Chromatic Pupillometry Methods for Assessing Photoreceptor Health in Retinal and Optic Nerve Diseases

The pupillary light reflex is mediated by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs), which also receive input from rods and cones. Melanopsin-dependent pupillary light responses are short-wavelength sensitive, have a higher threshold of activation, and are much slower to activate and de-activate compared with rod/cone-mediated responses. Given that rod/cone photoreceptors and melanopsin differ in their response properties, light stimuli can be designed to stimulate preferentially each of the different photoreceptor types, providing a read-out of their function. This has given rise to chromatic pupillometry methods that aim to assess the health of outer retinal photoreceptors and ipRGCs by measuring pupillary responses to blue or red light stimuli. Here, we review different types of chromatic pupillometry protocols that have been tested in patients with retinal or optic nerve disease, including approaches that use short-duration light exposures or continuous exposure to light. Across different protocols, patients with outer retinal disease (e.g., retinitis pigmentosa or Leber congenital amaurosis) show reduced or absent pupillary responses to dim blue-light stimuli used to assess rod function, and reduced responses to moderately-bright red-light stimuli used to assess cone function. By comparison, patients with optic nerve disease (e.g., glaucoma or ischemic optic neuropathy, but not mitochondrial disease) show impaired pupillary responses during continuous exposure to bright blue-light stimuli, and a reduced post-illumination pupillary response after light offset, used to assess melanopsin function. These proof-of-concept studies demonstrate that chromatic pupillometry methods can be used to assess damage to rod/cone photoreceptors and ipRGCs. In future studies, it will be important to determine whether chromatic pupillometry methods can be used for screening and early detection of retinal and optic nerve diseases. Such methods may also prove useful for objectively evaluating the degree of recovery to ipRGC function in blind patients who undergo gene therapy or other treatments to restore vision

Light-Induced Pupillary Responses in Alzheimer's Disease

The impact of Alzheimer's disease (AD) on the pupillary light response (PLR) is controversial, being dependent on the stage of the disease and on the experimental pupillometric protocols. The main hypothesis driving pupillometry research in AD is based on the concept that the AD-related neurodegeneration affects both the parasympathetic and the sympathetic arms of the PLR (cholinergic and noradrenergic theory), combined with additional alterations of the afferent limb, involving the melanopsin expressing retinal ganglion cells (mRGCs), subserving the PLR. Only a few studies have evaluated the value of pupillometry as a potential biomarker in AD, providing various results compatible with parasympathetic dysfunction, displaying increased latency of pupillary constriction to light, decreased constriction amplitude, faster redilation after light offset, decreased maximum velocity of constriction (MCV) and maximum constriction acceleration (MCA) compared to controls. Decreased MCV and MCA appeared to be the most accurate of all PLR parameters allowing differentiation between AD and healthy controls while increased post-illumination pupillary response was the most consistent feature, however, these results could not be replicated by more recent studies, focusing on early and pre-clinical stages of the disease. Whether static or dynamic pupillometry yields useful biomarkers for AD screening or diagnosis remains unclear. In this review, we synopsize the current knowledge on pupillometric features in AD and other neurodegenerative diseases, and discuss potential roles of pupillometry in AD detection, diagnosis and monitoring, alone or in combination with additional biomarkers

Genomic deletions in OPA1 in Danish patients with autosomal dominant optic atrophy

BACKGROUND: Autosomal dominant optic atrophy (ADOA, Kjer disease, MIM #165500) is the most common form of hereditary optic neuropathy. Mutations in OPA1 located at chromosome 3q28 are the predominant cause for ADOA explaining between 32 and 89% of cases. Although deletions of OPA1 were recently reported in ADOA, the frequency of OPA1 genomic rearrangements in Denmark, where ADOA has a high prevalence, is unknown. The aim of the study was to identify copy number variations in OPA1 in Danish ADOA patients. METHODS: Forty unrelated ADOA patients, selected from a group of 100 ADOA patients as being negative for OPA1 point mutations, were tested for genomic rearrangements in OPA1 by multiplex ligation probe amplification (MLPA). When only one probe was abnormal results were confirmed by additional manually added probes. Segregation analysis was performed in families with detected mutations when possible. RESULTS: Ten families had OPA1 deletions, including two with deletions of the entire coding region and eight with intragenic deletions. Segregation analysis was possible in five families, and showed that the deletions segregated with the disease. CONCLUSION: Deletions in the OPA1 gene were found in 10 patients presenting with phenotypic autosomal dominant optic neuropathy. Genetic testing for deletions in OPA1 should be offered for patients with clinically diagnosed ADOA and no OPA1 mutations detected by DNA sequencing analysis

Classification of SD-OCT Volumes for DME Detection: An Anomaly Detection Approach

