There is an unmet need in patients with geographic atrophy (GA) for treatments that preserve and improve functional vision to maintain their independence and quality of life. The limited number of available treatments for GA have demonstrated structural benefits, but none have consistently shown significant functional outcomes in clinical trials. Currently, best-corrected visual acuity (BCVA) is considered the gold standard functional endpoint in clinical trials; however, in the case of GA, it cannot fully evaluate visual impairment or treatment response, particularly in fovea-sparing GA lesions. In addition, BCVA may not fully capture the functional impact of foveal and parafoveal scotomas. There is emerging evidence for the utility of other functional assessments that may provide a more robust representation of the functional impact of GA; however, the current utilization of these tests in GA clinical trials varies widely. This review aims to evaluate current functional endpoints in GA and their strengths and limitations based on characteristics such as strength of structure-function correlation, practicality and feasibility, and patient perspective. There are many factors to consider when choosing a functional vision assessment when designing a GA clinical trial, and each functional vision assessment has several advantages and disadvantages, which are summarized in this review article.

Retinal image analysis has enjoyed groundbreaking advances in the last ten years due to seismic improvements in image analysis techniques from the field of computer vision. Previous reviews in deep learning and artificial intelligence (AI) [(Schmidt-Erfurth et al. 2018), (Ting et al. 2019)] have either focused on supervised learning, where labels are curated or manually created, or concentrated on the application of AI in specific image modalities and retina diseases [(Hormel et al. 2021), (Li et al.. 2024a)(Hormel et al., 2021; Li et al., 2024a)]. In this review, we sought to summarize the advances in the field with the shift towards label-free approaches using representational learning and the emergence of vision transformers as alternatives to convolutional neural networks for image analysis. These advances include semi-supervised learning, self-supervised learning and directly led to the advent of foundation models, vision-language models, and multi-modal models.

Over the last decade, vital dyes have revolutionized ophthalmic surgery, becoming indispensable tools in many intraocular procedures. These intraocular medical devices enhance visualization, facilitate tissue differentiation and improve surgical precision, ultimately optimizing outcomes. An understanding of their physicochemical properties and staining patterns is crucial for maximizing their benefits and achieving near-histological accuracy. In the recent years, increasing attention has been given to the biocompatibility of intraocular devices to enhance safety and minimise risks. Despite their widespread use, the long-term safety, interactions with intraocular devices, and optimal staining protocols of vital dyes remain insufficiently understood. Addressing these gaps is critical to improving surgical efficacy and patient safety. This review synthesizes recent findings to bridge these knowledge gaps and provide updated clinical insights, offering a comprehensive and detailed analysis of the physicochemical properties, staining mechanisms, and safety profiles of both traditional and newly developed vital dyes. Additionally, it examines how these properties influence surgical efficacy and biocompatibility. We also present an in-depth overview of experimental and clinical studies investigating the potential intraocular toxicity of vital dyes, focusing on crucial and controversial topics, such as surgical risk factors, the interaction between intraocular medical devices and the role of phototoxicity. Drawing on the latest experimental and clinical evidence, we propose updated guidelines to optimise the safe and effective use of vital dyes in intraocular surgery and patients outcomes.

Polypoidal choroidal vasculopathy (PCV) is an ocular condition predominantly affecting elderly individuals of Asian descent, characterized by the presence of polypoidal lesions and branching neovascular networks in the sub-retinal pigment epithelium (RPE) space. It has garnered increased attention for its potential differences from neovascular age-related macular degeneration. Genetic studies have identified specific genetic markers associated with PCV. Advances in imaging techniques, particularly optical coherence tomography (OCT) and OCT angiography, have significantly enhanced the diagnosis of PCV and our insight into its unique pathogenesis. Treatment strategies for PCV have evolved, with anti-vascular endothelial growth factor (VEGF) monotherapy becoming the primary treatment, and combination therapies including photodynamic therapy showing promising results. Consideration of targets beyond VEGF and the incorporation of artificial intelligence (AI) based analysis strategies may open the door to more personalized, precise, and effective treatments for patients. This review comprehensively discusses the current knowledge and recent advancements in PCV, including its epidemiology, genetics, biomarkers, pathogenesis, diagnosis, and management. It also highlights the need to explore mechanism underlying the higher prevalence of PCV in pigmented races, clarify the roles of pachychoroid and pachydrusen in PCV pathogenesis, and develop animal models that can better recapitulate the disease's pathological features.

