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Yuka Saito, Hiroshi Horiguchi, Kei Mizobuchi, Satoshi Katagiri, Hisato Gunji, Tadashi Nakano Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, JapanCorrespondence: Yuka Saito; Hiroshi HoriguchiDepartment of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, JapanTel +81-3-3433-1111 (ext. 3581)Fax +81-3-5378-8828Email y.saito@jikei.ac.jp; hhiro@jikei.ac.jpBackground: The reported features and effectiveness of heads-up surgery (HUS) for ophthalmic surgery include greater resolution, teaching, and significantly reduced endoillumination power.Objective: To report how to care for severe intraoperative photophobia using the HUS system during bilateral rhegmatogenous retinal detachment (RD) surgery in a patient with severe photophobia.Case Report: A man in his 50s, who had been followed up for photophobia and visual impairment underwent five ophthalmic surgeries for bilateral RD. In his early 40s, he had been referred to our hospital because of a complaint of bilateral visual impairment, including severe photophobia, approximately 2 years prior. His decimal best-corrected visual acuities were 0.7 and 0.6 in his right and left eyes, respectively. Optical coherence tomography showed diffuse thinning of the entire retinal layer in the macula of both eyes, which was considered to be a cause of the decrement of visual acuity and photophobia. Twelve years after his first visit, he noticed multiple floaters in his left eye. For RD excluding the macular area, we planned cataract and retinal surgery under retrobulbar anesthesia. However, as we could not continue retinal surgery after cataract surgery due to severe photophobia, we performed general anesthesia (GA) during the second surgery. Seventeen months after the surgery, he underwent the third surgery for RD in his right eye under GA. For RD recurring twice, we performed surgery with the HUS system under retrobulbar anesthesia for the fourth and fifth surgeries, which avoided photophobia due to the significantly reduced light stimulation of the HUS system.Conclusion: Lower light intensity achieved by the HUS system enabled us to eliminate the patient’s intraoperative discomfort. Consequently, we could perform the surgery under local anesthesia in this patient with RD who complained of severe photophobia that required GA using a conventional surgical system.Keywords: heads-up surgery, photophobia, vitrectomy, intraoperative discomfort, macular thinning

Effective conservation of globally distributed marine species relies on identification of demographically independent populations to ensure that management actions are directed at the appropriate scale. This identification is particularly challenging for species with complex life histories when local breeding populations have not been adequately sampled. We used mtDNA to analyze the population structure of loggerhead turtles from a total of 555 samples collected from 12 nesting sites in Japan in the Northwest Pacific, including previously unsampled rookeries in the Ryukyu Archipelago, for a comprehensive coverage of the nesting distribution. We identified a total of 9 haplotypes based on 820 bp of the mtDNA control region, including 5 variants of a single previously described 380 bp haplotype. We discovered that 1 haplotype (CcP1.1) previously rare in the North Pacific is common in the Ryukyu Archipelago. Based on analysis of haplotype frequencies, we found significant differentiation among regionally grouped nesting populations (analysis of molecular variance p < 0.0001, df = 8; pairwise FST ranging from 0.033 to 0.145). Our results provide evidence to support the recognition of 3 management units (MU) within the NW Pacific Regional Management Unit (RMU). These include (1) the Ryukyu MU that includes Okinawa, Okinoerabu and Amami, (2) Yakushima Island MU and (3) a Mainland MU that includes Bousou, Enshu-nada, Shikoku, Kii and Eastern Kyushu. These new data from Japan will provide important baseline data for global genetic stock assessments and contribute to our understanding of the population structure, ecology and life history of this migratory marine species in the northern Pacific.

Purpose: To ascertain the characteristics of achromatopsia (ACHM) in Japan by analyzing the genetic and phenotypic features of patients with ACHM., Methods: The medical records of 52 patients from 47 Japanese families who were clinically diagnosed with ACHM were reviewed in this retrospective observational study., Results: Thirty-six causative variants of ACHM were identified in 26 families via whole-exome sequencing: PDE6C (12 families), CNGA3 (10 families), CNGB3 (two families), and GNAT2 (two families). However, none of the 6 causative variants that are known to cause ACHM, or the 275 other genes listed in RetNet, were observed in 19 families. A significant trend toward older age and worsening of ellipsoid zone disruption on optical coherence tomography images was observed (P < 0.01). Progressive ellipsoid zone disruptions were observed in 13 eyes of seven patients during the follow-up visits. These patients harbored one or more variants in PDE6C., Conclusion: The ACHM phenotype observed in this study was similar to those observed in previous reports; however, the causative gene variants differed from those in Europe. The low identification ratio of causative genes in whole-exome sequencing suggests the presence of unique hotspots in Japanese patients with ACHM that were not detectable via ordinal whole-exome sequencing.