International audienceDiabetic Macular Edema (DME) is the leading cause of blindness amongst diabetic patients worldwide. It is characterized by accumulation of water molecules in the macula leading to swelling. Early detection of the disease helps prevent further loss of vision. Naturally, automated detection of DME from Optical Coherence Tomography (OCT) volumes plays a key role. To this end, a pipeline for detecting DME diseases in OCT volumes is proposed in this paper. The method is based on anomaly detection using Gaussian Mixture Model (GMM). It starts with pre-processing the B-scans by resizing, flattening, filtering and extracting features from them. Both intensity and Local Binary Pattern (LBP) features are considered. The dimensionality of the extracted features is reduced using PCA. As the last stage, a GMM is fitted with features from normal volumes. During testing, features extracted from the test volume are evaluated with the fitted model for anomaly and classification is made based on the number of B-scans detected as outliers. The proposed method is tested on two OCT datasets and achieved a sensitivity and a specificity of 80% and 93% on the first dataset, and 100% and 80% on the second one. Moreover, the experiments show that the proposed method achieves better classification performances than other recently published works

Clinical and Epidemiologic Research Vitamin D and Macular Thickness in the Elderly: An Optical Coherence Tomography Study

PURPOSE. Vitamin D insufficiency is associated with age-related macular degeneration. Our objective was to determine whether low serum 25-hydroxyvitamin D (25OHD) concentration was associated with macular thickness among older adults with no signs of macular dysfunction. METHODS. Sixty-two French older community-dwellers with no patent macular dysfunction (mean 6 SD, 71.2 6 5.0 years; 45.2% female) included in the Gait and Alzheimer Interaction Tracking (GAIT) study (ClinicalTrials.gov number, NCT01315717) were separated into two groups according to serum 25OHD level (i.e., insufficient < 50 nmol/L or sufficient ‡ 50 nmol/ L). The macular thickness was measured on 1000 lm central macula with optical coherence tomography, and further binarized according to normal values of macular thickness (i.e., 267.74 lm for males, and 255.60 lm for females). Age, sex, number of comorbidities, cognitive disorders, body mass index, mean arterial pressure, visual acuity, intraocular pressure, serum calcium concentration and season of testing were considered as potential confounders. RESULTS. The mean serum 25OHD concentration was 61.2 6 26.3 nmol/L. Patients with vitamin D insufficiency had a reduced macular thickness compared to those without (232.9 6 40.4 lm vs. 253.3 6 32.1 lm, P ¼ 0.042). After adjustment for potential confounders, vitamin D insufficiency was associated with a decreased macular thickness (b ¼ À59.4 lm, P ¼ 0.001). Consistently, the participants with vitamin D insufficiency had a 3.7-fold higher risk of having abnormally low macular thickness compared with those with sufficient 25OHD level (P ¼ 0.042). CONCLUSIONS. Vitamin D insufficiency was associated with reduced macular thickness among older patients with no patent macular dysfunction. This implies that vitamin D insufficiency may be involved in macular thinning, and provides a scientific base for vitamin D replacement trials in age-related macular degeneration. Keywords: macular thickness, vitamin D, neuroendocrinology, older adults, age-related macular degeneration, retina B eyond its classical contribution to bone health, vitamin D is a secosteroid hormone involved in several target tissues expressing vitamin D receptors, 1,2 including the retina. MATERIALS AND METHODS Participants We studied 73 community dwellers (mean age 70.9 6 4.9 years; 42.9% female) followed in the Memory Clinic of Anger

Classification of SD-OCT Volumes using Local Binary Patterns: Experimental Validation for DME Detection

International audienceThis paper addresses the problem of automatic classification of Spectral Domain OCT (SD-OCT) data for automatic identification of patients with Diabetic Macular Edema (DME) versus normal subjects. Optical Coherence Tomography (OCT) has been a valuable diagnostic tool for DME, which is among the most common causes of irreversible vision loss in individuals with diabetes. Here, a classification framework with five distinctive steps is proposed and we present an extensive study of each step. Our method considers combination of various pre-processings in conjunction with Local Binary Patterns (LBP) features and different mapping strategies. Using linear and non-linear classifiers, we tested the developed framework on a balanced cohort of 32 patients. Experimental results show that the proposed method outperforms the previous studies by achieving a Sensitivity (SE) and Specificity (SP) of 81.2% and 93.7%, respectively. Our study concludes that the 3D features and high-level representation of 2D features using patches achieve the best results. However, the effects of pre-processing is inconsistent with respect to different classifiers and feature configurations

