Active Mutual Conjoint Estimation of Multiple Contrast Sensitivity Functions.

Recent advances in nonparametric Contrast Sensitivity Function (CSF) estimation have yielded a new tradeoff between accuracy and efficiency not available to classical parametric estimators. An additional advantage of this new framework is the ability to independently tune multiple aspects of the estimator to seek further improvements. Machine Learning CSF (MLCSF) estimation with Gaussian processes allows for design optimization in the kernel, acquisition function and underlying task representation, to name a few. This paper describes a novel kernel for CSF estimation that is more flexible than a kernel based on strictly functional forms. Despite being more flexible, it can result in a more efficient estimator. Further, trial selection for data acquisition that is generalized beyond pure information gain can also improve estimator quality. Finally, introducing latent variable representations underlying general CSF shapes can enable simultaneous estimation of multiple CSFs, such as from different eyes, eccentricities or luminances. The conditions under which the new procedures perform better than previous nonparametric estimation procedures are presented and quantified.

Contrast response function estimation with nonparametric Bayesian active learning.

Multidimensional psychometric functions can typically be estimated nonparametrically for greater accuracy or parametrically for greater efficiency. By recasting the estimation problem from regression to classification, however, powerful machine learning tools can be leveraged to provide an adjustable balance between accuracy and efficiency. Contrast sensitivity functions (CSFs) are behaviorally estimated curves that provide insight into both peripheral and central visual function. Because estimation can be impractically long, current clinical workflows must make compromises such as limited sampling across spatial frequency or strong assumptions on CSF shape. This article describes the development of the machine learning contrast response function (MLCRF) estimator, which quantifies the expected probability of success in performing a contrast detection or discrimination task. A machine learning CSF can then be derived from the MLCRF. Using simulated eyes created from canonical CSF curves and actual human contrast response data, the accuracy and efficiency of the machine learning contrast sensitivity function (MLCSF) was evaluated to determine its potential utility for research and clinical applications. With stimuli selected randomly, the MLCSF estimator converged slowly toward ground truth. With optimal stimulus selection via Bayesian active learning, convergence was nearly an order of magnitude faster, requiring only tens of stimuli to achieve reasonable estimates. Inclusion of an informative prior provided no consistent advantage to the estimator as configured. MLCSF achieved efficiencies on par with quickCSF, a conventional parametric estimator, but with systematically higher accuracy. Because MLCSF design allows accuracy to be traded off against efficiency, it should be explored further to uncover its full potential.

Can Nutrition Play a Role in Ameliorating Digital Eye Strain?

Digital eye strain is a complex, multifactorial condition that can be caused by excessive screen time exposure to various electronic devices such as smartphones, tablets, e-readers, and computers. Current literature suggests oxidative damage concomitant with a chronic pro-inflammatory state represent significant etiopathogenic mechanisms. The present review aims to discuss the potential dietary role for micronutrients with nutraceutical properties to ameliorate various ocular and vision-related symptoms associated with digital eye strain. For ocular surface dysfunction, enhanced anti-inflammatory benefits with omega-3 polyunsaturated fatty acids have been well documented for treatment of dry eye disease. The anti-oxidative and immunosuppressive properties of anthocyanin phytochemicals may also confer protective effects against visually induced cognitive stress and digital asthenopia. Meanwhile, nutraceutical strategies involving xanthophyll macular carotenoids demonstrate enhanced cognitive functioning and overall visual performance that aids digital eye strain. Collectively, preliminary findings seem to offer a strong line of evidence to substantiate the need for additional randomized controlled trials aimed at treating digital eye strain with adjunctive nutraceutical strategies. Further RCT and comparisons on commercially available nutritional supplements are needed to quantify the clinical benefits.

Reply to Green-Gomez et al. Comment on "Richer et al. Night Vision and Carotenoids (NVC): A Randomized Placebo Controlled Clinical Trial on Effects of Carotenoid Supplementation on Night Vision in Older Adults. Nutrients 2021, 13, 3191".

We welcome the additional reviews and insights of Green-Gomez, Roche and Nolan [...].

Night Vision and Carotenoids (NVC): A Randomized Placebo Controlled Clinical Trial on Effects of Carotenoid Supplementation on Night Vision in Older Adults.

