Documenta Ophthalmologica最新文献

{"title":"Structure-function relationship between handheld photopic negative response and macular GCIPL thickness in chronic optic neuropathy.","authors":"Yuri Seo, Dongheon Surl, Jinu Han","doi":"10.1007/s10633-026-10123-9","DOIUrl":"https://doi.org/10.1007/s10633-026-10123-9","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether photopic negative response (PhNR) parameters obtained using a handheld electroretinography (ERG) device reflect quantitative indicators of residual retinal ganglion cell (RGC)-driven inner retinal function and how these functional measures relate to OCT-derived structural metrics in chronic unilateral non-glaucomatous optic neuropathy (ON).</p><p><strong>Methods: </strong>In this retrospective observational study, 27 patients (54 eyes) with unilateral chronic ON were examined using handheld full-field photopic ERG (RETeval™, LKC Technologies) without pupil dilation or corneal electrodes. Several ERG parameters, including the PhNR72 amplitude, PhNR minimum amplitude, P-ratio, and W-ratio, were analyzed. Optical coherence tomography (OCT)-derived ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thicknesses, and Humphrey field analyzer (HFA) indices were acquired on the same day. Linear mixed-effects models accounting for intereye correlation and false discovery rate (FDR) correction were used to assess structure-function relationships.</p><p><strong>Results: </strong>ON eyes showed significantly reduced PhNR72 and PhNR minimum amplitudes, and lower P-ratio (PhNR72/b-wave) and W-ratio (PhNR minimum/(b-wave minus a-wave) (all p < 0.01) compared with unaffected eyesof the patients. In multivariable models, the W-ratio was independently associated with GCIPL thickness in the inferotemporal sector (β = 0.45; 95% CI, 0.22-0.68; FDR-adjusted p < 0.05), whereas no significant associations were found with RNFL thickness or HFA indices.</p><p><strong>Conclusions: </strong>Handheld photopic ERG-derived PhNR parameters, particularly the W-ratio, are selectively associated with GCIPL thickness, suggesting preferential coupling with RGC-driven inner retinal function rather than axonal or field-level measures. Thus, portable ERG provides a practical functional biomarker complementary to OCT for evaluating residual RGC-driven inner retinal function in chronic ON.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital grouped albinotic spots of the retinal pigment epithelium-a case report.","authors":"Dhanashree Ratra, Devika Damle","doi":"10.1007/s10633-026-10124-8","DOIUrl":"https://doi.org/10.1007/s10633-026-10124-8","url":null,"abstract":"<p><strong>Purpose: </strong>To describe the clinical and multimodal imaging characteristics of congenital grouped albinotic spots (CGAS) and to explore their functional implications using full-field electroretinography (ERG).</p><p><strong>Methods: </strong>Two patients with incidentally detected CGAS underwent comprehensive ophthalmic examination, including best-corrected visual acuity, refraction, dilated fundus evaluation, swept-source optical coherence tomography (SSOCT), fundus autofluorescence (FAF) imaging, and full-field ERG. Longitudinal follow-up was available for one case over 7 years. Clinical and imaging findings were qualitatively compared with previously reported CGAS features and with differential diagnoses of flecked retina disorders.</p><p><strong>Results: </strong>Both patients demonstrated numerous, bilaterally symmetrical, flat hypopigmented lesions that were small and round at the posterior pole, sparing the fovea and larger, linear, and radially oriented in the periphery. FAF showed striking hyperautofluorescence corresponding to the hypopigmented patches. SSOCT in both cases showed preserved foveal contour, normal retinal architecture, and intact RPE-photoreceptor complex. Visual acuity was 20/20 in both patients at last examination, after refractive correction. ERG responses were largely within normal reference limits, although each case exhibited minimally reduced photopic responses.</p><p><strong>Conclusions: </strong>CGAS represents a benign, nonprogressive RPE abnormality with characteristic peripheral hypopigmented spots that are paradoxically hyperautofluorescent on FAF and associated with preserved retinal structure and good visual function. FAF and OCT are valuable, non-invasive tools for confirming the diagnosis, delineating lesion extent, and distinguishing CGAS from inherited flecked-retina dystrophies. Additional case series and genetic studies are warranted to clarify underlying mechanisms and potential associations.