Optic nerve head drusen (ONHD) are acellular hyaline deposits of calcium, amino and nucleic acids, and mucopolysaccharides, found in the prelaminar portion of the optic nerve head believed to arise from altered retinal ganglion cell (RGC) axoplasmic flow1,2. First described by Liebreich in 18683, ONHD have been reported to affect 0.4% to 20.4% of individuals.4ONHD may be difficult to detect in young patients, or confused with papilledema, as they tend to be buried beneath the surface of the optic disc, close to the lamina cribrosa5,6. Over time ONHD tend to enlarge and become located closer to the surface of the ONH, which acquires an irregular lumpy appearance7. While these changes typically occur slowly, in some patients ONHD can enlarge rapidly8.

Although ONHD are normally asymptomatic and detected incidentally, they are associated with visual field defects in up to 24% to 87% of affected adults1,7,9. The mechanism of ONHD-related visual field loss is poorly understood, however drusen typically enlarge slowly throughout life and this is often associated with slow progression of visual field loss1,7,9. Superficial ONHD are also more commonly associated with visual field defects than those located more deeply2. Despite the lack of quantitative longitudinal imaging studies, it is therefore seems likely that progressive field loss in patients with ONHD is due to progressive drusen enlargement.

Occasionally ONHD may be associated with rapid worsening of vision, with reported complications including choroidal neovascularization, serous maculopathy or acute vascular events such as central retinal arterial or venous occlusion or non-arteritic ischemic optic neuropathy101112. In the absence of these complications, there are no proven treatments for visual loss associated with ONHD.

It is hypothesized that ONHD-related visual field loss may occur as a result of mechanical stress on RGC axons within the prelaminar scleral canal resulting in retrograde axonal degradation and RGC death1,13. The mechanism of ONHD-related visual loss may therefore share some characteristics with glaucoma, in which RGC death is also believed to be due to interruption of retrograde axoplasmic flow14. This raises the possibility that treatments to lower intraocular pressure (IOP) might have a role in slowing visual field loss in patients with progressive ONHD-related field loss.

We present the case of a patient with bilateral ONHD with rapidly progressing visual field loss, who has had slowing of disease progression with topical IOP-lowering medication. The patient had extensive investigations to rule of out possible co-existing conditions that might have contributed to visual loss.

Despite rapid visual field loss over the preceding 12 months, the patient described in this case showed subjective and objective stabilization following instigation of IOP lowering medication. It is important to acknowledge that this is a single case and other patients may not respond similarly, however the cases raises the possibility that IOP-lowering may have a role in some patients with ONHD.

The mechanism of visual field loss in ONHD is poorly understood, however, it has been postulated that enlarging drusen may damage RGC axons directly through mechanical insult, or indirectly by compressing ONH vasculature leading to ischemia12. Therefore the suggested mechanism of visual loss in ONHD is not dissimilar from that believed to occur in the pathogenesis of glaucoma14. Progressive visual field loss is not infrequent15 with Mustonen and colleagues reporting visual field progression in 22% of patients with ONHD16. The rate of ONHD-related visual field loss is usually slow17, however our patient experienced a fast rate with a change in MD from -3.13 to -17.3 in the left eye and from -15.57 to – 22.50 in the right eye in just over 12 months.

Most previous cases of rapid visual loss in ONHD have been associated with an acute vascular event or choroidal neovascualarization. We performed FFA to investigate for secondary causes of visual loss and to look for disc leakage, however FFA was normal. Reduced amplitude and prolonged latency on the VEP, with a normal electroretinogram, suggested visual loss was due to an optic neuropathy. This is in agreement with previous studies, which have shown patients with ONHD to have prolonged latency on VEPs181920, a finding consistent with a mechanical compressive mechanism of axonal damage. The prolonged latency and reduced amplitude in our patient was likely due to the marked extent of the nerve damage 21. Although our patient had marked ONHD, as evident from the EDI-OCT, B scan ultrasonography and autofluorescence, it is not possible to be certain that ONHD was the sole cause of visual deterioration. It is conceivable that she also had coexisting normal tension glaucoma, however the rapid deterioration in visual field would not be characteristic of this condition. Given the difficulty of diagnosing glaucoma in patients with ONHD, and the possible increased risk of IOP-mediated RGC injury in an already compromised eye, we opted to treat our patient with topical IOP lowering medication7,22.

Discerning whether visual field loss is due to glaucoma or ONHD is challenging in eyes with confirmed ONHD, as drusen distort normal ONH anatomy, making detection of glaucomatous structural changes problematic. Furthermore, the pattern of visual field loss is not likely to be helpful in differentiating glaucomatous and ONHD-related visual losses, as the anatomical location of the pathology is similar. Although ONHD can lead to blind spot enlargement, which is not characteristic of glaucoma, drusen can also commonly result in glaucomatous-type defects such as nerve fibre bundle defects16,23.

