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. Gyrate atrophy is a rare genetical metabolic disorder affecting vision. Here, we report a 9-year-old boy with gyrate atrophy associated with bilateral macular edema at the time of diagnosis and the effect of long term metabolic control on macular edema.
Case Presentation
. A 9-year-old boy presented with a complaint of low visual acuity (best cor...
Citations
... It has been suggested that these changes are associated with choroidal vascular insufficiencies and are consistent with OCT and angiographic findings in our case 1. In humans, similar chorioretinal lesions have also been reported in patients with pathologic myopia, inherited retinal dysplasia, such as gyrate atrophy, and choroidal neoplasms, including malignant melanoma and metastatic carcinoma [12,[14][15][16]. However, approximately 15% of autopsied human eyes with or without other ocular pathology were also reported to have paving-stone degeneration, and 38% of the cases were bilateral [12]. ...
Background
A number of etiologies for different canine chorioretinal lesions have been proved or suggested but some fundic lesions remain unclear in terms of an etiologic diagnosis, treatment options and prognosis. The purpose of this case series is to describe atypical chorioretinal lesions observed in dogs with primary angle-closure glaucoma (PACG).
Case presentation
Two spayed-female Siberian Huskies (3- and 4-year-old) and one Siberian Husky/Australian Shepherd mixed breed dog (11-month-old) that had multifocal depigmented retinal lesions and PACG were included. Procedures: Ophthalmic examination, gross, and histopathologic examination findings are described. One of the dogs underwent further clinical diagnostics. Advanced clinical diagnostics on the fellow, presumed to be non-glaucomatous eye of a dog revealed: pectinate ligament dysplasia by gonioscopy, retinal thinning in the depigmented area and wedge shaped retinal thinning with delayed choroidal vascular perfusion by optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein and indocyanine green angiography. Quantifiable maze testing for the same eye revealed mild nyctalopia but the full-field electroretinogram showed no generalized decrease of retinal function. Genetic testing for mutations within the retinitis pigmentosa GTPase regulator gene causing X-linked progressive retinal atrophy in Siberian Huskies was negative. Histopathologic evaluations on enucleated eyes in two dogs confirmed goniodysgenesis, PACG with optic nerve head cupping, and diffuse inner retinal atrophy. In addition, segmental profound retinal atrophy, loss of retinal pigment epithelium, and adhesion of the retina to Bruch’s membrane was observed and coincided with multifocal depigmented lesions noted on fundic examination.
Conclusions
To our knowledge, this is the first case series with clinical and histopathologic data of chorioretinal lesions, most likely caused by severely impaired choroidal perfusion. Further studies are warranted to elucidate the etiology and pathophysiology, including its possible association with PACG.
... The effect of these treatment modalities on the ICS associated with gyrate atrophy has been, however, variable which suggests that the pathophysiology of ICS associated with GA may be due to other causes in addition to the hyperornithinemia. 14,15 In the current study, we found evidence of both structural and functional improvement of the macula of 5 eyes of 3 patients with ICS associated with GA evaluated by clinical examination, optical coherence tomography, OCTA, and microperimetry following 3 monthly intravitreal bevacizumab injections. Although our sample size was small, GA of the choroid and retina is a rare autosomal recessive condition and our study currently represents the largest study reported to date that Regarding GA patients with ICS who respond well to bevacizumab injections, we currently recommend close follow up of these patients after short periods of treatment and possible pro re nata regimen for future treatment as needed. ...
Purpose:
To evaluate the use of intravitreal bevacizumab injections for the treatment of intraretinal cystic spaces associated with gyrate atrophy of the choroid and retina.
Methods:
Retrospective chart review of 5 eyes of 3 patients with intraretinal cystic spaces associated with gyrate atrophy and treated with intravitreal bevacizumab injections was performed. Information obtained included history, examination findings, optical coherence tomography (OCT), OCT angiography, fluorescein angiography, and microperimetric findings before and after the injections.
Results:
The mean age of patients was 11 ± 4.6 years. All patients received three monthly bevacizumab injections. The mean corrected distance visual acuity was 0.27 ± 0.10 at baseline and improved to 0.36 ± 0.12 after the injections (P = .015). The mean central macular thickness was 569 ± 127 µm at baseline and improved to 422 ± 123 µm after the injections (P = .067). Microperimetry and OCT angiography performed in 1 patient before and after the three injections showed improved macular sensitivity and vascular density measurements following the injections.
Conclusions:
Intravitreal bevacizumab is safe and effective in the treatment of intraretinal cystic spaces associated with gyrate atrophy. [J Pediatr Ophthalmol Strabismus. 2020;57(6):400-406.].