Purpose: To clarify the genetic and clinical features of Japanese patients with ABCA4-associated retinopathy., Design: Retrospective, multicenter cohort study., Methods: Patients with retinal degeneration and biallelic ABCA4 variants were recruited from 13 different hospitals. Whole exome sequencing analysis was used for genetic testing. Comprehensive ophthalmic examinations were performed on matched patients. The primary outcome measure was identifying multimodal retinal imaging findings associated with disease progression., Results: This study included 63 patients: 19 with missense/missense, 23 with missense/truncation, and 21 with truncation/truncation genotypes. In total, 62 variants were identified, including 29 novel variants. Six patients had a mild phenotype characterized by foveal-sparing or preserved foveal structure, including 4 with missense/missense and 2 with missense/truncation genotypes. The p.Arg212His variant was the most frequent in patients with mild phenotypes (4/12 alleles). Clinical findings showed a disease duration-dependent worsening of the phenotypic stage. Patients with the truncation/truncation genotype exhibited rapid retinal degeneration within a few years and definite fundus autofluorescence imaging patterns, including hyper autofluorescence at the macula and few or no flecks., Conclusions: Our results indicate that missense/missense or missense/truncation genotypes, including the p.Arg212His variant, are associated with a relatively mild phenotype. In contrast, the truncation/truncation genotype causes rapid and severe retinal degeneration in Japanese patients with ABCA4-associated retinopathy. These data are vital in predicting patient prognosis, guiding genetic counseling, and stratifying patients for future clinical trials., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases., Methods: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines., Results: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases., Conclusion: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies., Competing Interests: Competing interests: KMN reports grants from JCR Pharmaceuticals Co, Sysmex and Novartis Pharma Co; consulting fees from Sysmex and Novartis Pharma Co; and lecture fees from Sysmex, Novartis Pharma Co and Janssen Co. KMN has patents related to gene therapy for retinitis pigmentosa. In addition, KMN is an advisory board member of Sysmex and Novartis Pharma Co., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: KCNV2-associated retinopathy causes a phenotype reported as "cone dystrophy with nyctalopia and supernormal rod responses (CDSRR; OMIM# 610356)," featuring pathognomonic findings on electroretinography (ERG). Here, we report the clinical courses of two siblings with CDSRR., Case Reports: Patient 1: A 3-year-old boy with intermittent exophoria was referred to our hospital. The patient's decimal best-corrected visual acuity (BCVA) at age 6 was 0.7 and 0.7 in the right and left eyes, respectively. Photophobia and night blindness were also observed. Because the ERG showed a delayed and supernormal b-wave with a "squaring (trough-flattened)" a-wave in the DA-30 ERG, and CDSRR was diagnosed. The patient's vision gradually worsened, and faint bilateral bull's eye maculopathy was observed at the age of 27 years, although the fundi were initially unremarkable. Genetic examination revealed a homozygous missense variant, c.529T > C (p.Cys177Arg), in the KCNV2 gene. Patient 2: The second patient was Patient 1's younger sister, who was brought to our hospital at 3 years of age. The patient presented with exotropia, mild nystagmus, photophobia, night blindness, and color vision abnormalities. The patients' decimal BCVA at age 13 was 0.6 and 0.4 in the right and left eyes, respectively, and BCVA gradually decreased until the age of 24 years. The fundi were unremarkable. The siblings had similar ERG findings and the same homozygous missense variant in the KCNV2 gene., Conclusions: The siblings had clinical findings typical of CDSRR. High-intense flash ERG is recommended for identifying pathognomonic "squaring" a-waves in patients with CDSRR., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neurofibromatosis type 1 (NF1) is a multisystem disorder that primarily affects the skin and peripheral nervous system and is caused by chromosomal abnormalities and mostly truncating variants in the NF1 gene. Ocular complications such as Lisch nodules and optic pathway gliomas (OPGs) can occur in NF1 patients. Herein, we report a novel NF1 variant in an NF1 patient with bilateral optic atrophy., Methods: Ophthalmological examinations and genetic analyses were performed using targeted next-generation sequencing (NGS)., Results: A 14-year-old girl diagnosed with NF1 visited our hospital with decreased visual acuity (VA). The patient had no family history of NF1 or visual impairment. Brain and orbital magnetic resonance imaging revealed no remarkable findings. Ophthalmoscopy revealed temporal pallor of the optic discs, which was confirmed by optical coherence tomography findings of significant thinning of the circumpapillary retinal nerve fiber layer in both eyes. At 23 years of age, the decimal-corrected VA had deteriorated to 0.2 in the right eye and 0.1 in the left eye. Additionally, the targeted NGS panel revealed a novel heterozygous stop-gain variant (p.Tyr628Ter) in the NF1 gene; however, no pathogenic variants in OPA1 or the mitochondrial DNA were identified., Conclusions: A patient with NF1 without OPGs developed bilateral optic atrophy and carried a novel de novo stop-gain variant of NF1 . Although the relationship between NF1 variants and bilateral optic atrophy remains unclear, further investigations are required.

Aim: To compare the surgical outcomes of a multifocal intraocular lens (IOL; Lentis Comfort LS-313 MF15) with those of an enhanced monofocal IOL (Tecnis Eyhance DIB00V)., Methods: This retrospective study included patients who underwent cataract surgery with LS-313 MF15 or Eyhance IOL implantation. Data regarding patient demographics, surgical records, and ophthalmic examination before the cataract surgery and one and three months postoperatively were collected. Visual acuities, refractive values, defocus curves, contrast sensitivities and subjective symptoms were evaluated., Results: Among the 71 eyes (47 patients) included in this study, 32 eyes (20 patients) underwent LS-313 MF15 IOL implantation, and 39 eyes (27 patients) underwent Eyhance IOL implantation. No significant differences were observed in age, axial length, or refractive error between the two groups preoperatively. Furthermore, the distance-corrected and uncorrected distance visual acuities one month postoperatively did not differ between the groups, and both groups had sufficient visual acuities at the distances of 5, 1 m, 70, 50, and 30 cm. Other ophthalmic data, including subjective symptoms based on the 14-item Visual Function Index Questionnaire, monocular defocus curves, contrast sensitivities, and halo and glare, did not differ between the groups three months postoperatively. Moreover, both groups had good outcomes. The spherical equivalent one month postoperatively was significantly myopic in the LS-313 MF15 group compared with that in the Eyhance group ( P =0.033); however, this difference was not observed three months postoperatively ( P =0.471)., Conclusion: Comparison of the surgical outcomes of LS-313 MF15 with those of Eyhance with different optical properties reveal that both IOLs show good postoperative outcomes, with no significant differences being noted between the two IOLs., (International Journal of Ophthalmology Press.)