Light and myopia: from epidemiological studies to neurobiological mechanisms

Myopia is far beyond its inconvenience and represents a true, highly prevalent, sight-threatening ocular condition, especially in Asia. Without adequate interventions, the current epidemic of myopia is projected to affect 50% of the world population by 2050, becoming the leading cause of irreversible blindness. Although blurred vision, the predominant symptom of myopia, can be improved by contact lenses, glasses, or refractive surgery, corrected myopia, particularly high myopia, still carries the risk of secondary blinding complications such as glaucoma, myopic maculopathy, and retinal detachment, prompting the need for prevention. Epidemiological studies have reported an association between outdoor time and myopia prevention in children. The protective effect of time spent outdoors could be due to the unique characteristics (intensity, spectral distribution, temporal pattern, etc.) of sunlight that is lacking in artificial lighting. Concomitantly, studies in animal models have highlighted the efficacy of light and its components in delaying or even stopping the development of myopia and endeavoured to elucidate possible mechanisms involved in this process. In this narrative review, we (1) summarize the current knowledge concerning light modulation of ocular growth and refractive error development based on studies in human and animal models, (2) summarize potential neurobiological mechanisms involved in the effects of light on ocular growth and emmetropization and (3) highlight a potential pathway for the translational development of noninvasive light-therapy strategies for myopia prevention in children.info:eu-repo/semantics/publishedVersio

Classification of SD-OCT volumes with multi pyramids, LBP and HOG descriptors: application to DME detections

International audienceThis paper deals with the automated detection of DME on OCT volumes.Our method considers a generic classification pipeline with preprocessing for noise removal and flattening of each B-Scan.Features such as HoG and LBP are extracted and combined to create a set of different feature vectors which are fed to a linear-SVM classifier.Experimental results show a promising sensitivity/specificity of 0.75/0.87 on a challenging dataset

The prophylaxis of major bacterial infections in the Apis mellifera carpathica bee through honey, pollen and bee bread control

For the purpose of controlling the evolution of major bacterial diseases in bees, which decimate bee colonies in Europe and Romania, respectively, we examined samples (honey, pollen and honeycombs) in the apicultural year 2016, from all over Romania. Sample collection and testing were done with the purpose to prevent the contamination of bee colonies with the etiological agents of major bacterial diseases, considering that worker bees and the food entering the hive (honey, pollen) represent the main contamination ways. The diagnosis method observed OIE regulations (2008) and was adapted in an original way in the Bee Pathology Laboratory in Bucharest. A total of 73 samples were examined, representing honey (51), honeycombs (6) and pollen/bee bread (16), from private apiaries all over the country, that presented depopulation without clinical evolution of contagious diseases in bees, and in which we diagnosed the presence of etiological agents of major bacterial bee diseases (36.98 %), while the rest of the samples were negative (63.02%). Of the 51 samples of honey that were examined, we identified 39.22% positive samples and 60.78% negative ones. Of the pollen samples that were examined, 31.25% were positive and 68.75% were negative, and the honeycombs samples showed 33.33% positive and 66.66% negative. Previous researches indicated that the positive samples (honey, pollen, bee bread), from apiaries in all the regions of the country, represented the basis for the prophylaxis of major bacterial diseases so that, by avoiding using them in bee nutrition, the evolution of major bee diseases did not confirm clinically or paraclinically in the following season (January-April 2017)

Serum vitamin D status is associated with the presence but not the severity of primary open angle glaucoma.

OBJECTIVES: Vitamin D is involved in visual health and function. Our objective was to determine whether age-related vitamin D insufficiency was associated with the presence and the severity of primary open angle glaucoma (POAG) in a case-control study of older adults. STUDY DESIGN: Case-control study. MAIN OUTCOME MEASURES: One hundred fifty cases diagnosed with moderate-to-severe POAG (mean, 75.1±8.5 years; 42.0% female) and 164 healthy controls (mean, 73.0±7.9 years; 59.8% female) were included. POAG diagnosis was based on classical diagnostic criteria of optic nerve cupping and/or RNFL thinning, measured with optical coherence tomography. Severe POAG was defined as Humphrey visual field mean deviation (MD) worse than -12dB. Vitamin D insufficiency was defined as serum 25OHD≤75nmol/L. Age, gender, mean arterial pressure, vitamin D supplementation, visual acuity, and intraocular pressure were used as potential confounders. RESULTS: POAG cases had lower mean serum 25OHD concentration than controls (42.9±25.7nmol/L versus 49.4±29.5nmol/L, P=0.039) and a greater prevalence of vitamin D insufficiency (90.7% versus 82.3%, P=0.032). Increased mean serum 25OHD concentrations were associated with lower POAG frequency, even after adjustment for potential confounders (OR=0.89 per 10nmol/L of 25OHD, P=0.045). Similarly, vitamin D insufficiency was associated with POAG (OR=2.09, P=0.034). Among POAG cases, no 25OHD difference was observed between moderate and severe POAG cases (respectively, 39.2±23.3nmol/L versus 45.1±26.7nmol/L, P=0.188); and no between-group difference regarding the prevalence of vitamin D insufficiency (88.9% versus 94.0%, P=0.313). CONCLUSIONS: Decreased serum 25OHD concentration was associated with POAG. There was no 25OHD difference between moderate and severe POAG