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical course of a patient with PRSS56-associated nanophthalmos (isolated microphthalmia) and uveal effusion syndrome.","authors":"Yukari Taguchi, Kazuki Kuniyoshi, Kei Mizobuchi, Chiharu Iwahashi, Masuo Sakamoto, Fukutato Mano, Takaaki Hayashi, Shunji Kusaka","doi":"10.1007/s10633-026-10115-9","DOIUrl":"https://doi.org/10.1007/s10633-026-10115-9","url":null,"abstract":"<p><strong>Purpose: </strong>To describe the detailed clinical course and genetic findings of a Japanese patient with nanophthalmos (isolated microphthalmia) who developed bilateral uveal effusion syndrome (UES).</p><p><strong>Case report: </strong>A 50-year-old Japanese man presented with distorted and decreased vision in his right eye. Ophthalmoscopy revealed non-rhegmatogenous retinal detachment with shifting subretinal fluid. The horizontal corneal diameter was 11.5 mm in both eyes, while the axial lengths were 15.6 and 15.3 mm in the right and left eyes, respectively, confirming the diagnosis of nanophthalmos (microphthalmia)-associated UES. After steroid pulse therapy followed by sclerectomy with vortex vein decompression (S-VVD), the UES resolved 10 months postoperatively. The eyes remained stable for 15 years, after which the patient developed bilateral cataracts and elevated intraocular pressure. Cataract surgery was done uneventfully, but signs of UES appeared in the left eye five days postoperatively. This was controlled with multiple treatments, including steroid pulse therapy, intravitreal anti VEGF injection, and oral carbonic anhydrase inhibitor. However, UES recurred after five months. S-VVD and vitrectomy with silicone oil tamponade were performed, and the UES resolved after one year postoperatively. Ultimately, electroretinography (ERG) became non-recordable, and the visual fields were constricted in both eyes. Whole-exome sequencing identified a previously unreported homozygous nonsense variant in PRSS56 (c.202C>T, p.Arg68Ter), classified as pathogenic based on the ACMG criteria.</p><p><strong>Conclusions: </strong>This report describes a patient with an unreported pathogenic PRSS56 variant who exhibited a typical and severe course of nanophthalmos (isolated microphthalmia) complicated by bilateral UES. Although the effusions eventually resolved after multiple interventions, the prolonged UES was challenging to manage and resulted in irreversible retinal dysfunction with a non-recordable ERG.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for RPE65 genetic variants in Egyptian children with inherited retinal disorders: a study from a tertiary eye care center in Egypt.","authors":"Ayman Elghonemy, Mahmoud Y Issa, Tarek Saad Shoala, Heba Metwally, Mohamed S Abdel-Hamid, Mohamed Gaber Abdallah","doi":"10.1007/s10633-026-10119-5","DOIUrl":"https://doi.org/10.1007/s10633-026-10119-5","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic variants in the RPE65 gene cause various forms of inherited retinal dystrophies (IRD), which include Leber congenital amaurosis (LCA), early childhood-onset retinal dystrophy (ECORD), and various forms of retinitis pigmentosa (RP). To date, no study has characterised the heterogeneity of RPE65 variants associated with IRD in the Egyptian population. This study aimed to identify RPE65 pathogenic variants in a cohort of Egyptian children with IRD, with implications for gene therapy eligibility.</p><p><strong>Methods: </strong>A total of 44 patients in the paediatric age group (from birth to 18 years old), from 27 unrelated Egyptian families with non-syndromic IRD, underwent detailed ophthalmic examination, which include electroretinogram (ERG), optical coherence tomography (OCT), and fundus autofluorescence (FAF), and their DNA samples were screened for RPE65 variants using Sanger sequencing.</p><p><strong>Results: </strong>Among the 44 patients studied, 8 (18.2%) harboured disease-causing pathogenic or likely pathogenic biallelic variants in the RPE65 gene. Of these, 47.7% were male and 52.3% female; in all affected individuals, symptom onset preceded the fourth birthday. Four distinct missense variants were identified: three classified as likely pathogenic and one as pathogenic. One variant (p.Phe472Ser) was novel, with no prior reports in the literature or public databases. Affected patients demonstrated visual impairment within the first decade of life. RPE65 variants were mainly associated with nystagmus and markedly reduced rod and cone function on ERG. There was bilateral thinning of outer retinal layers outside the fovea with the disruption of the ellipsoid Zzone (EZ) and retinal pigment epithelium (RPE) layers by OCT, as well as diminished normal fluorescence in fundus autofluorescence testing in patients harbouring disease-causing RPE65 genetic variants.