Introduction: Congenital 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., Methods: Medical 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., Results: OCT 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., Conclusion: In 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nakajima, Kuniyoshi, Iwahashi, Mano, Hayashi, Kondo, Mizobuchi, Matsushita, Suga, Yoshitake, Nakano, Iwata, Matsumoto and Kusaka.)

Purpose: This study aimed to clarify the effect of 1-year oral treatment with 9-cis-β-carotene-rich alga Dunaliella bardawil (Dunaliella supplementation) using full-field electroretinography (ERG) in patients with RDH5-related fundus albipunctatus (FAP)., Design: Prospective, interventional case series., Participants: The study included 12 patients (23 eyes) with RDH5-related FAP., Methods: Twelve patients (23 eyes) with RDH5-related FAP received Dunaliella supplementation (total daily dose of β-carotene was 74.0 mg, comprising 28.4 mg 9-cis-β-carotene and 45.6 mg all-trans-β-carotene at a ratio of 1:1.6) for 1 year and underwent ophthalmic examinations, including full-field ERG at baseline, 3 months, and 1 year after the initial treatment., Main Outcome Measures: The main outcome was changes in the amplitudes of responses of full-field ERG before and after treatment. A linear mixed-effects model was used to evaluate the adjusted mean difference between the amplitude of each response pretreatment and posttreatment., Results: Prolonged dark adaptation (DA) responses at 3 months revealed a significant impairment in the b-wave of DA 0.01 (adjusted mean difference, -34.7, 95% CI, -66.8 to -2.73, P = .041) and a-wave of DA 3.0 (-29.0, 95% CI, -50.6 to -7.41, P = .013) and DA 10.0 (-40.4, 95% CI, -67.8 to -13.0, P = .007), which were also observed at 1 year. Additionally, prolonged DA and light adaptation (LA) responses revealed statistically significant impairment at 1 year in the b-wave of DA 3.0 (-43.8, 95% CI, -82.9 to -4.78, P = .035), DA 10.0 (-59.7, 95% CI, -101.8 to -17.61, P = .009), LA 3.0 (-7.31, 95% CI, -13.6 to -1.04, P = .029), and LA 3.0 flicker (-7.53, 95% CI, -12.7 to -2.34, P = .007)., Conclusions: Our study results suggest that Dunaliella supplementation comprising low levels of 9-cis-β-carotene compared with those reported in a previous study (1:1 ratio) adversely affects ERG amplitudes in patients with RDH5-related FAP., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy. RPGRIP1 -related LCA accounts for 5-6% of LCA. We performed whole-exome sequencing and whole-genome sequencing (WGS) on 29 patients with clinically suspected LCA and examined ophthalmic findings in patients with biallelic pathogenic variants of RPGRIP1 . In addition to five previously reported cases, we identified five cases from four families with compound heterozygous RPGRIP1 variants using WGS. Five patients had null variants comprising frameshift variants, an Alu insertion, and microdeletions. A previously reported 1339 bp deletion involving exon 18 was found in four cases, and the deletion was relatively prevalent in the Japanese population (allele frequency: 0.002). Microdeletions involving exon 1 were detected in four cases. In patients with RPGRIP1 variants, visual acuity remained low, ranging from light perception to 0.2, and showed no correlation with age. In optical coherence tomography images, the ellipsoid zone (EZ) length decreased with age in all but one case of unimpaired EZ. The retinal structure was relatively preserved in all cases; however, there were cases with great differences in visual function compared to their siblings and a 56-year-old patient who still had a faint EZ line. Structural abnormalities may be important genetic causes of RPGRIP1 -related retinal dystrophy in Japanese patients, and WGS was useful for detecting them.

