Annual Review of Vision Science - Volume 7, 2021

The scientific study of reading has a rich history that spans disciplines from vision science to linguistics, psychology, cognitive neuroscience, neurology, and education. The study of reading can elucidate important general mechanisms in spatial vision, attentional control, object recognition, and perceptual learning, as well as the principles of plasticity and cortical topography. However, literacy also prompts the development of specific neural circuits to process a unique and artificial stimulus. In this review, we describe the sequence of operations that transforms visual features into language, how the key neural circuits are sculpted by experience during development, and what goes awry in children for whom learning to read is a struggle.

The simultaneous six-pack photo lineup is a standard eyewitness identification procedure, consisting of one police suspect plus five physically similar fillers. The photo lineup is either a target-present array (the suspect is guilty) or a target-absent array (the suspect is innocent). The eyewitness is asked to search the six photos in the array with respect to a target template stored in memory (namely, the memory of the perpetrator's face). If the witness determines that the perpetrator is in fact in the lineup (detection), then the next step is to specify the position of the perpetrator's face in the lineup (localization). The witness may also determine that the perpetrator is not present and reject the lineup. In other words, a police lineup is a detection-plus-localization visual search task. Signal detection concepts that have long guided thinking about visual search have recently had a significant impact on our understanding of police lineups.

Deep learning models currently achieve human levels of performance on real-world face recognition tasks. We review scientific progress in understanding human face processing using computational approaches based on deep learning. This review is organized around three fundamental advances. First, deep networks trained for face identification generate a representation that retains structured information about the face (e.g., identity, demographics, appearance, social traits, expression) and the input image (e.g., viewpoint, illumination). This forces us to rethink the universe of possible solutions to the problem of inverse optics in vision. Second, deep learning models indicate that high-level visual representations of faces cannot be understood in terms of interpretable features. This has implications for understanding neural tuning and population coding in the high-level visual cortex. Third, learning in deep networks is a multistep process that forces theoretical consideration of diverse categories of learning that can overlap, accumulate over time, and interact. Diverse learning types are needed to model the development of human face processing skills, cross-race effects, and familiarity with individual faces.

The first mobile camera phone was sold only 20 years ago, when taking pictures with one's phone was an oddity, and sharing pictures online was unheard of. Today, the smartphone is more camera than phone. How did this happen? This transformation was enabled by advances in computational photography—the science and engineering of making great images from small-form-factor, mobile cameras. Modern algorithmic and computing advances, including machine learning, have changed the rules of photography, bringing to it new modes of capture, postprocessing, storage, and sharing. In this review, we give a brief history of mobile computational photography and describe some of the key technological components, including burst photography, noise reduction, and super-resolution. At each step, we can draw naive parallels to the human visual system.

Color is a continuous variable, and humans can distinguish more than a million colors, yet world color lexicons contain no more than a dozen basic color terms. It has been understood for 160 years that the number of color terms in a lexicon varies greatly across languages, yet the lexical color categories defined by these terms are similar worldwide. Starting with the seminal study by Berlin and Kay, this review considers how and why this is so. Evidence from psychological, linguistic, and computational studies has advanced our understanding of how color categories came into being, how they contribute to our shared understanding of color, and how the resultant categories influence color perception and cognition. A key insight from the last 50 years of research is how human perception and the need for communication within a society worked together to create color lexicons that are somewhat diverse, yet show striking regularities worldwide.

Multifaceted and divergent manifestations across tissues and cell types have curtailed advances in deciphering the cellular events that accompany advanced age and contribute to morbidities and mortalities. Increase in human lifespan during the past century has heightened awareness of the need to prevent age-associated frailty of neuronal and sensory systems to allow a healthy and productive life. In this review, we discuss molecular and physiological attributes of aging of the retina, with a goal of understanding age-related impairment of visual function. We highlight the epigenome–metabolism nexus and proteostasis as key contributors to retinal aging and discuss lifestyle changes as potential modulators of retinal function. Finally, we deliberate promising intervention strategies for promoting healthy aging of the retina for improved vision.

The outer retina is nourished from the choroid, a capillary bed just inside the sclera. O2, glucose, and other nutrients diffuse out of the choroid and then filter through a monolayer of retinal pigment epithelium (RPE) cells to fuel the retina. Recent studies of energy metabolism have revealed striking differences between retinas and RPE cells in the ways that they extract energy from fuels. The purpose of this review is to suggest and evaluate the hypothesis that the retina and RPE have complementary metabolic roles that make them depend on each other for survival and for their abilities to perform essential and specialized functions.

Early detection and monitoring are critical to the diagnosis and management of glaucoma, a progressive optic neuropathy that causes irreversible blindness. Optical coherence tomography (OCT) has become a commonly utilized imaging modality that aids in the detection and monitoring of structural glaucomatous damage. Since its inception in 1991, OCT has progressed through multiple iterations, from time-domain OCT, to spectral-domain OCT, to swept-source OCT, all of which have progressively improved the resolution and speed of scans. Even newer technological advancements and OCT applications, such as adaptive optics, visible-light OCT, and OCT-angiography, have enriched the use of OCT in the evaluation of glaucoma. This article reviews current commercial and state-of-the-art OCT technologies and analytic techniques in the context of their utility for glaucoma diagnosis and management, as well as promising future directions.

