Wednesday, June 7, 2023
Molecular Genetic Profile of our DOA Cohort
Distribution of RNFL Indices for Our OPA1 Cohort
RNFL Thickness Data for OPA1 Patients and Normal Controls
Comparison of RNFL Thickness Between Pure DOA and DOA + Subgroups
This activity is intended for primary care clinicians, ophthalmologists, and other specialists who care for patients with DOA.
The goal of this activity is to review features of DOA and RGC loss in patients with the pure and syndromal forms of DOA.
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CME Released: 3/4/2011
Valid for credit through: 3/4/2012
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Purpose. The majority of patients with autosomal dominant optic atrophy (DOA) harbour pathogenic OPA1 mutations. Although DOA is characterised by the preferential loss of retinal ganglion cells (RGCs), about 20% of patients
with OPA1 mutations will develop a more severe disease variant (DOA +), with additional neuromuscular features. In this prospective,
observational case series, optical coherence tomography (OCT) was used to define the pattern of retinal nerve fibre layer
(RNFL) loss in patients with both the pure and syndromal forms of DOA.
Methods. Forty patients with a molecular diagnosis of DOA due to OPA1 mutations were prospectively recruited from our neuro-ophthalmology clinic: 26 patients with isolated optic atrophy and 14
patients manifesting DOA + features. Peripapillary RNFL thickness was measured with the Fast RNFL (3.4) acquisition protocol
on a Stratus OCT.
Results. There was a statistically significant reduction in average RNFL thickness in the OPA1 group compared with normal controls (P<0.0001). The percentage decrease was greatest in the temporal quadrant (59.0%), followed by the inferior (49.6%), superior
(41.8%), and nasal (25.9%) quadrants. Patients with DOA + features had worse visual outcomes compared with patients with pure
DOA. Except in the temporal quadrant, RNFL measurements were significantly thinner for the DOA + group. There was an inverse
correlation between average RNFL thickness and logarithm of the minimum angle of resolution (LogMAR) visual acuity (P<0.0001).
Conclusions. RGC loss in DOA is characterised by severe involvement of the temporal papillomacular bundle, with relative sparing of the
nasal fibres. RNFL thinning is more pronounced in patients with DOA + phenotypes.
Autosomal dominant optic atrophy (DOA, OMIM 605290) has an insidious onset in early childhood and it classically presents with bilateral, symmetrical, central visual loss and dyschromatopsia.[1,2] About 60% of families harbour mutations in the OPA1 gene (3q28-q29), and over 200 pathogenic mutations have been reported with mutational hotspots in the GTPase and dynamin central domains.[3,4] DOA is the most common inherited optic nerve disorder seen in the general population,[5,6] and the majority of patients experience significant visual morbidity owing to progressive retinal ganglion cell (RGC) loss.[7,8] Although the primary site of pathology is the RGC layer, up to 20% of patients with OPA1 mutations will also develop additional neuromuscular deficits, and we recently described the expanding clinical phenotypes associated with these complicated DOA + variants.[9-11] Sensorineural deafness was the most frequently observed extraocular feature, followed by chronic progressive external ophthalmoplegia, myopathy, ataxia, and peripheral neuropathy.[9]
The development of optical coherence tomography (OCT) has made it possible to quantify accurately the thickness of the retinal nerve fibre layer (RNFL) around the optic disc.[12,13] This technology is currently being investigated in the management of glaucoma[14,15] and other neuro-ophthalmological disorders such as multiple sclerosis[16-18] and idiopathic intracranial hypertension.[19] In this study, OCT imaging was used to compare the pattern of RGC loss in OPA1 patients with both the pure and syndromal forms of DOA, and to document the progression of RNFL thickness with disease duration.
