Search

Abstract Endothelial dysfunction exacerbates hypertension and other vascular complications in diabetes mellitus (DM). Circulating microparticles (MPs) and extracellular vesicles released in patients with DM have emerged as novel regulators of endothelial dysfunction. The obstruction of mineralocorticoid receptors (MRs) is a potential therapeutic approach to reduce cardiovascular complications. Their impact on the obstruction of MRs on circulating MPs and endothelial dysfunction in DM remains unclear. DM was induced in mice through a single intravenous dose of streptozotocin (STZ; 200 mg/kg). Esaxerenone (ESAX; 3 mg/kg/day), a MR blocker was administered via diet for 8 weeks. In this study, the aortas of the DM group showed the endothelial dysfunction and the administration of ESAX ameliorated the endothelial-dependent responses. Moreover, ESAX influences the impaired endothelial-dependent responses of DM-derived MPs. Interestingly, MP levels increased in DM whereas decreased after ESAX administration. In the aorta, the DM-derived MPs increased the expression of intercellular adhesion molecule-1 (ICAM-1). ESAX inhibited the adhesion of DM-derived MPs. Moreover, the ICAM-1 inhibitor A205804 shows similar effects as ESAX. These results indicate that the release and adhesion properties of MPs can be partially obstructed by ESAX via the ICAM-1 signaling pathway, which clarifies the other functions beyond the anti-hypertensive effects of ESAX.

Abstract Background Surveys using questionnaires to collect epidemiologic data may be subject to misclassification. Here, we analyzed a headache questionnaire to evaluate which questions led to a classification other than migraine. Methods Anonymized surveys coupled with medical claims data from individuals 19–74 years old were obtained from DeSC Healthcare Inc. to examine proportions of patients with primary headache disorders (i.e.; migraine, tension-type headache, cluster headache, and “other headache disorders”). Six criteria that determined migraine were used to explore how people with other headache disorders responded to these questions. Results Among the 21480 respondents, 7331 (34.0%) reported having headaches. 691 (3.2%) respondents reported migraine, 1441 (6.7%) had tension-type headache, 21 (0.1%) had cluster headache, and 5208 (24.2%) reported other headache disorders. Responses of participants with other headache disorders were analyzed, and the top 3 criteria combined with “Symptoms associated with headache” were “Site of pain” (7.3%), “Headache changes in severity during daily activities” (6.4%), and the 3 criteria combined (8.8%). The symptoms associated with headache were “Stiff shoulders” (13.6%), “Stiff neck” (9.4%), or “Nausea or vomiting” (8.7%), Photophobia” (3.3%) and “Phonophobia” (2.5%). Conclusions Prevalence of migraine as diagnosed by questionnaire was much lower than expected while the prevalence of “other headache” was higher than expected. We believe the reason for this observation was due to misclassification, and resulted from the failure of the questionnaire to identify some features of migraine that would have been revealed by clinical history taking. Questionnaires should, therefore, be carefully designed, and doctors should be educated, on how to ask questions and record information when conducting semi-structured interviews with patients, to obtain more precise information about their symptoms, including photophobia and phonophobia.

IntroductionIn Japan, inherited retinal dystrophy caused by biallelic variants of the RPE65 gene is exceedingly rare. The purpose of this study was to describe a Japanese male patient with a novel variant in RPE65 associated with Leber congenital amaurosis (LCA).Case reportThe patient, diagnosed with LCA, exhibited infantile nystagmus and reported experiencing night blindness since early childhood. At 27 years of age, the patient underwent an ophthalmologically evaluation. Corrected visual acuity was Snellen equivalent 20/133 in the right eye and Snellen equivalent 20/100 in the left eye. Fundus examination revealed alterations in the retinal pigment epithelium characterized by hypopigmentation and narrowing of retinal vessels. Fundus autofluorescence imaging demonstrated a generally diminished autofluorescent signal. Full-field electroretinography identified a generalized dysfunction of both rod and cone systems in each eye. Whole exome sequencing identified a novel missense variant in RPE65 (NM_000329.3): c.1172C > A p.(Ala391Asp), which was classified as pathogenic, as well as a recurrent variant p.(Arg515Trp).ConclusionThis study provides valuable insights into the genotype–phenotype correlation of RPE65-associated LCA in Japanese patients, with critical implications for enhanced diagnostic accuracy and informed therapeutic decisions.

