Association of nuclear cataract prevalence with UV radiation and heat load in lens of older people -five city study.

Epidemiological studies have reported that the frequency of nuclear cataracts (NUCs) is high among the elderly and in tropical countries. Ultraviolet (UV) irradiation and lens temperature are considered as key physical contributors, although their precise quantification is difficult. The aim of this study is to investigate the association of NUC prevalence with UV irradiation and heat load. First, we assessed the lens temperature using thermodynamic modeling considering the thermophysiological response. We then conducted a multivariate linear regression analysis for the epidemiological analysis of NUC prevalence across five cities. A strong correlation was observed between NUC prevalence and the combined effects of UV irradiation and cumulative equivalent minutes at 43 °C (CEM43°C) derived from the computed lens temperature (adjusted R2 = 0.933, p < 0.0001). Heat load significantly contributed to the prevalence at 52%, surpassing the contributions of UV irradiation (31%) and the decline in DNA repair capacity in the lens (17%). These results suggested that both UV radiation and heat load are associated with NUC, with heat load contributing more. Our findings provided important implications for future interventions, particularly in the context of global warming.

Aquaporins contribute to vacuoles formation in Nile grass type II diabetic rats.

Regulation of ion and water microcirculation within the lens is tightly controlled through aquaporin channels and connexin junctions. However, cataracts can occur when the lens becomes cloudy. Various factors can induce cataracts, including diabetes which is a well-known cause. The most common phenotype of diabetic cataracts is a cortical and/or posterior subcapsular opacity. In addition to the three main types and two subtypes of cataracts, a vacuole formation is frequently observed; however, their origin remains unclear. In this study, we focused on the aquaporins and connexins involved in diabetes-induced cataracts and vacuoles in Nile grass type II diabetes. The results showed that the expression of aquaporin 0 and aquaporin 5 increased, and that of connexin 43 decreased in diabetic rat lenses. Additionally, aquaporin 0 and 5 were strongly localized in peripheral of vacuoles, suggesting that aquaporins are involved in vacuoles formation. Transillumination photography revealed large vacuoles at the tip of the Y-suture in the anterior capsule of the diabetic lens, and several small vacuoles were observed in the posterior capsule. Within the vacuoles, cytoplasmic degradation and aggregation of fibrous material were observed. Our findings suggest that aquaporins are potential candidate proteins for preventing vacuole formation.

Function of mitochondrial cytochrome c oxidase is enhanced in human lens epithelial cells at high temperatures.

Enhancement of density via human lens epithelium (HLE) cell proliferation is the underlying cause of nuclear cataracts. Moreover, our previous epidemiological study demonstrated that the risk of nuclear cataract development is significantly higher under elevated environmental temperatures compared with under lower temperatures. The present study investigated the relationship between temperature and cell proliferation in terms of mitochondrial function, which is a nuclear cataract­inducing risk factor, using two different HLE cell lines, SRA01/04 and immortalized human lens epithelial cells NY2 (iHLEC­NY2). Cell proliferation was significantly enhanced under the high­temperature condition (37.5˚C) in both cell lines. The cell growth levels of SRA01/04 and iHLEC­NY2 cells cultured at 37.5˚C were 1.20­ and 1.16­fold those in the low­temperature cultures (35.0˚C), respectively. Moreover, the levels of cytochrome c oxidase mRNA (mitochondrial genome, cytochrome c oxidase­1­3) and its activity in SRA01/04 and iHLEC­NY2 cells cultured at 37.5˚C were higher compared with those in cells cultured at 35.0˚C. In addition, adenosine­5'­triphosphate (ATP) levels in SRA01/04 and iHLEC­NY2 cells were also significantly higher at 37.5˚C compared with those at 35.0˚C. By contrast, no significant differences in Na+/K+­ATPase or Ca2+­ATPase activities were observed between HLE cells cultured at 35.0 and 37.5˚C. These results suggested that expression of the mitochondrial genome was enhanced in high­temperature culture, resulting in a sufficient ATP content and cell proliferation for lens opacity. Therefore, elevated environmental temperatures may increase the risk of nuclear cataracts caused by HLE cell proliferation via mitochondrial activation.

