National Eye Institute

definitions

Eye diseases that lead to vision loss and blindness, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), cataracts, and glaucoma, affect millions of Americans of all ages, ethnicities, and backgrounds.These and other forms of vision disorders, like myopia, can restrict career choices and can impact people's mobility and independence.As the population ages, virtually all Americans will develop a visual problem.The National Eye Institute (NEI) supports vision research through approximately 1,800 research grants and training awards made to scientists at more than 260 medical centers, hospitals, and universities across 44 states and around the world.NEI also conducts laboratory and patient-oriented clinical research at its facilities in Maryland.
Artificial Intelligence (AI) has had a breakout year, astounding us with self-driving cars, generating images from scratch, and even emulating human dialogue.Medicine has also entered an era driven by AI and data science, particularly in the eye.Autonomous AI diagnostic devices detect potentially blinding diseases in their early stages; AI powers ocular imaging and telemedicine, predicts disease progression, and informs treatment decisions.A team of vision researchers was awarded one of the four grants in the NIH Common Fund Bridge2AI Initiative, which seeks to generate flagship datasets linking clinical information to ocular imaging to propel widespread adoption of AI.
It is no coincidence that NEI has been a pioneer in developing AI technologies and applying them to research and patient care.The transparent eye is easily imaged non-invasively, enabling widespread development and use of advanced imaging tools; the pixel-level details can reveal tiny biological changes undetectable by the human eye.The 2023 Lasker-DeBakey Clinical Medical Research Award, the top science prize in the United States, was awarded to NEIsupported scientists who developed optical coherence tomography (OCT), an incredibly sensitive device that uses low-power laser light to see biological structures in microscopic detail.Independently, President Biden also recognized these scientists with the 2023 National Medal of Technology and Innovation.OCT captures cross-section images of the light-sensing retina in the back of the eye.It has revolutionized the detection and treatment of leading causes of blindness, such as age-related macular degeneration (AMD), DR, and glaucoma.Since 1991, OCT has become the most common eye imaging procedure, performed 30 million times per year, almost once every second.With hundreds of thousands of images paired to medical records, AI based approaches can make predictions of disease diagnosis and progression.In glaucoma, for example, OCT can measure structural changes in the optic nerve, the biological cable that conveys vision information to the brain.The death of optic nerve cells causes gradual vision loss, with a disproportionate burden falling on Black and Hispanic populations.Accurate and NEI-3 NEI-4 prompt assessment of glaucoma progression is essential to determine whether escalation of funded researchers developed an AI model to predict individual glaucoma progression that significantly outperformed standard statistical models.
Using 14,000 OCT scans from 462 glaucoma patients over time, NEI-Early detection of eye disease followed by appropriate treatment can prevent blindness.However, with a limited supply of eye doctors, access to eye care is a public health challenge.Autonomous systems aim to alleviate the provider shortage by identifying individuals who have image findings that warrant a referral to a specialist.NEI-funded research led to the first autonomous AI system in any field of medicine, IDx-DR, a tool approved by Food and Drug Administration (FDA) in 2018 to detect referable DR in people with diabetes.NEI small business grants supported development of EyeArt, which just became the first FDA-approved AI tool for use across multiple camera vendors, reducing the need for clinics to buy specific equipment.Another NEI-funded small business, Notal Vision, recently demonstrated success of their patient-centric home-based OCT system, which allows doctors to manage AMD in real time, through remote monitoring and telemedicine.AMD is the leading cause of irreversible vision loss in older Americans.NEI has a database of hundreds of thousands of retinal images collected in an AMD clinical trial.AI systems can leverage these rich datasets to identify diagnostic patterns: looking at a spotted pattern of lesions called pseudodrusen, one algorithm developed by NEI could predict progression from intermediate to late AMD.NEI-funded small business iHealthScreen used this dataset to develop an AI tool for identifying the subset of AMD patients with rapidly advancing disease who could benefit from aggressive treatment.
Remarkably, the first foundational AI model for generalizable disease detection from unlabeled retinal images outperforms comparison models for diagnosis and prognosis of neurological diseases like Alzheimer's disease (AD), Parkinson's, and schizophrenia, as well as systemic conditions such as heart attacks, stroke, diabetes glucose control, and kidney disease, and can even determine an individual's age, sex, and smoking status.This first-of-its-kind model uses self-supervised learning that derives signals directly from the data, instead of requiring workintensive labeling by experts.The predictive power of AI only multiplies when other types of imaging and data like genomics are fed into the algorithm-the combined set of features was recently coined "oculomics."A new NEI-funded study correlated the distribution of specific inflammatory and neurodegenerative proteins in retinas donated from post-mortem AD patients to their cognitive scores.Since eyes are more accessible than brains, this result may lead to AD monitoring with non-invasive retinal imaging and biomarkers.therapy is necessary.