Objective To describe the characteristics of patients who sought medical attention for headache and those who did not.Design This observational study used a cross-sectional online survey and linked medical claims data.Setting Data from an online self-administered questionnaire survey conducted in November 2020 as well as linked medical claims data spanning December 2017 and November 2020 were provided by DeSC Healthcare Inc.Participants Of 21 480 respondents aged 19–74 years whose sex and age data matched the claims data, 7311 reported experiencing headache.Measures Outcomes included participant characteristics, status of medical attention seeking, medication use, quality of life (QOL) measured by Migraine-Specific QOL (MSQ) questionnaire V.2.1 and headache intensity.Results Of the 7311 respondents with headache, 735 sought medical attention and 6576 did not. Compared with those who did not seek medical attention, those who sought medical attention had more frequent headaches (median: 5 days/3 months vs 10 days/3 months in those who did not vs those who sought medical attention, respectively) had lower MSQ score (mean (SD) MSQ total score: 87.6 (13.0) vs 77.1 (18.1)) and were likely to experience moderately severe to severe headache (19.0% (1252/6576) vs 41.2% (303/735)) without headache medication. The inability to tolerate headache (36.5% (268/735)) was a common reason for seeking medical attention. Since the pain was not severe enough, 35.3% (2323/6576) of patients did not seek medical attention. Furthermore, a subgroup of respondents experiencing headache for ≥15 days were uncertain about which hospital or department to attend.Conclusions Patients typically seek help when the pain becomes unbearable. Still, some of them did not seek medical attention while they were experiencing headache for ≥15 days per month. Therefore, it is important to raise awareness and encourage seeking early medical attention before symptoms and associated burdens become too severe to be managed effectively.

IntroductionCongenital X-linked retinoschisis (XLRS) presents as macular retinoschisis/degeneration in almost all patients and as peripheral retinoschisis in half the patients. Although the optical coherence tomography (OCT) findings of macular retinoschisis have been well investigated, those of peripheral retinoschisis have rarely been reported. This study aimed to report the ultra-widefield OCT findings of the peripheral retina in patients with XLRS.MethodsMedical records of 10 Japanese patients (19 eyes) with clinically and/or genetically diagnosed XLRS were retrospectively reviewed. Funduscopic, electroretinographic, and OCT findings were reviewed and evaluated. Some were also genetically evaluated for the RS1 gene.ResultsOCT of the macula revealed schises and/or cystoid changes in the inner nuclear layer (INL) and outer nuclear layer. In contrast, OCT of the peripheral retina revealed schises and/or cystoid changes in the INL in eight eyes (44%), and/or splitting in the ganglion cell layer (GCL) in 10 (56%) of the 18 eyes with clear OCT images. No schisis or cystoid changes were found in the peripheral OCT images of eight eyes (44%). A 16-year-old boy presented with retinal splitting of the GCL and INL of the inferior retina, although he had no ophthalmoscopic peripheral retinoschisis. Genetic examinations were performed on three patients, all of whom had reported missense mutations in the RS1 gene.ConclusionIn XLRS, peripheral bullous retinoschisis results from GCL splitting in the retina. One of the 10 patients with XLRS showed intraretinal retinoschisis in the GCL in the inferior periphery, which was unremarkable on ophthalmoscopy (occult retinoschisis). Although both peripheral bullous retinoschisis and occult retinoschisis showed splitting/cystic changes in the GCL, further studies are needed to determine whether occult retinoschisis progresses to bullous retinoschisis.

