino (New Zealand white) rabbit eyes were exposed to UVB radiation in vivo. Fluence of radiation at the cornea was 2.8 J/cm2, 5.6 J/cm2, or 11.2 J/cm2. Eyes were examined 24 hours after UVB exposure and for as long as 10 days by slit lamp biomicroscopy. Mass spectrometry was used to measure PGE2, PGF2 alpha, and 6-keto-PGF1 alpha content of the lens and iris-ciliary body using authentic standards. To determine the effect of inhibition of prostaglandin synthesis on UVB-induced cataract formation, animals were given indomethacin intraperitoneally. Other pharmacologic agents, such as PGE2, PGF2 alpha, and misoprostol, were applied topically to the eye. The effect of UVB on K+ pump was determined by incubating isolated lenses with [86Rb+]. RESULTS: Twenty-four hours after UVB exposure, PGE2 and PGF2 alpha concentrations in aqueous humor were increased by 100- and 30-fold, respectively. Lens PGE2 and PGF2 alpha increased by 6- and 4-fold, respectively, after UVB radiation exposure. Pretreatment of animals with indomethacin prevented the rise in lens and aqueous humor PGE2 and PGF2 alpha levels. Furthermore, indomethacin was partially protective against UVB cataract formation and lowered cataract severity from stage 3 to stage 1, but it did not prevent UVB-induced lens changes completely. Topical application of PGE2 before UVB exposure completely prevented cataract formation in the UVB-exposed eye. In contrast, topical administration of PGF2 alpha increased cataract severity. UVB-induced cataract formation preceded changes in [86Rb]+ uptake in lenses subsequently incubated in K(+)-free Tyrode's. CONCLUSIONS: Enhanced synthesis of cyclooxygenase products of arachidonic acid metabolism in the lens is associated with UVB-induced cataract formation in albino rabbit eyes, and inhibition of cyclooxygenase by indomethacin decreased the severity of cataracts. PGE2, the principal arachidonic acid metabolite, appears to have a protective role because pretreatment of the eye with topical PGE2 completely prevented UVB-induced cataract formation, whereas PGF2 alpha increased the severity of the cataract. The evidence presented for a role of PGF2 alpha in the development of cataract suggests that caution be exercised in the use of PGF2 alpha derivatives in the therapy of glaucoma.

Changes in the internal structure of the human crystalline lens with age and accommodation.

Scheimpflug images were made of the unaccommodated and accommodated right eye of 102 subjects ranging in age between 16 and 65 years. In contrast with earlier Scheimpflug studies, the images were corrected for distortion due to the geometry of the Scheimpflug camera and the refraction of the cornea and the lens itself. The different nuclear and cortical layers of the human crystalline lens were determined using densitometry and it was investigated how the thickness of these layers change with age and accommodation. The results show that, with age, the increase in thickness of the cortex is approximately 7 times greater than that of the nucleus. The increase in thickness of the anterior cortex was found to be 1.5 times greater than that of the posterior cortex. It was also found that specific parts of the cortex, known as C1 and C3, showed no significant change in thickness with age, and that the thickening of the cortex is entirely due to the increase in thickness of the C2 zone. With age, the distance between the sulcus (centre of the nucleus) and the cornea does not change. With accommodation, the nucleus becomes thicker, but the thickness of the cortex remains constant.

Cortical and subcapsular cataracts: significance of physical forces.

Cortical cataracts usually begin with either sharp limited clear fluid clefts, resulting in opaque spokes, or clear lamellar separations, resulting in cuneiform opacities. They do not commence prior to 45 years of age. From this age on an increase in lens nuclei hardening can be detected. Therefore, during disaccommodation in older lenses, mechanical shear stresses must develop between the soft remaining cortices and the harder nuclei. These shear stresses are significant regarding the different cortical ruptures in predisposed lenses: in a privileged radial direction (according to zonular traction) of the sharp limited cortical spokes, or in parallel microridges at the commencement of lamellar separations, as observed when a rubber surface slides against a harder object. In pure cortical cataracts the ion pump (K+ > Na+) and investigated metabolic parameters remain largely intact. Therefore, it is not surprising that, in contrast to subcapsular cataracts, subcapsular opacities do not occur. Subcapsular cataracts are known to be caused by a variety of factors: aging, diabetes, corticosteroids, iridocyclitis, or X-ray, among many others. In contrast to cortical cataracts, subcapsular cataracts were found to be closely associated with ion pump damage (Na+ > K+) and a variety of metabolic activity alterations. In subcapsular cataracts passive fluids (from the vitreous and camera anterior) enter externally through the lens capsule. This initially forms numerous free clear, secondary grey, subcapsular fluid vacuoles. If the ion pump (metabolic barrier) is more severely damaged fluids may also enter the lens nucleus (secondary grey nuclear cataract), which rarely results in intumescent cataract. In cortical and subcapsular cataracts and lens perforations the main cause of grey opalescence appears to be the result of lens proteins (water-soluble crystalline) coming into direct contact with free fluids (water). In cortical cataracts this happens in the area of sharp limited mechanical cortical ruptures (fluid clefts), and in subcapsular cataracts during passive, external fluid entry, resulting in subcapsular fluid vacuoles and opacities, and also later grey-white nuclear opacities. The importance of water contact with water-soluble lens crystallines in behalf of light scattering and turbidness also has been investigated experimentally.

