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.

[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 Case of Foveoschisis Associated with Ornithine Aminotransferase Deficiency and Gyrate Atrophy.

Gyrate atrophy is a metabolic disorder characterised by typical progressive circular chorioretinal atrophy, myopia and early developmental cataract. The disease is caused by deficiency of ornithine aminotransferase (OAT) enzyme. Although OAT is expressed in most tissues of the body, but the main target of the disease appears to be the retina. A case is presented here of a 21-year woman, who came to our clinic with the complaint of decline in central vision for eight months. She had progressive poor night vision and was diagnosed with OAT deficiency five years ago. Her systemic history was unremarkable, except for femoral deep vein thrombosis (DVT) which occurred two years ago. Laboratory tests performed at that time had revealed elevated serum ornithine and low serum lysin levels. Optic coherence tomography (OCT) scans showed foveoschisis bilaterally. In summary, gyrate atrophy may present as macular involvement in the form of foveoschisis and may lead to impaired central vision. Key Words: Foveoschisis, Gyrate atrophy, Ornithine aminotransferase.

Ultrawide field imaging to document the progression of gyrate atrophy of the choroid and retina over 5 years.

A family of three siblings affected with gyrate atrophy of the choroid and retina is presented. Ultrawide field fundus imaging was used to monitor the progression of the disease objectively over 5 years.

A novel c.980C>G variant in OAT results in identifiable gyrate atrophy phenotype associated with retinal detachment in a young female.

Background: Gyrate atrophy of the choroid and retina (GA) is a rare autosomal recessive disorder characterized by nyctalopia, myopia, sharply demarcated expanding peripheral chorioretinal atrophic lesions, early cataract, progressive visual loss and hyperornithinemia. Only three cases of GA associated with rhegmatogenous retinal detachments (RRD) have been reported. The genotype-phenotype correlation of RRD in GA is limited by lack of genetic information in the previously reported cases. Here we report two young sisters with a characteristic GA phenotype associated with a novel variant in the ornithine aminotransferase gene (OAT), in whom one developed unilateral RRD at the age of 9 years.Materials and Methods: Retrospective report of two cases including genetic analysis and multimodal retinal imaging.Results: A 9-year-old Saudi girl presented with a funnel-shaped RRD, extensive proliferative vitreoretinopathy, peripheral choroidal detachment and neovascular glaucoma in her right eye. Fundus examination of her left eye showed an attached retina with sharply-demarcated peripheral chorioretinal atrophic patches suggestive of GA. Whole exome sequencing confirmed GA by revealing a homozygous c.980 C > G (p. Pro327Arg) variant in exon 8 of OAT. The RRD was inoperable. The chorioretinal lesions in the left eye enlarged slowly over 3 years of follow up. Examination of the proband's older sister revealed a similar but more advanced GA phenotype in both eyes.Conclusions: A characteristic GA phenotype associated with a novel variant in OAT is reported. This variant might be associated with childhood-onset RRD in the proband.

Optical Coherence Tomography Angiography and Macular Vessel Density Analysis of Cystoid Macular Edema in Gyrate Atrophy.

BACKGROUND AND OBJECTIVE: To understand the microvascular abnormalities in cystoid macular edema (CME) in gyrate atrophy. PATIENTS AND METHODS: Spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) were used in four consecutive female patients (eight eyes) with clinically and biochemistry-confirmed cases of gyrate atrophy and associated CME. Foveal avascular zone (FAZ) area and macular vessel density percentage were calculated and compared with normal subjects. RESULTS: The average age was 20 years (range: 13 years to 32 years). The mean refractive error was -6.5 diopters (D) (range: -1.0 D to -11.0 D). The average central macular thickness was 509 µm (range: 291 µm to 750 µm). OCTA showed an enlarged FAZ in the deep capillary plexus (DCP) with presence of hyporeflective cysts in both the superficial and deep capillary layers corresponding to CME. Compared to the normal subjects, the mean FAZ area was enlarged and macular vessel density was reduced in both the superficial capillary plexus and DCP; this was statistically significant (P < .05). En face OCT of the DCPs showed classical hyporeflective honeycomb pattern delineating the structural pattern of CME in the inner plexiform and outer plexiform layer. CONCLUSION: OCTA helps understand the basic pathophysiologic mechanisms in gyrate atrophy of choroid as well as etiology for CME and macular schisis. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:423-427.].

Bevacizumab for the treatment of intraretinal cystic spaces in a patient with gyrate atrophy of the choroid and retina.