</p><p><strong>Conclusion: </strong>RPE65 gene variants account for 18.2% of this selected paediatric IRD cohort and represent an important genetic cause of LCA and ECORD in the Egyptian population. Expanded access to gene therapy trials is critically needed for eligible patients.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of dynamic pupillary function after cataract surgery in eyes with pseudoexfoliation syndrome: a six-month longitudinal pupillometry study.","authors":"Goksu Alacamlı, Omer Ozer, Murat Kasıkcı","doi":"10.1007/s10633-026-10121-x","DOIUrl":"https://doi.org/10.1007/s10633-026-10121-x","url":null,"abstract":"<p><strong>Purpose: </strong>Impaired pupillary dynamics are a well-recognized feature of pseudoexfoliation syndrome (PXF), yet little is known about how cataract surgery influences postoperative iris function in these eyes. This study aimed to determine the longitudinal effects of cataract surgery on static pupil diameters and dilation velocity in eyes with pseudoexfoliation syndrome compared with age-matched controls.</p><p><strong>Methods: </strong>This longitudinal study included 166 eyes of 166 patients undergoing cataract surgery, comprising 91 eyes with pseudoexfoliation syndrome and 75 control eyes without pseudoexfoliation. Pupillary parameters were measured preoperatively and at six months postoperatively using automated pupillometry. Static pupil diameters were assessed under scotopic (0.04 lx), mesopic (4 lx), and photopic (40 lx) illumination conditions. Dynamic pupillary function was evaluated by measuring dilation velocity (DVel, mm/s) following a standardized light stimulus. Postoperative changes (Δ) were calculated as the difference between preoperative and postoperative measurements.</p><p><strong>Results: </strong>Static pupil diameters remained stable in the PXF group across all illumination conditions (p > 0.05). In contrast, the control group demonstrated a significant reduction in scotopic pupil diameter after surgery (p = 0.008), while mesopic and photopic diameters remained unchanged. The most notable finding was observed in pupillary kinetics: dilation velocity significantly increased in the PXF group from 0.13 ± 0.04 mm/s to 0.17 ± 0.05 mm/s (p < 0.001), whereas no significant change was detected in the control group. Between-group comparison showed a significantly greater improvement in dilation velocity in PXF eyes (p < 0.001). Cataract morphology was not associated with postoperative pupillary changes.</p><p><strong>Conclusion: </strong>These findings suggest that cataract surgery may be associated with measurable changes in dynamic pupillary behavior in PXF eyes, particularly in dilation velocity, while static pupil diameter remains largely unchanged.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of pupil dilation on IOL power calculation based on biometric measurements with Heidelberg Anterion.","authors":"Sara Marquina-Martín, Francisco J Segura-Calvo, Martín Puzo-Bayod, Marta Jiménez-García, Francisco J Castro-Alonso","doi":"10.1007/s10633-026-10117-7","DOIUrl":"https://doi.org/10.1007/s10633-026-10117-7","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the impact of pharmacologic pupil dilation (PD) on biometric measurements and intraocular lens (IOL) power calculation using different generation formulas in patients undergoing cataract surgery.</p><p><strong>Methods: </strong>This prospective study included 126 eyes from 75 patients. Biometric data were obtained before and after pharmacologic dilation using the Anterion Swept-Source OCT biometer (Heidelberg Engineering). Parameters recorded included axial length (AL), mean keratometry (Km), anterior chamber depth (ACD), lens thickness (LT), and white-to-white (WTW) distance. IOL power was calculated using six formulas: SRK/T, Haigis, Barrett Universal II (BUII), Kane, Hoffer QST, and Okulix. Statistical comparisons of biometric values and predicted IOL power before and after dilation were conducted using mixed-effects models.