Abstract Background Limited epidemiological data are available for headache disorders in Japan, and no recent studies have reported the impact of several primary headache disorders in Japan. This study aimed to report the up-to-date epidemiological data and impact of primary headaches on daily activities as well as the use of medical care, clinical features, and pain severity/activity impairment using nationwide data in Japan. Methods We used anonymized online survey data coupled with medical claims data, from individuals aged 19–74 years old, that were provided by DeSC Healthcare Inc. The outcomes included the prevalence of migraine, tension-type headache, cluster headache, and other headache types stratified by age and sex, use of medical care, clinical features, medication use, and severity of pain/activity impairment. All outcomes were examined separately for each headache type. This is the second paper reported concurrently with this research. Results The study population comprised 691/1,441/21/5,208 individuals with migraine/tension-type headache/cluster headache/other headache types, respectively. The prevalence of migraine and tension-type headache was higher in women than in men but was similar for cluster headache (male vs. female, 1.7% vs. 7.4%, 5.3% vs. 10.8%, and 0.1% vs. 0.1%, respectively). The percentage of individuals with migraine, tension-type headache, cluster headache who had not seen a doctor was 81.0%, 92.0%, 57.1%, respectively. The common headache triggers were fatigue in migraine and tension-type headache, and weather-related phenomena and turning of the seasons in migraine. Common activities refrained from or reduced by headaches were “operating a computer or smartphone”, “drinking alcohol”, and “going to crowded places” in all three headache types and housework-related activities in women. Among individuals taking medicines, 16.8%, 15.8%, 47.6% with migraine, tension-type headache, and cluster headache reported moderate to severe pain, respectively, and 12.6%, 7.7%, 19.0% reported moderate to severe disability, respectively. Conclusions This study found various triggers of headache attacks, and daily activities refrained from or reduced by headaches. Additionally, this study suggested that the disease burden in people possibly experiencing tension-type headaches, many of whom had not seen a doctor. The study findings are of clinical value for the diagnosis and treatment of primary headaches.

Consumers use online customer reviews as an indicator of product quality before making their purchase decisions. The brand is also a powerful cue of product quality for individual products from strong brands, and the impact of customer reviews for these products may be relatively low compared to that for products from weaker brands. However, in the existing literature, the role of customer reviews on the sales performance of products from strong brands has not been examined thoroughly. To address this problem, the present study examines sales of headset data in Japan using a fuzzy-set qualitative comparative analysis (fsQCA). The results show that products from strong brands can achieve high sales regardless of customer review ratings during the new product period. However, high customer review ratings play an important role, as an INUS condition, for these brands to be successful in terms of sales beyond the new product phase. This implies that even if a brand is strong, it is still important to develop superior products that result in high customer review ratings.

Abstract Background Migraine is a chronic disease characterized by episodic headache attacks. No recent studies have, however been conducted on the epidemiology of migraine or the treatment landscape in Japan. This study was conducted as a fact-finding survey using medical claims data and an online survey on migraine and headaches, conducted among members of health insurance associations with the objective of gaining an understanding of migraine prevalence and the treatment status in Japan. Methods The study methodology utilized a unique approach of combined data sources. The data sources used in this study are medical claims data and linked online survey data provided by DeSC Healthcare Inc (DeSC). The primary outcomes (from survey responses) were: the overall number and proportion of migraine patients; and the overall prevalence of migraine, stratified by age and sex. The secondary outcomes (from survey responses) were use of medical care; and clinical features/headache symptoms. The analysis population included all individuals who had response data for surveys conducted by DeSC. The online survey data and medical claims data were summarized. Results The data population comprised 21,480 individuals. On the basis of the survey results, including probable cases, the overall prevalence of migraine was 3.2%. The highest prevalence of migraine was observed in patients aged 30–39 years. The prevalence of migraine in women was 4.4 times higher than in men. The percentage of migraine patients who had not been seen by a doctor was 81.0%. More than 80% of patients were taking over-the-counter drugs and 4.8% took prescription medicines only. Approximately 52.9% of patients considered that the intensity of pain symptoms was severe. Moreover, the majority of patients (72.9%) considered that the impairment of daily life activities was of moderate or severe degree. Conclusions In Japan, the percentage of people with migraine who did not receive medical attention is as high as 80%. Additionally, the majority of patients tend to endure symptoms and continue with everyday activities. With innovative treatment approaches becoming available it is necessary to disseminate information that migraine is not a simple headache but an illness that requires medical treatment and consultation.

