Retinal microglia initiate neuroinflammation in ocular autoimmunity.

Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. While microglia have been studied extensively in autoimmune uveitis, their exact function remains uncertain. The objective of the current study was to determine whether resident microglia are necessary and sufficient to initiate and amplify retinal inflammation in autoimmune uveitis. In this study, we clearly demonstrate that microglia are essential for initiating infiltration of immune cells utilizing a murine model of experimental autoimmune uveoretinitis (EAU) and the recently identified microglia-specific marker P2ry12. Initiating disease is the primary function of microglia in EAU, since eliminating microglia during the later stages of EAU had little effect, indicating that the function of circulating leukocytes is to amplify and sustain destructive inflammation once microglia have triggered disease. In the absence of microglia, uveitis does not develop, since leukocytes cannot gain entry through the blood-retinal barrier, illustrating that microglia play a critical role in regulating infiltration of inflammatory cells into the retina.

Aged Mice Exhibit Severe Exacerbations of Dry Eye Disease with an Amplified Memory Th17 Cell Response.

The prevalence as well as the severity of dry eye disease increase with age. Memory T helper 17 (Th17) cells (CD4+IL-17A+CD44+) drive the chronic and relapsing course of dry eye disease. Here, we investigated the contribution of memory Th17 cells to age-related dry eye disease, and evaluated memory Th17 cell depletion with anti-IL-15 antibody as a strategy to abrogate the severe exacerbations of dry eye disease observed in aged mice. After initial exposure to desiccating stress, aged mice maintained higher frequencies of memory Th17 cells in the draining lymph nodes relative to young mice. Upon secondary exposure to desiccating stress, aged mice developed more severe corneal epitheliopathy than young mice, which is associated with increased local frequencies of Th17 cells (CD4+IL-17A+). Treatment with anti-IL-15 antibody decreased the enlarged memory Th17 pool in aged mice to frequencies comparable with young mice. Furthermore, anti-IL-15-treated mice showed significantly reduced conjunctival infiltration of Th17 cells and lower corneal fluorescein staining scores compared with saline-treated control mice. Our data suggest that age-related increases in the memory Th17 compartment predispose aged mice toward the development of severe corneal epithelial disease after exposure to a dry environment. Selectively targeting memory Th17 cells may be a viable therapeutic approach in the treatment of age-related dry eye disease.

Neurokinin-1 Receptor Antagonism Ameliorates Dry Eye Disease by Inhibiting Antigen-Presenting Cell Maturation and T Helper 17 Cell Activation.

Neuroinflammation plays an important role in the pathogenesis of ocular surface disease, including dry eye disease (DED), but little is known about the contribution of substance P (SP) to DED. In this study, we investigated the expression of SP at the ocular surface and evaluated its effect on maturation of antigen-presenting cells (APCs), the key cell component involved in the induction of type 17 helper T-cell (Th17) response in DED. The effect of topical blockade of SP signaling was further investigated using neurokinin-1 receptor (NK1R) inhibitors on APC maturation, Th17 cell activation, and disease severity in a mouse model of DED. The results demonstrate that SP is constitutively expressed at the ocular surface, and trigeminal ganglion neurons are the major source of SP in DED. SP derived from trigeminal ganglion enhanced the expression of major histocompatibility complex class II maturation marker by bone marrow-derived dendritic cells, an effect that is abrogated by blockade of SP signaling using NK1R antagonist spantide. Finally, using a well-established murine model of DED, topical treatment of DED mice with NK1R antagonists CP-99,994 and L-733,060 suppressed APC acquisition of major histocompatibility complex class II, reduced Th17 cell activity, and ameliorated DED severity. These findings are of translational value, as they suggest that antagonizing NK1R-mediated SP signaling may be an effective strategy in suppressing Th17-mediated ocular surface disease.

Regulatory T cells promote corneal endothelial cell survival following transplantation via interleukin-10.