BACKGROUND: Gyrate atrophy of the choroid and retina is a rare autosomal recessive condition characterized by chorioretinal atrophy due to deficiency of the enzyme ornithine aminotransferase that can be complicated by intraretinal cystic spaces. CASE REPORT: A 15-year-old female complaining of gradually progressive diminution of vision in both eyes preceded by night blindness was found to have gyrate atrophy of the choroid and retina with intraretinal cystic spaces that was evaluated using multimodal imaging including fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. Functional and anatomical improvement of the intraretinal cystic spaces was achieved with monthly intravitreal bevacizumab injections. CONCLUSION: Repeated intravitreal bevacizumab injections can result in anatomical and functional improvement of intraretinal cystic spaces in patients with gyrate atrophy of the choroid and retina.

Resolution of cystoid macular edema following arginine-restricted diet and vitamin B6 supplementation in a case of gyrate atrophy.

We report the outcome of 3 years of arginine-restricted diet and vitamin B6 supplementation in a boy who presented with gyrate atrophy of the choroid and retina and bilateral cystoid macular edema. The diagnosis of gyrate atrophy was made on the basis of clinical findings and increased plasma ornithine levels. Molecular genetic testing revealed a disease-causing homozygous mutation in the ornithine aminotransferase (OAT) gene. After 3 months of dietary modification and pyridoxine supplementation, visual acuity improved, and optical coherence tomography showed resolution of cystoid macular edema in both eyes. This anatomical and functional improvement was maintained during 3 years of follow-up.

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.

Carbonic Anhydrase Inhibitor with Topical NSAID Therapy to Manage Cystoid Macular Edema in a Case of Gyrate Atrophy.

PURPOSE: Gyrate atrophy of the choroid and retina (GACR) is a rare chorioretinal dystrophy characterized by a deficiency of the enzyme ornithine aminotransferase, inherited in an autosomal recessive pattern. CASE REPORT: We report a case of a 17-year-old girl with GACR, for whom the level of serum ornithine had been reduced by an arginine-restricted diet. The patient was responsive to an association of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and a carbonic anhydrase inhibitor (CAI) to reduce cystoid macular edema (CME). CONCLUSIONS: The efficacy of topical NSAIDs and systemic CAI association indicates that the imbalance in the distribution of retinal pigment epithelium membrane-bound carbonic anhydrase could play a major role in CME pathogenesis in GACR. To our knowledge, this is the first case of therapy with CAI treatment for GACR-related CME.

Intravitreal ranibizumab for choroidal neovascularization secondary to gyrate atrophy in a young patient: a multimodal imaging analysis.

PURPOSE: To present a case of choroidal neovascularization (CNV) due to gyrate atrophy (GA) treated with intravitreal ranibizumab. METHODS: A 35-year-old man presented with sudden loss of vision and central scotoma in the right eye, as well as progressive night vision deterioration over the past several years in both eyes. His best-corrected visual acuity (BCVA) was 6/60 in the right eye and 6/5 in the left eye. Funduscopy revealed bilateral confluent areas of chorioretinal atrophy and optical coherence tomography showed subretinal fluid consistent with CNV development in the right eye, which was confirmed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA). The left eye was normal. The patient had a family history of GA. Elevated levels of plasma ornithine were detected, establishing the diagnosis. RESULTS: The patient received a regimen of 3 monthly off-label intravitreal ranibizumab injections in the right eye. At the 6-month follow-up, no subretinal fluid was noticed and BCVA was 6/48. No other injections were performed, but the patient was advised to start an arginine-restricted diet and take vitamin B6 (pyridoxine) 300 mg daily. The BCVA was preserved and chorioretinal atrophy had not progressed on funduscopy, FFA, or ICGA 1 year later. CONCLUSIONS: Intravitreal ranibizumab can offer promising anatomical and functional results, maintaining visual acuity in patients with CNV secondary to GA, especially if used in combination with arginine-restricted diet and vitamin B6 supplementation.

Long-term follow-up of astrocytic hamartoma of the optic disc associated with gyrate atrophy.

This is a case report of a 15-year-old boy with multiple small peripapillary white growths in the right eye in the setting of gyrate atrophy. Over 3 years of follow-up, these lesions became more clearly delineated as astrocytic hamartomas of the retina and optic disc. In the setting of gyrate atrophy, astrocytic hamartomas are extremely rare. This report represents the second published case and includes characterization of these tumors using spectral-domain optical coherence tomography.

Treatment of cystic macular lesions in hereditary retinal dystrophies.

Cystic macular lesions frequently contribute to impaired visual acuity in hereditary retinal dystrophies. Their pathogenesis varies and is not entirely understood. Carbonic anhydrase inhibitors have proven to be potentially efficacious, although not in all cases. We discuss the various factors and mechanisms implicated in the etiology of cystic macular lesions (anatomical abnormalities, impairment of the blood-retinal barrier, tangential vitreous traction, and mutations in retinoschin, etc.) and the various treatments that have been proposed.