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While the power of AI is transforming medicine, it is critical to be vigilant of the dangers.To avoid introducing bias, AI systems need to be trained on a diverse population sample.To work towards reducing bias in retinal research that uses AI, NEI-funded scientists conducted an evaluation to explore racial bias in retinal images used to screen premature infants for retinopathy of prematurity, a potentially blinding condition if not treated immediately.Because race is associated with variations in retinal pigmentation, the team subtracted the color features of the image, prior to training, and yet the AI prediction model was still able to determine the self-identified race, highlighting the need for more work to prevent bias in AI.To increase the diversity of datasets for AI, the NIH Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD) Program, whose advisory committee is co-chaired by the NEI Director, is designed to boost participation and representation of researchers and communities currently underrepresented in AI development.

Data science and technology have led to next generation therapies
One year ago, there were no FDA approved therapies for geographic atrophy (GA), an advanced form of 'dry" AMD; now there are two new drugs, Syfovre and Izervay.The drugs target different proteins in the immune system's complement pathway, which protects against pathogens by triggering a cascade of proteins that enhance the body's immune response.In clinical trials, both drugs demonstrated an ability to slow the rate of GA progression, preserving sharp central vision.The impact of GA on vision depends on where the damage is in the eyethe closer to the central visual field, the greater the visual deficit, which may influence the decision to treat.Follow-up research is needed to understand which patients benefit the most from these new treatments relative to the risks.While the drugs were brought to market by the private sector, they represent years of research support from NEI.In 2005, three research teams initiated a new data-intensive technique that compares genomes of hundreds or thousands of patients and controls to identify genetic risks-AMD was the first success of this method, with the discovery of a complement gene variant that greatly increased risk.
Another promising new therapy for patients with intermediate AMD is light itself, specifically photobiomodulation (PBM).PBM uses specific wavelengths of light to boost output of mitochondria-the cell structures that generate energy.In a randomized clinical trial, AMD patients who received PBM had improved vision and slower lesion growth in their eyes relative to patients who received placebo treatment.While new therapies for GA may slow vision loss, NEI clinical trials are testing first-in-human stem cell-based tissue patches that can be transplanted in the retina where tissue has been lost.One trial is growing replacement tissues in a dish cloned from AMD patients' own cells.Their manufacturing process employs AI in quality control: AI networks were trained to identify visual indications of tissue maturation correlated with positive function to help select which potential patches have the highest likelihood of transplant success.
AI has also been used to design sustained drug delivery mechanisms to treat glaucoma.While eye drops can be effective when taken multiple times per day, frequent dosing can be a barrier for some patients to comply with their regimens.A new study used AI peptide engineering to design a non-toxic, therapeutic protein that tightly bound to melanin, the compound responsible for eye color, creating a slow-releasing drug reservoir in the eye.Animal models showed this drug was effective for 18 days following single administration.

