The dose-response relationship of subretinal gene therapy with rAAV2tYF-CB-hRS1 in a mouse model of X-linked retinoschisis.

Purpose: X-linked retinoschisis (XLRS), due to loss-of-function mutations in the retinoschisin (RS1) gene, is characterized by a modest to severe decrease in visual acuity. Clinical trials for XLRS utilizing intravitreal (IVT) gene therapy showed ocular inflammation. We conducted a subretinal dose-response preclinical study using rAAV2tYF-CB-hRS1 utilizing the Rs1 knockout (Rs1-KO) mouse to investigate short- and long-term retinal rescue after subretinal gene delivery. Methods: Rs1-KO mice were subretinally injected with 2 µL of rAAV2tYF-CB-hRS1 vector with 8E9 viral genomes (vg)/eye, 8E8 vg/eye, 8E7 vg/eye, or sham injection, and compared to untreated eyes. Reconstitution of human RS1 protein was detected using western blotting. Analysis of retinal function by electroretinography (ERG) and structural analysis by optical coherence tomography (OCT) were performed at 1, 2, 3, 5, 7, and 12 months post injection (MPI). Immunohistochemistry (IHC) was performed to evaluate cone rescue on the cellular level. Functional vision was evaluated using a visually guided swim assay (VGSA). Results: Western blotting analysis showed human RS1 protein expression in a dose-dependent manner. Quantification of western blotting showed that the RS1 protein expression in mice treated with the 8E8 vg dose was near the wild-type (WT) expression levels. ERG demonstrated dose-dependent effects: At 1 MPI the 8E8 vg dose treated eyes had higher light-adapted (LA) ERG amplitudes in 3.0 flash and 5 Hz flicker compared to untreated (p < 0.0001) and sham-treated eyes (p < 0.0001) which persisted until the 12 MPI endpoint, consistent with improved cone function. ERG b-wave amplitudes were higher in response to dark-adapted (DA) 0.01 dim flash and 3.0 standard combined response (SCR) compared to sham-treated (p < 0.01) and untreated eyes (p < 0.001) which persisted until 3 MPI, suggesting short-term improvement of the rod photoreceptors. All injections, including sham-treated, resulted in a cyst severity score of 1 (no cavities), with significant reductions compared to untreated eyes up to 3 MPI (p < 0.05). The high and low dose groups showed inconsistent ERG improvements, despite reduced cyst severity, emphasizing the dose-dependent nature of gene augmentation's efficacy and the tenuous connection between cyst reduction and ERG improvement. IHC data showed a significant cone rescue in eyes treated with the 8E8 vg dose compared to sham-treated and untreated eyes. VGSA showed better functional vision in 8E8 vg dose treated mice. Eyes treated with the highest dose showed occasional localized degeneration in the outer nuclear layer. Conclusion: Our data suggest that a dose of 8E8 vg/eye subretinally improves retinal function and structure in the Rs1-KO mouse. It improves cone function, rod function, and reduces cyst severity. Sham treatment resolves schisis cysts, but 8E8 vg/eye is needed for optimal retinal electrical function rescue. These findings offer a promising path for clinical translation to human trials.

Test-retest repeatability and agreement of the quantitative contrast sensitivity function test: towards the validation of a new clinical endpoint.

PURPOSE: The purpose of this study is to investigate test-retest reliability and agreement of the quantitative contrast sensitivity function test (qCSF) in the retina clinic. METHODS: A total of 121 right eyes of 121 patients were tested and consecutively re-tested with qCSF in the retina clinic. Outcomes included area under the logarithm of contrast sensitivity function curve (AULCSF), contrast acuity, and contrast sensitivity thresholds at 1-18 cycles per degree (cpd). Test-retest means were compared with paired t-test, variability was compared with the Brown-Forsythe test, and intraclass correlation coefficient (ICC) and Bland Altman plots evaluated reliability and agreement. RESULTS: Mean test-retest differences for all qCSF metrics ranged from 0.02 to 0.05 log units without statistically significant differences in variability. Standard deviations ranged from 0.08 to 0.14. Coefficients of repeatability ranged from 0.16 to 0.27 log units. ICC > 0.9 for all metrics except 1cpd (ICC = 0.84, all p < 0.001); AULCSF ICC = 0.971. CONCLUSION: qCSF-measured contrast sensitivity shows great test-retest repeatability and agreement in the retina clinic.

A visually guided swim assay for mouse models of human retinal disease recapitulates the multi-luminance mobility test in humans.

