Pinakin Gunvant Davey

Calpain-1 and calpain-2 play opposite roles in retinal ganglion cell degeneration induced by retinal ischemia/reperfusion injury.

Calpain has been shown to be involved in neurodegeneration, and in particular in retinal ganglion cell (RGC) death resulting from increased intraocular pressure (IOP) and ischemia. However, the specific roles of the two major calpain isoforms, calpain-1 and calpain-2, in RGC death have not been investigated. Here, we show that calpain-1 and calpain-2 were sequentially activated in RGC dendrites after acute IOP elevation. By combining the use of a selective calpain-2 inhibitor (C2I) and calpain-1 KO mice, we demonstrated that calpain-1 activity supported survival, while calpain-2 activity promoted cell death of RGCs after IOP elevation. Calpain-1 activation cleaved PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) and activated the Akt pro-survival pathway, while calpain-2 activation cleaved striatal-enriched protein tyrosine phosphatase (STEP) and activated STEP-mediated pro-death pathway in RGCs after IOP elevation. Systemic or intravitreal C2I injection to wild-type mice 2h after IOP elevation promoted RGC survival and improved visual function. Our data indicate that calpain-1 and calpain-2 play opposite roles in high IOP-induced ischemic injury and that a selective calpain-2 inhibitor could prevent acute glaucoma-induced RGC death and blindness.

Clinical evaluation of multiparameter correction equations for Goldmann applanation tonometry.

PurposeTo evaluate and compare the multiparameter equations in correcting intraocular pressure (IOP) measurements obtained using the Goldmann applanation tonometer (IOPG) for the effects of central corneal thickness (CCT), corneal curvature (R), and age in different ethnic populations.MethodsData of IOPG, CCT, R, and age were collected from three clinical centers. The sample size consisted of 945 eyes of 945 glaucoma patients or suspects (669 Europeans, 127 African Americans, and 149 Indians). The ‘corrected IOP’ was calculated using five multiparameter equations to decrease the association of CCT, R, and age with measured IOP. Regression analyses were performed to calculate variance (r2) and determine the association of CCT, R, and age with IOPG and corrected IOP (residual association).ResultsOverall, CCT accounted for the majority of variance in IOPG, while R and age had a much smaller effect, with the combined effect on IOPG ranging from 4.7 to 7.5% in the three data sets. The residual association of CCT, R, and age with corrected IOP in the three groups ranged from 0.2 to 1.3% and 0.5 to 1.8% with the application of the Elsheikh and the Chihara equations, respectively. The residual association of CCT, R, and age with corrected IOP calculated using the Ehlers, Orssengo and Pye, and Shimmoyo equations were 7–11.5, 1.8–11.7, and 4.6–8.3%, respectively.ConclusionThe Elsheikh and the Chihara equations better decreased the association of CCT, R, and age with measured IOP than the Ehlers, Orssengo and Pye, and Shimmoyo equations.

Effect of Misalignment between Successive Corneal Videokeratography Maps on the Repeatability of Topography Data.

Purpose To improve the reliability of corneal topographic data through the development of a method to estimate the magnitude of misalignment between successive corneal videokeratography (VK) maps and eliminate the effect of misalignment on the repeatability of topography data. Methods Anterior and posterior topography maps were recorded twice for 124 healthy eyes of 124 participants using a Pentacam, and the repeatability of measurements was assessed by calculating the differences in elevation between each two sets of data. The repeatability of measurements was re-assessed following the determination of the magnitude of misalignment components (translational displacements: x0, y0 and z0, and rotational displacements: α, β and γ) between each two data sets and using them to modify the second data set within each pair based on an Iterative Closest Point (ICP) algorithm. The method simultaneously considered the anterior and posterior maps taken for the same eye since they were assumed to have the same set of misalignment components. A new parameter, named Combined Misalignment parameter (CM), has been developed to combine the effect of all six misalignment components on topography data and so enable study of the association between misalignment and the data repeatability test results. Results The repeatability tests resulted in average root mean square (RMS) differences in elevation data of 8.46±2.75 μm before ICP map matching when simultaneously considering anterior and posterior surfaces. With map matching and misalignment correction, the differences decreased to 7.28±2.58 μm (P = 0.00). When applied to only the anterior maps, misalignment correction led to a more pronounced reduction in elevation data differences from 4.58±1.84 μm to 2.97±1.29 μm (P = 0.00). CM was found to be associated with the repeatability error (P = 0.00), with posterior maps being responsible for most of the error due to their relatively lower accuracy compared to anterior maps. Conclusions The ICP algorithm can be used to estimate, and effectively correct for, the potential misalignment between successive corneal videokeratography maps.