Vesicants, powerful chemical weapons of mass destruction, are agents that cause blistering of the skin and blindness upon accidental exposure or during warfare. In addition, their exposure induces a wide range of other symptoms, including those affecting the respiratory tract, digestive system, skin, and ocular tissues. The ocular tissue can be exposed through both direct and indirect routes, such as direct contact with the affected corneal tissue and systemic blood circulation. Investigating eye injuries caused by vesicants is a critical and growing field of research in ophthalmology and ocular toxicology. In this review, we present the current status of the research, covering significant advances made in the study of vesicant-induced corneal and retinal injuries. We also provide general information on vesicants and discuss animal models used to investigate the molecular mechanisms of vesicant exposure and to develop medical countermeasures. Finally, we identify gaps in the current knowledge of the molecular mechanisms of vesicant action and highlight future directions for this emerging field.

The global prevalence of myopia and pathologic myopia (PM) has dramatically increased, raising significant public health concerns due to associated vision-threatening complications, such as myopic maculopathy (MM). This comprehensive review integrates the latest evidence regarding the environmental, genetic, and epigenetic factors contributing to myopia, as well as recent advances in precision medicine and therapeutic approaches aimed at mitigating the disease's impact. We examine how environmental factors interact with polygenic risk factors and epigenetic changes to influence disease progression. The application of artificial intelligence (AI) enhances the integration of genomic, environmental, and clinical data, thereby improving risk assessment and personalizing treatment options. Therapeutic strategies, including the use of low-dose atropine, orthokeratology, and repeated low-level red-light therapy, have shown promise in controlling myopia. Furthermore, emerging gene-editing techniques are being developed, although they are unlikely to be implemented as treatments for myopia and PM in the near future. Despite these advancements, disparities in resource availability and the implementation of interventions continue to hinder global equity, underscoring the need for scalable solutions such as mobile health applications and community-based preventive programs. This review emphasizes the importance of interdisciplinary collaboration to merge precision medicine with public health strategies, ensuring that scientific breakthroughs are equitably translated into clinical care. By aligning environmental preventive measures, genetic discoveries, and AI-powered innovations, this review outlines a strategic plan for reducing the global burden of myopia and its complications.

The conjunctival blood vessels are the only microcirculatory system on the body surface that can be observed non-invasively. Anatomically interconnected with multiple craniofacial circulatory systems, these vessels can indirectly reflect the blood supply to these areas and the overall state of systemic microcirculation. We synthesize findings from 48 studies spanning 2020-2025. Overall, existing research has found that the conjunctival vascular parameters can change in various diseases such as diabetes, cardiovascular diseases, and autoimmune diseases, and may even precede organic lesions. Recent advancements in conjunctival vessel imaging and analysis technologies have enabled the identification and evaluation of various ocular and systemic diseases based on conjunctival vascular parameters. However, existing studies are limited by insufficient sample sizes, covariate interference, limited disease types, a lack of investigation into the underlying mechanisms of conjunctival vascular changes, and inadequate integration with emerging technologies, such as artificial intelligence. Future research should aim to broaden the scope of investigation, delve deeper into the mechanisms governing conjunctival vascular alterations, and integrate artificial intelligence to establish a solid foundation for the clinical application of conjunctival vascular parameters.

Fuchs endothelial corneal dystrophy (FECD) is a heritable disorder distinguished by a progressive degeneration of the corneal endothelium. In its late-onset form, FECD has been associated with a trinucleotide repeat (TNR) expansion (CTG18.1) located in an intronic region of the TCF4 gene, whose frequency is variable among different ancestry groups. Since its discovery, studies investigating CTG18.1-mediated pathogenesis have steadily increased, yet much concerning the unique and tissue-specific clinical features of the disease, as well as its heritable mode of transmission, remain poorly understood. The field of repeat expansion disorders has greatly informed mechanistic understanding of CTG18.1-mediated FECD. In particular, molecular mechanisms underlying myotonic dystrophy type 1, attributed to a CTG expansion in the 3' UTR of the DMPK gene, have considerably informed the FECD field, despite its stark contrast in terms of multisystemic manifestations and variable age at onset. In this work, we critically discuss the non-mutually shared pathogenic parallelisms existing between the pathologies, as well as the unique molecular signatures exhibited by FECD and DM1, speculating on potential research directions for future investigations. Moreover, we discuss the few studies published over the past decade describing the occurrence of FECD in DM1 patients. Here, we debate possible shared molecular signatures that could explain FECD development as a consequence of a non-coding CTG expansion, irrespective of loci (e.g. DMPK or TCF4), and discuss experimental approaches to explain whether these pathologies share toxic mechanisms that arise from these distinct repeat elements.

