Annual Review of Vision Science - Volume 9, 2023

I entered science at a particularly lucky time. By the mid-1960s, women were being encouraged to pursue serious scientific careers. During the 60-year span of my career, women have become equal partners with men in scientific research, particularly in the biological sciences. There also has been abundant funding for research, which allowed me to succeed in a “soft-money” position at Smith-Kettlewell Eye Research Institute, a place that was especially supportive for a woman scientist with children. In this article, I describe the findings that I think represent the most interesting and enduring scientific work from my career.

This narrative review summarizes the literature on factors related to eye care access and utilization in the United States. Using the Healthy People 2030 framework, this review investigates social determinants of health associated with general and follow-up engagement, screenings, diagnostic visits, treatment, technology, and teleophthalmology. We provide hypotheses for these documented eye care disparities, featuring qualitative, patient-centered research. Lastly, we provide recommendations in the hopes of appropriately eliminating these disparities and reimagining eye care.

Retinopathy of prematurity (ROP) is a complex disease involving development of the neural retina, ocular circulations, and other organ systems of the premature infant. The external stresses of the ex utero environment also influence the pathophysiology of ROP through interactions among retinal neural, vascular, and glial cells. There is variability among individual infants and presentations of the disease throughout the world, making ROP challenging to study. The methods used include representative animal models, cell culture, and clinical studies. This article describes the impact of maternal–fetal interactions; stresses that the preterm infant experiences; and biologic pathways of interest, including growth factor effects and cell–cell interactions, on the complex pathophysiology of ROP phenotypes in developed and emerging countries.

Global health security threats and the public health impact resulting from emerging infectious diseases including the ongoing COVID-19 pandemic and recent Ebola virus disease outbreaks continuously emphasize the need for a comprehensive approach to preparedness, management of disease outbreaks, and health sequelae associated with emergent pathogens. A spectrum of associated ophthalmic manifestations, along with the potential persistence of emerging viral pathogens in ocular tissues, highlight the importance of an ophthalmic approach to contributing to efforts in the response to public health emergencies from disease outbreaks. This article summarizes the ophthalmic and systemic findings, epidemiology, and therapeutics for emerging viral pathogens identified by the World Health Organization as high-priority pathogens with epidemic potential.

Although diabetic retinopathy (DR) is clinically diagnosed as a vascular disease, many studies find retinal neuronal and visual dysfunction before the onset of vascular DR. This suggests that DR should be viewed as a neurovascular disease. Prior to the onset of DR, human patients have compromised electroretinograms that indicate a disruption of normal function, particularly in the inner retina. They also exhibit reduced contrast sensitivity. These early changes, especially those due to dysfunction in the inner retina, are also seen in rodent models of diabetes in the early stages of the disease. Rodent models of diabetes exhibit several neuronal mechanisms, such as reduced evoked GABA release, increased excitatory glutamate signaling, and reduced dopamine signaling, that suggest specific neuronal deficits. This suggests that understanding neuronal deficits may lead to early diabetes treatments to ameliorate neuronal dysfunction.

The pervasiveness of mobile devices and other associated technologies has affected all aspects of our daily lives. People with visual impairments are no exception, as they increasingly tend to rely on mobile apps for assistance with various visual tasks in daily life. Compared to dedicated visual aids, mobile apps offer advantages such as affordability, versatility, portability, and ubiquity. We have surveyed hundreds of mobile apps of potential interest to people with vision impairments, either released as special assistive apps claiming to help in tasks such as text or object recognition (n = 68), digital accessibility (n = 84), navigation (n = 44), and remote sighted service (n = 4), among others, or marketed as general camera magnification apps that can be used for visual assistance (n = 77). While assistive apps as a whole received positive feedback from visually impaired users, as reported in various studies, evaluations of the usability of every app were typically limited to user reviews, which are often not scientifically informative. Rigorous evaluation studies on the effect of vision assistance apps on daily task performance and quality of life are relatively rare. Moreover, evaluation criteria are difficult to establish, given the heterogeneity of the visual tasks and visual needs of the users. In addition to surveying literature on vision assistance apps, this review discusses the feasibility and necessity of conducting scientific research to understand visual needs and methods to evaluate real-world benefits.

Rod and cone photoreceptors degenerate in retinitis pigmentosa and age-related macular degeneration, robbing the visual system of light-triggered signals necessary for sight. However, changes in the retina do not stop with the photoreceptors. A stereotypical set of morphological and physiological changes, known as remodeling, occur in downstream retinal neurons. Some aspects of remodeling are homeostatic, with structural or functional changes compensating for partial loss of visual inputs. However, other aspects are nonhomeostatic, corrupting retinal information processing to obscure vision mediated naturally by surviving photoreceptors or artificially by vision-restoration technologies. In this review, I consider the mechanism of remodeling and its consequences for residual and restored visual function; discuss the role of retinoic acid, a critical molecular trigger of detrimental remodeling; and discuss strategies for suppressing retinoic acid biosynthesis or signaling as therapeutic possibilities for mitigating vision loss.