Vision With Retrodots and Factors for Declining Visual Function.

Purpose: We investigated decline in the visual function of eyes with retrodots (RDs)-a subtype of cataract. Method: This study included 57 eyes with RD opacity only (mean age 72.3 ± 5.2 years) and 34 eyes with transparent lenses (mean age 71.4 ± 3.7 years). A physician diagnosed lens opacity. Using the Kanazawa Medical University Classification and Grading System, the eyes were classified into the RD-1 (37 eyes, RDs <25% of the 3-mm pupil area) and RD-2 (20 eyes, RDs ≥25% of the 3-mm pupil area) groups. Corrected distance visual acuity, contrast visual acuity, ocular refractive power, lens power, straylight, and backward light-scattering intensity and their relationship with visual function decline and optical characteristics of the eyeball were evaluated. Results: Corrected distance visual acuity was significantly lower in the RD eyes than in controls. Contrast visual acuity decreased significantly in the RD-2 eyes in all environments and in the RD-1 eyes in the evening (EVE) and EVE + glare. Straylight was significantly higher in the RD-2 eyes than in the controls and RD-1 eyes but not different between the RD-1 eyes and controls. The RD-2 eyes were significantly more myopic than the controls and RD-1 eyes. Conclusion: When the opacity of RD eyes is ≥25%, the visual acuity and contrast visual acuity decrease and straylight increases. Furthermore, myopia occurs as the refractive power of the lens increases. Moreover, visual function decline may be due to an increase in the straylight value, which is necessary for determining surgical indications.

Analyzing Effect of Waterclefts on Visual Functions Via Optical Simulations.

Purpose: To investigate the impact of the size and location of waterclefts (WC), which are one of several cataract subtypes, on visual function by optical simulation analysis. Methods: An optical simulation software (CODE V) was used to develop a schematic eye model and several sizes of WC central and peripheral types that were located below the anterior and posterior subcapsules of the crystalline lens, and analyses of refraction, higher-order aberrations (HOA), and the modulation transfer function (MTF) were performed. Results: An increase in the WC size increased the refraction and HOA and decreased the MTF. The impact of the WC below the posterior subcapsule on the visual function was more enhanced than that below the anterior subcapsule. Large WC demonstrated a remarkable hyperopic shift in refractive power as well as an increase in HOA. The MTF decreased slightly with increasing WC size at a spatial frequency of 20 cycles/mm, and it decreased remarkably at 60 cycles/mm. Conclusions: The impact on the visual function increased with increasing WC size. It was revealed that eyes with WC below the posterior subcapsule are more hyperopic than those with WC below the anterior subcapsule, and the former have a higher HOA and lower MTF than the latter.

Nationwide multicentre comparison of preoperative biometry and predictability of cataract surgery in Japan.

AIM: To compare the preoperative biometric data and the refractive accuracy of cataract surgery among major surgical sites in a nationwide multicentre study. METHODS: We prospectively obtained the preoperative biometric data of 2143 eyes of 2143 consecutive patients undergoing standard cataract surgery at major 12 facilities and compared the preoperative biometry as well as the postoperative refractive accuracy among them. RESULTS: We found significant differences in most preoperative variables, such as axial length (one-way analysis of variance, p=0.003), anterior chamber depth (p<0.001), lens thickness (p<0.001) and central corneal thickness (p<0.001), except for mean keratometry (p=0.587) and corneal astigmatism (p=0.304), among the 12 surgical sites. The prediction error using the Sanders-Retzlaff-Kraff/Theoretical (SRK/T formula was significantly more hyperopic than that using the Barrett Universal II formula (paired t-test, p<0.001). The absolute error using the SRK/T formula was significantly larger than that using the Barrett Universal II formula (p=0.016). The prediction error using the SRK/T formula was significantly more hyperopic than that using the Barrett Universal II formula at 10 of 12 institutions, but significantly more myopic at one institution. The absolute error using the SRK/T formula was significantly larger than that using the Barrett Universal II formula at 4 of 12 institutions but significantly smaller at two institutions. CONCLUSIONS: Regional divergences of the preoperative biometry were not necessarily negligible, and the optimised intraocular lens power calculation formula was individually different among the 12 facilities. Our findings highlight the importance of individual optimisation of these formulas at each facility, especially in consideration of these biometric variations.Trial registration numberClinical Trial Registry; 000039976.