Twilight and low luminance levels are visually challenging environments for the elderly, especially when driving at night. Carotenoid rich diets are known to increase macular pigment optical density (MPOD), which in turn leads to an improvement in visual function. It is not known whether augmenting MPOD can lead to a decrease in vision related night driving difficulties. Additionally, it is unknown if carotenoid supplementation provides additional measurable benefits to one's useful field of view (UFOV) along with a decreased composite crash risk score. The aim of the study was to evaluate changes in night vision function and UFOV in individuals that took carotenoid vitamin supplements for a six-month period compared to a placebo group. METHODS: A prospective, randomized, double-blind, six-month trial of a 14 mg zeaxanthin/7 mg lutein-based supplement was carried out. Participants were randomized into active or placebo group (approx 2:1). RESULTS: n = 33 participants (26 males/7 females) participated with 93% capsule intake compliance in the supplemented group (n = 24) and placebo group (n = 9). MPOD (mean/standard error SE) in the active group increased in the Right eye from 0.35 density units (du)/0.04 SE to 0.41 du/0.05 SE; p < 0.001 and in the Left eye from 0.35 du/0.05 SE to 0.37 du, p > 0.05). The supplemented group showed significant improvements in contrast sensitivity with glare in both eyes with improvements in LogMAR scores of 0.147 and 0.149, respectively (p = 0.02 and 0.01, respectively), monocularly tested glare recovery time improved 2.76 and 2.54 s, respectively, (p = 0.008 and p = 0.02), and we also noted a decreased preferred luminance required to complete visual tasks (p = 0.02 and 0.03). Improvements in UFOV scores of divided attention (p < 0.001) and improved composite crash risk score (p = 0.004) were seen in the supplemented group. The placebo group remained unchanged. CONCLUSIONS: The NVC demonstrates that augmenting MPOD in individuals with difficulty in night vision showed measurable benefits in numerous visual functions that are important for night vision driving in this small sample RCT. Additionally, we observed an improvement in UFOV divided attention test scores and decreased composite risk scores.

A Systematic Review of Carotenoids in the Management of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) remains a leading cause of modifiable vision loss in older adults. Chronic oxidative injury and compromised antioxidant defenses represent essential drivers in the development of retinal neurodegeneration. Overwhelming free radical species formation results in mitochondrial dysfunction, as well as cellular and metabolic imbalance, which becomes exacerbated with increasing age. Thus, the depletion of systemic antioxidant capacity further proliferates oxidative stress in AMD-affected eyes, resulting in loss of photoreceptors, neuroinflammation, and ultimately atrophy within the retinal tissue. The aim of this systematic review is to examine the neuroprotective potential of the xanthophyll carotenoids lutein, zeaxanthin, and meso-zeaxanthin on retinal neurodegeneration for the purpose of adjunctive nutraceutical strategy in the management of AMD. A comprehensive literature review was performed to retrieve 55 eligible publications, using four database searches from PubMed, Embase, Cochrane Library, and the Web of Science. Epidemiology studies indicated an enhanced risk reduction against late AMD with greater dietary consumption of carotenoids, meanwhile greater concentrations in macular pigment demonstrated significant improvements in visual function among AMD patients. Collectively, evidence strongly suggests that carotenoid vitamin therapies offer remarkable synergic protection in the neurosensory retina, with the potential to serve as adjunctive nutraceutical therapy in the management of established AMD, albeit these benefits may vary among different stages of disease.

A Systematic Review of Carotenoids in the Management of Diabetic Retinopathy.

Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine and Web of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.

Macular Pigment Reflectometry: Developing Clinical Protocols, Comparison with Heterochromatic Flicker Photometry and Individual Carotenoid Levels.

The study was designed to: (1) Analyze and create protocols of obtaining measurements using the Macular Pigment Reflectometry (MPR). (2) To assess the agreement of MPOD measurements obtained using the heterochromatic flicker photometry (MPS II) and MPR. (3) To obtain the lutein and zeaxanthin optical density obtained using the MPR in the central one-degree of the macula. The measurements were performed using the MPR and heterochromatic flicker photometry. The MPR measurements were performed twice without pupillary dilation and twice following pupillary dilation. The MPR measurements were performed for a 40-s period and the spectrometer signal was parsed at different time points: 10-20, 10-30, 10-40, 20-30, 20-40, and 30-40 s. The MPR analyzes the high-resolution spectrometer signal and calculates MPOD, lutein optical density and zeaxanthin optical density automatically. The MPR-MPOD data was compared with MPPS II-MPOD results. The MPR-MPOD values are highly correlated and in good agreement with the MPS II-MPOD. Of the various parsing of the data, the data 10-30 interval was the best at obtaining the MPOD, lutein, and zeaxanthin values (8-12% coefficient of repeatability). The lutein to zeaxanthin ratio in the central one-degree of the macula was 1:2.40. Dilation was not needed to obtain the MPOD values but provided better repeatability of lutein and zeaxanthin optical density. MPR generates MPOD measurements that is in good agreement with MPS II. The device can produce lutein and zeaxanthin optical density which is not available from other clinical devices.