Type 2 diabetes is a chronic, systemic, metabolic disorder characterized by persistent hyperglycemia and associated with a broad spectrum of complications, including those affecting the ocular surface. This article reviews the structural, biochemical, and neuropathic changes observed in the ocular surface of patients with diabetes. Hyperglycemia and associated metabolic imbalances lead to tear film instability, inflammation, oxidative stress, and peripheral neuropathy, contributing to the pathogenesis of dry eye disease, impaired corneal wound healing and corneal neuropathy. In addition, systemic factors such as glycemic control, inflammatory cytokines, and microvascular impairment have direct impact on ocular surface homeostasis. This review also evaluates the effects of antidiabetic therapies on the ocular surface. Recent studies suggest that drugs such as metformin, sodium-glucose co-transporter 2 inhibitors, glucagon like peptide-1 receptor agonists, and insulin along with glucose control, may offer the ocular surface protective benefits. Evidence supports their roles in reducing ocular surface inflammation, promoting corneal nerve regeneration, and improving tear film homeostasis. A comprehensive understanding of these factors may facilitate improved screening, early diagnosis, and integrative management of ocular surface disorders in type 2 diabetes.

Multiple Evanescent White Dot Syndrome (MEWDS) is a primary outer retinal inflammatory disorder, classically presenting as an acute, unilateral, self-limiting condition in young to middle-aged adults. It is characterized by multiple small white spots at the posterior pole, foveal granularity, wreath-like hyperfluorescence on fluorescein angiography, and a "dot-over-spot" hypofluorescent pattern on late-phase indocyanine green angiography. This PRISMA-compliant systematic review analyzed 592 eyes from 240 publications, supplemented by an institutional case series. While most cases conformed to the typical phenotype (62 %), nearly one-third were atypical (20 %) or secondary (18 %) to other chorioretinal diseases. Atypical forms included bilateral or recurrent presentations, distinctive angiographic patterns, or absence of spontaneous recovery with permanent structural damage. We also identified a previously unreported phenotype in older adults, featuring confluent hyperautofluorescence extending into the mid-periphery and hyperreflective outer retinal lesions, often with subacute worsening and partial steroid responsiveness. Secondary MEWDS occurred in association with various chorioretinal disorders, most commonly punctate inner choroiditis. Collectively, these findings support viewing MEWDS within the broader spectrum of outer retinal disorders sharing photoreceptor pathology but differing in triggers, imaging signatures, and outcomes. Recognition of atypical and secondary variants is essential for accurate diagnosis, risk stratification, and tailored management.

The alarming increase in childhood myopia has emerged as a significant public health concern. Due to its long-term consequences, there is also an expanding interest in adult-onset myopia. This review provides a comprehensive summary of interventions for slowing the onset and progression of myopia and discusses factors influencing their efficacy. Outdoor time is an effective intervention for at-risk pre-myopes, which can reduce myopia onset by up to 50 % and has been implemented on a large scale in some countries through school reforms. 0.05 % atropine and repeated low-level red light (RLRL) have also shown the potential to prevent myopia onset by approximately 50 %, though the cost-benefit of implementing them on a large scale warrants more research. Low-concentration atropine, various designs of peripheral defocus spectacles, contact lenses, and RLRL effectively slow myopia progression by at least 50 %. A history of higher baseline myopia status, faster baseline progression, parental myopia, high-risk lifestyle, and less outdoor time requires rigorous interventions. When combined with RLRL or atropine concentrations higher than 0.025 %, orthokeratology significantly improves myopia control in fast progressors and/or high myopes. Combining low-concentration atropine with peripheral defocus glasses or dual-focus contact lenses also yields better efficacy than monotherapy. There is limited research on adult myopia control, but offering comprehensive lifestyle and visual environment recommendations remains essential. Consistent use of these interventions and thorough safety monitoring are crucial for building clinical confidence. The success of myopia control hinges on personalization, given the diverse factors influencing efficacy and the challenges of large-scale implementation.