Purpose: Biallelic variants in POC1B are rare causes of autosomal recessive cone dystrophy associated with generalized cone system dysfunction. In this report, we describe the clinical characteristics of a Japanese male patient with POC1B-associated retinopathy with relatively preserved cone system function., Methods: We performed whole-exome sequencing (WES) to identify the disease-causing variants and a comprehensive ophthalmic examination, including full-field and multifocal electroretinography (ffERG and mfERG)., Results: Our WES analysis identified novel compound heterozygous POC1B variants (p.Arg106Gln and p.Arg452Ter) in the patient. His unaffected mother carried the p.Arg452Ter variant heterozygously. The patient experienced decreased visual acuity in his 50s. At the age of 63, his corrected visual acuity was 20/22 in the right and 20/20 in the left eye. Fundus and fundus autofluorescence images for each eye showed no remarkable finding, except for a subtle hyperautofluorescent spot in the fovea of the left eye. Cross-sectional optical coherence tomography demonstrated blurred but a relatively preserved ellipsoid zone. The ffERG showed that amplitudes of rod and standard-flash responses were within the reference range, whereas the cone and light-adapted 30-Hz flicker amplitudes were close to, or slightly below, the reference range. The mfERG revealed substantially reduced responses with relative preservation of central function., Conclusions: We reported the case of an older patient with POC1B-associated retinopathy, demonstrating late-onset visual decrease, good visual acuity, and relatively preserved cone system function. The disease condition was much milder than previously reported in patients with POC1B-associated retinopathy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Alport syndrome comprises a heterogeneous group of inherited kidney diseases that are associated with ocular complications. In this study, we aimed to detail the clinical characteristics of a patient with X-linked Alport syndrome., Methods: We performed next-generation sequencing (NGS) with hybridization capture to identify the disease-causing variant of Alport syndrome and a comprehensive ophthalmic examination, including full-field electroretinography (FF-ERG)., Results: Genetic testing using NGS with hybridization capture revealed a novel hemizygous variant [c.51&#95;52delGA (p.Trp20GlyfsTer19)] in exon 1 of COL4A5. The patient underwent cataract surgery in both eyes because of decreased visual acuity and photophobia. The best-corrected visual acuity improved from 0.9 and 0.7 in the right and left eyes, respectively, to 1.5 in both eyes. Anterior-segment optical coherence tomography (OCT) revealed anterior and posterior lenticonus. Fundus photographs showed central and peripheral fleck retinopathy. Wide-field fundus autofluorescence (AF) imaging showed mottled hyper- and hypo-AF in the peripheral retina, which was consistent with peripheral fleck retinopathy. Furthermore, OCT revealed thinning of the inner retinal layers, especially at the temporal macular, but the outer retinal layers were preserved. Ganglion cell analysis showed no progression for 5 years. FF-ERG was performed at 41 (phakia) and 46 (pseudophakia) years of age. The amplitudes of dark-adapted (DA) and light-adapted (LA) responses showed selective b-wave abnormalities. The b/a-wave ratios of DA 3.0 were 1.22 and 1.16 in the right and left eyes, respectively. The amplitudes of DA 3.0 oscillatory potentials (OP) were reduced. Five years later, the amplitudes of DA and LA responses revealed no remarkable changes, except for an OP wave of DA 3.0, which was substantially reduced., Conclusions: Our findings revealed electroretinographic abnormalities in a patient with Alport syndrome, which predominantly indicated impairment of the inner retina. Notably, little short-term progression was observed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by 6 primary features of rod-cone dystrophy, central obesity, polydactyly, cognitive impairment, hypogonadism and/or genitourinary malformations, and kidney abnormalities. At least 21 genes associated with BBS have been reported. To date, BBS associated with BBS12 variants has never been described in the Japanese population. We report a Japanese infant female with BBS with compound heterozygous BBS12 variants., Methods: In addition to the pediatric examination, fundus photography, full-field electroretinogram(ffERG) and whole exome sequencing (WES) were underwent., Results: The infant exhibited obesity, polydactyly, cognitive impairment, genitourinary malformations, and kidney dysfunction. At the age of 2 years, ffERG revealed severe reduction in both rod- and cone-mediated electroretinographic responses consistent with a severe form of rod-cone dystrophy, with minimal retinal abnormalities. WES revealed novel compound heterozygous BBS12 variants (c.591T > A, p.Tyr197* and c.1372dupA, p.Thr458Asnfs*5) in the infant. Her parents carried each of the variants, as confirmed by Sanger sequencing., Conclusions: The current observations will contribute to an expanded understanding of genotype-phenotype associations in BBS12-associated BBS., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A 51 years old male had underwent aortic valve replacement (AVR) by minimally invasive cardiac surgery (MICS) for aortic regurgitation. About one year after the surgery, bulging of the wound and pain appeared. His chest computed tomography showed an image of the right upper lobe protruding from the thoracic cavity through the right second intercostal space, and the patient was diagnosed as having an intercostal lung hernia and the surgical treatment was performed using a unsintered hydroxyapatite and poly-L-lactide (u-HA/PLLA) mesh plate and monofilament polypropylene (PP) mesh. Postoperative course was uneventful without any evidence of recurrence.

This study aimed to elucidate the prognostic influence of statins in relation to the degree of inflammation at the time of endovascular therapy (EVT) for patients with peripheral artery disease (PAD). This observational study included patients with PAD who underwent EVT, including 285 statin users and 275 statin non-users. They were assigned into four groups depending on C-reactive protein (CRP) level at the time of EVT: low CRP (<0.1 mg/dL), intermediate-low CRP (0.1-0.3 mg/dL), intermediate-high CRP (0.3-1.0 mg/dL), and high CRP (>1.0 mg/dL). A composite of death and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category. Overall, statin users showed a lower event rate than non-users (log-rank, p=0.02). However, the event rates did not differ significantly between statin users and non-users in the low, intermediate-low, and intermediate-high CRP categories. In the high CRP category, statin users showed a lower event rate than non-users (p=0.002). In this population, multivariate Cox regression analysis revealed that statin use was independently associated with the primary endpoint (hazard ratio: 0.28 [95% confidence interval: 0.14-0.55]). Statins may exert favorable prognostic effects in PAD patients with highly elevated CRP levels, but not in those with low-to-moderate CRP levels., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD., (© 2022 Wiley Periodicals LLC.)

Significance: Unilateral acute idiopathic maculopathy is a rare retinochoroidal disorder, the cause of which is unknown. Multimodal retinal imaging obtained in this case suggests that the cause of unilateral acute idiopathic maculopathy is impaired choroidal circulation., Purpose: This study aimed to report a patient with unilateral acute idiopathic maculopathy who showed improvement of choroidal circulation over time in optical coherence tomography angiography images., Case Report: A 33-year-old woman with a prodromal flu-like illness noticed a sudden central visual field abnormality in the right eye. Five days after the onset, best-corrected visual acuity was 0.15 in the right eye. Fundus photography showed a yellowish lesion at the macula in the right eye. Optical coherence tomography showed a blurred ellipsoid zone and a thickened retinal pigment epithelium at the fovea and a disrupted/blurred ellipsoid zone and retinal pigment epithelium at the parafovea. Optical coherence tomography angiography segmentation of the choriocapillaris revealed a hypointense region at the fovea with a hyperintense region surrounding it. One week after the onset, best-corrected visual acuity was improved from 0.15 to 2.0 in the right eye. Furthermore, the yellowish macula lesion shrank, and the outer retinal layers showed improvement in optical coherence tomography. Optical coherence tomography angiography showed reduction of the hypointense region and enlargement of the hyperintense region. Approximately 1 year after the onset, the yellowish lesion was faded. Optical coherence tomography revealed an almost normal ellipsoid zone but a thickened interdigitation zone. Optical coherence tomography angiography also revealed an apparent hyperintense instead of the hypointense region and increased choroidal blood flow., Conclusions: The current patient showed a gradual recovery of choroidal circulation and outer retinal layer morphology 1 year after the onset of unilateral acute idiopathic maculopathy. Optical coherence tomography angiography findings indicated that the primary cause of unilateral acute idiopathic maculopathy was impaired choroidal circulation, and choroidal vessels improved morphologically over the disease course., Competing Interests: Conflict of Interest Disclosure : None of the authors have reported a financial conflict of interest., (Copyright © 2022 American Academy of Optometry.)