Abstract Background This case report describes the surgical outcome in a patient with congenital X-linked retinoschisis (CXLRS) and the results of proteomic analysis of surgically extracted samples from both vitreous and intraschisis cavities by mass spectrometry. Case presentation A 3-month-old boy presented with extensive retinoschisis involving macula and retinal periphery in both eyes. Genetic analysis confirmed retinoschisin 1 mutation (c.554C > T), and an electroretinogram showed significant reduction of b-wave and decreased cone and rod responses, which led to a diagnosis of CXLRS. By performing pars plana vitrectomy, including inner wall retinectomy, clear visual axes with stable retinal conditions and functional vision in both eyes were obtained during the 4 years of follow-up. Proteomic analysis of surgically retrieved fluid from the intraschisis cavity revealed a higher expression of interphotoreceptor retinoid-binding protein (IRBP) than that from the vitreous humor. However, both samples showed equal levels of albumin, transferrin, and pigment epithelium-derived factor. Conclusions Cellular adhesive imperfection in CXLRS may cause IRBP diffusion from the interphotoreceptor matrix, resulting in the strong expression of IRBP in the intraschisis cavity. An impaired retinoid cycle caused by an absence of IRBP in the retina may potentially underlie the pathology of CXLRS.

FXR is a key molecule that modulates anti-inflammatory activity in the intestinal-liver axis. Although FXR has pleiotropic functions including regulation of liver inflammation and activation of macrophages, it remains unclear whether it is involved in macrophage polarization. In this paper we demonstrated that stimulation of macrophages derived from the bone marrow using an FXR agonist activated polarization toward M2 but not M1 macrophages. The treatment of mice with chitin skewed macrophage polarization towards M2 macrophages, while co-treatment with an FXR agonist further promoted the polarization toward M2 macrophages in vivo. This skewed polarization towards M2 macrophages by an FXR agonist was accompanied by increased expression of signaling molecules related to the retinoic acid receptor. Inhibition of the retinoic acid receptor suppressed FXR agonist-mediated M2 macrophage polarization, indicating that this polarization was, at least, partly dependent on the retinoic acid receptor pathway. These data demonstrate that FXR has a role in polarization toward M2 macrophages and suggest a possible therapeutic potential of FXR agonists in M2 macrophage-related conditions.

Abstract This study investigated the surgical outcomes of Coats disease and the role of external drainage (XD) of subretinal fluid (SRF). The study is a multicenter retrospective interventional case series of 26 consecutive eyes of 26 patients who underwent surgeries for advanced Coats disease with retinal detachment. Main outcomes measured were: 1) comparison of complete SRF resolution with or without XD, and 2) variables that were associated with functional postoperative best-corrected visual acuity (BCVA) defined as BCVA of 0.1 or better, 3) intraocular vascular endothelial growth factor (VEGF) levels. Complete SRF resolution was achieved in all 14 eyes in which XD had been performed and in 75% of 12 eyes in which XD had not been performed (P = .03). Multivariable logistic regression analysis revealed that initial BCVA was the only variable associated with functional postoperative BCVA (odds ratio 3.24, 95% CI 0.93–11.33; P = .04). Markedly elevated VEGF levels were noted in the SRF compared with those in the vitreous humor (49,760 ± 52,990 vs. 707 ± 611 pg/mL, P = .03). XD seems to provide better anatomical success than without XD in the treatment of advanced Coats disease as XD could effectively eliminate substantial amount of VEGF in the SRF.