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Neural networks (brain) before there were convolution neural networks (AI deep learning) Some of the fundamental secrets about how the brain develops, forms connections, organizes itself, and then reconstructs patterns and features of the outside world stem from Drs. Hubel and Wiesel's seminal Nobel Prize-winning research on the visual cortex.The relative weighting, or strength, of neuron connections in the brain are formed iteratively, through learning and experience, with feedback loops that can modify input cells based on outputs; not only do AI systems use the brain as a model-they even borrow the name artificial "neural networks."The NEI Visual Neuroplasticity Workshop in January 2024 explored vision as a paradigm for brain plasticity-the ability of the nervous system to modify its functional and structural connections in response to experience.Project Prakash is an NEI-funded scientific and humanitarian partnership in India that challenges the notion of an "all or none" critical period in which the brain learns to make sense of visual input, a window that closes around age six.Follow-up of older children (age 7-17) who have had congenital cataracts removed has shown they are able to learn a variety of visual tasks.To find structural neural correlates of this recovery, researchers used a technique called diffusion tensor imaging to show that sight surgery induced white matter (nerve fiber) plasticity in late visual pathways, which was distinct from normal maturational changes in age-matched children.
Cerebral/cortical visual impairment (CVI) results from neonatal injury to vision processing centers during the window of visual development.Children with CVI may exhibit a constellation of impairments, including cerebral palsy and cognitive delay, but may have a healthy eye exam, and therefore the condition has historically been under-recognized.The 2021 NEI Strategic Plan outlined strategies to develop methodologies to diagnose and classify CVI to ultimately understand the neural basis and structure/function relationships.NEI kicked off a NIH-wide CVI initiative with a workshop in November 2023 to develop a registry as a first step to diagnose and classify CVI.The interdisciplinary workshop included clinicians, occupational therapists, researchers, individuals with CVI, caregivers, and teachers.
Research has shown an association between the incidence of myopia (nearsightedness) and time spent reading and focusing on screens.Meanwhile, time outdoors and in sunlight appears to reduce the risk of myopia.A new study on vision neural circuits may explain why.From retina to visual cortex, neurons specialize in either the light ON pathway or OFF pathway.ON neurons respond better to bright light, large far-away objects, and to movement that stabilizes the retinal image as we move around in the world.On the other hand, OFF neurons are more engaged for close focus of central stimuli and for resolving the details of an image, as in reading.To support a theory that myopia is associated with the relative under-use of the ON pathway, researchers measured the extent to which walking outside produces stimuli that favor ON neurons, whereas reading black text on white background favors OFF neurons.This connection between neurophysiology, theory, and measurable visual perceptual impairment can potentially lead to the development of better diagnostics and therapies.
The NIH BRAIN Initiative is developing novel tools to map brain connections.Reflecting the fundamental contributions of the visual system to understanding neuroscience, one third of BRAIN projects are vision related.A team funded by NEI and BRAIN implanted brain organoids-stem-cell based tissues grown in a dish-into mouse visual cortex and demonstrated NEI-7 they functionally integrated and responded to visual stimuli.A key engineering breakthrough was using transparent graphene-based electrode arrays and brain imaging that enabled recording these cells over the course of months.This study opens the door to using organoids as a neuroprosthetic for damaged brain tissue, and as a research tool to model brain development and disease.
The visual system is a paradigm for health and disease across medical disciplines Beyond neuroscience, vision research has been on the cutting edge in fields ranging from data science to precision medicine.Meaningful data sharing is essential to facilitate and accelerate research.NEI is developing a knowledgebase-a web-based library of information for indexing NEI-supported research and datasets along with access requirements, data analysis tools, code, and contact information to encourage collaboration among data generators and data scientists.To incentivize individuals to share their data, NEI will lead a NIH-wide prize competition in 2024 to develop and validate a quantitative data sharing index ("s-index"), which will identify and reward exemplar data sharers (the score reflects how often a dataset is shared and how useful it is).NEI has been promoting universal adoption of international standards for ophthalmic imaging, especially by device manufacturers.NEI, the National Institute of Biomedical Imaging and Bioengineering, and the NIH All of Us Initiative convened a workshop with experts in vision, imaging technology, data science, and health disparities research to discuss opportunities to expand research with large retinal imaging cohorts.NEI is planning to incorporate eye imaging into All of Us, one of the largest, most diverse health databases of its kind.
While animal research is fundamental to developing new therapies, NEI has also developed complementary models that will more accurately model human outcomes.For example, NEI scientists bioprinted a 3D biodegradable scaffold, added blood vessel precursor cells, and then added retinal cells to create a model to study AMD interaction with capillary networks.The AMD Integrative Biology Initiative (AMD IBI) developed a research resource that combined AMD patient-derived stem cell lines with their deidentified patient medical history and genomic sequence data to study cell disease mechanisms.A cluster of genes on chromosome 10 are associated with AMD, but because they are tightly linked, it has been hard to isolate the effects of single mutations.One AMD IBI team used a gene editing tool called CRISPR to systematically test single DNA changes in stem cell-derived retinal cells from patients with AMD.They showed mutations in the ARMS2 gene were responsible for increased oxidative stress in these cells, but as a potential therapy, administering an antioxidant drug was able to reverse the tissue death caused by this mutation.The NEI 3D retinal organoid challenge (3D-ROC) helped promote the development of human stem cell-based tissue models of disease.NEI scientists used retinal organoids to screen 6,000 FDA-approved compounds to identify a drug, reserpine, that protects photoreceptors from dying in a genetic form of childhood blindness.
The NEI Audacious Goals Initiative (AGI) is originating regenerative medicine strategies to restore vision by regenerating neurons and their connections in the visual system.One of the most challenging steps in this goal is getting new neurons to form appropriate connections for communication, or synapses.AGI grantees grew retinal organoids in a dish and then separated them into individual neurons and cultured them to grow synapses.Using a fluorescent tracer that can only spread through functional synapses, they demonstrated these lab-grown retinal neurons could spontaneously form new circuits, demonstrating their potential to replace lost tissue.