Inherited and age-associated vision loss is often associated with degeneration of the cells of the retina, the light-sensitive layer at the back of the eye. The mammalian retina, being a postmitotic neural tissue, does not have the capacity to repair itself through endogenous regeneration. There has been considerable excitement for the development of cell replacement approaches since the isolation and development of culture methods for human pluripotent stem cells, as well as the generation of induced pluripotent stem cells. This has now been combined with novel three-dimensional organoid culture systems that closely mimic human retinal development in vitro. In this review, we cover the current state of the field, with emphasis on the cell delivery challenges, role of the recipient immunological microenvironment, and challenges related to connectivity between transplanted cells and host circuitry both locally and centrally to the different areas of the brain.

Because the central nervous system is largely nonrenewing, neurons and their synapses must be maintained over the lifetime of an individual to ensure circuit function. Age is a dominant risk factor for neural diseases, and declines in nervous system function are a common feature of aging even in the absence of disease. These alterations extend to the visual system and, in particular, to the retina. The retina is a site of clinically relevant age-related alterations but has also proven to be a uniquely approachable system for discovering principles that govern neural aging because it is well mapped, contains diverse neuron types, and is experimentally accessible. In this article, we review the structural and molecular impacts of aging on neurons within the inner and outer retina circuits. We further discuss the contribution of non-neuronal cell types and systems to retinal aging outcomes. Understanding how and why the retina ages is critical to efforts aimed at preventing age-related neural decline and restoring neural function.

This review examines the concept of the preferred retinal locus (PRL) in patients with macular diseases. Considering monocular and binocular viewing, we (a) explain how to identify the PRL and discuss the pitfalls associated with its measurement, (b) review the current hypotheses for PRL development, (c) assess whether the PRL is the new reference point of the ocular motor system, and discuss (d) the functional and (e) the clinical implications of the PRL. We conclude that the current definition of the PRL is probably incomplete and should incorporate the need to evaluate the PRL in the framework of binocular viewing. We emphasize the need for more research.

Proper eye structure is essential for visual function: Multiple essential eye tissues must take shape and assemble into a precise three-dimensional configuration. Accordingly, alterations to eye structure can lead to pathological conditions of visual impairment. Changes in eye shape can also be adaptive over evolutionary time. Eye structure is first established during development with the formation of the optic cup, which contains the neural retina, retinal pigment epithelium, and lens. This crucial yet deceptively simple hemispherical structure lays the foundation for all later elaborations of the eye. Building on descriptions of the embryonic eye that started with hand drawings and micrographs, the field is beginning to identify mechanisms driving dynamic changes in three-dimensional cell and tissue shape. A combination of molecular genetics, imaging, and pharmacological approaches is defining connections among transcription factors, signaling pathways, and the intracellular machinery governing the emergence of this crucial structure.

We live on a planet that is bathed in daily and seasonal sunlight cycles. In this context, terrestrial life forms have evolved mechanisms that directly harness light energy (plants) or decode light information for adaptive advantage. In animals, the main light sensors are a family of G protein–coupled receptors called opsins. Opsin function is best described for the visual sense. However, most animals also use opsins for extraocular light sensing for seasonal behavior and camouflage. While it has long been believed that mammals do not have an extraocular light sensing capacity, recent evidence suggests otherwise. Notably, encephalopsin (OPN3) and neuropsin (OPN5) are both known to mediate extraocular light sensing in mice. Examples of this mediation include photoentrainment of circadian clocks in skin (by OPN5) and acute light-dependent regulation of metabolic pathways (by OPN3 and OPN5). This review summarizes current findings in the expanding field of extraocular photoreception and their relevance for human physiology.

As we navigate and behave in the world, we are constantly deciding, a few times per second, where to look next. The outcomes of these decisions in response to visual input are comparatively easy to measure as trajectories of eye movements, offering insight into many unconscious and conscious visual and cognitive processes. In this article, we review recent advances in predicting where we look. We focus on evaluating and comparing models: How can we consistently measure how well models predict eye movements, and how can we judge the contribution of different mechanisms? Probabilistic models facilitate a unified approach to fixation prediction that allows us to use explainable information explained to compare different models across different settings, such as static and video saliency, as well as scanpath prediction. We review how the large variety of saliency maps and scanpath models can be translated into this unifying framework, how much different factors contribute, and how we can select the most informative examples for model comparison. We conclude that the universal scale of information gain offers a powerful tool for the inspection of candidate mechanisms and experimental design that helps us understand the continual decision-making process that determines where we look.