UV Index Does Not Predict Ocular Ultraviolet Exposure.

Purpose: The ultraviolet index (UVI), available online, is an international linear scale of levels from 0 to 13+ that warns about the risk of sunburn; however, it does not address the risk to eyes. Our purpose was to develop a useful instrument to warn the public against ocular ultraviolet (OUV) exposure and to serve as a tool for researching UV-induced ocular diseases. Methods: A rotating model head that included ultraviolet B (UVB) sensors documented UV irradiance at the crown and at the eyes spanning eight azimuths from sunrise to sunset under different climatic conditions in each season. The dose intensities obtained were compared with their respective UVI levels. Doses to the eyes were mathematically transformed to develop an OUV index with linear levels from 0 to 13+, similar to the UVI. Then, readings from both instruments were compared. Results: UV exposure at the crown increases with solar culmination, whereas that to the eye is greater under low rather than maximum solar altitude. The OUV index levels were higher than recorded UVI levels in the summer under low solar altitude in the early morning and mid- to late afternoon and were markedly higher all day in winter when solar altitude remains low. Conclusions: The UVI does not provide sufficient warning about the risks of ocular UV damage. The proposed OUV index is a useful instrument to warn the public against OUV exposure and to serve as a tool for researching UV-induced ocular diseases. Translational Relevance: The OUV index is useful to prevent ocular UV-related diseases.

Association among pterygium, cataracts, and cumulative ocular ultraviolet exposure: A cross-sectional study in Han people in China and Taiwan.

PURPOSE: Pterygium is an ocular surface disorder mainly caused by ultraviolet (UV) light exposure. This study explored the relationships between six cataract types with pterygium and UV exposure. METHODS: We have previously studied cataracts in residents of three regions in China and Taiwan with different UV intensities. From that study, we identified 1,547 subjects with information on the presence or absence of pterygium. Pterygium severity was graded by corneal progress rate. Cataracts were graded by classification systems as three main types (cortical, nuclear, posterior subcapsular) and three subtypes (retrodots, waterclefts, fiber folds) with high prevalence in middle-aged and elderly people. We calculated the cumulative ocular UV exposure (COUV) based on subject data and National Aeronautics and Space Administration data on UV intensities and used logistic regression to calculate odds ratios for the associations of COUV, cataract, and pterygium. RESULTS: We found an overall pterygium prevalence of 23.3%, with significant variation among the three regions. Four cataract types (cortical, nuclear, posterior subcapsular, and retrodots) were significantly associated with the presence of pterygium. CONCLUSIONS: There was a significant association between COUV and pterygium, indicating that COUV is associated with the risk of pterygium development and that pterygium is useful as an index of UV exposure. Furthermore, the type of cataract in eyes with pterygium may indicate the level of UV exposure.

Novel Technique for Retinal Nerve Cell Regeneration with Electrophysiological Functions Using Human Iris-Derived iPS Cells.

Regenerative medicine in ophthalmology that uses induced pluripotent stem cells (iPS) cells has been described, but those studies used iPS cells derived from fibroblasts. Here, we generated iPS cells derived from iris cells that develop from the same inner layer of the optic cup as the retina, to regenerate retinal nerves. We first identified cells positive for p75NTR, a marker of retinal tissue stem and progenitor cells, in human iris tissue. We then reprogrammed the cultured p75NTR-positive iris tissue stem/progenitor (H-iris stem/progenitor) cells to create iris-derived iPS (H-iris iPS) cells for the first time. These cells were positive for iPS cell markers and showed pluripotency to differentiate into three germ layers. When H-iris iPS cells were pre-differentiated into neural stem/progenitor cells, not all cells became positive for neural stem/progenitor and nerve cell markers. When these cells were pre-differentiated into neural stem/progenitor cells, sorted with p75NTR, and used as a medium for differentiating into retinal nerve cells, the cells differentiated into Recoverin-positive cells with electrophysiological functions. In a different medium, H-iris iPS cells differentiated into retinal ganglion cell marker-positive cells with electrophysiological functions. This is the first demonstration of H-iris iPS cells differentiating into retinal neurons that function physiologically as neurons.

