Posterior Polar Annular Choroidal Dystrophy: Genetic Insights and Differential Diagnosis in Inherited Retinal Diseases.

Posterior polar annular choroidal dystrophy (PPACD) is a rare ocular disorder and presents as symmetric degeneration of the retinal pigment epithelium (RPE) and the underlying choriocapillaris, encircling the retinal vascular arcades and optic disc. This condition distinctively preserves the foveal region, optic disc, and the outermost regions of the retina. Despite its distinct clinical presentation, due to the infrequency of its occurrence and the limited number of reported cases, the pathophysiology, and the genetic foundations of PPACD are still largely uncharted. This review aims to bridge this knowledge gap by investigating potential genetic contributors to PPACD, assessing current findings, and identifying genes that warrant further study. Emphasis is also placed on the crucial role of multimodal imaging in diagnosing PPACD, highlighting its importance in understanding disease pathophysiology. By analyzing existing case reports and drawing comparisons with similar retinal disorders, this paper endeavors to delineate the possible genetic correlations in PPACD, providing a foundation for future genetic research and the development of targeted diagnostic strategies.

Extending diagnostic practices in gyrate atrophy: Enzymatic characterization and the development of an in vitro pyridoxine responsiveness assay.

Gyrate atrophy of the choroid and retina (GACR) is caused by pathogenic biallelic variants in the gene encoding ornithine-δ-aminotransferase (OAT), and is characterized by progressive vision loss leading to blindness. OAT is a pyridoxal-5'-phosphate (PLP) dependent enzyme that is mainly involved in ornithine catabolism, and patients with a deficiency develop profound hyperornithinemia. Therapy is aimed at lowering ornithine levels through dietary arginine restriction and, in some cases, through enhancement of OAT activity via supraphysiological dosages of pyridoxine. In this study, we aimed to extend diagnostic practices in GACR by extensively characterizing the consequences of pathogenic variants on the enzymatic function of OAT, both at the level of the enzyme itself as well as the flux through the ornithine degradative pathway. In addition, we developed an in vitro pyridoxine responsiveness assay. We identified 14 different pathogenic variants, of which one variant was present in all patients of Dutch ancestry (p.(Gly353Asp)). In most patients the enzymatic activity of OAT as well as the rate of [14C]-ornithine flux was below the limit of quantification (LOQ). Apart from our positive control, only one patient cell line showed responsiveness to pyridoxine in vitro, which is in line with the reported in vivo pyridoxine responsiveness in this patient. None of the patients harboring the p.(Gly353Asp) substitution were responsive to pyridoxine in vivo or in vitro. In silico analysis and small-scale expression experiments showed that this variant causes a folding defect, leading to increased aggregation properties that could not be rescued by PLP. Using these results, we developed a diagnostic pipeline for new patients suspected of having GACR. Adding OAT enzymatic analyses and in vitro pyridoxine responsiveness to diagnostic practices will not only increase knowledge on the consequences of pathogenic variants in OAT, but will also enable expectation management for therapeutic modalities, thus eventually improving clinical care.

A cohort study of 19 patients with gyrate atrophy of the choroid and retina (GACR).

PURPOSE: Gyrate atrophy of the choroid and retina (GACR) is an autosomal recessive inherited metabolic disorder (IMD) characterised by progressive retinal degeneration, leading to severe visual impairment. The rapid developments in ophthalmic genetic therapies warrant knowledge on clinical phenotype of eligible diseases such as GACR to define future therapeutic parameters in clinical trials. METHODS: Retrospective chart analysis was performed in nineteen patients. Data were analysed using IBM SPSS Statistics version 28.0.1.1. RESULTS: Nineteen patients were included with a mean age of 32.6 years (range 8-58). Mean age at onset of ophthalmic symptoms was 7.9 years (range 3-16). Median logMAR of visual acuity at inclusion was 0.26 (range -0.18-3.00). Mean age at cataract surgery was 28.8 years (n = 11 patients). Mean spherical equivalent of the refractive error was -8.96 (range -20.87 to -2.25). Cystoid maculopathy was present in 68% of patients, with a loss of integrity of the foveal ellipsoid zone (EZ) in 24/38 eyes. Of the 14 patients treated with dietary protein restriction, the four patients who started the diet before age 10 showed most benefit. CONCLUSION: This study demonstrates the severe ophthalmic disease course associated with GACR, as well as possible benefit of early dietary treatment. In addition to visual loss, patients experience severe myopia, early-onset cataract, and CME. There is a loss of foveal EZ integrity at a young age, emphasising the need for early diagnosis enabling current and future therapeutic interventions.