Light scattering parameters of rat lenses with calcium-induced cataracts.

Light scattering intensities of rat lenses obtained in the I,, and I+ modes were analysed using the random density and orientation fluctuation theory. Rat lenses incubated in calcium rich media had the same density fluctuation parameters as rat lenses incubated in control (low-calcium) media. However, the correlation length of the orientation fluctuations decreased during cataract formation by 100 to 200 nm while the amplitude of the fluctuations increased. The correlation length, or the size of the optically anisotropic domains, is related to the size of the cytoskeleton, especially vimentin. Vimentin has been shown to degrade when calcium activates calpain. This has been observed in SDS-gel electrophoretic experiments in rat lenses in calcium rich media. The amplitude factor of orientation fluctuations, that is, the mean squared deviation from the average refractive index, increased between two- and seven-fold during cataractogenesis. These results indicate that calcium cataract formation at the beginning (first 72 hr incubation) has little to do with aggregation or syneresis but it is largely the result of changes in the intrinsic birefringence of the lens due to vimentin degradation.

Lenticular scattered and fluorescent light: biomicroscopic determination of their relative proportions.

Lenticular fluorescence was separated from scattered light using slit-lamp photography through two different spectral filters. The results from 10 subjects indicate that the cortex and nucleus show different rates of age-related change in fluorescence. Evidence was obtained for the presence of more than one fluorophor.

Contrast sensitivity in different types of early lens opacities.

The purpose of the present study was to evaluate the relationship of various types of early lens opacities with contrast sensitivity at different spatial frequencies. The Lens Opacities Classification System II and Lensmeter 701 were used in the grading of the lens status. The contrast sensitivity was tested with the Vistech VCTS 6500 distance test with optimal correction of refractive errors. Data from 995 eyes were available for the present study. Contrast sensitivity decreased by increasing lens opacification graded with the Lens Opacities Classification System II and also by increasing Lensmeter 701 reading. When the statistical model was adjusted for age and best corrected visual acuity, nuclear opacities and nuclear colour were not associated with decreased contrast sensitivity, however, there was a weak, but statistically significant correlation between contrast sensitivity reduction and cortical opacities at high spatial frequencies, and between contrast sensitivity and posterior subcapsular opacities at low and medium spatial frequencies.

Visual performance and objectively measured grades of cataract. A correlation of methods designed for use in longitudinal trials.

Objective quantification of cataract and subjective assessment of visual performance are essential features of anticataract or cataractogenic drug trials. The constrains of a longitudinal trial require a compromise in contrast sensitivity measurement between sensitivity and speed. Such a system has been developed for use in longitudinal anticataract trials. An objective cataract assessment system has also been developed for these trials. Visual performance parameters and objectively measured grades of cataract using these systems were correlated in a group of patients with early lens opacities. Overall the correlation was poor in all three morphological types of cataract. Possible reasons for this and implications for future anticataract trials are discussed.

Incidence and progression of cortical and posterior subcapsular opacities: the Longitudinal Study of Cataract. The LSC Group.