Effect of a Lens Protein in Low-Temperature Culture of Novel Immortalized Human Lens Epithelial Cells (iHLEC-NY2).

The prevalence of nuclear cataracts was observed to be significantly higher among residents of tropical and subtropical regions compared to those of temperate and subarctic regions. We hypothesized that elevated environmental temperatures may pose a risk of nuclear cataract development. The results of our in silico simulation revealed that in temperate and tropical regions, the human lens temperature ranges from 35.0 °C to 37.5 °C depending on the environmental temperature. The medium temperature changes during the replacement regularly in the cell culture experiment were carefully monitored using a sensor connected to a thermometer and showed a decrease of 1.9 °C, 3.0 °C, 1.7 °C, and 0.1 °C, after 5 min when setting the temperature of the heat plate device at 35.0 °C, 37.5 °C, 40.0 °C, and 42.5 °C, respectively. In the newly created immortalized human lens epithelial cell line clone NY2 (iHLEC-NY2), the amounts of RNA synthesis of αA crystallin, protein expression, and amyloid ß (Aß)1-40 secreted into the medium were increased at the culture temperature of 37.5 °C compared to 35.0 °C. In short-term culture experiments, the secretion of Aß1-40 observed in cataracts was increased at 37.5 °C compared to 35.0 °C, suggesting that the long-term exposure to a high-temperature environment may increase the risk of cataracts.

Model-based approach for analyzing prevalence of nuclear cataracts in elderly residents.

Recent epidemiological studies have hypothesized that the prevalence of cortical cataracts is closely related to ultraviolet radiation. However, the prevalence of nuclear cataracts is higher in elderly people in tropical areas than in temperate areas. The dominant factors inducing nuclear cataracts have been widely debated. In this study, the temperature increase in the lens due to exposure to ambient conditions was computationally quantified in subjects of 50-60 years of age in tropical and temperate areas, accounting for differences in thermoregulation. A thermoregulatory response model was extended to consider elderly people in tropical areas. The time course of lens temperature for different weather conditions in five cities in Asia was computed. The temperature was higher around the mid and posterior part of the lens, which coincides with the position of the nuclear cataract. The duration of higher temperatures in the lens varied, although the daily maximum temperatures were comparable. A strong correlation (adjusted R2 > 0.85) was observed between the prevalence of nuclear cataract and the computed cumulative thermal dose in the lens. We propose the use of a cumulative thermal dose to assess the prevalence of nuclear cataracts. Cumulative wet-bulb globe temperature, a new metric computed from weather data, would be useful for practical assessment in different cities.

Distribution of corneal spherical aberration in a Tanzanian population.

PURPOSE: To investigate the distribution of corneal spherical aberration (SA) in Tanzanian people of African descent, and to examine the correlation between corneal SA and ocular parameters. DESIGN: Cross-sectional population-based study. METHODS: Residents aged 40 years and older in three villages in the Mkuranga district in Tanzania were enlisted as study participants. Corneal higher-order aberrations (HOAs) for the right eye were measured with a wavefront analyzer (KR-1W, Topcon) and calculated for the central 6.0-mm zone. Corneal curvature radius (CR), corneal astigmatism, and axial length (AL) were also measured and their correlation with corneal SA was assessed. RESULTS: The right eyes of 657 participants (336 male, 321 female) were analyzed. The mean age of the subjects was 57.2 ± 10.3 years (mean ± SD). The mean corneal SA (Zernike spherical aberration coefficient C40) was 0.188 ± 0.095 µm (-0.242 to 0.613). The SAs in about three-quarters of all subjects were between 0.10 and 0.30 µm. The root mean squares of total corneal HOAs and the third- and fourth-order aberrations were 0.629 ± 0.250 µm, 0.539 ± 0.236 µm, and 0.269 ± 0.110 µm, respectively. Corneal SA showed weak significant correlations with CR (Spearman's rank correlation coefficient, r = -0.177, p < 0.001), corneal astigmatism (r = -0.142, p < 0.001), AL (r = -0.168, p < 0.001), and age (r = -0.085, p < 0.05). CONCLUSIONS: This finding may be beneficial for selecting aspheric intraocular lens in this population.