Macular telangiectasia type 2 (MacTel) is a rare neurodegenerative retinal disease defined by a unique combination of reduced macular pigment, a characteristic angiographic pattern, and a localized clinical presentation. The condition typically affects the temporal perifovea and leads to progressive visual impairment. No definitive treatment exists. Current management is limited to intravitreal anti-vascular endothelial growth factor (VEGF) injections for end-stage neovascular complications and the recently approved Encelto implant (Neurotech Pharmaceuticals, Inc.), which delivers ciliary neurotrophic factor (CNTF) for neuroprotection. To clarify the still enigmatic pathophysiology of MacTel, we conducted a comprehensive review of all human histopathology reports published in English through December 31, 2024. Findings were systematically evaluated with respect to tissue processing techniques, postmortem fixation times, disease stage at last recorded ophthalmologic evaluation, diagnostic certainty, inclusion of control specimens, and the anatomic origin of analyzed retinal sections. This approach aimed to identify histopathologic features most likely to represent core disease mechanisms. Each of the features identified as most likely to be pathophysiologically relevant was independently assessed for clinical and histopathologic specificity. These features were then further interpreted in the context of genetic, metabolic, and anatomic associations reported in the literature. Donor demographics, coexisting ocular conditions, and systemic comorbidities were also reviewed to support the development of an integrative hypothesis for MacTel pathogenesis. Drawing on this synthesis, we propose a histopathology-informed model of disease pathophysiology and outline a provisional timeline for the contribution of key factors to clinical expression. We also review current neuroprotective strategies and provide targeted recommendations for future therapeutic development and histopathologic research. The conceptual framework developed in this work -grounded in rigorous analysis of the most consistent and methodologically validated histopathologic findings, and interpretation of their mechanistic context- may serve as a model for deciphering rare retinal diseases and for generating focused, hypothesis-driven questions to guide future investigation.

Non-infectious uveitis is a group of complex inflammatory eye diseases shaped by genetic susceptibility, immune dysregulation, and environmental cues. Among these, the mucosal microbiome-including gut, oral, and ocular surface microbial communities-has emerged as a key player in modulating systemic and ocular immune responses. Recent evidence supports a gut-eye axis wherein microbial dysbiosis alters intestinal barrier function, perturbs T cell homeostasis, and drives systemic immune activation that can breach ocular immune privilege. Specific taxa, such as Prevotella and Faecalibacterium, as well as microbial metabolites including short-chain fatty acids, have been implicated in promoting or mitigating ocular inflammation. Human leukocyte antigen (HLA) alleles, notably HLA-B27 and HLA-A29, influence both microbiome composition and disease phenotype, suggesting a gene-microbiome-immunity triad of interaction in uveitis pathogenesis. Drawing on insights from metagenomics, metabolomics, in vitro and in vivo experimental and murine models, this review delineates four key mechanisms-immune imbalance, antigenic mimicry, epithelial barrier disruption, and bacterial translocation-that underpin the key roles of microbiome in uveitis. We combine current literature and integrate findings from our research programs to highlight diagnostic and therapeutic opportunities. Microbiome-informed strategies, such as rational probiotic design, dietary modulation, and targeted microbial therapies, hold promise for complementing existing immunosuppressive regimens. Translating these insights into clinical practice requires robust multi-omic studies, longitudinal cohorts, mechanistic studies, and precision-guided intervention trials. By framing uveitis within a mucosal immunological context, this review proposes a future precision medicine roadmap for integrating microbiome science into ocular inflammatory disease management.

