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Vision, Volume 5, Issue 4 (December 2021) – 16 articles

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Review
Validation of Digital Applications for Evaluation of Visual Parameters: A Narrative Review
Vision 2021, 5(4), 58; https://doi.org/10.3390/vision5040058 - 24 Nov 2021
Viewed by 204
Abstract
The current review aimed to collect and critically analyze the scientific peer-reviewed literature that is available about the use of digital applications for evaluation of visual parameters in electronic devices (tablets and smartphones), confirming if there are studies calibrating and validating each of [...] Read more.
The current review aimed to collect and critically analyze the scientific peer-reviewed literature that is available about the use of digital applications for evaluation of visual parameters in electronic devices (tablets and smartphones), confirming if there are studies calibrating and validating each of these applications. Three bibliographic search engines (using the search equation described in the paper) and the Mendeley reference manager search engine were used to complete the analysis. Only articles written in English and that are evaluating the use of tests in healthy patients to measure or characterize any visual function aspects using tablets or smartphones were included. Articles using electronic visual tests to assess the results of surgical procedures or are conducted in pathological conditions were excluded. A total of 19 articles meeting these inclusion and exclusion criteria were finally analyzed. One critical point of all these studies is that there was no mention of the characterization (spatial and/or colorimetrical) of screens and the stimuli used in most of them. Only two studies described some level of calibration of the digital device before the beginning of the study. Most revised articles described non-controlled comparatives studies (73.7%), reporting some level of scientific evidence on the validation of tools, although more consistent studies are needed. Full article
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Article
The Functional Network of the Visual Cortex Is Altered in Migraine
Vision 2021, 5(4), 57; https://doi.org/10.3390/vision5040057 - 18 Nov 2021
Viewed by 223
Abstract
Migraine is a common neurological disorder characterized by recurrent episodes of headache, frequently accompanied by various reversible neurological disturbances. Some migraine patients experience visually triggered migraine headache, and most attacks of migraine with aura are associated with the disturbance of vision and photophobia, [...] Read more.
Migraine is a common neurological disorder characterized by recurrent episodes of headache, frequently accompanied by various reversible neurological disturbances. Some migraine patients experience visually triggered migraine headache, and most attacks of migraine with aura are associated with the disturbance of vision and photophobia, suggesting an abnormal neural activity in the visual cortex. Numerous studies have shown a large cortical hemodynamic response to visual stimulation and an altered intrinsic visual functional connectivity network in patients with migraine. In this interictal study, we applied a novel data-driven method with fMRI to identify the functional network in the visual cortex evoked by visual stimulation and investigated the effect of migraine on this network. We found that the distribution of the functional network along both the ventral and dorsal visual pathways differed between migraine patients and non-headache healthy control participants, providing evidence that the functional network was altered in migraine between headaches. The functional network was bilateral in the control participants but substantially lateralized in the migraine patients. The results also indicated different effects of colored lenses on the functional network for both participant groups. Full article
(This article belongs to the Special Issue The Visual Aura in Migraine)
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Article
Application of Eye Tracking Technology in Medicine: A Bibliometric Analysis
Vision 2021, 5(4), 56; https://doi.org/10.3390/vision5040056 - 11 Nov 2021
Viewed by 367
Abstract
Eye tracking provides a quantitative measure of eye movements during different activities. We report the results from a bibliometric analysis to investigate trends in eye tracking research applied to the study of different medical conditions. We conducted a search on the Web of [...] Read more.
Eye tracking provides a quantitative measure of eye movements during different activities. We report the results from a bibliometric analysis to investigate trends in eye tracking research applied to the study of different medical conditions. We conducted a search on the Web of Science Core Collection (WoS) database and analyzed the dataset of 2456 retrieved articles using VOSviewer and the Bibliometrix R package. The most represented area was psychiatry (503, 20.5%) followed by neuroscience (465, 18.9%) and psychology developmental (337, 13.7%). The annual scientific production growth was 11.14% and showed exponential growth with three main peaks in 2011, 2015 and 2017. Extensive collaboration networks were identified between the three countries with the highest scientific production, the USA (35.3%), the UK (9.5%) and Germany (7.3%). Based on term co-occurrence maps and analyses of sources of articles, we identified autism spectrum disorders as the most investigated condition and conducted specific analyses on 638 articles related to this topic which showed an annual scientific production growth of 16.52%. The majority of studies focused on autism used eye tracking to investigate gaze patterns with regards to stimuli related to social interaction. Our analysis highlights the widespread and increasing use of eye tracking in the study of different neurological and psychiatric conditions. Full article
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Case Report
Chronic Macular Oedema as a Late MIRAgel-Related Complication
Vision 2021, 5(4), 55; https://doi.org/10.3390/vision5040055 - 08 Nov 2021
Viewed by 342
Abstract
Background: MIRAgel® (MIRA, Waltham, MA, USA) is a hydrogel scleral buckle introduced in 1979 to treat rhegmatogenous retinal detachments. Its use was discontinued because late complications that require surgical removal were reported. Methods: Case report. Results: We report a case of left [...] Read more.
