The Relationship between Intraocular Pressure and Optic Nerve Structural and Functional Damage in Patients with Optic Nerve Head Drusen

ABSTRACT

The aim of this retrospective study was to evaluate if, in ocular normotensive patients, at the time of diagnosis of optic nerve head drusen (ONHD), perimetric mean deviation (PMD) on visual field (VF) examination and retinal nerve fibre layer (RNFL) thickness on optical coherence tomography correlated with intraocular pressure (IOP). There was a significant association between IOP and PMD (Spearman’s rho = −0.863, p < .01) and between IOP and RNFL thickness (Spearman’s rho = −0.630, p < .01). A higher IOP was associated with a greater functional loss in the VF and a reduction in the RNFL thickness. These results suggest that a clinical trial of IOP reduction should be considered in patients with ONHD to decrease the progression of optic nerve damage over time.

Introduction

Optic nerve head drusen (ONHD) are calcified, congenital hyaline deposits that accumulate anterior to the lamina cribosa. They correspond to products resulting from the metabolism of ganglion cell axons.¹

ONHD are usually bilateral and are more prevalent in females and Caucasians.^2–4 Clinically, ONHD can present as optic disc elevation (pseudo-papilloedema) and blurred or tortuous disc margins. They are histologically present in 0.5–3.7% of the population but are clinically recognisable on fundus observation in only 0.3–0.4%. This discrepancy occurs because only 40% of ONHD are located on the surface of the optic nerve head.⁵

Possible and theoretical mechanisms to explain optic nerve axonal damage due to ONHD are: the direct mechanical compression induced by drusen on nerve fibres; abnormalities of axonal metabolism or transport and ischaemia. This damage will result in both structural and functional defects.⁶

In 24–87% of cases of ONHD, there are anomalies in the visual field (VF), mainly arcuate defects, blind spot enlargement, nasal step and constricted VFs.⁷

Some authors have proposed that lowering IOP in patients with ONHD may contribute to delaying the progression of optic nerve damage.^3,5,7,8

The purpose of this study was to assess if, at the time of diagnosis of ONHD in ocular normotensive patients, perimetric mean deviation (PMD) on VF examination and peri-papillary retinal nerve fibre layer (RNFL) thickness on optical coherence tomography (OCT) correlate with intraocular pressure (IOP).

Material and methods

This retrospective review included patients from a tertiary hospital, Centro Hospitalar São João, Oporto, Portugal who were diagnosed with ONHD between January 2016 and July 2019.

The inclusion criteria were a willingness to participate in the study, being aged over 12 years, having no complaints or history of sudden visual loss, and having a definitive diagnosis of ONHD. The diagnosis of ONHD was established due to clinical suspicion and then confirmed on fundus autofluorescence (FAF), B-mode ultrasonography (US) or optic nerve OCT via the enhanced depth imaging technique. ONHD were identified on OCT as hypo-reflective structures with full or partial hyper-reflective margins.

In patients with ONHD in both eyes, the eye with the worse visual field was chosen for further analysis.

The exclusion criteria included an unreliable VF (false negatives ≥33%, false positives ≥20% or fixation losses ≥20%), use of IOP-lowering therapy, central nervous system diseases, visual acuity that did not allow fixation, visually significant ocular co-morbidities, nystagmus, inability to co-operate with VF or OCT examination and an IOP ≥22 mmHg.

Best-corrected visual acuity was measured with a Snellen Chart. The IOP was determined by Goldmann applanation tonometry on a slit lamp, taking the average of three measurements, by the same experienced operator. All patients undertook achromatic computerised perimetry (Humphrey automated perimetry, Carl Zeiss Meditec AG, Jena, Germany) and an evaluation of peri-papillary RNFL thickness through OCT (Heidelberg Engineering, Heidelberg, Germany).

Data recorded from the initial visit included age, gender, eye, IOP, RNFL thickness, and PMD.

All statistical analyses were performed using SPSS Statistics V23 (IBM, Armonk, NY). Nonparametric Spearman’s rank test was used to examine a possible association between PMD or RNFL thickness and IOP (continuous variables). The level of statistical significance was set at p < .05.

Results

Thirty-six eyes from 36 patients met the inclusion criteria. 50.0% were females, and in 52.8% the ONHD was observed in the right eye (n = 19). The mean age was 49.4 years (range: 12–83 years).

The mean best corrected visual acuity was 0.9 (range 0.6–1.0). The mean IOP was 15.6 mmHg (range: 10–21 mmHg).

At the time of diagnosis 80.6% (n = 29) ONHD were visible on B-mode US, 33.3% (n = 12) on FAF and 27.8% (n = 10) on OCT.

The mean RNFL thickness was 86.5 μm (range: 49–129 μm). The average PMD was −4.3 dB (range −26.3 to +1.3 dB).