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Through AGI, researchers are learning from animal models that naturally regenerate in an attempt to induce regeneration in mammals.Newts have great regenerative capacities, including their lenses; researchers have now demonstrated the key role that immune cells called macrophages play in promoting a permissive regenerative environment in newt lenses, balancing cell proliferation with cell death.Depleting macrophages increased scarring and inflammation and reduced lens regeneration.This research could also inform therapies to prevent secondary cataract formation, which sometimes occurs a few months after undergoing cataract surgery.
The NEI Anterior Segment Initiative (ASI) explores unique properties of the front of the eye, such as the ocular microbiome, the microbial community on the ocular surface that impacts health and disease as well as the eye's own immune system.NEI recently launched the ASI ocular surface innervation consortium, with eight teams collaborating to understand corneal pain, tear formation in dry eye, migraine, and other conditions.The cornea is the outermost, transparent eye layer that bends light onto the retina.Researchers created 3D corneal organoid tissues that mimic proteins and cell types of the developing cornea in the womb.These models can be used to test safety as new drugs are developed.

Partnerships to reduce health disparities
To address vision health disparities, NEI has partnered with the National Institute on Minority Health and Health Disparities (NIMHD).In April 2023, NEI and NIMHD convened a workshop on advancing health equity that brought together experts in vision with experts in disparities research.Advancing equity involves understanding health disparities, creating strategies to integrate social and structural determinants of health into research, and developing implementation methods to address preventable causes.To explore biological, environmental, and social risk factors for vision loss, NEI has a portfolio of clinical and epidemiology projects, often conducted in partnerships to leverage resources.The Study of Latinos Ojos builds off the infrastructure of the Hispanic Community Health Study to conduct comprehensive eye exams and assess chronic eye diseases (e.g., DR, AMD, glaucoma, and cataract) in these communities.Other NEI studies include looking at the impact of social determinants of health on DR; health disparities in the development, persistence, and progression of ocular inflammation (uveitis); ethnic variation in strabismus (misaligned eyes); and intrauterine exposure to tobacco smoke and vision disorders including amblyopia ("lazy eye") and hyperopia (farsightedness) in preschool children.
Access to vision care is a major source of disparity impacting conditions like unoperated cataract and uncorrected refractive errors.The Public Health and Disparities Research area of the NEI Strategic Plan emphasizes strengthening community engagement and outreach.To that end, NEI has partnered with vision advocacy organizations to launch a public awareness campaign in 2024.Also, NEI is funding a project using participatory science to design an intervention for patients with undiagnosed DR.Input from these partners has identified barriers to care including transportation, employment, childcare constraints on making appointments, or health education and trust concerns.NIMHD recently designated people with disabilities as a population with health disparities.People with vision impairments may be unable to drive to medical appointments or may have difficulty with printed health information.NEI is developing an action plan for Section 508 compliance-the section of the Rehabilitation Act that ensures public materials are accessible to individuals with disabilities.NEI's Vision Rehabilitation portfolio is NEI-9 developing accessibility tools.For example, a new smartphone app, Commute Booster, designed for use in subway stations can interpret graphics or text-based signage, thus helping blind and low vision users navigate public transportation.