PURPOSE: The purpose of this study was to develop a visually guided swim assay (VGSA) for measuring vision in mouse retinal disease models comparable to the multi-luminance mobility test (MLMT) utilized in human clinical trials. METHODS: Three mouse retinal disease models were studied: Bardet-Biedl syndrome type 1 (Bbs1M390R/M390R), n = 5; Bardet-Biedl syndrome type 10 (Bbs10-/-), n = 11; and X linked retinoschisis (retinoschisin knockout; Rs1-KO), n = 5. Controls were normally-sighted mice, n = 10. Eyeless Pax6Sey-Dey mice, n = 4, were used to determine the performance of animals without vision in VGSA. RESULTS: Eyeless Pax6Sey-Dey mice had a VGSA time-to-platform (TTP) 7X longer than normally-sighted controls (P < 0.0001). Controls demonstrated no difference in their TTP in both lighting conditions; the same was true for Pax6Sey-Dey. At 4-6 M, Rs1-KO and Bbs10-/- had longer TTP in the dark than controls (P = 0.0156 and P = 1.23 × 10-8, respectively). At 9-11 M, both BBS models had longer TTP than controls in light and dark with times similar to Pax6Sey-Dey (P < 0.0001), demonstrating progressive vision loss in BBS models, but not in controls nor in Rs1-KO. At 1 M, Bbs10-/- ERG light-adapted (cone) amplitudes were nonrecordable, resulting in a floor effect. VGSA did not reach a floor until 9-11 M. ERG combined rod/cone b-wave amplitudes were nonrecordable in all three mutant groups at 9-11 M, but VGSA still showed differences in visual function. ERG values correlate non-linearly with VGSA, and VGSA measured the continual decline of vision. CONCLUSION: ERG is no longer a useful endpoint once the nonrecordable level is reached. VGSA differentiates between different levels of vision, different ages, and different disease models even after ERG is nonrecordable, similar to the MLMT in humans.

Development and clinimetric assessment of a performance-based functional vision tool in visually impaired children.

Objective: Appropriate functional vision is vital for the development of visually impaired (VI) children. However, the literature currently lacks a performance-based tool for assessing functional vision, unlike the existing self-reported tools. The objective of this study is to develop and conduct a clinimetric study on a Performance-Based Functional Vision Tool (PB-FVT) specifically designed for VI children aged 3-7 and 7-10 years old. Methods: This methodological study was conducted to assess the clinimetric properties of the PB-FVT. The assessment included face validity (evaluated through cognitive interviews and an Impact Score >1.5), content validity (with criteria including content validity ratio >0.63, item content validity index >0.78, scale content validity index or average >0.8, and Kappa value >0.7), criterion validity (assessed through a concurrent test using visual acuity scores), construct validity (utilizing the known group method), relative reliability (measured by the intra-class correlation coefficient), absolute reliability (determined by the standard error of measurement and minimal detectable changes), interpretability, responsiveness, sensitivity, and specificity (analyzed via ROC curve analysis). Results: The PB-FVT was developed with 32 items, divided into five components: activities of daily living, instrumental activities of daily living, education, play, and social interaction. The results indicate that the scale demonstrates suitability in terms of validity, reliability, and other measurement characteristics. Conclusions: The valid and reliable PB-FVT may accurately assess the level of functional vision during early childhood, helping to prevent negative impacts on a child's overall development. By utilizing the PB-FVT, any functional vision impairments can be identified appropriately, enabling the planning and implementation of effective rehabilitation interventions.

The PKG Inhibitor CN238 Affords Functional Protection of Photoreceptors and Ganglion Cells against Retinal Degeneration.

Hereditary retinal degeneration (RD) is often associated with excessive cGMP signalling in photoreceptors. Previous research has shown that inhibition of cGMP-dependent protein kinase G (PKG) can reduce photoreceptor loss in two different RD animal models. In this study, we identified a PKG inhibitor, the cGMP analogue CN238, which preserved photoreceptor viability and functionality in rd1 and rd10 mutant mice. Surprisingly, in explanted retinae, CN238 also protected retinal ganglion cells from axotomy-induced retrograde degeneration and preserved their functionality. Furthermore, kinase activity-dependent protein phosphorylation of the PKG target Kv1.6 was reduced in CN238-treated rd10 retinal explants. Ca2+-imaging on rd10 acute retinal explants revealed delayed retinal ganglion cell repolarization with CN238 treatment, suggesting a PKG-dependent modulation of Kv1-channels. Together, these results highlight the strong neuroprotective capacity of PKG inhibitors for both photoreceptors and retinal ganglion cells, illustrating their broad potential for the treatment of retinal diseases and possibly neurodegenerative diseases in general.