Purpose: Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders. NRL-associated autosomal dominant (AD)-RP is a rare form of AD-RP in the Japanese population. This study aimed to report a clinical characterization of NRL-associated retinopathy in a three-generation Japanese family., Case Presentation: A total of 4 patients from a Japanese family were referred to The Jikei University School of Medicine for clinical and genetic examination. The patients included a male proband (41 years old), his daughters (5 and 6 years old), and his mother (71 years old); they underwent ophthalmic examinations, and genetic testing was performed using whole exome sequencing analysis, revealing a known variant [c.152C > T (p.Pro51Leu)] heterozygously in exon 2 of the NRL gene. Fundus photograph showed that retinal degeneration expanded to the macular and peripheral retina in an age-dependent manner. Fundus autofluorescence imaging showed hyper-autofluorescence (AF) within the macular with slightly hypo-AF in younger patients and obvious hypo-AF in older patients. Optical coherence tomography showed that the length of the ellipsoid zone tended to be longer in younger patients than in older patients. Goldmann perimetry showed an age-dependent decrease in the visual field. Furthermore, full-field electroretinographic findings revealed non-recordable rod and cone function in older patients and non-recordable rod function with preserved cone function in younger patients., Conclusions: Our results indicated that retinal construction and function were aggravated in an age-dependent manner, and retinal degeneration, especially in the macular region, revealed milder findings than in previous cases with NRL-associated AD-RP., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disorder that affects multiple organs, including the muscle and eye, caused by a CTG triplet expansion of the 3' untranslated region (UTR) of the DMPK gene. Cataracts and retinal degeneration are major eye complications in patients with DM1. We reported the case of a Japanese patient with DM1 who exhibited submacular hemorrhage unilaterally, rarely complicating DM1., Case Report: A 56-year-old woman presented with loss of visual acuity in the left eye (LE). The patient was diagnosed with DM1, who carried expanded CTG repeats (1100) of the 3' UTR of DMPK. Her corrected visual acuities were 20/100 and 20/2000 in the right eye (RE) and LE, respectively. Cataracts were observed in both eyes. Fundoscopy and angiography revealed submacular hemorrhage in the LE due to polypoidal choroidal vasculopathy (PCV, also known as aneurysmal type 1 neovascularization). The patient underwent intravitreal injections of an anti-vascular endothelial growth factor drug and sulfur hexafluoride gas in the LE. Full-field electroretinography was performed, showing that the rod and standard-flash responses were reduced to 50% and below 10% in the RE and LE, whereas the cone and 30-Hz flicker responses were reduced to 40-50% and 15-20% in the RE and LE, respectively, compared with the controls. Multifocal electroretinography revealed that the overall responses were extinguished in the LE and considerably attenuated in the RE., Conclusions: This is the first patient with DM1 complicated with PCV. Widespread retinal dysfunction may be associated with expanded CTG repeats, which is significantly longer than the mean repeat number of patients with DM1., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: To investigate changes in the corneal shape caused by fluid-gas exchange after vitrectomy.This retrospective case-control study included 43 eyes that underwent a combination of cataract surgery and vitrectomy. The corneal shape was measured using anterior segment optical coherence tomography CASIA2. The corneal shape measurements were performed preoperatively, 1 day, 1 week, 1 month, and 3 months after surgery. After calculating the real K value from the actual measured values of the posterior shape of the corneal refracting power and the single posterior corneal refracting power value, Fourier analysis values were examined. Fluid-gas exchange was performed in 23 eyes (gas group), while it was not performed in 20 eyes (nongas group).There was a significant increase in the real K value in the regular and asymmetry components (0.61 ± 0.36, 0.82 ± 0.64) in the gas group only on the first day after surgery (Steel-Dwass test; P < .05). There was also a significant increase in the real K value in the higher-order irregular astigmatism components (Steel-Dwass test; P < .05) for longer periods in the gas versus the nongas group. The shape of the posterior cornea increased in all components in the gas group on the first day after surgery (spherical power -6.35 ± 0.20, regular astigmatism 0.32 ± 0.12, asymmetry 0.22 ± 0.13, and higher-order irregular astigmatism 0.12 ± 0.05, Steel-Dwass test; P < .05).Postoperative changes caused by surgical invasion in the corneal shape appeared to be greater in the gas versus the nongas group, in addition to affecting the time periods of the postoperative corneal shape changes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To determine the characteristics of eyes diagnosed with Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB) complicated by choroidal neovascularization (CNV)., Methods: This was a retrospective, multicenter observational case series. Fourteen genetically confirmed BVMD patients and 9 ARB patients who had been examined in 2 ophthalmological institutions in Japan were studied. The findings in a series of ophthalmic examinations including B-scan optical coherence tomography (OCT) and OCT angiography (OCTA) were reviewed., Results: CNV was identified in 5 eyes (17.9%) of BVMD patients and in 2 eyes (11.1%) of ARB patients. Three of 5 eyes with BVMD were classified as being at the vitelliruptive stage and 2 eyes at the atrophic stage. The CNV in 2 BVMD eyes were diagnosed as exudative because of acute visual acuity reduction, retinal hemorrhage, and intraretinal fluid, while the CNV in 3 BVMD eyes and 2 ARB eyes were diagnosed as non-exudative. The visual acuity of the two eyes with exudative CNV did not improve despite anti-VEGF treatments. None of the eyes with non-exudative CNV had a reduction of their visual acuity for at least 4 years. All of the CNV were located within hyperreflective materials which were detected in 16 eyes (57.1%) of the BVMD eyes and in 7 eyes (38.9%) of the ARB eyes., Conclusions: CNV is a relatively common complication in BEST1-related retinopathy in Asian population as well. The prognosis of eyes with exudative CNV is not always good, and OCTA can detect CNV in eyes possessing hyperreflective materials., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To characterize the clinical and genetic features of a Japanese male patient with foveal hypoplasia caused by a homozygous single nucleotide duplication in the SLC38A8 gene., Methods: We performed a comprehensive ophthalmic examination including full-field electroretinography (FF-ERG) and pattern-reversal visual evoked potentials (PR-VEPs). Whole-exome sequencing (WES) was performed to identify the disease-causing variant; Sanger sequencing was used for confirmation., Results: In the WES analysis, a homozygous single nucleotide duplication (c.995dupG; p.Trp333MetfsTer35) was identified in SLC38A8 of the patient. His unaffected mother carried the variant heterozygously. The patient exhibited hyperopia, congenital nystagmus, low visual acuity, and grade 4 foveal hypoplasia. Slit-lamp examination revealed mild posterior embryotoxon and goniodysgenesis. Fundus examination revealed the absence of foveal hyperpigmentation and foveal avascularity, but there were no retinal degenerative lesions. In the FF-ERG, the amplitudes of rod ERG, standard-flash, and bright-flash ERG were within the normal range; cone-mediated responses also showed nearly normal amplitudes. The PR-VEP findings revealed delayed P100 latencies and decreased amplitudes of the P100 components, but no chiasmal misrouting., Conclusions: This report is the first report on the clinical and genetic characteristics of SLC38A8-associated foveal hypoplasia in the Japanese population. This is also the first report of normal rod- and cone-mediated responses in a patient with this disorder., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To investigate the genotype and long-term clinical phenotype of patients with Bietti crystalline dystrophy (BCD) in Korea and Japan., Design: Retrospective case series., Participants: We analyzed 62 patients with clinical features of BCD who harbor pathogenic biallelic CYP4V2 variants in their homozygote or compound heterozygote., Methods: Data were collected from patient charts, including age, best-corrected visual acuity (BCVA), Goldmann perimetry results, fundus photography, OCT findings, fundus autofluorescence results, and electroretinography findings. We compared the clinical course of the patients with homozygous c.802-8&#95;810de117insGC [exon7del], the most common mutation in the East Asian population, with those of the patients with other genotypes., Main Outcome Measures: Best-corrected visual acuity, visual field (VF), and their changes during follow-up., Results: The mean age at the first visit was 55.2 years, with a mean follow-up of 7.1 years. The mean BCVAs at the first and last visits were 0.28 logarithm of the minimum angle of resolution (logMAR) and 0.89 logMAR, respectively. In genetic testing, c.802-8&#95;810de117insGC was detected in 86 of 124 alleles of the patients, and 36 patients were homozygous for this mutation. The age, BCVA, VF area, central foveal thickness, and abnormal hypoautofluorescent area at either the first or last visit were not different between the exon7del homozygotes and the others. The mean BCVA changes per year were 0.089 logMAR in the exon7del homozygotes and 0.089 logMAR in the others. An age- and gender-adjusted linear regression analysis showed no association between the exon7del homozygote status and the rate of vision loss. Characteristic crystalline deposits in the posterior pole were generally observed in younger patients and disappeared over time along with progressive retinochoroidal atrophy., Conclusions: Patients with BCD and a homozygote for c.802-8&#95;810de117insGC accounted for more than 50% of this cohort of Korean and Japanese patients, and the clinical effect of this deleterious variant was not severe in the spectrum of CYP4V2 retinopathy., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this report was to describe the case of a 68-year-old male patient with stage IV colon cancer who exhibited electroretinographic abnormalities that are similar to those of KCNV2 retinopathy., Methods: The patient presenting with photophobia, reduced visual acuity, and poor general conditions, the onset of which occurred ten days before presentation, was examined using fundoscopy, full-field electroretinography, blood tests, and abdominal computed tomography., Results: The patient's decimal best-corrected visual acuity (BCVA) was 0.4 in each eye. Fundoscopy showed bull's eye-like maculopathy in both eyes. Electroretinographic findings were similar to the characteristic findings of KCNV2 retinopathy: Rod electroretinogram showed delayed and preserved b-wave amplitudes; bright-flash electroretinogram showed double troughs of a-waves; b/a ratios shown by bright-flash electroretinogram were higher than those shown by standard-flash electroretinogram; and both cone and 30-Hz flicker electroretinograms showed extinguished responses. His serum potassium level increased to 6.2 mmol/L (normal range 3.6-4.8 mmol/L) owing to hydronephrosis resulting from disseminated carcinoma. After performing an emergency surgery to treat this condition, the serum potassium level immediately decreased to a normal range. Eleven days after presentation, rod and standard/bright-flash electroretinography showed improvement in the implicit time of the rod b-waves and the a-waves. Unexpectedly, the responses recorded by cone and 30-Hz flicker electroretinography became normal. The symptoms and maculopathy disappeared, and his BCVA improved to 1.2., Conclusions: The abnormal electroretinographic findings might be associated with the transient increase in serum potassium level., (© 2021. The Author(s).)