Background: MIRAgel® (MIRA, Waltham, MA, USA) is a hydrogel scleral buckle introduced in 1979 to treat rhegmatogenous retinal detachments. Its use was discontinued because late complications that require surgical removal were reported. Methods: Case report. Results: We report a case of left eye MIRAgel® buckle surgery 28 years ago presenting with a tender palpable erythematous swelling at the lower lid, with marked conjunctival chemosis and progressive ophthalmoplegia. Imaging revealed a large, well-defined, horseshoe-shaped lesion in the extraconal space of the left orbit with globe distortion, with histological confirmation of an expanded hydrogel buckle. He recovered well following removal of the explant but developed chronic macular oedema a year later, which persisted despite sub-Tenon’s triamcinolone injections. Repeat imaging demonstrated remaining hydrogel explant. Macular oedema settled well upon successful surgical removal with no recurrence to date. Conclusion: Our case is the first to describe macular oedema as a late MIRAgel-related complication, with complete removal of the explant being the definitive treatment. Macular oedema indicates postoperative inflammation secondary to the remaining explant fragments. Given the friability of hydrolysed MIRAgel®, we recommend ophthalmologists to warn patients regarding the possibility of further inflammation in the globe or the orbit in case of incomplete removal. Full article
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Review
From “Transient Hemiopsia” to Migraine Aura
Vision 2021, 5(4), 54; https://doi.org/10.3390/vision5040054 - 05 Nov 2021
Viewed by 225
Abstract
This paper outlines the historical development of the concept of the visual aura of migraine, from the first comprehensive published description by the physician Hubert Airy, in 1870. Airy’s description of the phenomenon he called “transient hemiopsia” became widely copied and highly influential [...] Read more.
This paper outlines the historical development of the concept of the visual aura of migraine, from the first comprehensive published description by the physician Hubert Airy, in 1870. Airy’s description of the phenomenon he called “transient hemiopsia” became widely copied and highly influential as a consequence of the language and images that he used in his presentation. This paper outlines the subsequent development of theories of aura from the time of Airy’s publication to the first demonstration of spreading oligaemia by Lautitzen and Olesen in the 1980s. Full article
(This article belongs to the Special Issue The Visual Aura in Migraine)
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Article
Visual Memory Scan Slopes: Their Changes over the First Two Seconds of Processing
Vision 2021, 5(4), 53; https://doi.org/10.3390/vision5040053 - 04 Nov 2021
Viewed by 193
Abstract
Using the prime–probe comparison paradigm, Jacob, Breitmeyer, and Treviño (2013) demonstrated that information processing in visual short-term memory (VSTM) proceeds through three stages: sensory visible persistence (SVP), nonvisible informational persistence (NIP), and visual working memory (VWM). To investigate the effect of increasing the [...] Read more.