The functional competence of corneal endothelial cells (CEnCs) is critical for survival of corneal allografts, but these cells are often targets of the immune response mediated by graft-attacking effector T cells. Although regulatory T cells (Tregs) have been studied for their role in regulating the host's alloimmune response towards the graft, the cytoprotective function of these cells on CEnCs has not been investigated. The aim of this study was to determine whether Tregs suppress effector T cell-mediated and inflammatory cytokine-induced CEnC death, and to elucidate the mechanism by which this cytoprotection occurs. Using 2 well-established models of corneal transplantation (low-risk and high-risk models), we show that Tregs derived from low-risk graft recipients have a superior capacity in protecting CEnCs against effector T cell-mediated and interferon-γ and tumor necrosis factor-α-induced cell death compared to Tregs derived from high-risk hosts. We further demonstrate that the cytoprotective function of Tregs derived from low-risk hosts occurs independently of direct cell-cell contact and is mediated by the immunoregulatory cytokine IL-10. Our study is the first to report that Tregs provide cytoprotection for CEnCs through secretion of IL-10, indicating potentially novel therapeutic targets for enhancing CEnC survival following corneal transplantation.

Outcomes of photorefractive keratectomy instead of phototherapeutic keratectomy for patients with granular corneal dystrophy type 2.

PURPOSE: The purpose of this study was to evaluate visual function and postoperative refractive errors in patients with granular corneal dystrophy type 2 (GCD2) and cataracts who underwent photorefractive keratectomy (PRK) instead of phototherapeutic keratectomy (PTK) following cataract surgery to avoid PTK-induced central island formation and reduce refractive errors after cataract surgery. METHODS: The medical records of 14 eyes from nine patients (one man and eight women; mean age, 69.0 ± 8.5 years) with GCD2 and cataracts were evaluated. All patients underwent PTK using the PRK mode 3 months after cataract surgery. We analyzed corrected distance visual acuity (CDVA), refractive errors, and corneal astigmatism derived from Fourier analysis and assessed the incidence of complications in cataract surgery and PTK. RESULTS: The mean CDVA logMAR values were 0.42 ± 0.19, 0.38 ± 0.18, and 0.16 ± 0.12 before and after cataract surgery and after PTK, respectively. CDVA improved significantly after PTK, as compared with both before and after cataract surgery (P < 0.001). The mean absolute errors after cataract surgery and PTK were 0.53 ± 0.43 and 1.61 ± 1.01 diopters, respectively. Pre- and postoperative Fourier indices did not significantly vary in the 3-mm diameter zone, and only the asymmetry component of the 6-mm diameter zone significantly (P <0.01) increased postoperatively. No central island formation and no other marked complications were observed postoperatively in any case. CONCLUSIONS: Performing PTK using the PRK mode following cataract surgery may be effective for patients with GCD2 and cataracts.

Amplified Natural Killer Cell Activity and Attenuated Regulatory T-cell Function Are Determinants for Corneal Alloimmunity in Very Young Mice.

BACKGROUND: Corneal transplantation outcomes are generally less favorable in young children compared with adults. The purpose of this study was to determine the immunological mechanisms underlying this difference. METHODS: A murine model of allogeneic corneal transplantation was used in the study, and graft survival was determined by evaluating opacity scores for 8 wk. Syngeneic transplantation in the very young host served as a surgical control. The frequencies of total and activated natural killer (NK) cells in cornea posttransplantation were kinetically evaluated using flow cytometry. The regulatory T cell (Treg) frequency and function in naive animals were assessed by flow cytometry and in vitro suppression assays, respectively. Finally, graft survival and immune responses were determined in NK cell-depleted, or adult naive Treg-transferred, young hosts. RESULTS: Corneal allograft survival in the very young recipients was significantly lower than in adult hosts. The frequencies of total NK cells and their interferon gamma-expressing subset in the cornea were significantly higher in the very young mice posttransplantation. In ungrafted mice, frequencies of Treg in draining lymph nodes as well as their capabilities to suppress NK-cell secretion of interferon gamma were lower in the very young compared with adults. In NK cell-depleted or adult Treg--transferred very young recipients, the allograft survival was significantly improved along with the suppressed NK-cell response. CONCLUSIONS: Our data demonstrate that amplified activity of NK cells, together with lower suppressive function of Treg, contributes to early rejection of corneal allografts in very young graft recipients.

Cayman ataxia protein caytaxin is transported by kinesin along neurites through binding to kinesin light chains.