Health care costs also impact access to care.A clinical trial funded by NEI in partnership with the National Institute for Diabetes and Digestive and Kidney Diseases showed DR patients starting with a less expensive medicine and switching to a more expensive medicine if vision does not improve sufficiently, gives results similar to starting off with the higher-priced drug.This 'step therapy' is an effective strategy informing treatment options, which could lower costs to patients.Findings about the clinical effectiveness of different treatments in head-to-head comparisons help guide practice guidelines and reduce less effective care.Ocular inflammation, or uveitis, can lead to fluid buildup and is vision threatening.The Macular Edema Ranibizumab versus Intravitreal Anti-inflammatory Therapy (MERIT) trial compared risks and benefits of three approved treatments, and found that while all reduced swelling, corticosteroid injections were superior and were the only treatment that improved vision.Another NEI-funded trial showed that low-dose atropine was no better than placebo for slowing myopia progression in children treated for two years.Importantly, the findings contradict results from recent trials, primarily in East Asia, which showed a benefit in slowing myopia.These mixed results show more atropine research is needed to test the benefit of different doses, populations, or combination therapies.The burden of myopia is increasing, affecting 30 percent of the global population and expected to grow to 50 percent by 2050.NEI has partnered with the National Academies of Sciences, Engineering, and Medicine to conduct a consensus study to understand myopia from a population public health perspective and to understand the interplay of biological and environmental factors behind the increased prevalence.Working with partners in medicine and harnessing the potential of data science and AI, NEI is poised to transform vision care far into the future.

Program Descriptions
Retinal Disease Research: The retina is the light-sensitive neural tissue that lines the inside of the eye and sends visual messages through the optic nerve to the brain.Damage to the retina through diseases such as macular degeneration or diabetic retinopathy are among the leading causes of blindness in the United States.The goals of this program are to increase the understanding of disease mechanisms that cause vision loss and to develop improved methods of prevention, diagnosis, and treatment.To meet these goals, NEI supports research in cell biology, physiology, neuroscience, and immunology related to the retina.Major areas addressed within the Retina Program include key causes of blindness such as: • Age-related Macular Degeneration.A leading cause of vision loss, AMD is a disease that blurs the sharp, central vision required for reading, driving, and face recognition.
There are two forms of advanced AMD: geographic atrophy ("dry") AMD, a breakdown of light sensing photoreceptor neurons; and neovascular ("wet") AMD, an abnormal growth of blood vessels underneath the retina.• Retinopathy.DR is a complication of diabetes mellitus in which abnormal blood vessels grow on the surface of the retina and may swell and leak fluid.Retinopathy of Prematurity (ROP) is a potentially blinding disorder that affects premature infants with very low birthweight.• Retinal monogenic disorders.Single genetic mutations cause some retinal degenerative diseases, including retinitis pigmentosa, Usher syndrome, and ocular albinism.

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• Uveitis.This group of inflammatory diseases produce swelling and destroy eye tissue, sometimes leading to severe vision loss.