Corneal topography matching by iterative registration

Videokeratography is used for the measurement of corneal topography in overlapping portions (or maps) which must later be joined together to form the overall topography of the cornea. The separate portions are measured from different viewpoints and therefore must be brought together by registration of measurement points in the regions of overlap. The central map is generally the most accurate, but all maps are measured with uncertainty that increases towards the periphery. It becomes the reference (or static) map, and the peripheral (or dynamic) maps must then be transformed by rotation and translation so that the overlapping portions are matched. The process known as registration, of determining the necessary transformation, is a well-understood procedure in image analysis and has been applied in several areas of science and engineering. In this article, direct search optimisation using the Nelder–Mead algorithm and several variants of the iterative closest/corresponding point routine are explained and applied to simulated and real clinical data. The measurement points on the static and dynamic maps are generally different so that it becomes necessary to interpolate, which is done using a truncated series of Zernike polynomials. The point-to-plane iterative closest/corresponding point variant has the advantage of releasing certain optimisation constraints that lead to persistent registration and alignment errors when other approaches are used. The point-to-plane iterative closest/corresponding point routine is found to be robust to measurement noise, insensitive to starting values of the transformation parameters and produces high-quality results when using real clinical data.

Macular pigment optical density: repeatability, intereye correlation, and effect of ocular dominance

Purpose To evaluate short-term repeatability, intereye correlation, and effect of ocular dominance on macular pigment optical density (MPOD) measurements obtained using the QuantifEye Heterochromatic Flicker Photometer. Patients and methods A total of 72 study participants were enrolled in this prospective, cross-sectional study. Participants underwent a comprehensive ocular evaluation, including visual acuity, evaluation of ocular dominance, slit lamp examination, intraocular pressure measurement, and optic nerve head and macula analysis using optical coherence tomography and fundus photography. All study participants after initial training underwent MPOD measurement twice in both eyes in a randomized sequence. The repeatability was tested using Altman and Bland plots for first measurements with the second measurements for right eye and left eye and additionally by grouping eyes as a function of ocular dominance. The Pearson correlation coefficient was performed to assess the intereye correlation of MPOD values. Results The mean age of study participants was 35.5 years (range 22–68 years). The mean MPOD measurements for OD (right eye) and OS (left eye) were 0.47 and 0.48, respectively, which followed a normal distribution (Shapiro–Wilk test, P=0.6 and 0.2). The 95% limits of agreement of Altman and Bland plots for the first and second measurements were −0.12 to +0.11 and −0.13 to +0.12 for OD and OS, respectively. The correlation coefficient of mean MPOD measurements of OD and OS was r statistic =0.94 (Pearson correlation coefficient P<0.0001; r2 0.89). The 95% limits of agreement of Altman and Bland plots when evaluated by laterality of eye or by ocular dominance were narrow, with limits of agreement ranging from −0.13 to +0.12. Conclusion The MPOD measurements obtained using the QuantifEye show good short-term repeatability. There is excellent intereye correlation, indicating that the MPOD values of one eye data can predict the fellow eye value with 89% accuracy. The ocular dominance had no bearing on the outcome of this psychophysical test in ocular healthy eyes.

Predicting individual contrast sensitivity functions from acuity and letter contrast sensitivity measurements.

Contrast sensitivity (CS) is widely used as a measure of visual function in both basic research and clinical evaluation. There is conflicting evidence on the extent to which measuring the full contrast sensitivity function (CSF) offers more functionally relevant information than a single measurement from an optotype CS test, such as the Pelli–Robson chart. Here we examine the relationship between functional CSF parameters and other measures of visual function, and establish a framework for predicting individual CSFs with effectively a zero-parameter model that shifts a standard-shaped template CSF horizontally and vertically according to independent measurements of high contrast acuity and letter CS, respectively. This method was evaluated for three different CSF tests: a chart test (CSV-1000), a computerized sine-wave test (M&S Sine Test), and a recently developed adaptive test (quick CSF). Subjects were 43 individuals with healthy vision or impairment too mild to be considered low vision (acuity range of −0.3 to 0.34 logMAR). While each test demands a slightly different normative template, results show that individual subject CSFs can be predicted with roughly the same precision as test–retest repeatability, confirming that individuals predominantly differ in terms of peak CS and peak spatial frequency. In fact, these parameters were sufficiently related to empirical measurements of acuity and letter CS to permit accurate estimation of the entire CSF of any individual with a deterministic model (zero free parameters). These results demonstrate that in many cases, measuring the full CSF may provide little additional information beyond letter acuity and contrast sensitivity.