... Characteristic sharply demarcated, scalloped areas of chorioretinal atrophy are noted at the equator. Visual decline in late childhood results from progressive myopia and nyctalopia [2][3][4][5][6][7][8][9][10][11][12][13][14]. Considerable variability is observed in the age at which visual acuities begin to decrease [2]. ...
... Other proposed minor causes for intraretinal fluid accumulation have included tangential vitreous forces and disruption of the retinal cell-to-cell adhesion. Arginine-restricted diet [5,11] and vitamin B6 supplementation [5,11] can be effective but when this strategy alone fails [12,13], additional approaches have been used to treat the intraretinal cysts in GA, including carbonic anhydrase inhibitors [8,9], topical non-steroid anti-inflammatory drugs [8,9], and intravitreal (or periocular [4]) corticosteroid [3] or vascular endothelial growth factor antagonists [14], either separately or in combination. ...
To evaluate the relationship between superficial, deep foveal avascular zone (FAZ) and foveal cyst areas in eyes with cystoid macular oedema (CMO) associated with gyrate atrophy of the choroid and retina (GA).
This is a retrospective collaborative multicenter study of optical coherence tomography-angiography (OCTA) images in GA. Superficial and deep FAZ and foveal cyst were measured using Image J by two independent experts. Values were corrected for myopia magnification. These values were compared with age-matched controls from normative data.
Twenty-three eyes from 12 patients with GA and CMO were included in the study. The mean ± standard deviation age was 22 ± 19.7 years, mean Snellen spectacle-corrected visual acuity of 20/70 with mean myopia of 5.7 ± 4.1 dioptres. Qualitatively, no focal occlusion of superficial and deep capillary plexus was noted. Mean superficial FAZ area (0.484 ± 0.317 mm²), deep FAZ area (0.626 ± 0.452 mm²), and foveal cyst area (0.630 ± 0.503 mm²) were significantly larger than superficial and deep FAZ areas in controls of same age range (p < 0.001). Macular cyst area correlated with superficial FAZ area (R = 0.59; p = 0.0057) and more strongly with deep FAZ area (R = 0.69; p < 0.001).
The superficial and deep FAZ area in GA-associated CMO were noted to be significantly larger than in controls. It seems that RPE dysfunction leads to foveal cyst enlargement displacing the capillary plexus with resultant enlarged superficial and deep FAZ area.
... In conclusion, patients usually benefit from arginine-restricted and low-protein diets in terms of IC reductions. However, in some cases, ICs can be resistant to diet (10) , or patients cannot adapt to their diets as re quired. Also, results of the vitamin B6 supplementation are variable in the literature. ...
Gyrate atrophy is a rare metabolic autosomal recessive disorder caused by ornithine aminotransferase enzyme deficiency that leads to characteristic progressive, degenerative chorioretinal findings. Patients complain mostly of low vision, night blindness, and peripheral vision loss. Posterior subcapsular cataract, myopia, choroid neovascularization, and intraretinal cysts may be accompanying factors related to vision loss. We encountered a patient with vision loss secondary to posterior subcapsular cataract and intraretinal cysts. After treatment with topical brinzolamide and nepafenac (and without any diet mo dification and/or supplementation), we observed 143- and 117-mm macular thickness resolutions with 2 and 1 Snellen lines of visual gain in his right and left eyes, respectively. Also, we detected a novel homozygous mutation in the ornithine aminotransferase gene: c.1253T>C (p.Leu418Pro). Carbonic anhydrase inhibitors and/or non-steroid anti-inflammatory drugs can control macular edema in patients with gyrate atrophy-associated intraretinal cysts. The genetic variants may also be a determinant in the responsiveness to the therapy type.
... Arginine restricted diet reduces the plasma ornithine level and slows the visual field problems but does not improve macular edema, if present. It has also been reported that if the diet started at an earlier age chorioretinal lesions will progress much slower (9,10). Because arginine is an essential amino acid, patients should not restrict arginine to complications like poor growth and skin problems. ...
... Arginine restricted diet reduces the plasma ornithine level and slows the visual field problems but does not improve macular edema, if present. It has also been reported that if the diet started at an earlier age chorioretinal lesions will progress much slower (9,10). Because arginine is an essential amino acid, patients should not restrict arginine to complications like poor growth and skin problems. ...
... Heller et al. [6] reported that the treatment with low protein intake and pyridoxine supplement may improve CME in GA patients. Contrary, protein restricted therapy resistant cases were reported [7]. Our patient was unable to administer protein restriction therapy due to economic reasons. ...