Background: Serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a disease-specific antibody against granulomatosis with polyangiitis. PR3-ANCA is a useful serological marker for disease severity in ulcerative colitis (UC). The purpose of this study was to investigate whether PR3-ANCA levels could also predict the success of induction therapy and to compare its performance against other markers, including serum CRP and fecal hemoglobin., Methods: This was a multicenter retrospective study. In total, 159 patients with active-phase UC underwent colonoscopy. Disease activity was measured using the Mayo endoscopic subscore (MES). PR3-ANCA positivity and the response to induction therapy, either 5-aminosalicylic acid or steroid, were assessed. PR3-ANCA, CRP, and fecal hemoglobin were measured during the active phase, and during clinical remission., Results: Eighty-five (53.5%) of 159 patients with active UC were positive for PR3-ANCA. PR3-ANCA titers were significantly higher in the group of patients with MES 3 compared to patients with MES 1 (P = 0.002) or MES 2 (P = 0.035). Steroid therapy was administered to 56 patients with a median partial Mayo score of 7 (5-9), which is equivalent to moderate-to-severe disease activity. PR3-ANCA positivity of non-responders to steroid therapy was significantly higher than that of responders (71.9% vs, 41.7%, P = 0.030), whereas CRP and fecal hemoglobin were not predictive of steroid response. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with non-response to steroid therapy (odds ratio 5.19; 95% confidence interval, 1.54-17.5; P = 0.008). Of the 37 patients treated to clinical remission who were also positive for PR3-ANCA during the active phase, 27 had an MES of ≥ 1, and 10 patients had an MES of 0. In clinical remission, the proportion of patients with MES 0 in 17 patients whose PR3-ANCA became negative was significantly higher than that in 20 patients whose PR3-ANCA remained positive (47.1% vs. 10.0%, P = 0.023)., Conclusions: PR3-ANCA not only serves as a marker of disease activity, but also predicts the failure of steroid therapy in moderate-to-severe UC., Trial Registration: This study was retrospectively registered in the UMIN Clinical Trials Registry System (000039174) on January 16, 2020., (© 2021. The Author(s).)