Cerebral visual impairment and effect of phase-wise stimulation strategies-An interim analysis.

Context: Cerebral visual impairment (CVI) is an overarching term, defined as a brain-based visual impairment with onset in childhood, unexplained by an ocular disorder and associated with unique visual and behavioral characteristics. Good vision and awareness of visual function in a child are highly essential as neuroplasticity is maximum in the first three years of life and response to intervention is utmost in this period. Awareness is lacking regarding CVI, and the diagnosis is largely missed. This can be easily addressed if a structured approach is employed. Purpose: This study aims to evaluate the etiology and radiological correlation with the severity of CVI and outcome after structured intervention in children with CVI. Settings and Design: Prospective-interventional study. Methods and Material: Children attending the Child Development Centre (CDC) of a tertiary care hospital in North Karnataka and diagnosed with CVI in the age group of six months to 12 years and meeting the sampling criteria were screened and enrolled consecutively after obtaining parental consent/assent. Statistical analysis used is nonparametric test with SPSS software. Results: Age showed a significant association with the phase of CVI. Perinatal insult was associated significantly with the severity of CVI. Magnetic resonance imaging (MRI) findings did not hamper the recovery of CVI. Conclusions: Enrolment in early intervention programs tailored according to child's specific needs should be encouraged, with stress on ophthalmic screening of preterm and high-risk babies with perinatal hypoxia and history of convulsions, as early as six months.

Parent-Reported Visual Concerns in Children with Cerebral Visual Impairment Presenting to a Pediatric Neurology Clinic.

Purpose: Children with cerebral visual impairment (CVI) present with delayed developmental milestones. Pediatricians and pediatric neurologists are usually the first point of contact, and eye exam largely remains referral based. This study documented the visual concerns reported by parents of children with CVI visiting a pediatric neurology clinic. Additionally, we investigated the association between visual concerns, functional vision measures and visual functions. Patients and Methods: A cross-sectional study was undertaken in children with CVI (chronological age range: 7 months-7 years). Visual concerns reported by the parents/caregivers were documented as open-ended statements. Additionally, a functional vision assessment was conducted using the CVI Range instrument with phase 1, 2 and 3 indicating low, moderate and high visual functioning, respectively. Grating acuity and contrast sensitivity were measured using Teller acuity cards-II and Ohio contrast cards respectively. Results: A total of 73 children (mean age of 2.84 ± 1.87 years) were recruited. Sixty-eight parents reported visual concerns that were broadly grouped into 14 unique concerns. Nineteen parents (27.9%) reported more than one visual concern. Difficulty maintaining eye contact and recognizing faces were the top two visual concerns in phases 1 and 2. Missing objects in the lower visual field was the top concern in phase 3. A larger number of visual concerns were reported in phase 1 (43%) than phase 2 (40.6%) and phase 3 (16.2%). Multiple regression analysis revealed that grating acuity, contrast sensitivity and chronological age were able to predict the functional vision, F (3, 55) = 63.0, p < 0.001, r2 = 0.77. Conclusion: Targeted questions enquiring about eye contact and face recognition can be included in history elicitation in children with CVI in pediatric neurology clinics. In the presence of visual concerns, it will be important to assess grating acuity and contrast sensitivity. A poor functional vision score requires referral for eye examination and vision rehabilitation services.

Development of an integrated telerehabilitation model in children with cerebral visual impairment in South India during the COVID-19 pandemic - A pilot study.

Purpose: Coronavirus disease 2019 (COVID-19) pandemic affected the in-person rehabilitation/habilitation services in families with children with cerebral visual impairment (CVI) in India. This study aimed to develop a structured and family-centered telerehabilitation model alongside conventional in-person intervention in children with CVI to observe its feasibility in the Indian population. Methods: This pilot study included 22 participants with a median age of 2.5 years (range: 1-6) who underwent a detailed comprehensive eye examination followed by functional vision assessment. The visual function classification system (VFCS) was administered to the children and the structured clinical question inventory (SCQI) to the parents. Every participant underwent 3 months of telerehabilitation including planning, training, and monitoring by experts. At 1 month, the parental care and ability (PCA) rubric was administered to the parents. After 3 months, in an in-person follow-up, all the measures were reassessed for 15 children. Results: After 3 months of Tele-rehabilitation there were significant improvements noted in PCA rubric scores (P<0.05). Also, statistically significant improvements were noted in functional vision measured using SCQI and VFCS scores (P<0.05) compared to baseline. Conclusion: The outcomes of the study provide the first steps towards understanding the use of a novel tele-rehabilitation model in childhood CVI along-side conventional face-to-face intervention. The added role of parental involvement in such a model is highly essential.