Purpose: Gyrate atrophy (GA) of the fundus is a rare, progressive metabolic disease secondary to the deficiency of the pyridoxal phosphate-dependent enzyme, ornithine aminotransferase. GA may lead to cystoid macular edema (CME) resulting from chronic inflammation. We aimed to report a child case with CME secondary to gyrate atrophy.
Methods: Herein we presented a GA case treated with posterior sub-Tenon triamcinolone acetonide injection.
Results: Optical coherence tomography examination revealed the disappearance of the macular edema that is a vision-threatening complication in GA.
Conclusion: The present case showed that the posterior sub-Tenon injection of long acting steroids might be a promising treatment in CME secondary to GA.
... Indeed, only a few cases of GA complicated by CME and initiated on arginine-restricted diet have been reported. [6][7][8][9] Feldman and colleagues 6 reported a 26-year-old woman with no changes in CME secondary to GA after 5 months of a low-protein diet. Katagiri and colleagues 7 reported 2 Japanese brothers affected by GA who went from virtually no clinically significant CME on initial OCT scan to significant CME on the long-term follow-up OCT scan, despite early initiation of arginine-restricted diet. ...
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.
... The prevalent theory suggests that retinal pigment epithelium (RPE) dysfunction leads to outer bloodretinal barrier (BRB) disruption which in turn leads to increased permeability and diffusion of fluid into the inner retina. 8, 9 Other possible mechanisms include failure of RPE pumping, [10][11][12][13] or tangential vitreous traction. 11 Treatments with carbonic anhydrase inhibitors, intra-vitreous (I-V) injections of anti-vascular endothelial growth factor (VEGF) antibodies, or steroids are all viable options; 11 however, for GA-related CME, available data are consisted of a single report that has demonstrated transient effect using intra-vitreous triamcinolone injection. ...
... 13 GA treatment involves restricting dietary arginine intake which limits the source of ornithine in the blood, [14][15][16] and for a fraction of "pyridoxine responders" patients, its supplementation is also adavantageous. [17][18][19][20][21][22][23] Notably, while these treatments were considered beneficial on the long-term progression rates of the atrophic lesions, 10,[14][15][16]24,25 their efficacy on CME has not been recognized to date. 10,25 In the present study, we have screened OAT for mutations in two unrelated families, and identified a novel splice site mutation. ...
... [17][18][19][20][21][22][23] Notably, while these treatments were considered beneficial on the long-term progression rates of the atrophic lesions, 10,[14][15][16]24,25 their efficacy on CME has not been recognized to date. 10,25 In the present study, we have screened OAT for mutations in two unrelated families, and identified a novel splice site mutation. c.900+1G>A. ...
Purpose:
This study reports the presentation of two families with gyrate atrophy (GA). The aim of this study was to characterize the potential effect of therapeutic regimens on macular edema.
Methods:
Two unrelated patients with GA were studied for the potential effect of low protein diet (≤ 0.8 g/kg/d), and oral administration of pyridoxine (500 mg/day), on serum ornithine levels, best corrected visual acuity (BCVA), slit-lamp, OCT, and auto-fluorescence findings. Blood samples for DNA, mRNA, and exons of the OAT gene were screened for mutations and splicing effect when relevant.
Results:
At presentation, both patients manifested typical ophthalmic features of GA including cystoid macular edema (CME). One patient also exhibited optic nerve head hamartoma. Following treatment ornithine levels have lessened, BCVA improved, and central macular thickness (CMT) markedly decreased in all four studied eyes. The molecular pathologic features included a novel splice site mutation (c.900+1G>A).
Conclusions:
We have identified a novel mutation and two formerly described mutations in patients with GA. Of them, one patient comprised an unusual phenotype including bilateral astrocytic hamartomas. We have recognized for the first time improvement in CME following treatment with low protein intake and pyridoxine supplement. This finding may have significance in the understanding of treatment options for macular edema regardless of underlying etiology.
Cystoid macular oedema (CMO), which is defined as a macular thickening and cystic changes due to accumulation of fluid, could be asymptomatic and only diagnosed using paraclinical techniques. Fluorescein angiography (FA) and optical coherence tomography (OCT) are useful in detecting CMO in clinical practice. Non-leaking CMO, also known as angiographically silent CMO, is referred to as cases of CMO without leakage in fluorescein angiography. This type of CMO has been reported in some retinal dystrophies, in cases of maculopathy as a side effect of certain drugs, and also in some systemic disorders. The exact mechanism and treatment options for this type of CMO are still not clear. This literature review aims to discuss different causes of non-leaking CMO, proposed mechanisms, and management options. Three sections including drugs, retinal dystrophies, and systemic disorders are discussed in this review.