Some visual properties are consistent across a wide range of environments, while other properties are more labile. The efficient coding hypothesis states that many of these regularities in the environment can be discarded from neural representations, thus allocating more of the brain's dynamic range to properties that are likely to vary. This paradigm is less clear about how the visual system prioritizes different pieces of information that vary across visual environments. One solution is to prioritize information that can be used to predict future events, particularly those that guide behavior. The relationship between the efficient coding and future prediction paradigms is an area of active investigation. In this review, we argue that these paradigms are complementary and often act on distinct components of the visual input. We also discuss how normative approaches to efficient coding and future prediction can be integrated.

Patterns of brain activity contain meaningful information about the perceived world. Recent decades have welcomed a new era in neural analyses, with computational techniques from machine learning applied to neural data to decode information represented in the brain. In this article, we review how decoding approaches have advanced our understanding of visual representations and discuss efforts to characterize both the complexity and the behavioral relevance of these representations. We outline the current consensus regarding the spatiotemporal structure of visual representations and review recent findings that suggest that visual representations are at once robust to perturbations, yet sensitive to different mental states. Beyond representations of the physical world, recent decoding work has shone a light on how the brain instantiates internally generated states, for example, during imagery and prediction. Going forward, decoding has remarkable potential to assess the functional relevance of visual representations for human behavior, reveal how representations change across development and during aging, and uncover their presentation in various mental disorders.

The visual system must reconstruct the dynamic, three-dimensional (3D) world from ambiguous two-dimensional (2D) retinal images. In this review, we synthesize current literature on how the visual system of nonhuman primates performs this transformation through multiple channels within the classically defined dorsal (where) and ventral (what) pathways. Each of these channels is specialized for processing different 3D features (e.g., the shape, orientation, or motion of objects, or the larger scene structure). Despite the common goal of 3D reconstruction, neurocomputational differences between the channels impose distinct information-limiting constraints on perception. Convergent evidence further points to the little-studied area V3A as a potential branchpoint from which multiple 3D-fugal processing channels diverge. We speculate that the expansion of V3A in humans may have supported the emergence of advanced 3D spatial reasoning skills. Lastly, we discuss future directions for exploring 3D information transmission across brain areas and experimental approaches that can further advance the understanding of 3D vision.

The superior colliculus (SC) is a subcortical brain structure that is relevant for sensation, cognition, and action. In nonhuman primates, a rich history of studies has provided unprecedented detail about this structure's role in controlling orienting behaviors; as a result, the primate SC has become primarily regarded as a motor control structure. However, as in other species, the primate SC is also a highly visual structure: A fraction of its inputs is retinal and complemented by inputs from visual cortical areas, including the primary visual cortex. Motivated by this, recent investigations are revealing the rich visual pattern analysis capabilities of the primate SC, placing this structure in an ideal position to guide orienting movements. The anatomical proximity of the primate SC to both early visual inputs and final motor control apparatuses, as well as its ascending feedback projections to the cortex, affirms an important role for this structure in active perception.

The basal ganglia (BG) make up a prominent nexus between visual and motor-related brain regions. In contrast to the BG's well-established roles in movement control and value-based decision making, their contributions to the transformation of visual input into an action remain unclear, especially in the context of perceptual decisions based on uncertain visual evidence. This article reviews recent progress in our understanding of the BG's contributions to the formation, evaluation, and adjustment of such decisions. From theoretical and experimental perspectives, the review focuses on four key stations in the BG network, namely, the striatum, pallidum, subthalamic nucleus, and midbrain dopamine neurons, which can have different roles and together support the decision process.

Perception and memory are traditionally thought of as separate cognitive functions, supported by distinct brain regions. The canonical perspective is that perceptual processing of visual information is supported by the ventral visual stream, whereas long-term declarative memory is supported by the medial temporal lobe. However, this modular framework cannot account for the increasingly large body of evidence that reveals a role for early visual areas in long-term recognition memory and a role for medial temporal lobe structures in high-level perceptual processing. In this article, we review relevant research conducted in humans, nonhuman primates, and rodents. We conclude that the evidence is largely inconsistent with theoretical proposals that draw sharp functional boundaries between perceptual and memory systems in the brain. Instead, the weight of the empirical findings is best captured by a representational-hierarchical model that emphasizes differences in content, rather than in cognitive processes within the ventral visual stream and medial temporal lobe.

Using natural scenes is an approach to studying the visual and eye movement systems approximating how these systems function in everyday life. This review examines the results from behavioral and neurophysiological studies using natural scene viewing in humans and monkeys. The use of natural scenes for the study of cerebral cortical activity is relatively new and presents challenges for data analysis. Methods and results from the use of natural scenes for the study of the visual and eye movement cortex are presented, with emphasis on new insights that this method provides enhancing what is known about these cortical regions from the use of conventional methods.