Beyond vision:Cataract and health status in old age, a narrative review.

Cataract is a leading cause of visual impairment in old age. Lens opacification is notoriously associated with several geriatric conditions, including frailty, fall risk, depression and cognitive impairment. The association is largely attributable to visual impairment, while other mechanisms, associated with extraocular comorbidity and lifestyle, might partly explain this correlation. Available literature suggests that cataract surgery may be effective in decreasing fall risk, improving depressive symptoms and limiting the risk of cognitive impairment and dementia incidence, although intervention studies on these outcomes are still limited. In this review we also emphasize the need to move from the concept of visual acuity to functional vision, especially in the context of the geriatric patient. Research is needed regarding the effect on the cited outcomes of different cataract treatment strategies, such as systematic bilateral versus monolateral surgery and use of different intraocular lenses.

Outcomes of 35-year duration of type 1 diabetes and proliferative diabetic retinopathy on functional vision and quality of life: Benefits of good glycemic control.

AIMS: To evaluate clinical outcomes, functional vision and quality of life (QoL) after 35-year duration of type 1 diabetes (T1D) and proliferative diabetic retinopathy (PDR). METHODS: A population-based cohort study of T1D. Data from laboratory tests, ophthalmic examinations, multifunctional vision-test, and 15D-QoL measurements were analysed. RESULTS: 35 % of the original cohort (n = 216) had PDR, and 48 % of them were re-evaluated. They were 41 ± 3 [34-46] years old and 62 % were males. The duration of T1D was 35 ± 4 [29-41] years. 76 % had transdermal glucose monitoring. HbA1c had decreased from 80.1 mmol/mol to 63.6 mmol/mol (p < 0.001). Visual acuity was 73-77 ETDRS-letters. Two patients had visual impairment. Visual field sensitivities were lower in PDR vs. healthy controls (23.2 ± 3.9 dB vs. 26.9 ± 1.0 dB, and 14.9 ± 5.6 dB vs. 21.0 ± 2.0 dB, respectively, p < 0.001). Contrast sensitivity was similar, but the reaction time was longer in the PDR group (490.5 ms vs. 462.8 ms, p = 0.004). QoL-parameters concerning sleeping, usual activities, discomfort and symptoms, and sexual activity had decreased, but improved for mobility and distress. CONCLUSIONS: Long-term visual prognosis and QoL remained good despite the declined functional vision caused by PDR.

Multi-luminance Mobility Testing Endpoint.

An individual's functional vision may be measured via visual assessment and performance on mobility tasks. Since traditional mobility performance tests neglect to examine the effects of illumination on performance, the multi-luminance mobility test (MLMT) was designed to quantitatively assess the effects of illumination levels on an individual's mobility performance. In this chapter, we describe how the MLMT is conducted and scored in order to properly evaluate a participant's mobility under various light conditions.

Photoreceptor and vision protective effects of astragaloside IV in mice model with light-evoked retinal damage.

Cone cell-enriched macular degeneration is a major cause of functional vision deterioration. Astragaloside IV (Asg IV), an active triterpenoid saponin component with properties of anti-oxidative and anti-apoptotic damage, which benefit retinal tissue and capillaries. But, the nutraceutical therapeutic effects on functional vision have not been fully evaluated. In this study, mice were administrated to high-intensity light exposure after either receiving a vehicle or Asg IV (0.05, 0.5, and 50 mg/kg, BID). During this time, their spatial-visual performance, visual acuity (VA), and visual contrast sensitivity function (VCSF) were measured using the behavioral optomotor reflex method. Morphological changes in the retina were determined by histological examination. High energy light-evoked visual damage was confirmed by the loss in structural tissue integrity in the retina accompanied by a decline in both VA and VCSF, whereas the retina tissue exhibited loss of cone cell density and severe cone-specific opsin misplacement. In contrast, prophylactic oral Asg IV (0.5, and 50 mg/kg, BID)-treated exerted protective and improvement effects against light-evoked deterioration of functional vision. Asg IV treatment significantly improved the thresholds of VA and VCSF. In particular, Asg IV (50 mg/kg, BID) modulated and increased the survival of the photoreceptors, especially the cone cells, which targeted and enhanced the high spatial frequency-characterized VCSF. In contrast, the cellular protective effect of Asg IV (50 mg/kg, BID) on photoreceptors was significantly reversed by synchronous injection of a glucocorticoid receptor (GR) antagonist (mifepristone). This study demonstrated the major neuroretina-protective effect and functional vision-improving effect of Asg IV in vivo.