Carotenoids in the Management of Glaucoma: A Systematic Review of the Evidence.

Primary open-angle glaucoma (POAG) remains a leading cause of irreversible blindness globally. Recent evidence further substantiates sustained oxidative stress, and compromised antioxidant defenses are key drivers in the onset of glaucomatous neurodegeneration. Overwhelming oxidative injury is likely attributed to compounding mitochondrial dysfunction that worsens with age-related processes, causing aberrant formation of free radical species. Thus, a compromised systemic antioxidant capacity exacerbates further oxidative insult in glaucoma, leading to apoptosis, neuroinflammation, and subsequent tissue injury. The purpose of this systematic review is to investigate the neuroprotective benefits of the macular carotenoids lutein, zeaxanthin, and meso-zeaxanthin on glaucomatous neurodegeneration for the purpose of adjunctive nutraceutical treatment in glaucoma. A comprehensive literature search was conducted in three databases (PubMed, Cochrane Library, and Web of Science) and 20 records were identified for screening. Lutein demonstrated enhanced neuroprotection on retinal ganglion cell survival and preserved synaptic activity. In clinical studies, a protective trend was seen with greater dietary consumption of carotenoids and risk of glaucoma, while greater carotenoid levels in macular pigment were largely associated with improved visual performance in glaucomatous eyes. The data suggest that carotenoid vitamin therapy exerts synergic neuroprotective benefits and has the capacity to serve adjunctive therapy in the management of glaucoma.

Visual Function and Macular Carotenoid Changes in Eyes with Retinal Drusen-An Open Label Randomized Controlled Trial to Compare a Micronized Lipid-Based Carotenoid Liquid Supplementation and AREDS-2 Formula.

PURPOSE: To compare the changes in visual and ocular parameters in individuals with retinal drusen who were treated with two commercially available nutritional supplements. METHODS: An open-label, single-center, randomized, parallel-treatment with an observational control group design was utilized. The treatment groups included individuals with fine retinal drusen sub-clinical age-related macular degeneration (AMD), while the control group consisted of ocular normal individuals. The treatment groups were randomly assigned to the micronized lipid-based carotenoid supplement, Lumega-Z (LM), or the PreserVision Age-Related Eye Disease Study 2 (AREDS-2) soft gel (PV). Visual performance was evaluated using the techniques of visual acuity, dark adaptation recovery and contrast sensitivity, at baseline, three months, and six months. Additionally, the macular pigment optical density (MPOD) was measured. The control group was not assigned any carotenoid supplement. The right eye and left eye results were analyzed separately. RESULTS: Seventy-nine participants were recruited for this study, of which 68 qualified and 56 participants had useable reliable data. Of the individuals who completed this study, 25 participants belonged to the LM group, 16 belonged to the PV group, and 15 to the control group. The LM group demonstrated statistically significant improvements in contrast sensitivity function (CSF) in both eyes at six months (p < 0.001). The LM group displayed a positive linear trend with treatment time in CSF (p < 0.001), with benefits visible after just three months of supplementation. Although there was a trend showing improvement in CSF in the PV group, the change was not significant after a Bonferroni-corrected p-value of p < 0.00625. Visual acuity, dark adaptation recovery and MPOD did not significantly improve in either treatment groups. CONCLUSION: The LM group demonstrated greater and faster benefits in visual performance as measured by CSF when compared to the PV group. This trial has been registered at clinicaltrials.gov (NCT03946085).

Differences in macular pigment optical density across four ethnicities: a comparative study.