Abstract Background To evaluate the correlation between visual acuity improvement and vision-related QOL after ranibizumab treatment in Japanese patients with AMD. Methods In this one-year prospective, interventional, open-label, multicenter study involving four sites, patients with neovascular AMD were enrolled and observed for 12 months. Treatment-naïve patients received 0.5 mg ranibizumab as needed after three initial monthly doses. The best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at every visit. Evaluations with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and patient satisfaction questionnaire were performed at baseline and 3 and 12 months after initial treatment. The primary endpoint was change in BCVA and QOL 3 months after ranibizumab treatment. QOL outcomes were also assessed in the better and poor BVCA subgroups. Results The study enrolled 100 patients. The mean logMAR BCVA after treatment improved significantly from 0.43 to 0.30 at 3 months (p 0.6, p=0.1) at 3 months. There were no significant differences in the satisfaction questionnaire score from baseline to at 3 months (p=0.54) and 12 months (p=0.23). The average CMT improved significantly from 340 to 264 μm at 3 months (p

Immunoproteasomes regulate the degradation of ubiquitin-coupled proteins and generate peptides that are preferentially presented by MHC class I. Mutations in immunoproteasome subunits lead to immunoproteasome dysfunction, which causes proteasome-associated autoinflammatory syndromes (PRAAS) characterized by nodular erythema and partial lipodystrophy. It remains unclear, however, how immunoproteasome dysfunction leads to inflammatory symptoms. Here, we established mice harboring a mutation in Psmb8 (Psmb8-KI mice) and addressed this question. Psmb8-KI mice showed higher susceptibility to imiquimod-induced skin inflammation (IMS). Blockade of IL-6 or TNF-α partially suppressed IMS in both control and Psmb8-KI mice, but there was still more residual inflammation in the Psmb8-KI mice than in the control mice. DNA microarray analysis showed that treatment of J774 cells with proteasome inhibitors increased the expression of the Cxcl9 and Cxcl10 genes. Deficiency in Cxcr3, the gene encoding the receptor of CXCL9 and CXCL10, in control mice did not change IMS susceptibility, while deficiency in Cxcr3 in Psmb8-KI mice ameliorated IMS. Taken together, these findings demonstrate that this mutation in Psmb8 leads to hyperactivation of the CXCR3 pathway, which is responsible for the increased susceptibility of Psmb8-KI mice to IMS. These data suggest the CXCR3/CXCL10 axis as a new molecular target for treating PRAAS.

BNT162b2, a nucleoside-modified mRNA vaccine for SARS-CoV-2 spike glycoprotein (S), provides approximately 95% efficacy for preventing COVID-19. However, it remains unclear how effectively memory CD8+ T cells are generated and which genetic and environmental factors affect the generation and function of memory CD8+ T cells elicited by this vaccine. Here, we investigated the frequency and functions of memory CD8+ T cells 3 weeks after the second vaccination in the Japanese population. Using a peptide-MHC pentamer, we detected an increased number of memory CD8+ T cells together with increased serum anti-S protein antibody in females compared with that in males, but the frequency of pentamer-positive cells was not positively correlated with antibody titers. Memory precursor effector cells (KLRG1-CD127+) among both CD8+ cells and pentamer+ cells and effector cells (CD38-HLA-DR+) among pentamer+ cells were more abundant in females than in males. Upon S protein-mediated stimulation of T cells, the intensity of CD107a and granzyme B expression was increased in females compared with that in males, indicating stronger memory CD8+ T cell responses in females than in males. Our studies showed that the BNT162b2 vaccine elicits increased memory CD8+ T cell proliferation and secondary CTL responses in females compared with those in males in the Japanese population. These findings provide an important basis for the distinct sex difference in cellular immune responses to mRNA vaccination and suggest that memory precursor effector cells can be one of markers to evaluate and boost cellular immunity induced by BNT162b2.