Using the prime–probe comparison paradigm, Jacob, Breitmeyer, and Treviño (2013) demonstrated that information processing in visual short-term memory (VSTM) proceeds through three stages: sensory visible persistence (SVP), nonvisible informational persistence (NIP), and visual working memory (VWM). To investigate the effect of increasing the memory load on these stages by using 1, 3, and 5 display items, measures of VSTM performance, including storage, storage-slopes, and scan-slopes, were obtained. Results again revealed three stages of VSTM processing, but with the NIP stage increasing in duration as memory load increased, suggesting a need, during the NIP stage, for transfer and encoding delays of information into VWM. Consistent with this, VSTM scan-slopes, in ms/item, were lowest during the first NIP stage, highest during the second NIP stage, and intermediate during the third, non-sensory VWM stage. The results also demonstrated a color-superiority effect, as all VSTM scan-slopes for color were lower than those for shape and as all VSTM storages for color are greater than those for shape, and the existence of systematic pair-wise correlations between all three measures of VSTM performance. These findings and their implications are related to other paradigms and methods used to investigate post-stimulus processing in VSTM. Full article
(This article belongs to the Special Issue Sensory and Working Memory: Stimulus Encoding, Storage, and Retrieval)
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Article
Aura Mapping: Where Vision and Somatosensation Meet
Vision 2021, 5(4), 52; https://doi.org/10.3390/vision5040052 - 30 Oct 2021
Viewed by 310
Abstract
While migraine auras are most frequently visual, somatosensory auras are also relatively common. Both are characterized by the spread of activation across a cortical region containing a spatial mapping of the sensory (retinal or skin) surface. When both aura types occur within a [...] Read more.
While migraine auras are most frequently visual, somatosensory auras are also relatively common. Both are characterized by the spread of activation across a cortical region containing a spatial mapping of the sensory (retinal or skin) surface. When both aura types occur within a single migraine episode, they may offer an insight into the neural mechanism which underlies them. Could they both be initiated by a single neural event, or do the timing and laterality relationships between them demand multiple triggers? The observations reported here were carried out 25 years ago by a group of six individuals with migraine with aura. They timed, described and mapped their visual and somatosensory auras as they were in progress. Twenty-nine episode reports are summarized here. The temporal relationship between the onset of the two auras was quite variable within and across participants. Various forms of the cortical spreading depression hypothesis of migraine aura are evaluated in terms of whether they can account for the timing, pattern of symptom spread and laterality of the recorded auras. Full article
(This article belongs to the Special Issue The Visual Aura in Migraine)
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Communication
SARS-CoV-2 in Conjunctiva and Tears and Ocular Symptoms of Patients with COVID-19
Vision 2021, 5(4), 51; https://doi.org/10.3390/vision5040051 - 22 Oct 2021
Viewed by 436
Abstract
This study investigates the presence of SARS-CoV-2 in conjunctival secretions and tears and evaluates ocular symptoms in a group of patients with COVID-19. We included 56 hospitalized patients with COVID-19 in this cross-sectional cohort study. Conjunctival secretions and tears were collected using flocked [...] Read more.
This study investigates the presence of SARS-CoV-2 in conjunctival secretions and tears and evaluates ocular symptoms in a group of patients with COVID-19. We included 56 hospitalized patients with COVID-19 in this cross-sectional cohort study. Conjunctival secretions and tears were collected using flocked swabs and Schirmer strips for SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR). Assessment of ocular surface manifestations included an OSDI (Ocular Surface Disease Index) questionnaire. Patients had been admitted to hospital for an average of 2.4 days (range 0–7) and had shown general symptoms for an average of 7.1 days (range 1–20) prior to ocular testing. Four (7.1%) of 56 conjunctival swabs and four (4%) of 112 Schirmer strips were positive for SARS-CoV-2. The mean E-gene cycle threshold values (Ct values) were 31.2 (SD 5.0) in conjunctival swabs and 32.9 (SD 2.7) in left eye Schirmer strips. Overall, 17 (30%) patients presented ocular symptoms. No association was found between positive ocular samples and ocular symptoms. This study shows that SARS-CoV-2 can be detected on the conjunctiva and tears of patients with COVID-19. Contact with the ocular surface may transmit the virus and preventive measures should be taken in this direction. Full article
Article
Developmental Trajectories of Size Constancy as Implicitly Examined by Simple Reaction Times
Vision 2021, 5(4), 50; https://doi.org/10.3390/vision5040050 - 19 Oct 2021
Viewed by 245
Abstract
It is still unclear whether size constancy is an innate ability or whether it develops with age. As many developmental studies are limited to the child’s comprehension of the task instructions, here, an implicit measure of perceived size, namely, simple manual reaction time [...] Read more.