Deficiency of caytaxin results in hereditary ataxia or dystonia in humans, mice and rats. Our yeast two-hybrid screen identified kinesin light chains (KLCs) as caytaxin-binding proteins. The tetratricopeptide-repeat region of KLC1 recognizes the ELEWED sequence (amino acids 115-120) of caytaxin. This motif is conserved among BNIP-2 family members and other KLC-interacting kinesin cargo proteins such as calsyntenins. Caytaxin associates with kinesin heavy chains (KHCs) indirectly by binding to KLCs, suggesting that caytaxin binds to the tetrameric kinesin molecule. In cultured hippocampal neurons, we found that caytaxin is distributed in both axons and dendrites in punctate patterns, and it colocalizes with microtubules and KHC. GFP-caytaxin expressed in hippocampal neurons is transported at a speed ( approximately 1 mum/second) compatible with kinesin movement. Inhibition of kinesin-1 by dominant-negative KHC decreases the accumulation of caytaxin in the growth cone. Caytaxin puncta do not coincide with vesicles containing known kinesin cargos such as APP or JIP-1. A part of caytaxin, however, colocalizes with mitochondria and suppression of caytaxin expression by RNAi redistributes mitochondria away from the distal ends of neurites. These data indicate that caytaxin binds to kinesin-1 and functions as an adaptor that mediates intracellular transport of specific cargos, one of which is the mitochondrion.

The functions of IL-23 and IL-2 on driving autoimmune effector T-helper 17 cells into the memory pool in dry eye disease.

Long-lived memory T-helper 17 (Th17) cells actively mediate the chronic inflammation in autoimmune disorders, including dry eye disease (DED). The mechanisms responsible for the maintenance and reactivation of these cells in autoimmunity have been subject of investigation. However, the process through which memory Th17 are generated from their effector precursors remains to be elucidated. Herein, using our murine model of DED, we detect a linear transition from effector-to-memory Th17 cells during the abatement phase of acute inflammation, which is accompanied by persistently high levels of IL-23 and diminished levels of IL-2. In addition, in vitro culture of effector Th17 cells derived from the DED animals with IL-23, but not IL-2, leads to significant generation of memory Th17 cells, along with upregulated expression levels of IL-7R and IL-15R by these cells. Furthermore, supplementation of IL-2 abolishes and blockade of IL-2 enhances IL-23-induced generation of memory Th17 cells in vitro. Finally, in vivo blockade of IL-23 signaling during the contraction phase of primary response inhibits the generation of memory Th17 cells from their effector precursors. Together, our data demonstrate a new dichotomy between IL-23 and IL-2 in driving effector Th17 cells into the memory pool in autoimmune-mediated ocular surface inflammation.

Local Delivery of Regulatory T Cells Promotes Corneal Allograft Survival.

BACKGROUND: Regulatory T (Treg) cell-based immunotherapies have been studied as potential cell-based modalities for promoting transplant survival. However, the efficacy of local delivery of Treg cells in corneal transplantation has not been fully elucidated. Herein, we investigated the kinetics of migration of subconjunctivally injected Treg cells and their role in promoting corneal allograft survival. METHODS: GFPCD4CD25Foxp3 Treg cells were isolated from draining lymph nodes (DLNs) of GFP transgenic mice and were subconjunctivally injected to corneal allograft recipients. Next, Treg cells, conventional T cells (Tconv) or a combination of both was locally injected to graft recipients, and graft survival was determined by evaluating opacity scores for 10 weeks. Transplanted mice without treatment served as controls. The frequencies of major histocompatibility complex-IICD11b antigen-presenting cells, IFNγCD4 Th1 cells, and CD45 cells in the DLNs and cornea were evaluated at week 2 posttransplantation using flow cytometry. Expressions of IFNγ, IL-10 and TGF-ß in the grafts were assessed using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: GFP Treg cells were detected in the ipsilateral cornea and DLNs of recipients 6 hours after injection. Subconjunctival injection of Treg cells significantly decreased the frequencies of mature antigen-presenting cells in the graft and DLNs, suppressed Th1 frequencies in DLNs, and inhibited CD45 cell infiltration to the graft. Finally, locally delivered Treg cells significantly reduced the expression of IFN-γ, enhanced the levels of IL-10 and TGF-ß in the graft, and promoted long-term allograft survival. CONCLUSIONS: Our study elucidates the kinetics of migration of locally delivered Treg cells and shows their role in suppressing host immune response against the allograft.

High-Performance SAW Resonator With Simplified LiTaO3/SiO2 Double Layer Structure on Si Substrate.