Intraocular pressure (IOP) is the cardinal and only modifiable risk factor for glaucoma, the leading cause of irreparable blindness worldwide. Twin and family studies estimate the heritability of IOP to be 40–70%, and linkage studies for IOP have identified numerous loci. Mutations in MYOC can cause markedly elevated IOP and aggressive glaucoma often requiring surgical intervention. However, the majority of the genetic basis for raised IOP and glaucoma in populations is complex, and recent large genome-wide association studies (GWASs) have identified over 100 common variants that contribute to IOP variation. In combination, these loci are predictive for primary open-angle glaucoma in independent populations, achieving an area under the receiver operating characteristic curve of 76% for high-pressure primary open-angle glaucoma; this suggests the possibility of targeted screening in the future. Additionally, GWAS findings have identified important biological pathways underlying IOP regulation, including lymphangiogenesis and lipid metabolism, providing novel targets for new therapies.

Inherited retinal diseases (IRDs) are at the forefront of innovative gene-specific treatments because of the causation by single genes, the availability of microsurgical access for treatment delivery, and the relative ease of quantitative imaging and vision measurement. However, it is not always easy to choose a priori, from scores of potential measures, an appropriate subset to evaluate efficacy outcomes considering the wide range of disease stages with different phenotypic features. This article reviews measurements of visual function and retinal structure that our group has used over the past three decades to understand the natural history of IRDs. We include measures of light sensitivity, retinal structure, mapping of natural fluorophores, evaluation of pupillary light reflex, and oculomotor control. We provide historical context and examples of applicability. We also review treatment trial outcomes using these measures of function and structure.

In healthy vision, the fovea provides high acuity and serves as the locus for fixation achieved through saccadic eye movements. Bilateral loss of the foveal regions in both eyes causes individuals to adopt an eccentric locus for fixation. This review deals with the eye movement consequences of the loss of the foveal oculomotor reference and the ability of individuals to use an eccentric fixation locus as the new oculomotor reference. Eye movements are an integral part of everyday activities, such as reading, searching for an item of interest, eye–hand coordination, navigation, or tracking an approaching car. We consider how these tasks are impacted by the need to use an eccentric locus for fixation and as a reference for eye movements, specifically saccadic and smooth pursuit eye movements.

Eye movements are indispensable for visual image stabilization during self-generated and passive head and body motion and for visual orientation. Eye muscles and neuronal control elements are evolutionarily conserved, with novel behavioral repertoires emerging during the evolution of frontal eyes and foveae. The precise execution of eye movements with different dynamics is ensured by morphologically diverse yet complementary sets of extraocular muscle fibers and associated motoneurons. Singly and multiply innervated muscle fibers are controlled by motoneuronal subpopulations with largely selective premotor inputs from task-specific ocular motor control centers. The morphological duality of the neuromuscular interface is matched by complementary biochemical and molecular features that collectively assign different physiological properties to the motor entities. In contrast, the functionality represents a continuum where most motor elements contribute to any type of eye movement, although within preferential dynamic ranges, suggesting that signal transmission and muscle contractions occur within bands of frequency-selective pathways.

Abnormalities in cranial motor nerve development cause paralytic strabismus syndromes, collectively referred to as congenital cranial dysinnervation disorders, in which patients cannot fully move their eyes. These disorders can arise through one of two mechanisms: (a) defective motor neuron specification, usually by loss of a transcription factor necessary for brainstem patterning, or (b) axon growth and guidance abnormalities of the oculomotor, trochlear, and abducens nerves. This review focuses on our current understanding of axon guidance mechanisms in the cranial motor nerves and how disease-causing mutations disrupt axon targeting. Abnormalities of axon growth and guidance are often limited to a single nerve or subdivision, even when the causative gene is ubiquitously expressed. Additionally, when one nerve is absent, its normal target muscles attract other motor neurons. Study of these disorders highlights the complexities of axon guidance and how each population of neurons uses a unique but overlapping set of axon guidance pathways.

The beginning of the twenty-first century was marked by the innovative use of pharmacochemical interventions, which have since expanded to include gene-based molecular therapies. For years, treatment has focused on tackling the pathophysiology of monogenic orphan diseases, and one of the first applications of these novel genome editing technologies was the treatment of rare inherited retinal dystrophies. In this review, we present recent, ongoing, and future gene therapy–based treatment trials for choroideremia, X-linked retinitis pigmentosa, Stargardt disease, and age-related macular degeneration. As these trials pave the way toward halting the progression of such devastating diseases, we will begin to see the exciting development of newer, cutting-edge strategies including base editing and prime editing, ushering in a new era of precision medicine.

Clinical trials for conditions affecting the visual system need to not only conform to the guidelines for all clinical trials, but also accommodate the possibility of both eyes of a single patient qualifying for the trial. In this review, I present the interplay of the key components in the design of a clinical trial, along with the modifications or options that may be available for trials addressing ocular conditions. Examples drawn from published reports of the design and results of clinical trials of ocular conditions are provided to illustrate application of the design principles. Current approaches to data analysis and reporting of trials are outlined, and the oversight and regulatory procedures to protect participants in clinical trials are discussed.