Visual Function and Functional Decline in Patients With Waterclefts.

Purpose: To investigate visual function in eyes with three subtypes of waterclefts (WCs). Methods: Of patients in Kanazawa Medical University Hospital (2013-2017) and participants of Monzen Eye Study (2013-2016), 77 transparent lenses, mean age 66.7 years, and 70 eyes with only WC opacity of 70 patients, mean age 68.1 years, divided into peripheral-, central-, and total-type WC groups, were analyzed. Opacity was classified by one ophthalmologist using slit-lamp microscopy. Corrected-distance visual acuity (CDVA), contrast visual acuity (CVA), spherical equivalent (SE), astigmatism values, corneal refractive power (CP), axial length (AL), straylight, backward light scattering (BLS), and higher order aberrations (HOA) were measured and lenticular refractive power (LP) was calculated based on the values of AL, CP, and SE. Results: Central-type WC showed significant decrease in CDVA and CVA and increase in straylight compared with control. Total-type WC showed significant decreases in CDVA, CVA, and LP, and increase in straylight, compared with control and peripheral-type WC. Total- and central-type WCs had significantly higher ocular total HOA and total-type WC had significantly higher internal total HOA than control. HOA correlated positively with CDVA (P < 0.001) and straylight (P = 0.020), and CDVA negatively with straylight in eyes with WCs (P = 0.008). Conclusions: Total-type WC was associated with decreased LP, causing hyperopia, decreased CDVA and higher straylight; thus, such lenticular change should be considered for surgery indication. Significant correlations between HOA and both CDVA and straylight suggested increased HOA may decrease visual function in eyes with WCs.

Correction: Association between ultraviolet radiation exposure dose and cataract in Han people living in China and Taiwan: A cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0215338.].

Association between ultraviolet radiation exposure dose and cataract in Han people living in China and Taiwan: A cross-sectional study.

PURPOSE: We investigated associations between ocular ultraviolet (UV) radiation exposure dose and cataract opacities among Han people living in China and Taiwan, to assess the effects of UV exposure intensity. METHODS: This cross-sectional study included Han people aged ≥40 years (1,801 individuals, 450 in Sanya, 636 in Taiyuan, and 715 in Taichung) as subjects who completed a questionnaire including items about diabetes, smoking, steroid use, work history, and time spent outdoors, and underwent an ophthalmic examination. Right eye axial length was measured using A-mode ultrasonography or IOLMaster. Slit-lamp imaging under maximum mydriasis was used to classify cataracts into three major types [cortical (COR), nuclear (NUC), and posterior subcapsular cataracts (PSC)] and two subtypes [retrodots (RD) and waterclefts (WC)] by one ophthalmologist. COR was divided into opacity presence (CEN+) or absence (CEN-) in the central 3-mm diameter area of the pupil. COR was also subdivided into three groups according to opacity shape: axle-shaped opacity concomitant with WC, wedge-shaped opacity around the pupil to the eye center, and ring-shaped opacity in the lens equator along the pupillary margin. The cumulative ocular UV exposure (COUV) was calculated. A logistic regression analysis was used for multivariate analysis. RESULTS: Cataract odds ratios in high COUV eyes were 5.35 for NUC, 1.87 for PSC, and 1.35 for RD. In eyes with WC, risk of COR ring-shaped opacity significantly increased but that of wedge-shaped opacity (CEN+) significantly decreased. In eyes without WC, risk of COR axle-shaped opacity (CEN-) and ring-shaped opacity significantly increased but that of wedge-shaped opacity (CEN+) significantly decreased. CONCLUSIONS: Increased COUV level among Han people may be a risk factor for the development of nuclear cataracts, PSC, retrodots and ring-shaped cortical cataract. Risk of ocular UV exposure for cortical cataract may differ by opacity shape.

Optical simulation for subsurface nanoglistening.