It is still unclear whether size constancy is an innate ability or whether it develops with age. As many developmental studies are limited to the child’s comprehension of the task instructions, here, an implicit measure of perceived size, namely, simple manual reaction time (RT), was opted for based on the assumption that perceptually bigger objects generate faster detection times. We examined size constancy in children (from 5 to 14 years of age) and adults using a simple RT approach. Participants were presented with pictures of tennis balls on a screen that was physically moved to two viewing distances. Visual stimuli were adjusted in physical size in order to subtend the same visual angle across distances, determining two conditions: a small-near tennis ball vs. a big-far tennis ball. Thanks to size constancy, the two tennis balls were perceived as different even though they were of equal size on the retina. Stimuli were also matched in terms of luminance. Participants were asked to react as fast as possible to the onset of the stimuli. The results show that the RTs reflected the perceived rather than the retinal size of the stimuli across the different age groups, such that participants responded faster to stimuli that were perceived as bigger than those perceived as smaller. Hence, these findings are consistent with the idea that size constancy is already present in early childhood, at least from the age of five, and does not require extensive visual learning. Full article
(This article belongs to the Special Issue Size Constancy for Perception and Action)
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Article
Characteristics of Visual Saliency Caused by Character Feature for Reconstruction of Saliency Map Model
Vision 2021, 5(4), 49; https://doi.org/10.3390/vision5040049 - 19 Oct 2021
Viewed by 295
Abstract
Visual saliency maps have been developed to estimate the bottom-up visual attention of humans. A conventional saliency map represents a bottom-up visual attention using image features such as the intensity, orientation, and color. However, it is difficult to estimate the visual attention using [...] Read more.
Visual saliency maps have been developed to estimate the bottom-up visual attention of humans. A conventional saliency map represents a bottom-up visual attention using image features such as the intensity, orientation, and color. However, it is difficult to estimate the visual attention using a conventional saliency map in the case of a top-down visual attention. In this study, we investigate the visual saliency for characters by applying still images including both characters and symbols. The experimental results indicate that characters have specific visual saliency independent of the type of language. Full article
(This article belongs to the Special Issue Eye Tracking in Human–Computer Interaction)
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Article
The Effects of Sex, Oral Contraception, and Menstrual Cycle Phase on Intraocular Pressure, Central Corneal Thickness, and Foveal Thickness: A Descriptive Analysis
Vision 2021, 5(4), 48; https://doi.org/10.3390/vision5040048 - 18 Oct 2021
Viewed by 388
Abstract
The primary goal of this study was to investigate the effects of sex, oral contraceptive (OC) use, and menstrual cycle phase on common ocular parameters assessed during ophthalmic evaluations, namely intraocular pressure (IOP), central corneal thickness (CCT), and foveal thickness (FT), in young [...] Read more.
The primary goal of this study was to investigate the effects of sex, oral contraceptive (OC) use, and menstrual cycle phase on common ocular parameters assessed during ophthalmic evaluations, namely intraocular pressure (IOP), central corneal thickness (CCT), and foveal thickness (FT), in young healthy adults. We measured IOP, CCT, and FT in 60 participants (16 men, 16 contraceptive users, and 28 cycling women) over two sessions that characterized the menstrual cycle phase in women. For men in our study, two sessions were separated by two weeks. For women, the two sessions were scheduled during the follicular and luteal phases of the menstrual cycle. There was a trend towards higher IOP in men, and the difference was significant for white, non-Hispanic subjects and for white subjects considered separately. There was also a trend for thicker corneas in women, but men had significantly thicker foveae. CCT and FT were not different between men and OC-users, hinting at a moderating hormonal effect of oral contraceptive use. We found that IOP, CCT, and FT were equivalent between the follicular and luteal phases, which may be owing to the timing of our sessions. However, our findings strongly suggest that clinicians should consider contraceptive use during routine ophthalmic evaluations, as it could inform glaucomatous risk in women. Full article
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Article
Impact of TCF4 Repeat Number on Resolution of Corneal Edema after Descemet’s Stripping Only in Fuchs Dystrophy: A Pilot Study
Vision 2021, 5(4), 47; https://doi.org/10.3390/vision5040047 - 09 Oct 2021
Viewed by 389
Abstract
Purpose: To investigate whether Fuchs endothelial corneal dystrophy (FECD) genotype, specifically transcription factor 4 (TCF4) CTG triplet repeat “load” predicts time to clearance following Descemet’s Stripping Only (DSO). Methods: This prospective, interventional trial was conducted on consecutive FECD patients undergoing DSO. Genetic [...] Read more.
