Optic disc drusen are calcified deposits of extruded mitochondria that appear in the optic nerve head in approximately 2% of the population (1,2). Patients often are noted to have elevated optic discs found incidentally on routine examination and are referred for neuro-ophthalmic evaluation. Optic disc drusen can be buried and/or superficial. If buried, they may be difficult to identify by direct visualization with additional testing required, including B-scan ultrasonography, optical coherence tomography (OCT), and autofluorescence fundus imaging (3).
While retinal nerve fiber layer loss with resulting visual field deficits (4) and, less commonly, reduced visual acuity (5), have been reported with optic disc drusen, the pathophysiology of these events remains speculative. We report the OCT angiography (OCT-A) findings in a patient with visually significant optic disc drusen and retinal nerve fiber layer thinning. OCT-A revealed novel insights into the superficial microvasculature of the optic nerve head associated with the optic disc drusen.
A woman in her fifth decade of life with a known history of optic disc drusen, found incidentally at the age of 14 years, was evaluated 1 year after experiencing sudden painless visual loss in her right eye. She described a central “grey” or “whitish” area in the visual field of her right eye that was constant. She was otherwise healthy. The patient was using topical latanoprost drops in each eye nightly and 81 mg aspirin daily, as advised by her ophthalmologist. Contrast-enhanced magnetic resonance imaging of the orbits and neck done 1 year previously was normal.
Examination revealed visual acuities of 20/30, right eye and 20/15, left eye. Color vision (Ishihara plates) testing showed no dyschromatopsia. Amsler grid testing, pupillary reactions and slit-lamp examinations were all normal. Funduscopic examination revealed bilateral optic disc elevation with extensive optic disc drusen and peripapillary atrophy (Fig. 1). Automated (Humphrey 24-2) perimetry showed central loss in the right eye and superior field loss in the left eye (Fig. 2). OCT demonstrated segmental retinal nerve fiber layer thinning in each eye (Fig. 3A), whereas retinal ganglion cell layer segmentation revealed focal bilateral macular thinning (Fig. 3B).
OCT-A of the right optic disc revealed drop-out in the radial peripapillary capillary plexus corresponding to the papillomacular bundle in the right eye (Fig. 4A, B). There were no visible drusen directly over or underlying this region. There was a significant blockage effect imparted by the drusen in the deeper lamina (Fig. 4C, D). There were areas of focal superficial retinal capillary network attenuation in both optic discs that corresponded to the location of superficial optic disc drusen (Fig. 5). The density of the capillary network was decreased, but the capillaries that remained seemed of normal caliber and with similar clarity compared with regions not directly associated with drusen. OCT-A of the right eye revealed extension of the wedge-shaped region of the superficial retinal capillary plexus attenuation into the fovea (Fig. 4B). In the left eye, there was focal attenuation of the retinal microvasculature (Fig. 6A) corresponding to the area of retinal ganglion cell layer thinning inferotemporal to the fovea (Fig. 3D). Laminar analysis revealed that this attenuation was in the superficial retinal capillary plexus (Fig. 6B) but not in the deep retina capillary plexus or the choriocapillaris (Fig. 6C, D).
Little is known about the microvascular changes associated with optic disc drusen. To this point, fluorescein angiography has not been helpful in answering this question because the resolution is inadequate to reliably image the radial capillary plexus (6). In contrast, OCT-A provides a noninvasive mode for laminar analysis of the microvasculature with micrometer precision (7,8).
Whether drusen cause retinal nerve fiber injury directly through axonal compression or indirectly through vascular compression and nerve fiber layer ischemia remains controversial. It has long been hypothesized that the step-wise pattern of visual field loss supports a vascular mechanism (5). Superficial drusen are more likely than buried drusen to cause focal retinal nerve fiber layer thinning and visual field defects (4). Anterior migration and/or growth of optic disc drusen could impart progressive compressive stress on the superficial microvasculature of the optic nerve head.
In our patient, OCT-A analysis of the superficial capillary plexus of the optic disc revealed focal attenuation associated with the more prominent and superficial optic disc drusen. The distribution of these drusen correlated with the pattern of retinal nerve fiber layer thinning in each eye. For example, in the left eye, the microvascular attenuation was greatest in the inferotemporal sector corresponding to large superficial drusen and reflected in the distribution of macular ganglion cell layer thinning and the patient's superonasal visual field defect. It is unlikely that these changes represent blockage artifacts and B-scan images excluded focal failure of the segmentation algorithm as an explanation for these findings. The attenuation of the capillary signal on OCT-A could represent compression or displacement of the capillary network by drusen. Whether these microvascular changes result in ischemia of the retinal nerve fiber layer, or represent secondary displacement by drusen remains uncertain.
Our patient experienced reduction in visual acuity in her right eye that was likely because of nonarteritic anterior ischemic optic neuropathy. Patients with optic disc drusen have an increased risk of developing ischemic optic neuropathy (3). There was attenuation of the superficial radial peripapillary capillaries evident on OCT-A analysis that extended from the temporal side of the disc to the right macula, corresponding to ganglion cell layer thinning most prominent in the superonasal perifoveal region. Similar correspondence between capillary drop-out on OCT-A analysis and retinal nerve fiber layer thinning has been reported in glaucoma (9,10).
The increased risk of vascular occlusive diseases associated with optic nerve head drusen, including anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion (3,11), is consistent with vascular alterations on a larger scale. Abego Pinto et al (12) measured lower systolic and diastolic flow velocities using retrobulbar Doppler ultrasound in the central retinal artery of eyes with optic disc drusen. Similar findings were detected in short ciliary arteries. In addition, visual field loss correlated with the degree of these flow changes in patients with optic disc drusen.
Patients with optic disc drusen show retinal vascular changes, including increased venous branching in close proximity to the disc margin compared to controls (13). Since retinal vascular development precedes formation of optic disc drusen, it has been postulated that these venous changes predispose to drusen formation. One might argue that the microvascular changes seen on OCT-A analysis contribute to drusen formation rather than represent an effect of their presence, growth, or migration. However, microvascular attenuation was not associated with all drusen, arguing against this hypothesis. In addition, electron microscopic analysis of optic disc drusen has shown vascular changes, including disruption of the blood-retinal barrier (2). But since these changes are not seen in all optic nerves with drusen, they are unlikely to underlie the pathogenesis of drusen formation. There are examples of drusen with associated microvascular attenuation that do not correspond to any thinning of the retinal nerve fiber layer. In our patient, these include the superficial druse at 7 o'clock in the right eye and the large superficial drusen complex in the left eye (Fig. 5). These examples support the notion that vascular attenuation precedes retinal nerve fiber loss and are consistent with a causal relationship. However, there may be other mechanisms for visual loss in patients with optic disc drusen that are not captured in our patient. Correlation between visual and/or nerve fiber layer loss and these microvascular changes in more patients and longitudinally within patients will serve to characterize how microvascular alterations relate to nerve fiber layer loss in the presence of optic disc drusen.
STATEMENT OF AUTHORSHIP
Category 1: a. Conception and design: E. D. Gaier, J. B. Miller, and D. M. Cestari; b. Acquisition of data: E. D. Gaier, J. B. Miller, and J. F. Rizzo; c. Analysis and interpretation of data: E. D. Gaier and J. B. Miller. Category 2: a. Drafting the manuscript: E. D. Gaier; b. Revising it for intellectual content: E. D. Gaier, J. B. Miller, J. F. Rizzo, and D. M. Cestari. Category 3: a. Final approval of the completed manuscript: E. D. Gaier, J. B. Miller, J. F. Rizzo, and D. M. Cestari.
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