Oxygen is the major element for metabolism in the retina. Reduced oxygen supply causes significant changes in cellular metabolism and gene expression in the retina initiating inflammasome activation, apoptosis of retinal cells, mitochondrial damage, oxidative stress and neurodegeneration. Physiologically, retinal hypoxia plays important role regulating vasculogenesis during our development in early life. Retinal hypoxia also plays key regulatory roles during the onset and progression of many retinopathy conditions including neovascularization at later stages of our life. Though the exact mechanism of neovascularization is still largely unknown, hypoxia may contribute to the over expression of vascular endothelial growth factor (VEGF), and VEGF is a known inducer of neovascularization. Thus, molecular imaging of retinal hypoxia could be an important diagnostic tool assessing the risk of retinopathy, its progression, and response to therapy. Imaging retinal hypoxia is also an important diagnostic tool assessing the risk of inflammasome activation, mitochondrial damage, oxidative stress and apoptosis of retinal cells at molecular levels. This review will provide an overview of technologies to detect retinal hypoxia in the living retinal tissues before the onset of tissue damage. This review will also discuss the design and development of HYPOX-4, a highly sensitive molecular imaging probe capable of detecting retinal hypoxia in the living retina before the onset of neovascularization. The author will further discuss a quantitative method to assess HYPOX-4 fluorescence intensity measurement by computational methods, correlating with levels of retinal hypoxia and create a predictive biomarker for retinal neovascularization. An overview of the technology development will also include Dr. Linsenmeier's early development of microelectrode for our fundamental understanding of retinal tissue oxygenation using an invasive measurement technique. An overview of the other emerging technologies, including retinal oximetry, phosphorescence lifetime imaging and photoacoustic imaging will be discussed.

Eyelid dermatitis (ED) is an interdisciplinary medical challenge affecting thousands of patients worldwide. ED management can be difficult in view of the numerous differential diagnoses and limited treatment options. We review the diagnostic work-up for ED patients, with a special focus on the latest innovative solutions.

Axial myopia is characterized by a panoply of morphological, clinical and histological, features in association with longer axial length. It includes changes in the region peripheral to the optic nerve head (reduction in the density of photoreceptors and retinal pigment epithelium (RPE) cells and retinal thinning); in the optic nerve head region in moderately myopic eyes (shift of Bruch's membrane (BM) opening typically in the temporal/inferior direction, leading to a secondary BM overhang into the nasal intrapapillary compartment, BM absence in the temporal parapapillary region ("gamma zone"), and optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter; and widening of the RPE opening leading to myopic parapapillary beta zone), and in highly myopic eyes (BM opening enlargement resulting in a circular gamma zone, elongation and thinning of the lamina cribrosa ("secondary macrodisc") and of the peripapillary scleral flange ("parapapillary delta zone"); and in the macular region with an elongation of the fovea-optic disc distance, reduction in angle kappa, straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibers (leading to a re-arrangement of the retinal nerve fibers with a myopia-specific regional distribution of the retinal nerve fiber layer thickness profile), choroidal thinning most pronounced at the posterior pole and affecting mainly the medium-sized and large choroidal vessel layer), and scleral thinning. Pathologic changes in the macular region are extrafoveally located, linear RPE layer defects (lacquer cracks), potentially widening to round RPE layer defects (patchy atrophies), in some eyes with central BM defects; BM defects with RPE layer defects in the foveal region, accompanied by macular neovascularization or subsequent subretinal RPE cell proliferation ("macular atrophy"); myopic macular retinoschisis; and staphylomas. With longer axial length, the prevalence of non-glaucomatous optic neuropathy and glaucoma-like/glaucomatous optic neuropathy steeply increases beyond an axial length of 26.0-26.5 mm. With BM thickness being independent of axial length and in view of eye shape change from an oblate or sphere in emmetropia to a prolate rotational ellipsoid in myopia, the myopia specific morphological changes may be associated with a primary BM enlargement in the region peripheral to the optic disc.

pediatric inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders characterized by progressive visual function impairment, often manifesting from early childhood. These conditions arise from dysfunction in retinal morphogenesis, phototransduction, and cellular maintenance pathways, involving photoreceptors, the retinal pigment epithelium, and glial systems. This review provides an integrated analysis of the molecular underpinnings, phenotypic variability, diagnostic advancements, and emerging therapeutic avenues for pediatric IRDs. By systematically retracing the literature and leveraging over a decade of laboratory experience, we dissect each major form of pediatric IRD-such as Leber congenital amaurosis, retinitis pigmentosa, Stargardt disease, achromatopsia, and syndromic entities like Usher and Bardet-Biedl syndromes-emphasizing genotype-phenotype correlations and shared pathogenic pathways. Additionally, we discuss next-generation sequencing, advanced bioinformatics, and AI-based diagnostics, along with gene therapy, genome editing, and emerging biotechnologies. By mapping IRDs to molecular networks through Cytoscape and functional genomics, we identify converging pathogenic mechanisms and therapeutic targets. This compendium aims to serve as a reference for clinicians, researchers, and genetic counselors navigating the evolving IRD landscape.