Background: Revesz syndrome is a rare type of the dyskeratosis congenita spectrum disorder that is characterized by nail dystrophy, oral leukoplakia, and abnormal skin pigmentation. The retinal features are similar to those of exudative retinopathy with avascular areas of the peripheral retina. There are only a few publications describing patients with Revesz syndrome who underwent ocular treatments for the retinal complications. We report a Case of Revesz syndrome with bilateral retinal detachments that were successfully reattached by pars plana vitrectomy. Observations: A 3-year-old Japanese girl with Revesz Syndrome had progressive vitreal hemorrhages and tractional retinal detachments in both eyes. She underwent pars plana vitrectomy with lensectomy on both eyes. A retinal attachment with vision improvement was achieved by a single surgery for the right eye and after repeated surgeries for the left eye. Postoperative electroretinographic (ERG) examinations of the right eye showed a negative type ERG with the b-wave/a-wave ratio

Introduction Retinopathy of prematurity (ROP) is a vascular proliferative disorder that occurs in preterm infants. Existing treatments are only indicated in severe ROP cases due to the high invasiveness and the potential risk of irreversible side effects. We previously elucidated that ripasudil, a selective inhibitor of the Rho-associated protein kinase, has the ability to inhibit abnormal retinal neovascularisation in animal models. In addition, ripasudil eye drops (Glanatec ophthalmic solution 0.4%) have been already used for the treatment of glaucoma. Since eye drop therapy is less invasive, early intervention for ROP is possible. The purpose of this phase I/II trial is to evaluate the safety and efficacy of ripasudil eye drops for preterm infants with ROP.Methods and analysis This is a multicentre, open-label, single-arm phase I/II trial. To evaluate the safety and efficacy of ripasudil as much as possible, ripasudil will be administered to all enrolled preterm infants with zone I/II, stage 1, or worse ROP. The safety and efficacy of ripasudil in treated patients will be assessed in comparison to a historical control group. Because this is the first trial of ripasudil in preterm infants, a dose-escalation study (once daily for 1 week, then two times per day for 2 weeks) will be conducted in phase I. After obtaining approval from the independent data and safety monitoring board to continue the trial after the completion of phase I, phase II will be conducted. In phase II, ripasudil eye drops will be administered two times per day for 12 weeks. The primary endpoint in phase II is also safety. Efficacy and pharmacokinetics will be evaluated as secondary endpoints.Ethics and dissemination This study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.Trial registration numbers NCT04621136 and jRCT2071200047.

Abstract Blue cone monochromacy (BCM) is characterized by loss of function of both OPN1LW (the first) and OPN1MW (the downstream) genes on the X chromosome. The purpose of this study was to investigate the first and downstream genes in the OPN1LW/OPN1MW array in four unrelated Japanese males with BCM. In Case 1, only one gene was present. Abnormalities were found in the promoter, which had a mixed unique profile of first and downstream gene promoters and a −71A > C substitution. As the promoter was active in the reporter assay, the cause of BCM remains unclear. In Case 2, the same novel mutation, M273K, was present in exon 5 of both genes in a two-gene array. The mutant pigments showed no absorbance at any of the wavelengths tested, suggesting that the mutation causes pigment dysfunction. Case 3 had a large deletion including the locus control region and entire first gene. Case 4 also had a large deletion involving exons 2–6 of the first gene. As an intact LCR was present upstream and one apparently normal downstream gene was present, BCM in Case 4 was not ascribed solely to the deletion. The deletions in Cases 3 and 4 were considered to have been caused by non-homologous recombination.

Foveal hypoplasia is a retinal disorder in which there is a lack of full development of the morphology of the fovea. The optical coherence tomography (OCT) and functional findings are presented in relation to the underlying genetic and developmental conditions. Recent advancements of high-resolution OCT imaging have unveiled characteristics of foveal hypoplasia that were not detected by conventional imaging methods. An absence of a foveal pit does not necessarily imply poor visual acuity, and the maturation of the cone photoreceptors is important for the visual acuity. Regardless of the degree of the development of the inner retinal layers, the visual acuity can be preserved as in diseases such as Stickler syndrome that is a newly identified retinal disorder associated with foveal hypoplasia.

