|Year : 2023 | Volume
| Issue : 1 | Page : 20
Kjer's optic neuropathy
Lucas Pinheiro Machado Teles1, Lyara Meira Marinho Gindri1, Nathalie Stéphanie Meneguette2, Eric Pinheiro de Andrade1
1 Department of Ophthalmology of State Public Servant Hospital (HSPE), Institute of Medical Assistance to the State Public Servant (IAMSPE), São Paulo, SP, Brazil
2 Department of Ophthalmology, Provisão – Eye Hospital of Maringá, Maringá, PR, Brazil
|Date of Submission||19-Apr-2023|
|Date of Decision||24-Apr-2023|
|Date of Acceptance||28-Apr-2023|
|Date of Web Publication||27-Jun-2023|
Lucas Pinheiro Machado Teles
Fagundes Filho Avenue, 830, São Paulo, SP
Source of Support: None, Conflict of Interest: None
Kjer's optic neuropathy, also known as optic atrophy type 1 (OPA-1), is a genetic condition that usually presents with the bilateral pallor of the optic disc (OD) associated with decreased visual acuity (VA), in addition to defects in the visual field (VF) and color vision. This article aims to report a case of OPA-1 diagnosed through genetic testing. A 22-year-old male patient searched for neuro-ophthalmological care, complaining of low VA, difficulty adapting to both light and dark, and photophobia in both eyes (BE) since 6 years old. He denies VF loss, nyctalopia, or hearing deficit and has maternal relatives with similar conditions. The patient presented VA of 20/63 in the right eye (RE) and 20/50 in the left eye (LE) with dyschromatopsia and bilateral OD pallor, in addition to reduced foveal brightness. Humphrey's visual perimetry showed centrocecal scotoma in the LE only and a nonspecific loss in the RE. He brought a pattern electroretinography (PERG) examination showing the reduced function of ganglion cells in the macular area and optic nerve in BE and multifocal electroretinogram with cone system function slightly reduced in BE. A genetic panel was performed to search for mutations in the OPA-1 gene, which showed a variant associated with this disease in the patient described and in his mother. Thus, this report exemplifies a case of OPA-1 hereditary OPA, emphasizing the importance of combining clinical evaluation, electrophysiological, and genetic tests for a precise and accurate diagnosis.
Keywords: Genetic counseling, optic atrophy, visual acuity
|How to cite this article:|
Machado Teles LP, Marinho Gindri LM, Meneguette NS, de Andrade EP. Kjer's optic neuropathy. Pan Am J Ophthalmol 2023;5:20
| Introduction|| |
Kjer's optic neuropathy, also known as optic atrophy type 1 (OPA-1), is a genetic condition that was first described in the late 50s, by Kjer, in a study on Danish families. Patients affected by this condition usually present with bilateral and symmetrical pallor of the optic nerve associated with an insidious decrease in visual acuity (VA) (usually between 4 and 6 years old), visual field (VF), and color vision defects. The diagnosis of OPA-1 is made based on a combination of clinical findings, electrophysiological studies, and family history and/or by identifying a heterozygous pathogenic variant in OPA-1, and the only gene known to be associated with OPA-1, by molecular genetic testing. Treatment of the disease is based on the patient's clinical findings, and it is mandatory to establish the extent of the disease. This article aims to report a case of Kjer-type optic neuropathy, also called OPA-1, diagnosed through all available tools – typical clinical findings, electrophysiological examinations, and genetic testing.
| Case Report|| |
A 22-year-old male patient searched for the Neuro-Ophthalmology sector of the HSPE-IAMSPE with progressive low VA (LVA), difficulty adapting to light/dark, and mild photophobia in both eyes (BE) since 6 years old. He denies VF loss, nyctalopia, or hearing deficit. Presents acne and allergic rhinitis as previous pathologies. He also reports two maternal uncles and his mother all with a history of low VA without apparent cause since childhood. There were no reports of consanguinity in the family. On examination, he presented corrected VA, with the early treatment diabetic retinopathy study (ETDRS) chart, of 20/63 in the right eye (RE) and 20/50 in the left eye (LE), without improvement with pinhole and dyschromatopsia in BE; extraocular motricity, pupillary reflexes, and biomicroscopy of the anterior segment without alterations in BE; and intraocular pressure of 16 mmHg (at 2 pm) in BE; fundoscopy with bilateral optic disc (OD) pallor, more evident temporally, in addition to reduced macular brightness. Humphrey's VF showed a centrocecal scotoma on the LE and a nonspecific loss on the RE [Figure 1]. Pattern electroretinography (PERG) was performed, showing reduced macular and optic nerve ganglion cell function in BE, and a multifocal electroretinogram demonstrated a reduction in macular function in BE [Figure 2]. A genetic panel was then requested to search for mutations in the OPA-1 gene, which showed a variant associated with this disease in the patient described and his mother [Figure 3].