PURPOSE: To determine whether subsurface nanoglistening in hydrophobic acrylic intraocular lenses (IOL) diminishes visual performance. SETTING: Department of Ophthalmology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. DESIGN: Experimental study. METHODS: The effect of subsurface nanoglistenings was simulated using optical design software Lighttools and Code V with the Liou-Brenann model eye and an acrylic IOL. Peak irradiance of the retina, forward light scattering, and modulation transfer function (MTF) were evaluated. During optical simulation, particle diameters were set at 100 nm, 150 nm, and 200 nm and volume ratios at 0%, 0.05%, 0.1%, 0.2%, 0.5%, and 1.0%. RESULTS: Peak irradiance decreased as subsurface nanoglistening volume ratio and particle size increased. At a volume ratio of 0.05%, the peak irradiance of subsurface nanoglistening particles 100 nm, 150 nm, and 200 nm in diameter decreased 0.7%, 1.8%, and 2.9%, respectively, compared with those at volume ratio 0% (no subsurface nanoglistenings). At a volume ratio of 0.1%, the peak irradiance of subsurface nanoglistening particles 100 nm, 150 nm, and 200 nm decreased 1.5%, 3.6%, and 5.7%, respectively. Forward light scattering increased with increased size of subsurface nanoglistening particle and volume ratio. The MTF was not altered by changes in subsurface nanoglistening particle size or volume ratio. CONCLUSIONS: Subsurface nanoglistenings increased forward scattering slightly and reduced irradiance but significantly diminished retinal image. The effect of subsurface nanoglistenings on visual function in the absence of severe retinal disease was minimal. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Change in retinal image contrast with age in eyes with transparent lenses.

PURPOSE: To compare and evaluate changes in the retinal image with age in Japanese adults with transparent crystalline lenses. SETTING: Shibuya-ku, Tokyo, Japan. DESIGN: Cross-sectional study. METHODS: The study comprised right eyes with corrected distance visual acuity better than 0.0 logMAR. A point-spread function analyzer (PSF-1000) was used to measure retinal image contrast with 3.0 mm pupils under maximum mydriasis. A wavefront analyzer (KR9000PW) was used to measure higher-order aberrations (HOAs) with 4.0 mm pupils. The lens transparency property was estimated by the backward light-scattering intensity of each layer of the lens and the optical distance (mm) photographed by an anterior segment analysis system (EAS-1000). The Pearson product-moment correlation (R(2)) was used for statistical analysis; the significance level was 5%. RESULTS: The study comprised 269 patients (mean age 39.7 years ± 7.7 [SD]). The retinal image contrast degenerated significantly with age; the largest difference was seen with the 0.423 logMAR optotype, for which the decrease was 5.4% every decade. Backward light-scattering intensity (R(2) = 0.030, P<.01) and HOAs (R(2) = 0.032, P<.01) correlated negatively with retinal image contrast. CONCLUSION: Retinal image contrast in eyes with transparent lenses degenerated with age. The decrease was most prominent at the middle frequency domain and was due to the increase in HOAs and light-scattering intensity.

UV-B exposure to the eye depending on solar altitude.

PURPOSE: To assess the validity of the solar ultraviolet index (UVI) as a determiner of eye risk under different conditions of facial profiles and orientation, and reflected light. METHODS: Ocular UV radiation (UVR) exposure was measured as a function of the time of the day (solar altitude) using a two-dummy-type mannequin dosimetry system with embedded UVR (260-310 nm) sensors, in September and November in Kanazawa, Japan, on a motorized sun-tracking mount with one dummy face directed toward the sun and the other away from the sun. RESULTS: A bimodal distribution of UV-B exposure was found in September for the face directed toward the sun, which differed dramatically from the pattern of ambient UVR exposure and measurements taken on the top of the head and those for the eye taken later in the year. Although the overall level was lower, a higher solar altitude is associated with higher UVR exposure in the condition facing away from the sun. CONCLUSIONS: The UVI is based on ambient solar radiation on an unobstructed horizontal plane similar to our measures taken on the top of the head, which differed so much from our measures of ocular exposure that UVI as a determiner of eye risk is deemed invalid. The use of the UVI as an indicator for the need for eye protection can be seriously misleading. Doctors should caution patients with regard to this problem, and eye protection may be warranted throughout the year.