</p><p><strong>Results: </strong>No significant changes were observed in AL, CCT, LT or Km after dilation. However, ACD, WTW distance and PD showed statistically significant increases (both p < 0.01). IOL power estimations based on SRK/T, Haigis, Hoffer QST, BUII and Kane were not significantly affected after dilation. In contrast, Okulix formulas demonstrated statistically significant variations in calculated IOL power post-dilation (p < 0.0001).</p><p><strong>Conclusions: </strong>Pharmacologic pupil dilation induces changes in ACD and WTW measurements obtained using the Anterion Swept-Source biometer, thereby influencing IOL power estimation in formulas incorporating these parameters. Ray-tracing Okulix formula is more sensitive to dilation, whereas third-generation formulas remain more stable. Consistency in pupil status during biometry acquisition is essential to ensure refractive predictability.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Best vitelliform macular dystrophy caused by a BEST1 p.(Ser246Asn) variant coexisting with diabetic retinopathy.","authors":"Yusuke Tatemoto, Takaaki Hayashi, Kei Mizobuchi, Seika Den, Tadashi Nakano","doi":"10.1007/s10633-025-10056-9","DOIUrl":"10.1007/s10633-025-10056-9","url":null,"abstract":"<p><strong>Purpose: </strong>To report a 42 year-old male patient with Best vitelliform macular dystrophy (BVMD) complicated by diabetic retinopathy, who harbored a missense variant in the BEST1 gene.</p><p><strong>Methods: </strong>Comprehensive ophthalmological examinations, including full-field electroretinography (ERG) and electrooculography (EOG), were performed. Whole exome sequencing (WES) was conducted to identify potential disease-causing variant(s), and Sanger sequencing was used for confirmation.</p><p><strong>Results: </strong>Fundus photography and fluorescein angiography revealed macular degeneration and non-proliferative diabetic retinopathy with macular leakage. Although the light peak/dark trough (Arden) ratio on EOG was relatively preserved, a reduced light rise and attenuated dark trough amplitudes were observed. ERG demonstrated normal rod and cone system function. Based on optical coherence tomography findings, the BVMD stage was classified as a stage between the Vitelliruptive and Atrophic stages in the right eye, and as the Pseudohypopyon stage in the left eye. WES identified a previously unreported BEST1 variant, c.737G > A: p.(Ser246Asn) heterozygously, confirmed by Sanger sequencing.</p><p><strong>Conclusions: </strong>This case emphasizes the importance of EOG assessment and genetic analysis in establishing an accurate diagnosis of BVMD, particularly in patients with coexisting conditions such as diabetic retinopathy.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":"393-400"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of the clinical electrooculogram - Part 2: the bestrophinopathies and modified protocols.","authors":"Srikanta Kumar Padhy, Maja Šuštar Habjan, Paul A Constable","doi":"10.1007/s10633-026-10093-y","DOIUrl":"10.1007/s10633-026-10093-y","url":null,"abstract":"<p><p>The light-rise of the electro-oculogram (EOG) is used as a clinical marker for a collection of disorders known as the 'bestrophinopathies.' This review provides an overview of these conditions including Best Vitelliform Macular Dystrophy (BVMD, Autosomal Recessive Bestrophinopathy (ARB), Adult Onset Vitelliform Macular Dystrophy (AVMD) and Autosomal Dominant Vitreoretinalchoriodopathy (ADVIRC) and potential future therapies. One drawback of the EOG is the time to administer the test and shortened protocols that have been developed to improve the clinical testing of the EOG which include incorporating measures during recordings of the ERG or shortening the period of dark and light adaptation. The companion paper summarizes the cellular mechanism of the EOG, and this review is focused on the clinical applications of the EOG.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":"287-307"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The luminance-response function of the photopic negative response (PhNR): analysing different stimulation, recording and measurement approaches.","authors":"Oliver R Marmoy, Emma Hodson-Tole, Dorothy A Thompson","doi":"10.1007/s10633-026-10102-0","DOIUrl":"10.1007/s10633-026-10102-0","url":null,"abstract":"<p><strong>Purpose: </strong>The photopic negative response (PhNR) is a measure of generalised retinal ganglion cell function. There has been heterogenous methodology to record this, with varied electrode type, stimulus luminance, temporal frequency and measurement approach. This study aimed to empirically explore these features to identify an optimal PhNR luminance-response protocol which produces the lowest variance and maximal efficiency to guide clinical protocols.