In response to the increased mobile data traffic, there is a growing need for more low-loss RF band filters with steep frequency characteristics, and high-quality ( Q )-factor and low-temperature coefficient of frequency (TCF) resonators are required to achieve this. We previously reported that for a surface acoustic wave (SAW) resonator on a three-layer structure, which is composed of a thin LiTaO3 (LT) plate whose orientation is 50° rotated YX propagation, SiO2 layer, and AlN layer on a Si substrate, a Q-factor several times higher than that of an SAW resonator on a standard 42° rotated YX propagation LiTaO3 (42YX-LT) substrate could be obtained. In this study, we investigated this layer structure and found that a two-layer structure, in which the AlN layer is removed, achieves a high Q -factor. Numerical analyses using a finite element method showed that the acoustic wave energy can be confined to the surface of the two-layer substrate, and the TCF and electromechanical coupling coefficient ( k2 ) were improved by optimizing the thickness of each layer. We fabricated and evaluated prototype one-port resonators with the two-layer structure and the standard 42YX-LT SAW substrate with resonant frequencies from 0.95 to 3.6 GHz. An improvement of the Q-factor of 3 to 4 times compared with that of the resonator with standard 42YX-LT substrate was observed for the two-layer structure, which means that a reduction of complexity of the layer structure could be obtained without performance loss. The two-layer structure was applied to a 2.4-GHz band Wi-Fi filter to achieve high performances such as low-loss, better steepness, and high attenuation.

The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection.

Adenosine triphosphate (ATP) is released into the extracellular environment during transplantation, and acts via purinergic receptors to amplify the alloimmune response. Here, using a well-established murine model of allogeneic corneal transplantation, we investigated the immunomodulatory mechanisms of the purinergic receptor antagonist oxidized ATP (oATP). Corneal transplantation was performed using C57BL/6 donors and BALB/c hosts. oATP or sterile saline was administered via intraperitoneal injection for 2 weeks postoperatively. Frequencies of CD45+ leukocytes, CD11b+MHCII+ antigen presenting cells (APCs), CD4+IFN-γ+ effector Th1 cells and CD4+Foxp3+ regulatory T cells (Tregs) were evaluated by flow cytometry. Slit-lamp microscopy was performed weekly for 8 weeks to evaluate graft opacity and determine transplant rejection. Treatment with oATP was shown to significantly reduce graft infiltration of CD45+ leukocytes, decrease APC maturation and suppress effector Th1 cell generation relative to saline-treated control. No difference in Treg frequencies or Foxp3 expression was observed between the oATP-treated and control groups. Finally, oATP treatment was shown to reduce graft opacity and increase graft survival. This report demonstrates that oATP limits the alloimmune response by regulating APC maturation and suppressing the generation of alloreactive Th1 immunity.

Corneal Tissue From Dry Eye Donors Leads to Enhanced Graft Rejection.

PURPOSE: To assess the effect of dry eye disease (DED) in graft donors on dendritic cell (DC) maturation, host T-cell sensitization, and corneal allograft rejection. METHODS: Corneas of control (healthy donor) and DED mice (C57BL/6) were transplanted onto fully allogeneic naive BALB/c recipients (n = 10 mice/group). Long-term allograft survival was evaluated for 8 weeks. Corneas and draining lymph nodes (dLNs) were harvested at posttransplantation day 14 (n = 5 mice/group). The frequencies of MHCII CD11c DCs in the donor corneas and host dLNs and the frequencies of interferon (IFN)-γ and IL-17 CD4 T cells and Foxp3 expression by Tregs in host dLNs were investigated using flow cytometry. The enzyme-linked immunospot assay was used to assess host T-cell allosensitization through direct and indirect pathways (n = 3/group). RESULTS: Recipients of DED donor corneas showed significantly reduced graft survival (10%) compared with control mice (50% survival, P = 0.022), and had significantly increased frequencies of mature DCs in the grafted cornea (DED donor 44.0% ± 0.36% vs. healthy donor 35.4 ± 0.5%; P < 0.0001) and host dLNs (DED donor 25.1% ± 0.66% vs. healthy donor 13.7% ± 1.6%; P = 0.005). Frequencies of IFN-γ and IL-17 T cells were increased in the dLNs of recipients of DED corneas, whereas the expression (mean fluorescence intensity) of Foxp3 in Tregs was decreased significantly in these mice (DED donor 6004 ± 193 vs. healthy donor 6806 ± 81; P = 0.0002). Enzyme-linked immunospot analysis showed that the direct pathway of allosensitization was significantly amplified in recipients of grafts with DED (P = 0.0146). CONCLUSIONS: Our results indicate that DED in the donor is a significant risk factor for subsequent corneal allograft rejection.

Scaling and maintenance of corneal thickness during aging.