Biochemical Studies on Human Ornithine Aminotransferase Support a Cell-Based Enzyme Replacement Therapy in the Gyrate Atrophy of the Choroid and Retina.

The gyrate atrophy of the choroid and retina (GACR) is a rare genetic disease for which no definitive cure is available. GACR is due to the deficit of ornithine aminotransferase (hOAT), a pyridoxal 5'-phosphate-dependent enzyme responsible for ornithine catabolism. The hallmark of the disease is plasmatic ornithine accumulation, which damages retinal epithelium leading to progressive vision loss and blindness within the fifth decade. Here, we characterized the biochemical properties of tetrameric and dimeric hOAT and evaluated hOAT loaded in red blood cells (RBCs) as a possible enzyme replacement therapy (ERT) for GACR. Our results show that (i) hOAT has a relatively wide specificity for amino acceptors, with pyruvate being the most suitable candidate for ornithine catabolism within RBCs; (ii) both the tetrameric and dimeric enzyme can be loaded in RBC retaining their activity; and (iii) hOAT displays reduced stability in plasma, but is partly protected from inactivation upon incubation in a mixture mimicking the intracellular erythrocyte environment. Preliminary ex vivo experiments indicate that hOAT-loaded RBCs are able to metabolize extracellular ornithine at a concentration mimicking that found in patients, both in buffer and, although with lower efficiency, in plasma. Overall, our data provide a proof of concept that an RBC-mediated ERT is feasible and can be exploited as a new therapeutic approach in GACR.

Biochemical and Bioinformatic Studies of Mutations of Residues at the Monomer-Monomer Interface of Human Ornithine Aminotransferase Leading to Gyrate Atrophy of Choroid and Retina.

Deficit of human ornithine aminotransferase (hOAT), a mitochondrial tetrameric pyridoxal-5'-phosphate (PLP) enzyme, leads to gyrate atrophy of the choroid and retina (GA). Although 70 pathogenic mutations have been identified, only few enzymatic phenotypes are known. Here, we report biochemical and bioinformatic analyses of the G51D, G121D, R154L, Y158S, T181M, and P199Q pathogenic variants involving residues located at the monomer-monomer interface. All mutations cause a shift toward a dimeric structure, and changes in tertiary structure, thermal stability, and PLP microenvironment. The impact on these features is less pronounced for the mutations of Gly51 and Gly121 mapping to the N-terminal segment of the enzyme than those of Arg154, Tyr158, Thr181, and Pro199 belonging to the large domain. These data, together with the predicted ΔΔG values of monomer-monomer binding for the variants, suggest that the proper monomer-monomer interactions seem to be correlated with the thermal stability, the PLP binding site and the tetrameric structure of hOAT. The different impact of these mutations on the catalytic activity was also reported and discussed on the basis of the computational information. Together, these results allow the identification of the molecular defects of these variants, thus extending the knowledge of enzymatic phenotypes of GA patients.

[Gyrate atrophy of the choroid and retina with ornithinemia and foveoschisis (clinical observation)]. / Atrofiya girate khorioidei i setchatki s ornitinemiei i foveoshizisom (klinicheskoe nablyudenie).

Gyrate chorioretinal atrophy (GCA) is a rare hereditary disease with certain complications; one extremely rare complication of GCA is foveoschisis. For the first time in Russian ophthalmology, a 10-year-old female child has been described to have genetically verified GCA associated with the OAT gene in combination with ornithinemia and foveoschisis. The diagnosis was made on the basis of fundus examination, perimetry data, autofluorescence, optical coherence tomography, fluorescence angiography, electroretinography, mass spectrometry with confirmation by molecular genetic research. The presented clinical case illustrates the need for an interdisciplinary approach to the diagnosis of GCA with diagnostic algorithm involving various examination methods and doctors of different specialties.