Surgical outcomes and observation in exotropia cerebral palsy children with cortical visual impairment.

PURPOSE: Cortical visual impairment (CVI) is the common cause of pediatric visual impairment in cerebral palsy (CP) while exotropia is the most common strabismus associated with CP. We aim to observe the strabismic surgery outcomes in pediatric patients with CP and CVI. METHOD: Our medical records were collected from pediatric patients treated in our hospital from May 1, 2017 to Jan 1, 2022. With normal intelligence assessment and diagnosis of exotropia in children with CP and CVI, microsurgeries were performed under intravenous combined inhalation anesthesia. The strabismus was examined by the prism test under best vision correction and the contrast sensitivity testing (CST) was measured at five levels of spatial frequencies. RESULT: A total of 38 exotropia patients with CP and CVI were identified and included for analysis during the study period with age ranged from 5 to 12 years (mean 8.45 years) and mean follow up duration was 8.7 months (6-42 months). After bilateral lateral rectus recession (with/without medial rectus resection or inferior oblique transposition), the exotropia amount of participants were obviously revealed from - 30 ~ - 140 (median, IQR: - 50, 40) prism diopters (PD) preoperatively to 0 ~ - 15 (0, 5) PD postoperatively. Statistically significantly improvements were observed at all levels of spatial frequency on CST postoperatively, especially at high spatial frequency areas (p < 0.05). CONCLUSION: Our results demonstrated that the effect of strabismus surgery on exotropia in children with CP and CVI were stable and monocular contrast sensitivity post- operation increased significantly at all spatial frequencies levels.

When We Study the Ability to Attend, What Exactly Are We Trying to Understand?

When we study the human ability to attend, what exactly do we seek to understand? It is not clear what the answer might be to this question. There is still so much to know, while acknowledging the tremendous progress of past decades of research. It is as if each new study adds a tile to the mosaic that, when viewed from a distance, we hope will reveal the big picture of attention. However, there is no map as to how each tile might be placed nor any guide as to what the overall picture might be. It is like digging up bits of mosaic tile at an ancient archeological site with no key as to where to look and then not only having to decide which picture it belongs to but also where exactly in that puzzle it should be placed. I argue that, although the unearthing of puzzle pieces is very important, so is their placement, but this seems much less emphasized. We have mostly unearthed a treasure trove of puzzle pieces but they are all waiting for cleaning and reassembly. It is an activity that is scientifically far riskier, but with great risk comes a greater reward. Here, I will look into two areas of broad agreement, specifically regarding visual attention, and dig deeper into their more nuanced meanings, in the hope of sketching a starting point for the guide to the attention mosaic. The goal is to situate visual attention as a purely computational problem and not as a data explanation task; it may become easier to place the puzzle pieces once you understand why they exist in the first place.

Visual Function and Neuropsychological Profile in Children with Cerebral Visual Impairment.

Cerebral Visual Impairment (CVI) has become the leading cause of children's visual impairment in developed countries. Since CVI may negatively affect neuropsychomotor development, an early diagnosis and characterization become fundamental to define effective habilitation approaches. To date, there is a lack of standardized diagnostic methods to assess CVI in children, and the role of visual functions in children's neuropsychological profiles has been poorly investigated. In the present paper, we aim to describe the clinical and neuropsychological profiles and to investigate the possible effects of visual functions on neuropsychological performance of a cohort of children diagnosed with CVI. Fifty-one children with CVI were included in our retrospective analysis (inclusion criteria: verbal IQ > 70 in Wechsler scales; absence of significant ocular involvement). For each participant, we collected data on neuropsychological assessment (i.e., cognitive, cognitive visual, and learning abilities), basic visual functions (e.g., Best Corrected Visual Acuity­BCVA, contrast sensitivity, and ocular motor abilities) and global development features (e.g., neurological signs and motor development delay) based on standardized tests, according to patients' ages. The results showed that oculomotor dysfunction involving saccades and smooth pursuit may be a core symptom of CVI and might have a significant impact on cognitive visual and other neuropsychological abilities. Furthermore, visual acuity and contrast sensitivity may influence cognitive, cognitive visual, and academic performances. Our findings suggest the importance of a comprehensive assessment of both visual and neuropsychological functions in children when CVI is suspected, which is needed to provide a more comprehensive functional profile and define the best habilitation strategy to sustain functional vision.