Corneal thickness is tightly regulated by its boundary endothelial and epithelial layers. The regulated set-point of corneal thickness likely shows inter-individual variations, changes by age, and response to stress. Using anterior segment-optical coherence tomography, we measure murine central corneal thickness and report on body size scaling of murine central corneal thickness during aging. For aged-matched mice, we find that corneal thickness depends on sex and strain. To shed mechanistic insights into these anatomical changes, we measure epithelial layer integrity and endothelial cell density during the life span of the mice using corneal fluorescein staining and in vivo confocal microscopy, respectively and compare their trends with that of the corneal thickness. Cornea thickness increases initially (1 month: 114.7 ± 3.0 µm, 6 months: 126.3 ± 1.6 µm), reaches a maximum (9 months: 129.3 ± 4.4 µm) and then reduces (12 months: 127 ± 2.9 µm, 13 months: 119.5 ± 7.6 µm, 14 months: 110.6 ± 10.6 µm), while the body size (weight) increases with age. We find that endothelial cell density reduces from 2 months old to 8 months old as the mice age and epithelial layer accumulates damages within this time frame. Finally, we compare murine corneal thickness with those of several other mammals including humans and show that corneal thickness has an allometric scaling with body size. Our results have relevance for organ size regulation, translational pharmacology, and veterinary medicine.

Medically uncontrolled conjunctival pyogenic granulomas: correlation between clinical characteristics and histological findings.

BACKGROUND: Conjunctival pyogenic granulomas are commonly seen after ocular surgeries or at an ocular wound site. The aim of this study is to describe a novel histological classification for medically uncontrolled conjunctival pyogenic granulomas (MUCPG), and to explore whether the diversity in clinical features correlates to different histological subtypes of MUCPG. METHODS: This is an observational cross-section case series. We reviewed 46 consecutive patients with conjunctival pyogenic granulomas who did not respond to topical corticosteroids and underwent surgical excision from January 1, 2006 through December 31, 2015. Clinical features and histological findings were presented and analyzed. RESULTS: Ocular surgery, accidental injury, and chalazion were the main predisposing causes of MUCPG. The lesions tended to occur unilaterally on the bulbar conjunctiva. Forty patients (87%) presented an enrichment of inflammatory cells and proliferated capillaries in their pathological sections (inflammatory pattern). Six patients (13%) showed relatively few inflammatory cells and capillaries within fibrous stroma (fibrous pattern). Patients with the inflammatory pattern were older (p = 0.025) and tended to be located in bulbar conjunctiva (p = 0.002). The predisposing causes were also different between two histological subtypes (p = 0.007). CONCLUSIONS: We found the correlation between clinical presentation and histological subtypes in patients with MUCPG, indicating this disease may need a new classification scheme.

High-Performance SAW Resonator on New Multilayered Substrate Using LiTaO3 Crystal.

To develop the high-performance filters and duplexers required for recent long-term evolution frequency bands in mobile handsets, a surface acoustic wave (SAW) resonator is needed that has a higher quality (Q) and a lower temperature coefficient of frequency (TCF). To achieve this, the authors focused on acoustic energy confinement in the depth direction for a rotated Y-X LiTaO3 (LT) substrate. Characteristics of multilayered substrates with low-impedance and high-impedance layers under LT layer were studied numerically in terms of acoustic energy distribution, phase velocity, coupling coefficient, and temperature characteristics employing a finite-element method simulation. After several calculations, a novel multilayered structure was developed that uses SiO2 for a low-impedance layer and AlN for a high-impedance layer under the thin LT layer. A one-port resonator using the new substrate was fabricated, and its experimental results showed that the developed resonator had a Bode-Q over 4000 and TCF of -8 ppm/°C, which are four times higher than and one-fifth as small as those of a conventional 4° YX-LT SAW resonator, respectively. By applying this technology, a band 25 duplexer with very narrow duplex gap was successfully developed, which shows extremely low insertion loss, steep cutoff characteristics, and stable temperature characteristics.

Chemo-radio-gene therapy for colorectal cancer cells using Escherichia coli uracil phosphoribosyltransferase gene.

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic agents, and is known to be a radiosensitizer. Previously, we reported that adenoviral transduction of the Escherichia coli (E. coli) uracil phosphoribosyltransferase (UPRT) gene induced marked sensitivity in human colon cancer cells to 5-FU. The aim of the current study was to investigate the efficacy of virally-directed UPRT and 5-FU to enhance the radiosensitivity of HT29 human colon cancer cells. Cytotoxicity as a result of radiation treatment following AdCA-UPRT infection and 5-FU exposure was confirmed by radiation dose-response analysis with colony formation assay. In vivo chemoradio-gene therapy using the UPRT/5-FU/radiation system showed tumor regressive effects even against large HT29-established subcutaneous tumors in nude mice. Our results suggested that adenovirus-mediated UPRT gene transduction combined with 5-FU administration and radiation may be an effective new chemo-radio-gene therapy for colorectal cancer.