A review of treatment modalities in gyrate atrophy of the choroid and retina (GACR).

Gyrate atrophy of the choroid and retina (GACR) is a rare inborn error of amino acid metabolism caused by bi-allelic variations in OAT. GACR is characterised by vision decline in early life eventually leading to complete blindness, and high plasma ornithine levels. There is no curative treatment for GACR, although several therapeutic modalities aim to slow progression of the disease by targeting different steps within the ornithine pathway. No international treatment protocol is available. We systematically collected all international literature on therapeutic interventions in GACR to provide an overview of published treatment effects. METHODS: Following the PRISMA guidelines, we conducted a systematic review of the English literature until December 22nd 2020. PubMed and Embase databases were searched for studies related to therapeutic interventions in patients with GACR. RESULTS: A total of 33 studies (n = 107 patients) met the inclusion criteria. Most studies were designed as case reports (n = 27) or case series (n = 4). No randomised controlled trials or large cohort studies were found. Treatments applied were protein-restricted diets, pyridoxine supplementation, creatine or creatine precursor supplementation, l-lysine supplementation, and proline supplementation. Protein-restricted diets lowered ornithine levels ranging from 16.0-91.2%. Pyridoxine responsiveness was reported in 30% of included mutations. Lysine supplementation decreased ornithine levels with 21-34%. Quality assessment showed low to moderate quality of the articles. CONCLUSIONS: Based primarily on case reports ornithine levels can be reduced by using a protein restricted diet, pyridoxine supplementation (variation-dependent) and/or lysine supplementation. The lack of pre-defined clinical outcome measures and structural follow-up in all included studies impeded conclusions on clinical effectiveness. Future research should be aimed at 1) Unravelling the OAT biochemical pathway to identify other possible pathologic metabolites besides ornithine, 2) Pre-defining GACR specific clinical outcome measures, and 3) Establishing an international historical cohort.

Partial regression of foveoschisis following vitamin B6 supplementary therapy for gyrate atrophy in a Chinese girl.

BACKGROUND: To report a case of genetically confirmed gyrate atrophy (GA) of choroid and retina, who showed partial regression of foveoschisis following vitamin B6 supplementary therapy. CASE PRESENTATION: A 6-year-old Chinese girl complained about night blindness and progressive decreased vision in both eyes. Her best corrected visual acuity (BCVA) was 20/63 OD and 20/100 OS. Fundus examination showed bilateral multiple, sharply demarcated, scallop-shaped chorioretinal atrophy areas in the midperipheral and peripheral of the fundus. Spectral domain optical coherence tomography (SD-OCT) showed increased central macular thickness (CMT) with multiple intraretinal cystic spaces in the both eyes. There was no leakage or staining in the macular area in late phase of fluorescein angiography (FA). Blood tests confirmed hyperornithinemia and genetic analysis revealed two heterozygous mutations on ornithine aminotransferase (OAT) gene. Based on clinical presentation and genetic test, the patient was diagnosed as GA of the choroid and retina and further treated with vitamin B6 supplementary for three weeks. Her serum ornithine levels did not change but CMT on SD-OCT declined with partial regression of intraretinal cystic spaces. Then, the patient discontinued the drug because of severe muscle pain, and foveoschisis increased to initial level a month later. CONCLUSIONS: Foveoschisis is a rare complication of GA. Vitamin B6 supplementation may alleviate foveoschisis, but its effort for reducing serum ornithine level might be limited. Potential drug adverse effects should be noted in pediatric patients.

Autosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant.