The Functional Vision Restorative Effect of Crocin via the BDNF-TrkB Pathway: An In Vivo Study.

Abnormal dislocation of cone opsin protein affects the sensitivity function of photoreceptors and results in depressed central vision. Nutraceutical therapy is needed to restore the residual function of photoreceptors. Crocin is a natural substance for retinal health. However, its effect on the restoration of functional vision and its underlying mechanisms have not been fully studied. This study analyzed the restorative effect of crocin on residual functional vision in vivo in a mouse model. High-energy light-evoked photoreceptor dysfunction was confirmed by M opsin dislocation in the retina accompanied by a loss of functional vision. Crocin treatment significantly increased brain-derived neurotrophic factor (BDNF) protein in retinas, thus contributing to the re-localization of the M opsin protein, restoration of the visual acuity (VA), and high spatial frequency-characterized visual contrast sensitivity function (VCSF). In contrast, such effects were significantly reversed after the washout period. Additionally, the restorative effect of crocin on functional vision and M opsin re-localization can be reversed and blocked by synchronous injection of a tropomyosin receptor kinase B (TrkB) receptor antagonist (ANA-12). This study demonstrated the major functional vision-rescuing or restoring effect of crocin in vivo by modulating M opsin location plasticity and increasing the capacity of the residual photoreceptor function through the BDNF-TrkB receptor pathway.

Visual Function Score: A New Clinical Tool to Assess Visual Function and Detect Visual Disorders in Children.

Introduction: A comprehensive assessment of visual functioning at an early age is important not only for identifying and defining visual impairment but also for planning personalized rehabilitation programs based on the visual diagnosis. Since existing tools to evaluate visual functioning present some important limitations (e.g., they are based on qualitative reports, they do not take into account environmental adaptations of visual testing or they have not been formally validated as clinical instruments), the present work has the main aim to propose a new clinical tool (Visual Function Score, VFS) to detect and define visual disorders at an early age. Methods: The Visual Function Score was administered to one hundred visually impaired children (age range 4 months to 17.75 years old) in the form of a professional-reported protocol for a total of 51 items, each of which is assigned a score from 1 to 9 (or from 0 to 9 in some specific cases). The VFS produces three sub-scores and a global score (from 0 to 100), resulting in a quantitative evaluation of visual functioning. Results: The VFS can detect the well-known differences between different types of visual impairment (cerebral, oculomotor, and peripheral or grouped as central and peripheral) and takes into account different environments in the definition of a quantitative score of visual functioning. Discussion: Overall, the use of a quantitative tool to evaluate visual functions and functional vision such as the VFS would be fundamental to monitor the progresses of patients over time in response to rehabilitation interventions.

Protective Effect of a Water-Soluble Carotenoid-Rich Extract of Cordyceps militaris against Light-Evoked Functional Vision Deterioration in Mice.

Light-evoked retinal photodamage is considered an important factor contributing to functional vision deterioration and can even lead to light maculopathy or dry age-related macular degeneration. Loss of visual acuity (VA) and visual contrast sensitivity function (VCSF) are the major symptoms of retinal degenerative diseases. Cordyceps militaris is a carotenoid-rich Chinese medicinal fungus with antioxidant, anti-inflammatory, and immunomodulatory functions. C. militaris extract is a natural substance, and its bioactive constituents have been shown to confer health benefits, but their application in retinal tissue and functional vision protection in vivo remain incompletely understood. In the present study, we evaluated the influence of water-soluble, carotenoid-rich C. militaris extracts on the visual performance of light-damaged mouse retinas in vivo, using adult female CD-1® (ICR) albino mice. We showed that oral administration of this C. militaris extract (10 mg/kg, twice daily) protected the neural retina tissue against light-evoked photoreceptor cell death, reduced Müller cell hypertrophic gliosis, and elevated GSH levels and promoted the recovery of VA- and VCSF-thresholds, especially for high spatial frequency-characterized vision. These results suggest that, probably because of its water-soluble carotenoids, C. militaris extract has the potential to prevent or treat light-induced visual dysfunction.