Purpose: To investigate whether Fuchs endothelial corneal dystrophy (FECD) genotype, specifically transcription factor 4 (TCF4) CTG triplet repeat “load” predicts time to clearance following Descemet’s Stripping Only (DSO). Methods: This prospective, interventional trial was conducted on consecutive FECD patients undergoing DSO. Genetic analysis using patients’ saliva was performed to assess the extent of CTG expansion using short tandem repeat analysis, corroborated gel electrophoresis and Sanger sequencing. Polymerase chain reaction and bidirectional Sanger sequencing was undertaken. Partial least square regression and logistic regression modelling was used to evaluate the predictive power of TCF4 repeats on corneal clearance. Results: Of 11 eyes of 11 patients, 8 showed complete corneal clearance. For these 8 patients, mean TCF4 allele repeat was 24.8 (SD: 23.7, range: 11–63) and 63.4 (SD: 30.3; range: 11–97), respectively. In total, 9/11 (81.8%) had expanded CTG repeats (>40) in one allele. In cases with an allele repeat ≥80, there was a significantly increased risk of corneal non-clearance (odds ratio 18.2, p = 0.009). Conclusion: Whilst it was not possible to predict time to corneal clearance based on CTG repeats, there is a significant correlation between allele repeats and achievement of corneal clearance. Full article
Review
Vision through Healthy Aging Eyes
Vision 2021, 5(4), 46; https://doi.org/10.3390/vision5040046 - 30 Sep 2021
Viewed by 438
Abstract
As life expectancy grows, so too will the number of people adversely affected by age. Although it is acknowledged that many conditions and diseases are associated with age, this mini-review will present a current update of the various visual changes that generally occur [...] Read more.
As life expectancy grows, so too will the number of people adversely affected by age. Although it is acknowledged that many conditions and diseases are associated with age, this mini-review will present a current update of the various visual changes that generally occur in healthy individuals disregarding the possible effects of illness. These alterations influence how the world is perceived and in turn can affect efficiency or the ability to perform ordinary daily tasks such as driving or reading. The most common physical developments include a decreased pupil size and retinal luminance as well as changes both in intercellular and intracellular connections within the retina along the pathway to the visual cortex and within the visual cortex. The quantity and the physical location of retinal cells including photoreceptors, ganglion and bipolar retinal cells are modified. The clarity of intraocular organs, such as the intraocular lens, decreases. These all result in common visual manifestations that include reduced visual acuity, dry eyes, motility changes, a contraction of the visual field, presbyopia, reduced contrast sensitivity, slow dark adaptation, recovery from glare, variation in color vision and a decreased visual processing speed. Highlighting these prevalent issues as well as current and possible future innovations will assist providers to formulate treatments and thereby conserve maximum independence and mobility in the modern mature population. Full article
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Article
Ferrara Rings for Visual Rehabilitation in Eyes with Keratoconus and Previous Cross-Linking Using the Ferrara Ring Nomogram
Vision 2021, 5(4), 45; https://doi.org/10.3390/vision5040045 - 29 Sep 2021
Viewed by 374
Abstract
Purpose: To report the visual, refractive and tomographic outcomes following the implantation of intrastromal corneal ring segments (ICRS) (Ferrara rings, AJL Ophthalmics, Miñano, Spain) in eyes with a history of keratoconus and corneal cross-linking using the Ferrara ring nomogram. Methods: Retrospective, interventional case [...] Read more.