We present a long-term follow-up in autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD) and propose a possible genotype/phenotype correlation. Ophthalmic examination of six patients from two families revealed confluent areas of choroidal atrophy resembling gyrate atrophy, starting in the second decade of life. Progression continued centrally, reaching the fovea at about 60 years of age. Subretinal deposits, retinal pigmentation or choroidal neovascularization as seen in late-onset retinal degeneration (LORD) were not observed. Whole genome sequencing revealed a novel missense variant in the C1QTNF5 gene (p.(Q180E)) which was found in heterozygous state in all affected subjects. Haplotype analysis showed that this variant found in both families is identical by descent. Three-dimensional modeling of the possible supramolecular assemblies of C1QTNF5 revealed that the p.(Q180E) variant led to the destabilization of protein tertiary and quaternary structures, affecting both the stability of the single protomer and the entire globular head, thus exerting detrimental effects on the formation of C1QTNF5 trimeric globular domains and their interaction. In conclusion, we propose that the p.(Q180E) variant causes a specific phenotype, adGALCD, that differs in multiple clinical aspects from LORD. Disruption of optimal cell-adhesion mechanisms is expected when analyzing the effects of the point mutation at the protein level.

Multimodal imaging of foveoschisis and macular pseudohole associated with gyrate atrophy: a family report.

BACKGROUND: To report the results of multimodal imaging of a biochemically confirmed case of a family with gyrate atrophy (GA) associated with foveoschisis and macular pseudohole. CASE PRESENTATION: Two sisters presented to us with progressive bilateral decreased vision. The 26-year old sister had a best corrected visual acuity (BCVA) of 20/32 in the right eye (RE) and 20/100 in the left eye (LE). Dilated fundus examination revealed multiple bilateral chorioretinal atrophy areas in the midperipheral and peripheral retina. Fluorescein angiography did not show any leak in the macular area. Swept-source optical coherence tomography (SS-OCT) showed increased central macular thickness in both eyes with foveoschisis. Optical coherence tomography angiography (OCTA) showed petaloid non-reflective areas and some perifoveal microvascular alterations similar to telangiectasias in the deep capillary complex. The 30-year-old sister had a BCVA of 20/20 in the RE and 20/32 in the LE. SS-OCT was normal in the RE and demonstrated a macular pseudohole with a fine epiretinal membrane in the LE. The persistent retinal tissue at the base of the pseudohole was disorganised. Blood tests showed hyperornithinemia in the 2 cases. Based on these observations, the patients were diagnosed with gyrate atrophy of the choroid and retina and were treated with a pyridoxine supplement and an arginine-restricted diet. CONCLUSIONS: Foveoschisis and macular pseudohole may be associated in GA, increasing the risk of rapid vision loss. OCTA is an interesting imaging tool that can help to better understand the pathophysiological mechanism of these macular involvements in GA.

Inborn Errors of Metabolism: Gyrate Atrophy.

Gyrate atrophy is an autosomal recessive dystrophy in which night blindness starts early in the first decade of life. In the early stages, large areas of retinal pigment epithelium (RPE) and choriocapillaris (CC) atrophy in the far periphery (lobular shape, Fig. 37.1). (In choroideremia, atrophy appears in the mid periphery.) Later, these areas coalesce to form a characteristic scalloped border at the junction of healthy and diseased RPE. Myopia and subcapsular cataract are common by the end of second or third decade. Unlike in choroideremia (which is X-linked), patients with gyrate atrophy show areas of hyperpigmentation of the remaining RPE (Fig. 37.2). Patients with gyrate atrophy do not show the choroidal atrophy (as seen in choroideremia) until the late stages. Treatment includes a low-protein, arginine-restricted diet for all patients. In some cases, vitamin B6 (pyridoxine) may help in lowering plasma ornithine levels.

Bilateral choroidal neovascularization associated with gyrate atrophy managed with intravitreal bevacizumab.