Purpose: Thus far, only one Japanese patient with autosomal recessive rod-cone dystrophy (AR-RCD) associated with the phosphodiesterase 6A gene (PDE6A) has been reported. The purpose of this study was to analyze the clinical features of a Japanese female patient with AR-RCD with a novel missense variant in PDE6A., Methods: We performed whole-exome sequencing (WES) to identify the disease-causing variant and a comprehensive ophthalmic examination including full-field electroretinography (ERG)., Results: WES analysis revealed that the patient carried a novel homozygous missense variant (c.1631G > A; p.Arg544Gln) in PDE6A. Her unaffected parents carried the heterozygous variant. The patient reported night blindness in her early 20 s. At the age of 25 years, she underwent a comprehensive ophthalmic examination. Her corrected visual acuity was 20/13 in the right and 20/10 in the left eyes. Fundus images showed degenerative changes with bone spicule pigmentation in the mid-peripheral retina, and peripheral retinal vessels were not attenuated. Ultra-wide-field fundus autofluorescence images demonstrated large hypoautofluorescent regions corresponding to the degenerative changes, surrounded by hyperautofluorescence. Cross-sectional optical coherence tomography demonstrated a preserved ellipsoid zone and retinal thickness in the center of the macula, with perifoveal atrophy. ERG responses were subnormal, revealing that rod-mediated responses were more affected than cone-mediated responses, consistent with findings observed in RCD., Conclusions: This is the second case of a patient with AR-RCD associated with PDE6A in the Japanese population. These findings will contribute to a better clinical understanding of PDE6A-associated RCD and valuable insights for gene therapy trials.

Background: In industrialized countries, vitamin A deficiency (VAD) is extremely rare, except association with bariatric surgeries and hepatobiliary disorders. It is unusual that VAD develops during hemodialysis due to reduced glomerular filtration of vitamin A-binding protein. We reported the case of a 58-year-old Japanese male hemodialysis patient diagnosed with VAD., Case Presentation: The patient undergoing hemodialysis for more than 15 years presented with progressive photophobia and night blindness and was ophthalmologically examined. He denied a history of cancer or hepatobiliary disease and reported that he loved eating prepackaged noodle bowls and foods, with prolonged low intake of fruits/vegetables. He had good visual acuity. Fundus images showed numerous white dots in the midperipheral retinae, but no degenerative changes. In baseline full-field electroretinography (ERG), b-wave responses were extremely reduced in rod ERG, a-wave amplitudes in standard-flash/strong-flash ERG were reduced to 20-25% of our controls, a- and b-wave amplitudes in cone ERG were reduced to 40-50% of the controls. Whole-exome sequencing identified no pathogenic variant for any inherited retinal disorder. He was diagnosed with VAD because of reduced serum vitamin A levels and treated with retinol palmitate. Two months after treatment commencement, the serum vitamin A level was within the normal range. Full-field ERG showed that the scotopic ERG responses markedly improved compared with baseline., Conclusions: This is the first report of VAD associated with undernutrition in the Japanese hemodialysis population.