OBJECTIVE: The purpose of the study is to estimate incidence and progression rates of cortical and posterior subcapsular (PSC) opacities in the Longitudinal Study of Cataract (LSC). DESIGN: An epidemiologic study of the natural history of lens opacities in a clinic-based population. PARTICIPANTS: The LSC was based on 764 participants in an earlier case-control study of lens opacities. MAIN OUTCOME MEASURES: Baseline data, collected until 1988, included color slit and retroillumination photographs. The same data were collected at follow-up visits from 1989 to 1993. The Lens Opacities Classification System III (LOCS III) was used to assess lens changes between baseline and follow-up photographs. The product-limit method was used to estimate the incidence and progression rates. RESULTS: After 5 years of follow-up, the incidence rates for developing cortical and PSC opacities were 7.7% and 4.3%, respectively. The progression rate of pre-existing cortical opacities was 16.2% after 5 years, and was twice as high as the incidence rate. The progression of pre-existing PSC opacities was much higher, and reached 55.1% after 5 years of follow-up. The incidence of newly developed cortical or PSC opacities increased with age. The incidence of PSC opacities also increased when coexisting opacities were present at baseline. CONCLUSIONS: After 5 years, 1 in every 13 patients developed new cortical opacities, and 1 in 24 developed new PSC opacities. The 5-year progression rates for cortical and PSC opacities were much higher than the incidence rates. These results can be used to estimate the rate of cortical and PSC changes in similar populations.

Measured changes in cataract over six months: sensitivity of the Nidek EAS-1000.

Lens opacities in 98 eyes from 63 consecutive outpatients with cataract were recorded by both retroillumination and Scheimpflug slit methods by one operator. This was repeated at 26 +/- 1 weeks. Image analysis used the EAS-1000 software. Cortical and posterior subcapsular (PSC) cataracts were measured in retroillumination images as density more than 14 cct units below background density. Linear densitometry of white scattered light along the optical axis was measured for slit images by both peak density and mean density ('area under the curve'). Retroillumination images showed no discernible change over 6 months (the regression coefficient being as for the intersession reliability). Half of the Scheimpflug slit images could not be analysed because overlying cortical changes masked the more posterior parts of the lens. The other 49 eyes showed a significant increase in nuclear white scatter after 6 months, with greater degrees of change occurring in those eyes with the greatest amount of nuclear cataract initially. This is reflected by the decreased intraclass correlation coefficient (R = 0.42). The area of lens showing greatest change was the anterior fetal nucleus. The Nidek EAS-1000 is able to detect changes over a 6-month period in nuclear density but not in cortical or PSC cataract. The rate of progression of nuclear white scatter increases as the lens opacity becomes more dense. The ability to detect change in cataract over 6 months has implications for epidemiological studies and for trials of anti-cataract drugs.

Incidence and progression of lens opacities in the Barbados Eye Studies.

OBJECTIVE: To provide 4-year cumulative incidence and progression rates of age-related lens opacities in a population > or =40 years of age, which is mainly of African origin. DESIGN: Cohort study that reexamined surviving members of the population-based Barbados Eye Study 4 years after baseline. PARTICIPANTS: Three thousand four hundred twenty-seven members of the Barbados Eye Study cohort (85% of those eligible). MAIN OUTCOME MEASURES: The Lens Opacities Classification System II (LOCS II) was used at the slit lamp. Cumulative incidence was defined as the development of any nuclear, cortical or posterior subcapsular (PSC) opacities (LOCS II scores > or =2) among persons without that opacity type at baseline. Cumulative progression was defined by at least two-step increases in scores among persons with preexisting lens opacities. RESULTS: The incidence of cortical opacities was about five times greater in black than white participants (age-gender adjusted relative risk = 4.7; 95% confidence interval: 1.9-11.4). In the black population, the 4-year incidence rates were 22.2% (20.4%-24.0%) for any cortical, 9.2% (8.2%-10.4%) for any nuclear, and 3.3% (2.7%-4.0%) for any PSC opacities; rates increased greatly with age. Four-year progression rates were 12.5% for cortical, 3.6% for nuclear, and 23.0% for PSC opacities, without consistent pattern by age. Women had a greater risk of cortical and nuclear opacities (P<0.05) than men and greater progression of nuclear opacities. The presence of PSC opacities at baseline seemed to at least double the incidence and progression rates of other opacities. In persons initially opacity free, single cortical opacities were the predominant type to develop at followup. Visual acuity loss frequently accompanied incident opacities. CONCLUSIONS: This longitudinal study provides new population-based data on the natural history of lens opacities. Incidence and progression of opacities, especially of cortical opacities, were high. After 4 years of followup, 1 in 4 to 5 participants developed cortical opacities, 1 in 11 developed nuclear opacities, and 1 in 30 developed PSC opacities. The information obtained attests to the public health impact of age-related cataract, as well as its extent, in this and similar black populations.