Purpose: To report the visual, refractive and tomographic outcomes following the implantation of intrastromal corneal ring segments (ICRS) (Ferrara rings, AJL Ophthalmics, Miñano, Spain) in eyes with a history of keratoconus and corneal cross-linking using the Ferrara ring nomogram. Methods: Retrospective, interventional case series performed at the Corneoplastics Unit, Queen Victoria Hospital, East Grinstead, United Kingdom. Results: 21 eyes of 19 patients with a history of keratoconus and prior corneal collagen cross-linking had Ferrara Intrastromal Corneal Ring Segments implanted between December 2015 and October 2017. The number, thickness and length of ring segments was chosen based on the Ferrara ring company nomogram. Mean uncorrected visual acuity (UDVA) improved from 0.88 to 0.52 logMAR (p < 0.001). Mean corrected visual acuity (CDVA) improved from 0.47 to 0.36 logMAR (p = 0.046). The percentage of eyes achieving 20/40 UDVA and CDVA increased from 5% to 38% and from 38% to 67%, respectively. Of the eyes, 52.3% gained at least two lines of CDVA. The spherical equivalent improved from −7.51D to −3.76D (p < 0.001) and the refractive astigmatism magnitude improved from 5.14D to 2.76D (p = 0.004). There were significant improvements in the corneal tomography with mean keratometry (KM) improving from 50.40D (3.53) to 48.24D (3.00) (p = 0.01) and keratometric astigmatism magnitude improving from 5.14D (2.91) to 2.76D (1.67) (p = 0.004). Conclusion: Insertion of Ferrara rings in keratoconic eyes with a history of prior cross-linking using the company nomogram results in significant improvements in visual, refractive and tomographic outcomes. Full article
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Article
Optical Sensitivity of Camera-Like Eyes to White Light
Vision 2021, 5(4), 44; https://doi.org/10.3390/vision5040044 - 28 Sep 2021
Viewed by 437
Abstract
Gastropod mollusks are convenient model organisms for studying the functioning of the visual system. The purpose of this work is to estimate the value of the optical sensitivity to white light for the camera-like eyes of gastropod mollusks and humans and analyze its [...] Read more.
Gastropod mollusks are convenient model organisms for studying the functioning of the visual system. The purpose of this work is to estimate the value of the optical sensitivity to white light for the camera-like eyes of gastropod mollusks and humans and analyze its effect on the spatial resolving power in two regions of the retina: in the center—for single photoreceptors of the first/second type in a mollusk and single cones in humans—and in the periphery—for single photoreceptors of the first/second type in a mollusk, as well as for single rods/cones and their groups, subject to spatial summation in humans. The methods of histology, light and transmission electron microscopy, morphometry, calculations and methods of statistical analysis are used in the work. In a mollusk, with a fixed pupil area, the value of the optical sensitivity of the eye to white light in the center of the retina for single photoreceptors of the first/second type is 0.5/0.006 μm2·sr and in the periphery of the retina, 0.9/0.009 μm2·sr. In humans, at the minimum and maximum pupil area, respectively, the value of the optical sensitivity of the eye to white light in the center of the retina (foveola) for single cones varies from 0.00053 to 0.028 μm2·sr, and in the periphery of the retina (far periphery) for single rods from 0.011 to 0.575 μm2·sr, for single cones from 0.025 to 1.319 μm2·sr, for the groups of rods from 3859 to 204,094 μm2·sr and for the groups of cones from 2.5 to 131 μm2·sr. The value of the optical sensitivity of the eyes to white light for single photoreceptors of the first/second type in both regions of the retina in a mollusk, as well as for single cones in the center and groups of rods/cones in the periphery of the retina in humans, corresponds to the ambient light conditions during periods of activity and does not affect the spatial resolving power. Full article
Review
The Limbal Niche and Regenerative Strategies
Vision 2021, 5(4), 43; https://doi.org/10.3390/vision5040043 - 22 Sep 2021
Viewed by 481
Abstract
The protective function and transparency provided by the corneal epithelium are dependent on and maintained by the regenerative capacity of limbal epithelial stem cells (LESCs). These LESCs are supported by the limbal niche, a specialized microenvironment consisting of cellular and non-cellular components. Disruption [...] Read more.
The protective function and transparency provided by the corneal epithelium are dependent on and maintained by the regenerative capacity of limbal epithelial stem cells (LESCs). These LESCs are supported by the limbal niche, a specialized microenvironment consisting of cellular and non-cellular components. Disruption of the limbal niche, primarily from injuries or inflammatory processes, can negatively impact the regenerative ability of LESCs. Limbal stem cell deficiency (LSCD) directly hampers the regenerative ability of the corneal epithelium and allows the conjunctival epithelium to invade the cornea, which results in severe visual impairment. Treatment involves restoring the LESC population and functionality; however, few clinically practiced therapies currently exist. This review outlines the current understanding of the limbal niche, its pathology and the emerging approaches targeted at restoring the limbal niche. Most emerging approaches are in developmental phases but show promise for treating LSCD and accelerating corneal regeneration. Specifically, we examine cell-based therapies, bio-active extracellular matrices and soluble factor therapies in considerable depth. Full article
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