EPHA2 Polymorphisms and Age-Related Cataract in India

Objective: We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India. Methods: We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear >= 4, cortical >= 3, posterior sub-capsular (PSC) >= 2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location. Results: 7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p > 0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract. Conclusions: Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians

An Objective Scatter Index Based on Double-Pass Retinal Images of a Point Source to Classify Cataracts

PURPOSE: To propose a new objective scatter index (OSI) based in the analysis of double-pass images of a point source to rank and classify cataract patients. This classification scheme is compared with a current subjective system. METHODS: We selected a population including a group of normal young eyes as control and patients diagnosed with cataract (grades NO2, NO3 and NO4) according to the Lens Opacities Classification System (LOCS III). For each eye, we recorded double-pass retinal images of a point source. In each patient, we determined an objective scatter index (OSI) as the ratio of the intensity at an eccentric location in the image and the central part. This index provides information on the relevant forward scatter affecting vision. Since the double-pass retinal images are affected by both ocular aberrations and intraocular scattering, an analysis was performed to show the ranges of contributions of aberrations to the OSI. RESULTS: We used the OSI values to classify each eye according to the degree of scatter. The young normal eyes of the control group had OSI values below 1, while the OSI for subjects in LOCS grade II were around 1 to 2. The use of the objective index showed some of the weakness of subjective classification schemes. In particular, several subjects initially classified independently as grade NO2 or NO3 had similar OSI values, and in some cases even higher than subjects classified as grade NO4. A new classification scheme based in OSI is proposed. CONCLUSIONS: We introduced an objective index based in the analysis of double-pass retinal images to classify cataract patients. The method is robust and fully based in objective measurements; i.e., not depending on subjective decisions. This procedure could be used in combination with standard current methods to improve cataract patient surgery scheduling

Prevalence of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma in Upper Egypt

<p>Abstract</p> <p>Background</p> <p>Pseudoexfoliation (PXF) is a recognized risk factor for developing cataract, glaucoma and lens dislocation. PXF is also associated with increased risk of complications during cataract surgery due to poor mydriasis and zonular weakness. The aim of this study is to report the prevalence of pseudoexfoliation among Upper Egyptians attending the ophthalmology clinic of Assiut University Hospital.</p> <p>Methodology</p> <p>A retrospective, chart review study conducted in the period from February 2002 to August 2009. A total of 7738 patients aged 40 years or older attending the general ophthalmic clinics were included in this study. A detailed evaluation including ophthalmic and general history, slit lamp biomicroscopy, intraocular pressure measurement, gonioscopy and dilated eye examination were performed. Patients with pseudoexfoliative material on the anterior lens surface and ⁄ or the pupillary margin in either or both eyes were labeled as having PXF.</p> <p>Results</p> <p>Out of the 7738 patients included, three hundred twenty (4.14%) subjects had PXF. Mean age of PXF group was 68.15 years (SD 8.16, range 40-92 years). PXF was bilateral in 82.2% of cases. It was significantly associated with cataract, glaucoma and hearing loss. Of the PXF patients, 65% had cataract, 30.3% had glaucoma and 8.1% had hearing loss.</p> <p>Conclusion</p> <p>Pseudoexfoliation appears to be a common disorder in older individuals in Upper Egypt.</p

Optimising the glaucoma signal/noise ratio by mapping changes in spatial summation with area-modulated perimetric stimuli

Identification of glaucomatous damage and progression by perimetry are limited by measurement and response variability. This study tested the hypothesis that the glaucoma damage signal/noise ratio is greater with stimuli varying in area, either solely, or simultaneously with contrast, than with conventional stimuli varying in contrast only (Goldmann III, GIII). Thirty glaucoma patients and 20 age-similar healthy controls were tested with the Method of Constant Stimuli (MOCS). One stimulus modulated in area (A), one modulated in contrast within Ricco's area (C R ), one modulated in both area and contrast simultaneously (AC), and the reference stimulus was a GIII, modulating in contrast. Stimuli were presented on a common platform with a common scale (energy). A three-stage protocol minimised artefactual MOCS slope bias that can occur due to differences in psychometric function sampling between conditions. Threshold difference from age-matched normal (total deviation), response variability, and signal/noise ratio were compared between stimuli. Total deviation was greater with, and response variability less dependent on defect depth with A, AC, and C R stimuli, compared with GIII. Both A and AC stimuli showed a significantly greater signal/noise ratio than the GIII, indicating that area-modulated stimuli offer benefits over the GIII for identifying early glaucoma and measuring progression

Impact of measurement error on testing genetic association with quantitative traits

10.1371/journal.pone.0087044PLoS ONE91-POLN

Detection of early age-related macular degeneration using novel functional parameters of the focal cone electroretinogram