PURPOSE: To report a case with gyrate atrophy (GA) complicated by bilateral choroidal neovascularization (CNV) treated with intravitreal bevacizumab. CASE PRESENTATION: A 20-year-old man presented with a complaint of sudden visual decrease in his both eyes. Best-corrected visual acuity (BCVA) was 20/400 and 20/500, with a spherical refractive error of -2.00 and -1.75 D, in the right and left eyes, respectively. Dilated fundus examination revealed multiple bilateral, sharply defined chorioretinal atrophy areas in the midperipheral and peripheral zone with the suspicion of CNV in both eyes. Spectral-domain optical coherence tomography revealed bilateral cystoid macular edema consistent with CNV development which was confirmed by fundus fluorescein angiography. Single dose of intravitreal bevacizumab injections were performed to both eyes of the patient. At the first month after the injection, the BCVA improved and OCT revealed scar formation without any intraretinal/subretinal fluid in both eyes. At the first-year follow-up, the maculas remained dry on the OCT and the BCVA was preserved. No additional injections were needed. CONCLUSION: Intravitreal bevacizumab might be a treatment alternative, which provides satisfactory anatomical and functional results and leads to a better central vision in cases with GA complicated by CNV.

Progression of gyrate atrophy measured with ultra-wide-field imaging.

The study aims to determine the progression of gyrate atrophy by measuring the area growth of chorioretinal atrophic lesions using ultra-wide-field images (UWFI). A retrospective, observational, and comparative study was conducted and UWFI (200°) were obtained from two patients with gyrate atrophy at baseline and follow-up. Measurements of atrophy were obtained for three types of lesions: Solitary atrophic lesions (SAL), De novo solitary lesions (DNSL), and peripapillary atrophy (PPA). Comparison of baseline and follow-up was done using t tests. Two patients with gyrate atrophy were included. Patient 1 presented 16 SAL, 5 DNSL, and PPA measured for both eyes (BE). Overall area growth (OAG) for SAL (expressed in decimals) presented a mean of 3.41, σ 3.07. DNSL area for BE presented a mean of 1586.08 P (2), σ 1069.55. OAG for PPA presented a mean of 1.21, σ 0.17. Patient 2 presented 5 SAL, no DNSL, and PPA was measured for BE. OAG for SAL presented a mean of 1.58, σ 1.05 (range 1.02-3.47). OAG for PPA presented a mean of 1.05, σ 0.001. Gyrate atrophy progression can be determined by measuring the changes in area using UWFI.

Clinical characteristics of gyrate atrophy compared with a gyrate atrophy-like retinal phenotype.

INTRODUCTION: Gyrate atrophy (GA) is a rare retinal dystrophy due to biallelic pathogenic variants in the ornithine aminotransferase (OAT) gene, causing a 10-fold increase in plasma ornithine levels. It is characterized by circular patches of chorioretinal atrophy. However, a GA-like retinal phenotype (GALRP) without elevated ornithine levels has also been reported. The aim of this study is to compare the clinical characteristics of GA and GALRP and to identify possible discriminators. METHODS: A multicenter, retrospective chart review was performed at three German referral centres on patient records between 01/01/2009 and 31/12/2021. Records were screened for patients affected by GA or GALRP. Only patients with examination results for plasma ornithine levels and / or genetic testing of the OAT gene were included. Further clinical data was gathered where available. RESULTS: Ten patients (5 female) were included in the analysis. Three suffered from GA, while seven had a GALRP. Mean age (± SD) at onset of symptoms was 12.3 (± 3.5) years for GA compared with 46.7 (± 14.0) years for GALRP patients (p = 0.002). Mean degree of myopia was higher in GA (-8.0 dpt. ± 3.6) compared to GALRP patients (-3.8 dpt. ± 4.8, p = 0.04). Interestingly, all GA patients showed macular oedema, while only one GALRP patient did. Only one patient with GALRP had a positive family history, while two were immunosuppressed. DISCUSSION: Age of onset, refraction and presence of macular cystoid cavities appear to be discriminators between GA and GALRP. GALRP may encompass both genetic and non-genetic subtypes.

A Novel Ornithine Aminotransferase Splice Site Mutation Causes Vitamin B6-Responsive Gyrate Atrophy.