There were significant negative correlations between IOP and PMD (Spearman’s rho = −0.863, p < .01) (Figure 1) and between IOP and RNFL thickness (Spearman’s rho = −0.630, p < .01) (Figure 2).

Figure 1.

Scatterplot of perimetric mean deviation versus intraocular pressure.

Figure 2.

Scatterplot of retinal nerve fibre layer thickness versus intraocular pressure.

Discussion

The therapeutic approach to ONHD is determined by complications and progressive VF loss. The rate of progression of visual field loss has been estimated at 1.58% ± 0.28% each year.⁹

The pathophysiology of ONHD and associated VF loss is not completely understood. Most VF defects associated with the presence of ONHD may mimic those of glaucoma patients (arcuate defects and nasal steps), but despite the overlapping location of the disease and damage to the VF, the relationship between these two diseases remains uncertain. VF loss in patients with ONHD may have a vascular aetiology. Erkkilä and Lorentzen showed that patients with ONHD often had dilated veins and retinal arteries with pronounced tortuosity, abnormal early branching and vascular loops.^10,11

Besides that, Abegão Pinto et al. observed that patients with ONHD had low blood flow velocities in the vessels around the optic nerve head and these findings were similar in patients with glaucoma.¹² However, they observed that, unlike patients with glaucoma, in patients with ONHD, the central retinal artery blood flow velocity patterns correlated with the extent of the VF defect.¹² The explanation of these findings is unclear, but it is hypothesised that since the prelaminar portion of the optic disc head is relatively inexpansible, the presence of drusen may induce direct external compression on the surrounding retinal axons and vessels, and consequently a decrease in blood flow. However, it is unlikely that in glaucoma patients these findings are related to external compression, but to a not yet fully characterised vascular dysfunction. Having this vascular aetiology in mind, in theory, lowering IOP could improve optic nerve head perfusion pressure.^13,14

Some authors have proposed that decreasing IOP may delay the progression of optic nerve damage.^3,8,15 Out of the hypotensive drugs, it has been suggested that brimonidine should be the drug of choice because of its hypotensive and neuroprotective effects. However, the neuroprotective effect has only been demonstrated in animal models.¹⁶

Some authors, like Gripo et al. and Spalding, recommend lowering IOP in patients with ONHD and ocular hypertension since the existence of defects in the VF and its progression is greater when the two pathologies coexist. The harmful effect of elevated IOP on already damaged but functional retinal ganglion cells may accelerate the process of cell death leading to VF loss. The goal is to prevent further VF loss and improve blood flow.^7,17

Schargus and Gramer showed that patients taking IOP-lowering therapy had a slower progression of VF loss when compared with patients who did not take hypotensive therapy.¹⁸ Pojda-Wilczek and Wycislo-Gawron demonstrated that patients treated with brinzolamide for one year had less progression of optic nerve damage and better retinal ganglion cell function than patients who were not treated.⁵ However, Nolan et al. demonstrated that, at first observation, in normotensive eyes, there was no association between higher IOP and greater VF loss or reduced thickness of the RFNL, suggesting that decreasing IOP may not have an impact on delaying optic nerve damage.¹⁹

The available literature provides no consensus on the use of hypotensive therapy in ocular normotensive patients with ONHD.

In our study, we demonstrated that in ocular normotensive patients, at diagnosis, there was a correlation between loss of VF and reduction in RNFL thickness with the presence of higher IOP. These data, like some studies already mentioned, suggest that decreasing IOP may lead to delaying optic nerve damage and that IOP lowering agents may be useful to prevent sustained progression of VF loss over time.

Nevertheless, our study had some limitations: a small sample; each patient only performed one OCT and one VF; no evaluation of retinal ganglion cell layer was made; no corneal thickness measurement was enacted, and therefore the real IOP value may be different from that obtained.

Conclusion

Some authors suggest that lowering IOP can be useful in slowing progressive optic nerve damage in ONHD. In our study, we observed that in ocular normotensive eyes, at the first evaluation, a higher IOP was associated with functional loss of the VF, and with a reduction in the RNFL thickness. This suggests that a clinical trial of IOP reduction should be considered in patients with ONHD to decrease the progression of optic nerve damage over time.

Abbreviations

ONHD:

Optic nerve head drusen

VF:

Visual Field

IOP:

Intraocular Pressure

PMD:

perimetric mean deviation

RNFL:

retinal nerve fibre layer

OCT:

optical coherence tomography

FAF:

fundus autofluorescence

Authors’ contributions

Cláudia Oliveira-Ferreira, Mariana Leuzinger-Dias, João Tavares-Ferreira, and F. Falcão-Reis performed the literature research and collected the data. Olinda Faria examined the patients. All authors read and approved the manuscript.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declaration of interest statement

The authors report no conflicts of interest in this work.