The focal cone electroretinogram is a sensitive marker for macular disease, but have we unlocked its full potential? Typically assessment of waveform parameters is subjective and focuses on a small number of locations (e.g. the a-wave). This study evaluated the discriminatory and diagnostic potential of 4 conventional and 15 novel, objectively determined, parameters in patients with early Age-related Macular Degeneration. Focal cone electroretinograms were recorded in 54 participants with early Age-related Macular Degeneration (72.9±8.2 years) and 54 healthy controls (69±7.7 years). Conventional a and b wave amplitudes and implicit times were measured and compared to novel parameters derived from both the 1st and 2nd derivatives and the frequency-domain power spectrum of the electroretinogram.Statistically significant differences between groups were shown for all conventional parameters, the majority of 1st and 2nd derivative parameters and the power spectrum at 25 and 30 Hz. Receiver operating characteristics showed that both conventional and 1st and 2nd derivative implicit times had provided the best diagnostic potential. A regression model showed a small improvement over any individual parameter investigated. The non-conventional parameters enhanced the objective evaluation of the focal electroretinogram, especially when the amplitude was low. Furthermore, the novel parameters described here allow the implicit time of the electroretinogram to be probed at points other than the peaks of the a and b waves. Consequently these novel analysis techniques could prove valuable in future electrophysiological investigation, detection and monitoring of Age-related Macular Degeneration

Short-term stability in refractive status despite large fluctuations in glucose levels in diabetes mellitus type 1 and 2

Purpose: This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes. Methods: Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration. Results: Blood glucose concentration at different times was found to vary significantly within (p0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects. Conclusion: This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients

Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells

Aging is enhanced by hypoxia and oxidative stress. As the lens is located in the hypoglycemic environment under hypoxia, aging lens with diabetes might aggravate these stresses. This study was designed to examine whether low glucose under hypoxic conditions induces the unfolded protein response (UPR), and also if the UPR then generates the reactive oxygen species (ROS) in lens epithelial cells (LECs). The UPR was activated within 1 h by culturing the human LECs (HLECs) and rat LECs in <1.5 mM glucose under hypoxic conditions. These conditions also induced the Nrf2-dependent antioxidant-protective UPR, production of ROS, and apoptosis. The rat LECs located in the anterior center region were the least susceptible to the UPR, whereas the proliferating LECs in the germinative zone were the most susceptible. Because the cortical lens fiber cells are differentiated from the LECs after the onset of diabetes, we suggest that these newly formed cortical fibers have lower levels of Nrf2, and are then oxidized resulting in cortical cataracts. Thus, low glucose and oxygen conditions induce the UPR, generation of ROS, and expressed the Nrf2 and Nrf2-dependent antioxidant enzymes at normal levels. But these cells eventually lose reduced glutathione (GSH) and induce apoptosis. The results indicate a new link between hypoglycemia under hypoxia and impairment of HLEC functions

Optical effects of exposing intact human lenses to ultraviolet radiation and visible light

<p>Abstract</p> <p>Background</p> <p>The human lens is continuously exposed to high levels of light. Ultraviolet radiation is believed to play a causative role in the development of cataract. In vivo, however, the lens is mainly exposed to visible light and the ageing lens absorbs a great part of the short wavelength region of incoming visible light. The aim of the present study was to examine the optical effects on human lenses of short wavelength visible light and ultraviolet radiation.</p> <p>Methods</p> <p>Naturally aged human donor lenses were irradiated with UVA (355 nm), violet (400 and 405 nm) and green (532 nm) lasers. The effect of irradiation was evaluated qualitatively by photography and quantitatively by measuring the direct transmission before and after irradiation. Furthermore, the effect of pulsed and continuous laser systems was compared as was the effect of short, intermediate and prolonged exposures.</p> <p>Results</p> <p>Irradiation with high intensity lasers caused scattering lesions in the human lenses. These effects were more likely to be seen when using pulsed lasers because of the high pulse intensity. Prolonged irradiation with UVA led to photodarkening whereas no detrimental effects were observed after irradiation with visible light.</p> <p>Conclusions</p> <p>Irradiation with visible light does not seem to be harmful to the human lens except if the lens is exposed to laser irradiances that are high enough to warrant thermal protein denaturation that is more readily seen using pulsed laser systems.</p

Quantification of Visual Field Loss in Age-Related Macular Degeneration

Background An evaluation of standard automated perimetry (SAP) and short wavelength automated perimetry (SWAP) for the central 10–2 visual field test procedure in patients with age-related macular degeneration (AMD) is presented in order to determine methods of quantifying the central sensitivity loss in patients at various stages of AMD. Methods 10–2 SAP and SWAP Humphrey visual fields and stereoscopic fundus photographs were collected in 27 eyes of 27 patients with AMD and 22 eyes of 22 normal subjects. Results Mean Deviation and Pattern Standard Deviation (PSD) varied significantly with stage of disease in SAP (both p<0.001) and SWAP (both p<0.001), but post hoc analysis revealed overlap of functional values among stages. In SWAP, indices of focal loss were more sensitive to detecting differences in AMD from normal. SWAP defects were greater in depth and area than those in SAP. Central sensitivity (within 1°) changed by −3.9 and −4.9 dB per stage in SAP and SWAP, respectively. Based on defect maps, an AMD Severity Index was derived. Conclusions Global indices of focal loss were more sensitive to detecting early stage AMD from normal. The SWAP sensitivity decline with advancing stage of AMD was greater than in SAP. A new AMD Severity Index quantifies visual field defects on a continuous scale. Although not all patients are suitable for SWAP examinations, it is of value as a tool in research studies of visual loss in AMD