Background: Complete congenital stationary night blindness (CSNB) is a retinal disorder thought to be non-progressive. The purpose of this study was to characterize the clinical and genetic findings of middle-aged and older adult patients with X-linked complete CSNB., Methods: Three male CSNB patients (aged 62, 72, and 51 years) and one unaffected female carrier in a Japanese family were included in this study. Whole-exome sequencing (WES) was performed to determine the disease-causing variants. Co-segregation was confirmed in the family members. We performed a comprehensive ophthalmic examination on each patient., Results: In the 62-year-old patient, a novel hemizygous variant (c.648 C > A; p.Asn216Lys) of the NYX gene was identified by WES analysis. The other two patients carried the variant hemizygously, and the unaffected carrier harbored the variant heterozygously. The clinical and electroretinography (ERG) findings were very similar among all three patients. Fundus images exhibited high myopic chorioretinal atrophy with long axial length. Ultra-wide field fundus autofluorescence images showed no retinal degenerative changes except for changes resulting from high myopia and previous retinal diseases. The ERG findings showed no response in rod ERG, electronegative configuration with preserved a-waves in standard/bright-flash ERG, and preserved responses in cone and 30-Hz flicker ERG, which were compared with age-matched controls with high myopia., Conclusions: We identified a novel missense NYX variant in a Japanese family with complete CSNB. Our clinical findings indicated that photoreceptor mediated ERG responses are well preserved even in middle-aged and older adult patients.

Background: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive inherited disorder caused by biallelic variants in the CDH3 gene encoding P-cadherin. Here, we report two Japanese sibling patients with HJMD., Methods: Whole-exome sequencing (WES) was performed to identify disease-causing variants. In addition, ophthalmic and dermatological examinations were performed to classify the phenotype of each patient., Results: The WES analysis revealed novel compound heterozygous CDH3 variants [c.123&#95;129dupAGGCGCG (p.Glu44fsX26) and c.2280+1G>T] in both patients; the unaffected, nonconsanguineous parents each exhibited one of the variants. Both patients showed the same clinical findings. Ophthalmologically, they exhibited progressive loss of visual acuity and chorioretinal macular atrophy, as examined with fundoscopy, fundus autofluorescence imaging, and optical coherence tomography. Full-field electroretinography, assessing generalized retinal function, revealed nearly normal amplitudes of both rod- and cone-mediated responses. Multifocal electroretinography, reflecting macular function, showed extremely decreased responses in the central area, corresponding to the chorioretinal atrophy. Dermatological examination revealed diffuse thinning of the scalp hair, which was sparse and fragile., Conclusion: This is the first report of Japanese patients with HJMD and novel compound heterozygous truncating variants in CDH3. Our findings can expand the knowledge and understanding of CDH3-related HJMD, which could be helpful to ophthalmologists and dermatologists., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Little is known about genotype-phenotype correlations of RP1 -associated retinal dystrophies in the Japanese population. We aimed to investigate the genetic spectrum of RP1 variants and provide a detailed description of the clinical findings in Japanese patients., Methods: In total, 607 patients with inherited retinal diseases were examined using whole-exome/whole-genome sequencing (WES/WGS). PCR-based screening for an Alu element insertion (c.4052&#95;4053ins328/p.Tyr1352AlafsTer9) was performed in 18 patients with autosomal-recessive (AR)-retinitis pigmentosa (RP) or AR-cone dystrophy (COD)/cone-rod dystrophy (CORD), including seven patients with heterozygous RP1 variants identified by WES/WGS analysis, and 11 early onset AR-RP patients, in whom no pathogenic variant was identified. We clinically examined 25 patients (23 families) with pathogenic RP1 variants, including five patients (five families) with autosomal-dominant (AD)-RP, 13 patients (11 families) with AR-RP, and seven patients (seven families) with AR-COD/CORD., Results: We identified 18 pathogenic RP1 variants, including seven novel variants. Interestingly, the Alu element insertion was the most frequent variant (32.0%, 16/50 alleles). The clinical findings revealed that the age at onset and disease progression occurred significantly earlier and faster in AR-RP patients compared to AD-RP or AR-COD/CORD patients., Conclusions: Our results suggest a genotype-phenotype correlation between variant types/locations and phenotypes (AD-RP, AR-RP, and AR-COD/CORD), and the Alu element insertion was the most major variant in Japanese patients with RP1 -associated retinal dystrophies.

Background: Little is known about whether patients with complete congenital stationary night blindness (CSNB) maintain visual function throughout their lifetime. The purpose of this report was to describe clinical and genetic features of an elderly female patient with complete CSNB that we followed for 5 years., Methods: Molecular genetic analysis using whole-exome sequencing (WES) was performed to detect disease-causing variants. We performed a comprehensive ophthalmic examination including full-field electroretinography (ERG)., Results: In the patient, WES identified two novel variants (c.1034delT; p.Phe345SerfsTer16 and c.1880T>A; p.Met627Lys) in the TRPM1 gene. Her unaffected daughter has one of the variants. The patient reported that her visual acuity has remained unchanged since elementary school. At the age of 68 years old, fundus and fundus autofluorescence imaging showed no remarkable findings except for mild myopic changes. Goldmann perimetry showed preserved visual fields with all V-4e, I-4e, I-3e and I-2e isopters. Optical coherence tomography demonstrated preserved retinal thickness and lamination. Rod ERG showed no response; bright-flash ERG showed an electronegative configuration with minimally reduced a-waves, and cone and 30-Hz flicker ERG showed minimally reduced responses. Overall, the ERG findings of ON bipolar pathway dysfunction were consistent with complete CSNB., Conclusions: This is the oldest reported patient with complete CSNB and biallelic TRPM1 variants. Our ophthalmic findings suggest that some patients with TRPM1-related CSNB may exhibit preserved retinal function later in life.