Retinitis Pigmentosa (RP) is an incurable disorder characterized by progressive vision loss due to photoreceptor degeneration, typically following a rod-cone sequence. Rods die first, driven by primary genetic mutations; cones then degenerate secondarily through bystander mechanisms. As cones mediate daylight and high-acuity vision, crucial to human visual function, even partial preservation of these cells can profoundly enhance quality of life, regardless of the underlying genetic defect. Although significant progress has been made in understanding RP genetics and developing targeted therapies such as gene augmentation, a universal cure remains out of reach. This review centers on the biological drivers of secondary cone degeneration, with a focus on oxidative stress, metabolic dysfunction, and inflammation. Inflammation, now recognized as a key contributor to RP progression, involves the activation of microglia and infiltration by macrophages, both of which exacerbate retinal damage and offer promising therapeutic targets. We briefly survey current treatment modalities that have advanced to clinical application, including gene therapies, retinal prostheses, and neuroprotective strategies. Building on this therapeutic landscape, we propose a rationale for exploring ocular glucocorticoids-specifically dexamethasone-as a treatment avenue. Recent in vivo evidence from the rd10 mouse model demonstrates that intraocular dexamethasone, a long-approved agent for ocular inflammation, can preserve cone photoreceptors and protect the retinal pigment epithelium, a critical barrier for retinal homeostasis. Glucocorticoids may thus represent a class of mutation-agnostic therapeutics with strong translational promise. Their repurposing for RP could help safeguard photoreceptors and visual function, addressing a pressing and unmet clinical need.

Diabetic macular edema (DME) is the most common cause of vision-threatening diabetic retinopathy (VTDR) with an increasing prevalence tied to the global epidemic in diabetes. Despite significant advances, the management of DME remains a dynamic field with many unresolved controversies. Optical coherence tomography (OCT) allows objective assessment, however, correlation between vision and morphological changes can be inconsistent, causing disagreements on treatment strategies. DME is a complex disease with multifactorial pathophysiological pathways, leading to heterogenous treatment responses. There is a lack of standardized definition of treatment "non-response" and protocol for switching to second-line or adjuvant treatments. New anti-vascular endothelial growth factor (anti-VEGF) drugs and multi-targeted therapies seem to demonstrate improved durability, but long-term data is not yet available. Research in artificial intelligence (AI) is developing rapidly, however, rigorous appraisal of its reliability and generalizability are necessary before its implementation. Significant vision loss from DME in pregnant women, young children and elderly patients with systemic comorbidities are challenging conundrums. An international panel of experts (IPE) comprising 36 experts from 16 countries formulated and voted on the consensus statements in 5 key areas: 1) Diagnostic controversies around classification and imaging; 2) Treatment controversies; 3) Management paradigm between protocol-based and individualized approaches; 4) Emerging controversies in novel therapeutics and AI application, and 5) Special considerations for specific patient populations. There is an imminent need for mutual agreement on the best-possible approach to DME management in order to promote the optimal patient outcomes and to identify specific issues that require prioritization of resources and research.

Exposure of the eye to bright bleaching light produces a large decrease in photoreceptor sensitivity, followed by a slow return during adaptation to darkness. Although much progress has been made understanding the nature of this phenomenon, particularly its biochemistry, less is known about the physiology of dark adaptation. In this review, we summarize the evidence for desensitization produced by photoproducts of bleaching, especially apo-opsin, that is opsin without bound chromophore. We describe the relationship between these studies and diseases such as vitamin A deprivation and congenital stationary night blindness; the effects of analogs of chromophore on photoreceptor sensitivity; and the roles of transducin, rhodopsin kinase, and arrestin. We review many specialized features of dark adaptation in cones, including the role of retinal G protein-coupled receptor (RGR) opsin. For both rod and cone dark adaptation, we summarize some of the principal uncertainties in our understanding. We hope our review will provide a guide to past work as well as an indicator of many possible areas of future research.