OBJECTIVE: The aim of this study is to compare macular pigment optical density levels across four different ethnicities and study its influence on ganglion cell layer and retinal nerve fibre layer thickness across these ethnicities. METHODS: Consenting adults visiting the ophthalmology and optometry clinics for a routine eye examination without any ocular comorbidity were enrolled. Participants underwent optical coherence tomography for macular thickness, retinal nerve fibre layer thickness and ganglion cell layer thickness. The macular pigment optical density levels were determined in the dominant eye using the QuantifEye device by trained observers. RESULTS: In total, 336 eyes of 336 participants with a mean age of 39.2 ± 14.4 years were included of which 103 (30%) were Caucasians, 111 (33%) were African Americans, 29 (9%) were South Asian Indians and 94 (28%) were Hispanics. The mean macular pigment optical density value across the entire study population was 0.47 ± 0.15. South Asian Indians (0.58 ± 0.16) and Hispanics (0.52 ± 0.15) had significantly higher mean macular pigment optical density values compared with Caucasians (0.41 ± 0.16) and African Americans (0.38 ± 0.15). Linear regression analysis showed that there was a significant association between ethnicities and macular pigment optical density values when adjusted for age (ß coefficient = 0.31, 95% confidence interval = 0.029-0.58, p < 0.001 for South Asian Indian and Hispanic ethnic groups compared with African Americans). There were no differences in the retinal nerve fibre layer and ganglion cell layer thickness across ethnic groups. Linear regression analysis also did not reveal any significant association between macular pigment optical density levels and retinal nerve fibre layer or ganglion cell layer thickness. CONCLUSION: Caucasians and African Americans have lower macular pigment optical density compared with South Asian Indians and Hispanics. There is no clinically significant association between macular pigment optical density levels and retinal nerve fibre layer and ganglion cell layer thickness in healthy individuals across races.

Efficacy of Commercially Available Nutritional Supplements: Analysis of Serum Uptake, Macular Pigment Optical Density and Visual Functional Response.

Purpose: To compare the change in serum carotenoids, macular pigment optical density (MPOD) and visual function with the intake of two commercially available nutritional supplements. Methods: Participants were given a 24-week supply of a lipid-based micronized liquid medical food, Lumega-Z™ (LM), containing 28 mg of the macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ), or given PreserVision™ AREDS 2 Formula (gel-caps; PV) containing 12 mg of the macular carotenoids L and Z, but no reported MZ. Serum levels of L, Z and MZ were obtained at baseline and after 12 weeks. Macular pigment optical densities (MPOD) and visual function were assessed at baseline and after 24 weeks. Results: Average blood serum concentrations of L, Z and MZ in the two groups at baseline were similar. The increases in L, Z and MZ were 0.434, 0.063 and 0.086 mol/L vs. 0.100, 0.043 and 0.001 mol/L, respectively, in the LM vs. PV group. From baseline to week 24, average MPOD in the LM-group increased by 0.064 from 0.418 to 0.482, whereas in the PV-group, it was essentially unchanged (0.461 to 0.459;). Although log-contrast sensitivity was improved in all groups under three conditions (photopic, mesopic and mesopic with glare), the change in log-contrast sensitivity was not statistically significant. Conclusion: Despite only a 2.3-fold higher carotenoid concentration than PV, LM supplementation provides approximately 3-4-fold higher absorption, which leads to a significant elevation of MPOD levels.

Measurement of Carotenoids in Perifovea using the Macular Pigment Reflectometer.

The macular pigment reflectometer (MPR) objectively measures the overall macular pigment optical density (MPOD) and further provides the lutein optical density (L-OD) and zeaxanthin optical density (Z-OD) in the central 1 degree of the fovea. A modification of the technique was developed to evaluate in vivo carotenoid density eccentric to the fovea. An adjustable track system with red LED lights was placed 6.1 m away from the participant to facilitate ocular fixation. Lights were spaced appropriately to create increments of 1 degree retinal disparity during the reflectometry measurements. All reflectometry measurements were obtained with pupillary dilation. The mean MPR-MPOD value for the central measurement was 0.593 (SD 0.161) with an L-OD to Z-OD ratio of 1:2.61. The MPR-MPOD value at 1 degree was 0.248 and the mean MPR-MPOD value at 2 degrees in the parafoveal region was 0.143. The L-OD to Z-OD ratio at 1 degree and 2 degrees off center was 1.38:1.0 and 2.08:1.0, respectively. The results demonstrate that MPOD measurements obtained using the MPR decrease as a function of retinal eccentricity and that there is a higher concentration of zeaxanthin centrally compared to lutein. The L-OD to Z-OD ratio changes with foveal eccentricity, with twice more lutein than zeaxanthin at 2 degrees off center. Our technique successfully provides a quick in vivo method for the measurement of macular pigment optical density at various foveal eccentricities. The results agree with prior published in vivo and in vitro xanthophyll carotenoid density distribution measurements.