Resonator filters using shear horizontal-type leaky surface acoustic wave consisting of heavy-metal electrode and quartz substrate.

The authors have succeeded in exciting a new type of leaky surface acoustic wave (LSAW) having only a shear horizontal (SH) component that has a large electromechanical coupling factor, a large reflection coefficient, and excellent temperature stability, by combining interdigital transducers (IDTs) and reflectors made of heavy-metal films such as gold (Au), tantalum (Ta), and tungsten (W) on the ST-cut 90 degrees X propagation (direction perpendicular to the X-axis) quartz substrate. This LSAW does not have a propagation decay. The square of the electromechanical coupling factor is 2.1-2.7 times larger than, the reflection coefficient is 30 times larger than, and the temperature characteristic is the same as those of a Rayleigh wave on an ST-cut X propagation quartz substrate. The authors applied this SH LSAW to resonators and resonator filters. As a result, we succeeded in developing the low loss and very small-sized resonators and resonator filters (1/5-1/4 of conventional device sizes) with IDTs with a small number of finger pairs and very small reflectors, for the first time.

The role of mislocalized phototransduction in photoreceptor cell death of retinitis pigmentosa.

Most of inherited retinal diseases such as retinitis pigmentosa (RP) cause photoreceptor cell death resulting in blindness. RP is a large family of diseases in which the photoreceptor cell death can be caused by a number of pathways. Among them, light exposure has been reported to induce photoreceptor cell death. However, the detailed mechanism by which photoreceptor cell death is caused by light exposure is unclear. In this study, we have shown that even a mild light exposure can induce ectopic phototransduction and result in the acceleration of rod photoreceptor cell death in some vertebrate models. In ovl, a zebrafish model of outer segment deficiency, photoreceptor cell death is associated with light exposure. The ovl larvae show ectopic accumulation of rhodopsin and knockdown of ectopic rhodopsin and transducin rescue rod photoreceptor cell death. However, knockdown of phosphodiesterase, the enzyme that mediates the next step of phototransduction, does not. So, ectopic phototransduction activated by light exposure, which leads to rod photoreceptor cell death, is through the action of transducin. Furthermore, we have demonstrated that forced activation of adenylyl cyclase in the inner segment leads to rod photoreceptor cell death. For further confirmation, we have also generated a transgenic fish which possesses a human rhodopsin mutation, Q344X. This fish and rd10 model mice show photoreceptor cell death caused by adenylyl cyclase. In short, our study indicates that in some RP, adenylyl cyclase is involved in photoreceptor cell death pathway; its inhibition is potentially a logical approach for a novel RP therapy.

Foveal sparing in patients with Japanese Stargardt's disease and good visual acuity.

PURPOSE: Patients with Stargardt's disease usually have a poor visual prognosis. However, in our clinical practice we have observed some patients with dark-red foveal pigmentation (sparing) who had good best corrected visual acuity (BCVA) despite the presence of a late-stage disease. The purpose of this study was to investigate the BCVA outcomes in Japanese patients with Stargardt's disease with foveal sparing. METHODS: Eighteen consecutive patients (36 eyes) with Stargardt's disease underwent ophthalmoscopy, fluorescein angiography, fundus autofluorescence imaging, and near-infrared fundus autofluorescence (NIA) imaging. The patients were divided into two groups based on the presence or absence of foveal sparing. The presence of foveal sparing was determined based on ophthalmoscopy and NIA imaging results. The association between foveal sparing and BCVA was assessed statistically by Students' t test. RESULTS: Of the 36 eyes, ten (27.8 %) had dark-red foveal sparing. The mean BCVA of the group with sparing was 0.16 ± 0.31, expressed in logarithm of the minimum angle of resolution (logMAR) units, and that of the group without sparing was 1.03 ± 0.39 logMAR units, which is a significant difference (p = 0.0000002507). CONCLUSION: A subgroup of Japanese patients with late-stage Stargardt's disease and dark-red foveal sparing maintained a relatively good BCVA. The pigmentation was clearly observed using NIA and proved useful for assessing the BCVA prognosis.