Accomplishments:
• Light perception in the eye takes place in one of two kinds of photoreceptors, cone and rod cells, which are responsible for bright light and color vision and low-light vision, respectively.Retinitis pigmentosa primarily kills rod cells but ultimately the retinal degeneration also damages cone cells, leading to blindness.Researchers interested in understanding cone cell degeneration have isolated single cells and discovered that they remain responsive to light even as degeneration is progressing.With this discovery, therapies targeted at preserving cone cells may be able to save or even restore vision in patients with this disease.• A complication of Type 1 diabetes, retinopathy progressively damages retinal blood capillaries.The source of this damage appears to lie in the belly, with a leaky small intestine that weakens the barrier between gut bacteria and the blood, promoting inflammation throughout the body.New research has revealed a potential way to fight this inflammation; in mice, supplementation with a probiotic treatment restored gut barrier function and even reversed damage in eyes affected by DR.Investigators hope this intervention will eventually prove effective in humans.
Budget Policy: The FY 2025 President's Budget request for Retinal Disease Research is $349.0 million, a decrease of $1.6 million or -0.4 percent compared with the FY 2023 Final level.
Corneal Disease, Cataract, and Glaucoma Research: Corneal disease, cataracts, and glaucoma prompt more visits to ophthalmologists each year than other vision disorders.NEI supports research to address these conditions that originate in the front of the eye.
• Corneal disease.Corneal injuries, infections, and diseases can be blinding, extremely painful and require immediate medical attention.The ocular surface is the front line against environmental insults, such as viruses (herpes simplex, herpes zoster, bacteria (causing trachoma), fungus (sometimes associated with contact lens wear) and ocular inflammation (uveitis).These conditions can be serious and lead to permanent vision loss.NEI's corneal research encompasses ocular injuries sustained from sports and other recreational activities, from workplace accidents, and from eye trauma associated with falls and motor vehicle accidents.• Cataract.A clouding of the lens in the eye that affects vision, cataracts are the leading cause of blindness worldwide.NEI-funded researchers investigate strategies to prevent cataract formation and progression and to understand the physiological basis of how the lens in the healthy eye remains transparent for much of the lifespan.• Glaucoma.Glaucoma refers to a group of blinding diseases that result from damage to the optic nerve, the bundle of fibers that transmit signals from the eyes to the brain.Because there are no early symptoms, an estimated half of people with glaucoma don't know they have it.Over time individuals with glaucoma slowly lose side (peripheral) vision.Those who are over age 60, who are Black or Hispanic, or who have a family history of glaucoma, have a much higher disease risk.Current therapies focus on NEI-22 reducing excessive fluid pressure in the eye, which causes nerve damage in the most common form of glaucoma.

Accomplishments:
• In keratoconus, the cornea thins and bulges outward and becomes conical, causing blurry or distorted vision or scarring, possibly leading to blindness.Researchers investigating extracellular vesicles (EVs)a small cellular messenger and a focus of recent scientific interest -found that EVs in the tears of patients with keratoconus are present in increased concentration and have different characteristics from healthy subjects, suggesting a possible role for these vesicles in the development of this disease.• Crystallins are structural proteins, so called because their patterned alignment in the lens makes them transparent and allows them to refract light.Researchers recently identified a mutation in one type of crystallin that reduces the lens fiber cell's ability to make gap junctions used for communicating and sharing molecules with neighboring cells.This in turn results in buildup of mineral deposits (mainly calcium) in the lens, leading to cataract formation.eyeglasses or contact lenses, but these conditions often worsen and therefore remain a costly, recurring economic and personal burden to many in the United States.The steadily growing prevalence of these conditions is a public health concern.People with complications such as severe nearsightedness can also be at risk of vision loss from glaucoma or retinal detachment.The major goals of this program are to discover the biochemical pathways that govern eye growth and to uncover the risk factors associated with refractive errors with the goal of prevention of disease onset or progression.• Rehabilitation research.Some causes of blindness and visual impairment are not treatable at this point.Low vision is the term used to describe chronic visual conditions whose visual impairment is not correctable by eyeglasses or contact lenses.NEI supports rehabilitation research to improve the quality of life for people with visual impairments by helping them maximize the use of remaining vision and by developing improved assistive and adaptive aids and strategies.