Summary: The thymic function to produce self-protective and self-tolerant T cells is chiefly mediated by cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs). Recent studies including single-cell transcriptomic analyses have highlighted a rich diversity in functional mTEC subpopulations. Because of their limited cellularity, however, the biochemical characterization of TECs, including the proteomic profiling of cTECs and mTECs, has remained unestablished. Utilizing genetically modified mice that carry enlarged but functional thymuses, here we show a combination of proteomic and transcriptomic profiles for cTECs and mTECs, which identified signature molecules that characterize a developmental and functional contrast between cTECs and mTECs. Our results reveal a highly specific impact of the thymoproteasome on proteasome subunit composition in cTECs and provide an integrated trans-omics platform for further exploration of thymus biology. : Ohigashi et al. show that the use of cyclin D1-transgenic mice allows quantitative proteomic analysis of cortical and medullary thymic epithelial cells (TECs). Results provide a trans-omics platform for further exploration of TEC biology and reveal the specific impact of the thymoproteasome on proteasome subunit composition in cortical TECs. Keywords: cortical thymic epithelial cells, medullary thymic epithelial cells, proteome, trans-omics, thymoproteasome, Psmb11, cyclin D1

Purpose: Vitrectomy is usually only indicated for familial exudative vitreoretinopathy (FEVR) cases with progressive retinal folds or macular dragging. In this report, we present our experience reversing the progression of macular dragging by performing early eye vitrectomies in a 1-month-old male baby with FEVR. Observations: A 7-day-old, full-term male baby was examined by a pediatric ophthalmologist. His sister had a laser ablation treatment after being diagnosed with FEVR. The ophthalmologist found the baby had avascular retinas, fibrovascular membranes, and vitreous hemorrhages in both eyes, and performed retinal photocoagulations the next day. Although the retinal folds had not yet formed, the arcade vessels began to linearize after the procedure, strongly suggesting disease progression. Therefore, we performed lens-sparing vitrectomies in both eyes on the twenty-ninth day of life. After surgery, the macular dragging reversed, as evidenced by vascular arcade angle measurements. Three years after the surgery, the boy's visual acuity was 0.4 in both eyes. Conclusions and Importance: In this case, we believe the good postoperative outcomes were due to early vitrectomies before the vitreoretinal traction became severe. In addition, the retinal photocoagulation performed on the eighth day of life may have reduced disease activity, at least partially. This case highlights the importance of prompt diagnosis and appropriate treatment of FEVR. Keywords: Familial exudative vitreoretinopathy, Vitrectomy, Early treatment, Laser photocoagulation, Retinal fold

Background/Purpose: To report the ocular findings in three patients with a mutation in the ATOH7 gene. Methods: The clinical findings were collected from the medical records including those for magnetic resonance imaging. Three patients of two families who had poor vision since infancy were studied. Genetic testing of the ATOH7 gene was performed. Results: The three patients had varying degrees of intraocular vascular proliferation associated with advanced retinal detachments as falciform retinal folds or total retinal detachments. This state is referred to as congenital retinal nonattachment. One eye of a sibling had fluorescein angiographic findings of excessive branching of the retinal vessels and fluorescent dye leakage that were consistent with those of familial exudative vitreoretinopathy. Bilateral hypoplasia of the optic nerve was found in all three patients by magnetic resonance imaging. Genetic analysis showed a known in-frame deletion of the ATOH7 gene in all three patients. Conclusion: This is the first report of a patient with a mutation in the ATOH7 gene that had typical vascular patterns of familial exudative vitreoretinopathy in the peripheral retina. The ocular features associated with mutations in the ATOH7 gene overlap those with familial exudative vitreoretinopathy at the early and advanced stages. [ABSTRACT FROM AUTHOR]