|Figure 1: Humphrey's visual field showing a centrocecal scotoma on the LE. LE: Left eye|
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|Figure 2: mfERG with macular function reduced in BE and a PERG demonstrating reduced macular and optic nerve ganglion cell function in BE. mfERG: Multifocal electroretinogram, BE: Both eyes, PERG: Pattern electroretinography|
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|Figure 3: Genetic test showing a variant associated with this disease in the patient described|
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| Discussion|| |
Kjer's optic neuropathy or dominant OPA is the most common form of hereditary optic neuropathy with an estimated disease prevalence between 0.01% and 0.002%., This condition usually affects children and adolescents, and half of the individuals present clinical manifestations before the age of 10.
It is well known that the most typical clinical features of this disease are decrease in VA, changes in VF, such as centrocecal, paracentral, or central defects, and changes in color vision as well, the most common being blue-yellow loss (tritanopia). In the ophthalmological examination, findings such as pallor in the OD and changes in macular brightness are usually noted. Furthermore, up to 10% of patients with this condition may have extra-ophthalmological findings, such as sensorineural hearing loss, ataxia, and myopathy. When it comes to LVA, this can vary greatly according to the current literature, and most individuals with this pathology have moderate visual loss (VA between 20/30 and 20/100) and only 15% of patients affected by OPA-1 have VA <20/200. In the patient reported in this work, the visual loss was moderate, VA in the RE of 20/63 and the LE of 20/50.
As for VF defects, the most common are centrocecal, central, or paracentral defects, usually in patients with the most severe form of the disease. In the individual in question, there was a centrocecal scotoma in the LE, in addition to nonspecific loss in the RE.
The color vision alteration most associated with OPA-1 is tritanopia (blue–yellow loss)., The patient in this case, in slight disagreement with the literature, had diffuse difficulty in perceiving and differentiating colors.
The pallor of the OD, which reflects the atrophy of this structure, can be diffuse or temporally localized – as in the case in question – and varies in intensity, from mild to intense., Extraocular manifestations, such as sensorineural hearing loss, ataxia, or myopathy, are observed in only 1/10 of the patients and were not present in the patient described.
Extraocular manifestations, such as sensorineural hearing loss, ataxia, or myopathy, are observed in only 1/10 of the patients and were not present in the patient described.
For more confidence in the diagnosis, ruling out other pathologies that cause optic nerve atrophy is important. The main differential diagnoses are Leber hereditary optic neuropathy, Leigh syndrome, Costeff OPA syndrome, normal-tension glaucoma, and nutritional deficiencies. The patient in question had most of these diagnoses refuted, both through biomicroscopic physical examination and visual perimetry (normal-tension glaucoma) and genetic tests (Leber hereditary optic neuropathy and Leigh syndrome).,
Genetic tests, if available, are extremely important for guidance and counseling for patients affected by Kjer's optic neuropathy., In the reported patient and his mother, there was diagnostic confirmation through a specific genetic test that detected, in both of them, pathogenic variants associated with this condition.
Although several treatment options have been examined for the management of OPA-1, including vitamin supplements, ubiquinone analogs (in particular, idebenone), and, more recently, gene therapy, more evidence from clinical trials is needed.
| Conclusion|| |
The present report demonstrates a case of Kjer's optic neuropathy, emphasizing the importance of combining clinical evaluation, electrophysiological studies, and genetic tests to define the etiological diagnosis and enable proper clinical follow-up and genetic counseling.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In this case, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]