Accomplishments:
• AMD patients develop strategies to compensate for loss of central vision, such as shifting the eye's focus during tasks to rely on peripheral rather than central vision.However, the exact mechanisms behind the preferred retinal locus development are still unknown.Individuals may employ multiple focal points or different strategies depending on the visual task.Recent work simulating vision loss in healthy volunteers revealed participants' compensatory strategies differed, sometimes dependent on the visual task.
Improved understanding of these compensatory mechanisms may lead to new methods of visual rehabilitation for patients with low vision.• Our eyes convey a large and complex set of information to our brains, and vision researchers continue to make strides in understanding how the brain triages and processes this input.A recent study found that changes in activity level, including waking versus sleep and motion versus stillness, impact the levels of signaling molecules such as serotonin in the brain, which in turn activate specific visual processing regions.These pathways allow the brain to "turn on" the functions most useful for a specific activity, and visual neuroscientists can now show that the brain is smarter than we thought, with multiple systems to micromanage its own inputs.
OCT (bottom) aligned with retina photo (top) shows retinal neural layers and support tissue.
Research 1,717 Grants Awarded 20 Supplements to Promote Diversity in Research Highlights of NEI recent progress • NEI-funded scientists win 2023 Lasker-DeBakey Award ("America's Nobel Prize") and 2023 National Medal of Technology & Innovation for inventing Optical Coherence Tomography (OCT) • FDA approved first drugs to treat dry age-related macular degeneration (AMD), a leading cause of vision impairment • NEI grantees grew mini-retinas (organoids) in a dish, extracted individual neurons, and induced connections (synapse formation), demonstrating a new method of neural regeneration • TEMPO tool combines AI with complete protein analysis from eye fluid biopsy to yield biomarkers for eye diseases states at cell level , FY 2023) NEI Director Michael F. Chiang, newly elected to the National Academy of Medicine, delivers a talk to winners of the Eye on the Future Teen Video Contest, a competition which encourages teens to consider a career in vision science.
InstituteWelcome to the Oculome Eyes are the window to the body Oculomics: The integration of eye information from cellular and molecular data and structural and functional imaging to assess health and diseaseDisruptive technologies for non-invasive imagingThe retina is a directly accessible extension of the brain, enabling noninvasive examination of neurons, circuits, tissue layers, and blood capillaries • Optical Coherence Tomography (OCT)-Low-power laser light to see microscopic detail of retina layers in cross-section • OCT-Angiography-Non-invasive imaging of retinal capillary network • Adaptive Optics (AO)-Correcting aberrations in optical path with tiny mirrors yielding exquisite resolution at cellular level • Diffusion Tensor Imaging (DTI)-MRI technique using diffusion to map the nerve fiber tract organization of the brain OCT-Angiography, courtesy of NEI.AO image of rods (blue) and cones (orange), courtesy of Johnny Tam, NEI.DTI of late visual nerve tracts, courtesy of NEI-funded Project Prakash.NEI-supported AI-based tools for eye and systemic health • IDx-DR-First autonomous AI tool in any field of medicine approved by FDA in 2018 to detect diabetic retinopathy (DR) • EyeArt -Autonomous DR screening tool approved for use across multiple camera vendors; has screened two million eye images * • Notal Vision -Patient-centric home-based OCT system, which allows doctors to manage AMD through remote monitoring * • iHealthScreen -AI tool for identifying rapidly advancing AMD patients who could benefit from aggressive treatment * • Glaucoma progression prediction-OCT-based AI model outperformed standard statistical models • REShAPE-Single cell shape analysis tool spots disease risk • Neurological Disease, cardiac disease, stroke-AI models predict risk for Alzheimer's disease, Parkinson's disease, schizophrenia and other conditions from retinal biomarkers *NEI small business grant recipient NEI Future Initiatives • Cerebral/Cortical Visual Impairment (CVI)-Patient registry; methodologies to diagnose and classify CVI • Advancing Vision Health Equity-Integrating vision and health disparities expertise and partnering with community • Visual Neuroplasticity-Exploring retinal remodeling, brain cellular mechanisms, and functional reorganization • NEI Knowledgebase-Web-based library of information for indexing NEI supported research and datasets • S-index Prize Competition-Develop and validate a quantitative data sharing index • Patient-Reported Outcomes-Patient-centered effort to capture functional vision and quality of life in clinical trials For more information, visit https://nei.nih.govNEI-13

MAJOR CHANGES Major Changes in the Budget Request Major
changes by budget mechanism and/or budget detail are briefly described below.Note that there may be overlap between budget mechanisms and activity detail and these highlights will not sum to the total change for the FY 2025 President's Budget.The FY 2025 President's Budget for the National Eye Institute (NEI) is $898.8 million, an increase of $2.7 million from the FY 2023 Final level of $896.1 million.
Research Management and Support (+$2.7 million; total $45.2 million): NEI will increase funding for Research Management and Support to accommodate costs of employee salary and benefits increases and increases to centrally funded services.