Purpose: Gyrate atrophy of the choroid and retina (GACR) is a rare congenital disorder and mutations in the ornithine aminotransferase (OAT) gene has been specified as the underlying cause. Patients show a high level of ornithine in body fluids which may be controlled by low protein diets. Pyridoxine (vitamin B6) supplementation may also be effective, however, most patients appear to be nonresponsive to this modality of treatment. Case Report: Here, we report a characterized case of a vitamin B6-responsive GACR who had a splicing mutation in the OAT gene. The GACR diagnosis was confirmed through the clinical features, imaging, biochemical findings, and whole-exome sequencing (WES) results. WES data revealed the splicing mutation in intron 4 of the OAT gene (NM_001322967: c.425-1G>A). Conclusion: Our knowledge about the diagnosis and treatment of GACR can be improved by identifying novel mutations in the OAT gene and accurate follow-up of the patients to determine how they respond to treatment.

Mild Phenotypes of Gyrate Atrophy in a Heterozygous Carrier with One Variant Allele of OAT.

This study aimed to identify whether gyrate atrophy of the choroid and retina (GACR) heterozygous individuals have possible clinical manifestations and to explore the potential pathogenic mechanism. In this retrospective study, we surveyed a two-generation pedigree of an individual diagnosed with GACR. Two family members underwent ophthalmological, hematologic, and genetic tests. An arginine-restricted diet with vitamin B6 supplementation was implemented; clinical assessments were repeated every 3 months during follow-up. The relative OAT mRNA expression was determined using a real-time quantitative polymerase chain reaction. The 19-year-old compound heterozygous daughter (OAT: c.1186C>T; c.748C>T) had bilateral pathologic myopia, posterior staphyloma, chorioretinal atrophy, macular abnormalities, and elevated hematologic ornithine. The 54-year-old heterozygous mother (OAT: c.1186C>T) presented with bilateral pathologic myopia, asymmetric posterior staphyloma, retina and choroidal capillary layer atrophy, retinal pigment epithelium abnormalities, and mildly elevated hematologic ornithine. Compared to normal individuals, the daughter and mother had 29% and 46% relative OAT mRNA expression, respectively (p < 0.001). We believe that this is the first report of a carrier of one OAT variant allele exhibiting a mild phenotype, suggesting that family members should be aware of the possibility of clinical involvement in carriers with some autosomal recessive conditions. Additional data suggest that nonsense-mediated, decay-initiated mRNA degradation may cause GACR.

Widefield Retinal Imaging in Gyrate Atrophy: Correlation of Structural, Biochemical, and Functional Characteristics.

OBJECTIVES: To profile a cohort of gyrate atrophy patients classified by widefield retinal imaging and correlate the structural, biochemical, and functional characteristics. DESIGN: Retrospective observational cohort study. PARTICIPANTS: Sixty-five patients (129 eyes) with gyrate atrophy. METHODS: Data of participants with a diagnosis of gyrate atrophy were retrieved from their electronic medical records (January 2015 to December 2023). Retinal involvement was classified into three zones using widefield retinal images. Zone 3 had atrophic patches in the area anterior to the equator; Zone 2 had involvement limited to the arcades but posterior to the equator; Zone 1 had involvement within the vascular arcades and/or peripapillary region, with or without any other zone involvement. Macular assessment was performed using swept-source OCT (n=104). Flash ERG was performed in 40 eyes. serum ornithine levels (n=35) were measured, and genetic analysis was conducted (n=18). MAIN OUTCOME MEASURES: Demography, patient profile, zone of retina involved, macular features, and serum ornithine levels. RESULTS: The average age at presentation was 26.4 (range: 5-67) years, majority were male. Nyctalopia (n=35, 53.8%) and blurred vision (n=29, 44.6%) were the most common symptoms. Positive family history was reported in 32.3% of patients. Most eyes were myopic (69.8%<-3 D). Posterior subcapsular cataracts were documented in 36.4% of eyes. The highest frequency of retinal area affected was Zone 1 (57.14%), followed by Zone 2 (33.33%) and Zone 3 (9.52%), correlating with age at presentation. Foveoschisis was observed in 57.7% of eyes, with a higher prevalence in eyes with Zone 1 disease. Elevated serum ornithine levels (>163 µmol/L) were found in 77.14% of patients. ERG showed non-recordable (n=32) or severely reduced (n=8) responses in scotopic and photopic phases. Genetic analysis of 18 patients identified mutations in the OAT gene, including a novel missense variant (c.290T>C). CONCLUSIONS: This large cohort of patients with gyrate atrophy revealed symmetrical involvement, predominantly in Zone 1. Most patients presented between the first and third decades, experienced nyctalopia, vision reduction, early posterior subcapsular cataracts, and varying degrees of myopia. Zone 1 involvement was strongly associated with foveoschisis and visual compromise.