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.

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.

Evaluation of intraocular pressure estimates obtained using an iCare rebound tonometer.

BACKGROUND: 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. METHODS: The IOP estimates were obtained by two observers, twice on one eye, of 114 subjects using an iCare tonometer on the central cornea. Additionally, IOP and corneal thickness were measured in 38 subjects at three locations, namely, central, at 1.5 mm nasally and at 1.5 mm temporally from the central cornea. Agreement among measurements was assessed using Bland and Altman plots and the difference in measurements obtained by the observers was compared using paired t-test. Values obtained from central, nasal and temporal regions were compared using one-way analysis of variance. RESULTS: The mean IOP measurements obtained by observer 1 on two attempts were 16.2 and 16.0 mmHg (p > 0.05) were significantly different from the IOP values obtained by observer 2 on two occasions (16.3 and 15.7 mmHg; p < 0.0001). The limits of agreement (LOA) of intra-observer repeatability were -2.9 to +2.6 mmHg and -3.4 to +2.2 for observers 1 and 2, respectively. The LOA of inter-observer repeatability for first and second sequences were -2.8 to +3.0 mmHg and -3.3 to +2.7 mmHg with the second sequence of measurements being significantly different (p = 0.03). Although the corneal thickness was significantly greater nasally and temporally, when compared to the central location, by 32 and 20 microns respectively (p < 0.0001), the measured IOPs on those locations were not significantly different, when compared to the central measurements (p = 0.14). CONCLUSION: There is good intra- and inter-observer repeatability of IOP data, as obtained by the iCare rebound tonometer, although the results may be slightly influenced by practitioner experience. The difference in IOP estimates obtained by different observers is unlikely to be of clinical significance. Corneal thickness showed regional variation; however, this did not influence IOP measurements obtained from those locations.

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.

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; r (2) 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.

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.

Comparison of retinal nerve fiber layer and macular thickness for discriminating primary open-angle glaucoma and normal-tension glaucoma using optical coherence tomography.

PURPOSE: The aim of this study was to evaluate the discrimination capabilities of macular and peripapillary retinal nerve fiber layer (pRNFL) thickness parameters as measured using spectral domain optical coherence tomography (SD-OCT) between primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). METHODS: A total of 90 subjects were enrolled: 30 healthy subjects, 30 subjects with POAG and 30 subjects with NTG, consecutively. Retinal nerve fiber layer thickness, macular thickness and volume measurements were obtained with circular and radial SD-OCT scans. All parameters were compared between groups using an analysis of variance test. Areas under receiver-operating characteristic (AROC) curves with sensitivities at specificities greater than or equal to 90 per cent were generated to compare discrimination capabilities of various parameters between POAG and NTG. RESULTS: Macular thickness and volume measurements were the highest in normal subjects, followed by NTG and POAG (p < 0.05). Average retinal nerve fiber layer thickness had perfect discrimination for normal-POAG (AROC: 1.000; sensitivity: 100 per cent) and near perfect discrimination for normal-NTG (AROC: 0.979; sensitivity: 93 per cent) as well as NTG-POAG pairs (AROC: 0.900; sensitivity: 60 per cent). Inferior outer macular thickness (IOMT) and total volume were the best macular thickness and volume parameters having similar AROCs and sensitivities between normal and POAG (IOMT, AROC: 0.987; sensitivity: 92 per cent and total volume, AROC: 0.997; sensitivity: 97 per cent), normal and NTG (IOMT, AROC: 0.862, sensitivity: 47 per cent and total volume, AROC: 0.898, sensitivity: 67 per cent) and also between NTG and POAG (IOMT, AROC: 0.910, sensitivity: 53 per cent and total volume, AROC: 0.922, sensitivity: 77 per cent). In each comparison group, there was no statistically significant difference in AROCs between average retinal nerve fiber layer and inferior outer macular thickness, as well as total volume. CONCLUSIONS: The macular parameters offer comparable performance to pRNFL parameters for the discrimination of NTG and POAG. Average retinal nerve fiber layer thickness, total macular volume and inferior outer macular thickness were the best SD-OCT parameters with superior discriminating capabilities.