Improvements in technologies such as EDI-OCT and Swept Source OCT might enable better identification of glaucomatous changes in eyes with ONHD as they allow imaging of deep ocular structures13,24,25. The ability of EDI-OCT to image structures 500-800 um deeper than conventional OCT allows the posterior limit of the drusen to be imaged13. Several studies have recently shown that using EDI-OCT or Swept Source OCT it is possible to visualise the extent of ONHD and to examine the thickness of neighbouring neural tissue13. Our patient had marked RNFL loss on SDOCT, particularly in the right eye. The RNFL thickness was outside normal limits, however, normative databases should be interpreted with caution in eyes with ONHD particularly as the risk of segmentation errors is likely to be higher due to abnormal anatomy. Although glaucomatous RNFL thinning characteristically involves the inferior-temporal and superior-temporal circumpapillary RNFL, the pattern of RNFL loss may not help differentiate whether this is related to ONHD or glaucoma as the location of RNFL defects associated with ONHD is likely to vary depending on location of the ONHD.

There is little previous literature regarding the coexistence of glaucoma and ONHD, however, Samples and colleagues reported a small cases series of 5 patients22. The authors concluded that keeping the IOP as low as possible was advisable due to the difficulty of monitoring optic nerve changes. Mamikonian and colleagues examined 35 eyes of 21 patients with ONHD, of which 8 eyes also had glaucoma. Patients with glaucoma were found to have significantly reduced ocular blood flow compared to controls, suggesting ocular blood flow might be useful in differentiating these conditions26. However, some eyes with ONHD also have impaired blood flow as evident from the increased risk of ocular vascular events. In an additional manuscript, Roh and colleagues presented 2 cases of combined ONHD and glaucoma where both patients had significant RNFL thinning on time domain-OCT. One of the patients had glaucoma in both eyes but ONHD only in one eye. RNFL thinning was more pronounced in the eye with ONHD, which was suggested to be a result of a possible synergistic effect of both conditions in damaging the RNFL27.

An interesting consideration is whether ONHD might increase the likelihood of glaucoma. It has been proposed that structural differences within the ONH could contribute to individual susceptibility to IOP-mediated damage in glaucoma. Eyes with a particular combination of ONH anatomy, mechanical strength or blood supply may be more susceptible to damage at normal levels of IOP, whereas others may be less vulnerable28. Recent studies have shown that IOP elevation results in displacement of the lamina cribrosa and expansion of the scleral canal 29. Eyes that are less able to dampen IOP changes are likely to be higher risk of RGC loss due to mechanical pressure on RGC axons passing through the lamina pores. It is likely that eyes with ONHD may be less able to dampen IOP changes, potentially exposing RGCs to greater mechanical strain, perhaps at levels of IOP that are normally physiological. Other authors have recognised the importance of biomechanical factors in ONHD-related visual loss and it has been proposed that patients with ONHD and congenitally small scleral canals might be at higher risk of visual loss due to lack of space for enlarging drusen30.

In conclusion, rapid visual loss is uncommon in patients with ONHD but may due to an acute vascular event, choroidal neovascular membrane or non-arteritic ischemic optic neuropathy. Our patient had none of the above, but nonetheless had rapid loss of visual field over 12 months following initial presentation. Although we could not conclusively establish a diagnosis of glaucoma, objective and subjective measures of vision have stabilised since she was commenced on IOP-lowering topical medication. Structural differences within the ONH are likely to contribute to individual susceptibility to IOP-mediated damage and we propose that ONH with ONHD may be less able to dampen IOP stress and strain contributing to loss of RGCs in these patients. IOP-lowering should be considered as a treatment option if other causes of visual loss have been excluded.

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

AION: Anterior ischaemic optic neuropathy

EDI: Enhanced depth imaging

FFA: Fundus fluorescein angiography

IOP: Intraocular pressure

MD: Mean deviation

ONHD: Optic nerve head drusen

RGC: Retinal ganglion cell

RNFL: Retinal nerve fibre layer

SAP: Standard automated perimetry

VEP: Visual evoked potential

KE: Data collection, reviewing the literature, preparing the illustrations and figures and drafting the manuscript

AT: Revising the manuscript critically for important intellectual content and giving final approval of the version to be published

NHS Scotland Career Research Fellowship (AJT)

The author(s) have made the following disclosure(s): A.J.T. – research support from Heidelberg Engineering