Effect of Varying Levels of Glare on Contrast Sensitivity Measurements of Young Healthy Individuals Under Photopic and Mesopic Vision

Contrast sensitivity (CS), the ability to detect small spatial changes of luminance, is a fundamental aspect of vision. However, while visual acuity is commonly measured in eye clinics, CS is often not assessed. At issue is that tests of CS are not highly standardized in the field and that, in many cases, optotypes used are not sensitive enough to measure graduations of performance and visual abilities within the normal range. Here, in order to develop more sensitive measures of CS, we examined how CS is affected by different combinations of glare and ambient lighting in young healthy participants. We found that low levels of glare have a relatively small impact on vision under both photopic and mesopic conditions, while higher levels had significantly greater consequences on CS under mesopic conditions. Importantly, we found that the amount of glare induced by a standard built-in system (69 lux) was insufficient to induce CS reduction, but increasing to 125 lux with a custom system did cause a significant reduction and shift of CS in healthy individuals. This research provides important data that can help guide the use of CS measures that yield more sensitivity to characterize visual processing abilities in a variety of populations with ecological validity for non-ideal viewing conditions such as night time driving.

Physiologic anisocoria under various lighting conditions

Purpose To evaluate the measurement of anisocoria in a group of ocular healthy subjects using a standardized protocol in scotopic, mesopic, and photopic lighting conditions, and determine the optimal threshold of difference in pupil diameter in determining physiologic anisocoria. Methods Right and left pupil diameters of 126 ocular healthy subjects with a mean age 30.5±7.8 years (40 males and 86 females) were measured sequentially under photopic conditions using a monocular infrared pupillometer. A sub-group of 51 individuals had right and left pupil measurements performed under three additional lighting conditions, allowing for a 2-minute recovery between measurements. A white light emitting diode (LED) in the eyecup of the pupillometer produced three controlled light settings: scotopic (0 lux), low mesopic (0.3 lux), and high mesopic (3 lux). The criterion for anisocoria was defined as ≥0.4 mm difference in pupil diameter between the eyes. Results In the 126 subjects tested, 23.8% (n=30) exhibited anisocoria in photopic conditions. In the sub-group measured under three additional light settings, 43.1% (n=22) exhibited anisocoria in scotopic conditions, 43.1% (n=22) in low mesopic conditions, and 47.1% (n=24) in high mesopic conditions. Approximately 73% of subjects exhibited anisocoria in at least one light setting, while only approximately 8% had anisocoria in every light setting. When the criterion for anisocoria was shifted to ≥0.2 mm or ≥0.6 mm, the prevalence of anisocoria shifted significantly. Using a higher cutoff of ≥0.6 mm effectively reduced the number of healthy individuals who exhibit anisocoria in every light setting to almost zero. Conclusion Based on our data, anisocoria is more prevalent under varied lighting conditions. To ensure the anisocoria is due to physiologic reasons, one should ensure that it is present under all lighting conditions to avoid excessive false positives.

The development of a reference database with the Topcon 3D OCT-1 Maestro

Importance The paper presents the range for measurements taken with a new spectral domain optical coherence tomography (OCT) device to establish a reference database for discrimination purposes. Objective To report the range of thickness values for the new Topcon Maestro 3D OCT device with 2 scan size settings: the 12×9 mm wide field and 6×6 mm scans. Design Prospective, multicenter cohort study conducted at 7 clinical sites across the USA. Setting Primary eyecare clinics within academic, hospital, and private practice locations. Participants Healthy volunteers; all enrolled participants underwent a complete ophthalmological examination to confirm healthy ocular status prior to being enrolled in the study. Main outcome measure Average and 1st, 5th, 95th, and 99th percentile ranges for OCT parameters Early Treatment Diabetic Retinopathy Study macula full retinal thickness, ganglion cell + inner plexiform layer thickness (GCL + IPL), ganglion cell complex (GCC) thickness, circumpapillary retinal nerve fiber layer (cpRNFL) thickness. Results Three hundred and ninety-nine eyes of 399 subjects were included in the analysis. Mean (SD) age was 46.3 (16.3) years (range 18–88 years). Forty-three percent of the subjects were male. Mean (SD) measurements (in μm) for the 12×9 mm wide scan were as follows: foveal thickness=237.079 (20.899), GCL + IPL=71.363 (5.924), GCC=105.949 (8.533), cpRNFL=104.720 (11.829); measurements for the 6×6 mm scans were as follows: foveal thickness=234.000 (20.657), GCL + IPL=71.726 (5.880), GCC=106.698 (9.094), cpRNFL=104.036 (11.341). Conclusion The overall normal thickness values reported with Topcon 3D OCT-1 Maestro were like those studies with OCT from different manufactures. The reference limits at the 1st, 5th, 95th, and 99th percentile points establish the thresholds for the quantitative comparison of the cpRNFL and the macula in the human retina to a database of known healthy subjects.

Evaluation of intraocular pressure estimates obtained using an iCare rebound tonometer

The aims of this study were to evaluate the intra‐ and inter‐observer repeatability of intraocular pressure (IOP) estimates obtained using an iCare rebound tonometer and to investigate the variation in IOP measurements due to positional differences in probe placement on the cornea.