Gyrate atrophy of the choroid and retina: Update on diagnosis and treatment.

Gyrate atrophy of the choroid and retina (GACR) is a rare autosomal recessive disease characterised by elevated plasma ornithine levels due to deficiency of the enzyme ornithine aminotransferase (OAT). The accumulation of this amino acid in plasma leads to the development of patches of chorioretinal atrophy in the peripheral retina extending into the macular area. Patients usually present with night blindness followed by constriction of the visual field and, finally, decreased central vision and blindness. The disease is diagnosed by the presence of the characteristic clinical picture, the presence of hyperornithinaemia in plasma and the detection of mutations in the OAT enzyme gene. There is currently no effective gene therapy and the most common therapeutic intervention mainly involves dietary modifications with arginine restriction. This article aims to summarise the pathogenesis, clinical and diagnostic findings and treatment options in patients with GACR.

Foveoschisis associated with gyrate atrophy in ornithine aminotransferase deficiency: A case report.

Ornithine aminotransferase (OAT) deficiency is an autosomal recessive disease characterized by elevated serum ornithine levels caused by mutations in genes encoding for ornithine aminotransferase, a vitamin B6-dependent mitochondrial matrix enzyme. Gyrate atrophy (GA) is characteristic findings in OAT that characterized by sharply demarcated circular, pigmentary, brain-like areas of chorioretinal atrophy in the peripheral retina. This case report presents rare assosiation between OAT and GA and describes the characteristic imaging findings of this unique, not fully understood clinical entity. The coexistence of GA and foveoschisis is extremely rare in OAT deficiency. We report a case of foveoschisis in a patient with OAT, and we will discuss the possible mechanisms that lead to it. A 24-year-old male patient presented with complaints of decreased vision and nictalopia for 1 year. The patient, who was diagnosed with oat 6 years ago, had typical gyrate atrophy in his Fundus floresein angiography and foveoschisis in his Optical coherence tomography. He was diagnosed with gyrate atrophy and foveoschisis. GA caused by OAT deficiency may present with macular involvement in the form of foveoschisis causing central visual impairment. Ophthalmologists should not ignore detailed fundus examination in children and young patients with visual impairment and should be aware of possible systemic diseases.

Regression of treatment-resistant gyrate atrophy-associated intraretinal cystic spaces using long-term diet restriction: A case report.

PURPOSE: Gyrate atrophy of the choroid and retina (GA) is a rare genetic ophthalmologic condition which primarily manifests in childhood. It is characterized by hyperornithinemia and progressive chorioretinal atrophy. Patients may develop macular intraretinal cystic spaces (ICS) for which various treatment modalities have been reported. We report a patient who failed to demonstrate visual or anatomic improvement following multiple treatments for GA-associated ICS but showed improvement following prolonged dietary modification and vitamin supplementation. CASE DESCRIPTION: A 6-year-old male patient presented with previously undiagnosed GA associated with ICS. He received 6 consecutive monthly intravitreal bevacizumab injections as well as topical nepafenac and dorzolamide for treatment of ICS without significant change detected by optical coherence tomography (OCT) following treatment. He was also maintained on an arginine restricted diet with vitamin B6 supplementation. Over the course of the ensuing year, the patient was lost to follow-up due to the coronavirus disease 2019 pandemic. When he returned, his vision was stable, and OCT showed regression of the ICS. His mother reported that he had continued only on dietary restriction and vitamin B6 supplementation with no other medications or interventions. Plasma ornithine level measurement confirmed dietary compliance. Further follow-up showed continued stabilization of the condition. CONCLUSION: In addition to retarding progressive chorioretinal atrophy, prolonged dietary modifications may result in improvement of treatment-resistant GA-associated ICS. Parents' education on the value of dietary modifications for patients with GA is highly recommended.