</p><p><strong>Methods: </strong>Twelve healthy participants were recruited (age range 27-51y). Flash ERGs were simultaneously recorded from infraorbital skin and corneal fibre electrodes to a range of red flash stimuli (- 0.3-2.4 log cd.s/m², incremented in 0.3 log units), whilst varying temporal frequency (1-5 Hz), background blue luminance (1, 1.5, 2 log cd/m²), and PhNR measurement approach (from baseline or b-wave, as an amplitude or ratio). The luminance-response series data were analysed for changes according to these variables, alongside a calculation of variability.</p><p><strong>Results: </strong>The PhNR luminance-response curves showed few significant differences with increasing temporal frequency, though inter-subject variability was highest for the slowest (1 Hz) and highest flash (5 Hz) stimulation rates. Background luminance reduced the relative sensitivity (K) but not maximal amplitude of the luminance-response curves (V_max). With skin electrodes the b-PhNR amplitude and b-PhNR ratio showed the lowest levels of variability compared with other measurement approaches or electrodes.</p><p><strong>Conclusion: </strong>This study demonstrates that temporal frequency can be increased significantly, optimally at 4 Hz, without compromising the PhNR. PhNR variance is lower with skin electrode recordings and PhNR amplitude measurements from the b-wave compared to corneal fibre electrodes and baseline-PhNR amplitudes.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":"341-356"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autosomal dominant Riggs-type congenital stationary night blindness with fundus sheen and retinal atrophy due to a novel GNAT1 p.Gln200Arg variant.","authors":"Jeremy J Chou, Rachael C Heath Jeffery, Jennifer A Thompson, Samuel McLenachan, Enid S Chelva, Tina M Lamey, Terri L McLaren, Fred K Chen","doi":"10.1007/s10633-026-10100-2","DOIUrl":"10.1007/s10633-026-10100-2","url":null,"abstract":"<p><strong>Purpose: </strong>To report an Australian family with congenital stationary night blindness (CSNB, OMIM#139,330) harbouring a novel GNAT1 c.599A > G (p.Gln200Arg) variant. In contrast to previous case reports we observed a fundus sheen, outer retinal changes and electrophysiological features of cone dysfunction in addition to a Riggs-type CSNB.</p><p><strong>Methods: </strong>Ophthalmic history, clinical examination and multimodal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT) were obtained. Full-field electroretinography (ERG) was conducted according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Genetic testing was performed using a targeted next-generation sequencing panel with familial segregation confirmed by Sanger sequencing. In silico prediction tools and protein structural modelling were used to evaluate the pathogenicity and functional impact of the GNAT1 p.Gln200Arg variant respectively.</p><p><strong>Results: </strong>Our proband, a 21-year-old transgender male, and his 62-year-old mother had a lifelong history of nyctalopia and visual acuity of 6/6 OU. The mother exhibited a golden sheen, sectoral chorioretinal atrophy and bone spicules. In the proband FAF imaging revealed hypoAF inferiorly with an arc of hyperAF whilst his mother had regions of hypoAF associated with outer retinal atrophy. Full-field electroretinography in the proband showed a cone-isolated retina with normal light-adapted responses. The mother had reduced and delayed light-adapted 30 Hz flicker. Both carried the GNAT1 variant NM_000172.4:c.599A > G (p.Gln200Arg). In silico analysis predicted impaired GTPase activity in Arg200 and constitutively active signally after photoactivation. The c.599A > G variant was classified as likely pathogenic.</p><p><strong>Conclusions: </strong>Our study suggests the GNAT1 p.Gln200Arg variant can manifest as both a Riggs-type CSNB and a rod-cone dystrophy within the same pedigree. This work expands the phenotypic spectrum of GNAT1-associated retinopathy and identifies GNAT1 as another potential cause of a fundus sheen.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":" ","pages":"381-391"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}