Cost of laboratory supplies, materials, other expenses, and non recurrine: costs
j. Cost of laboratory supplies, materials, other expenses, and non (Dollars in Thousands)FY

Director NATIONAL INSTITUTES OF HEALTH National Eye Institute
Authorizing Legislation: Section 301 and Title IV of the Public Health Service Act, as amended.
• Includes FTEs whose payroll obligations are supported by the NIH Common Fund.Overall Budget Policy: The FY 2025 President's Budget request for the National Eye Institute (NEI) is $898.8 million, an increase of $2.7 million or 0.3 percent compared with the FY 2023 Final level.This funding level will allow NEI to execute key priorities in its 2021 strategic plan in basic, clinical, and translational vision research.
Vision is the dominant sensory system in humans, with over one third of the brain cortex involved in visual processing.NEI funds basic and applied research on the brain as it relates to the visual system and perception, and research on rehabilitation for individuals with low vision.NEIfunded neuroscientists have made remarkable progress in understanding what goes on in the faceprocessing areas in the brain.

283 Total Budget Authority by Object Class $896,549 1 Includes FTEs whose payroll obligations are supported by the NIH Common Fund.
Scientists developed the REShAPE tool, which uses AI to provide single cell morphometric data, meaning it is able to analyze the health of a cell based on its shape and other observable characteristics captured by a photo image.They used REShAPE to NEI-25 generate a complete single cell resolution map of retinal pigment epithelium (RPE) tissue.They identified five statistically distinct RPE subpopulations.Furthermore, they discovered that these subpopulations had different disease vulnerabilities in individuals with and without AMD.This tool has been shared as a research resource for other labs.•Eachhuman cell contains a massive amount of DNA but requires only small portions of this information at any given time.To keep things organized, DNA is packaged into a structure called chromatin.Scientists recently mapped the physical structure of chromatin in the human retina, and then integrated that topology map with data on retinal genes and regulatory elements.What emerged was a dynamic picture of interactions within chromatin over time, including gene activity hot spots and areas with varying degrees of insulation from other regions of DNA.This map is expected to reveal genes associated with retinal diseases, revealing mechanisms and potential therapeutic pathways.•Stargardt disease is an untreatable genetic disease that causes progressive loss of central and night vision.The vision loss is associated with the toxic build-up of lipid-rich deposits in the RPE, whose main job is to support and nourish the retina's light sensing photoreceptors.The mechanisms of this disease are not well understood, but studies using a recently developed stem-cell model reveal the role of the ABAC4 gene in RPE damage.Researchers will establish a bank of patient-derived stem cells with ABAC4 gene mutations to help advance research on this disease.Budget Policy: The FY 2025 President's Budget request for Intramural Research is $114.1 million, an increase of $3.2 million or 2.9 percent compared with the FY 2023 Final level.In 2023, NEI conducted two international searches for top leadership positions.Dr. Kapil Bharti is the new NEI Scientific Director.He has been leading the first in-human trial using patient-derived stem cell-based tissue patches to treat severe vision loss in advanced dry AMD.NEI's new Clinical Director, Dr. Richard Lee, has a strong background in immunology, and his research focuses on how the immune system interacts with the eye, with a special interest in glaucoma and cataract.• NEI has also developed a strategic plan for diversity, equity, inclusion, and accessibility (DEIA).NEI is in the process of recruiting a Chief Diversity Officer to lead implementation of the DEIA plan.
Budget Policy: The FY 2025 President's Budget request for Research Management and Support is $45.2 million, an increase of $2.7 million or 6.5 percent compared with FY 2023.

DETAIL OF FULL-TIME EQUIVALENT EMPLOYMENT (FTE) NATIONAL INSTITUTES OF HEALTH National Eye Institute Detail of Full-Time Equivalent Employment (FTE)
1Includes FTEs whose payroll obligations are supported by the NIH Common Fund.