Overtreated Hypertension Results in Sequential Nonarteritic Ischemic Optic Neuropathy

doi: 10.62055/71746371Zg

ABSTRACT

BACKGROUND

Non-arteritic anterior ischemic neuropathy (NAION) is the most common optic neuropathy in patients over 50 years old, classically presenting as monocular vision loss with unilateral hemorrhagic disc edema and altitudinal field loss in an anatomically small optic nerve. Vascular disease causes arterial hypoperfusion to the anterior portion of the optic nerve resulting in ischemia, disc edema and a consequent compartment syndrome.²

CASE REPORT

A 78-year-old Caucasian male presented with clinical features consistent with a classic NAION in his right eye. This diagnosis was relayed to his medical providers and subsequently two of his four hypertensive medications were reduced. Three months later, he presented with features of an incipient NAION in his left eye that developed into a fulminant NAION with significant vision loss. Overtreated hypertension was deemed the cause of his bilateral, sequential NAION after an extensive work up was completed.

CONCLUSION

It is critical to know the natural history and expected presentation of NAION, as well as appropriate testing when atypical cases present. Communication with other medical providers is critical to remediate risk factors that can precipitate NAION.

Keywords: non-arteritic anterior ischemic optic neuropathy, hypertension, systemic disease

 

INTRODUCTION

Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common optic neuropathy of elderly patients and has a known association with systemic diseases including: diabetes, sleep apnea, hypertension, and particularly nocturnal hypotension. The classic presentation includes unilateral vision loss with hemorrhagic disc edema within anatomically small optic nerves, often described as ‘discs at risk.’ This case highlights a bilateral, sequential nonarteritic anterior ischemic optic neuropathy in the setting of symptomatic hypotension.

CASE REPORT

A 78-year-old Caucasian male reported to the eye clinic complaining of inferior visual field loss in his right eye when he woke up that morning. He had been seen four months prior for a complete dilated eye exam which was remarkable for: discs-at-risk (without evidence of disc drusen), bilateral pseudophakia with excellent acuity and congenital color blindness. The patient reported that his vision was normal the evening prior and upon awakening that morning the inferior portion of his vision in the right eye was missing. With review of additional symptoms, he denied new headache, numbness, tingling, weakness, aphasia or diplopia. He had not experienced transient vision loss, malaise, fever, scalp, neck or jaw pain.  He endorsed feeling lightheaded and dizzy, most significantly when waking in the morning, though attributed this to his recent back injury.

His medical history was significant for stage three chronic kidney disease with renal insufficiency and secondary anemia, hypertension, hyperlipidemia, gout, obstructive sleep apnea, obesity and prostate cancer treated with seed implants. He was managed on nifedipine 60 mg bid, hydralazine 100 mg tid, labetalol 200 mg tid, torsemide 10 mg daily, simvastatin 20 mg daily, allopurinol 300 mg daily and was compliant with nightly continuous positive airway pressure machine use.

Upon testing, he maintained 20/20 acuity in each eye and normal ocular motilities. Newly noted findings were inferior constriction on confrontation fields in the right eye only and a 1+ right afferent pupillary defect. The intraocular pressure was measured to be 16 mmHg OD and 18 mmHg OS by applanation tonometry. The right optic nerve was edematous with blurred disc margins, lack of a cup and a mild hyperemic appearance (Figure 1). This was confirmed by OCT imaging demonstrating nerve fiber layer thickening, more so superiorly (Figure 2). The optic nerve of the left eye was a small disc with a 0.25 cup-to-disc ratio and distinct margins.  The remainder of his dilated ocular health was unremarkable. Visual field testing revealed an inferior altitudinal defect in the right eye and a full visual field in the left eye (Figure 3).

 

 

 

Given the unilateral inferior altitudinal vision loss with afferent pupillary defect, hyperemic disc edema and a negative review of arteritic symptoms along with a disc at risk in the fellow eye, a diagnosis of non-arteritic anterior ischemic optic neuropathy OD was made. The patient’s report of dizziness upon awakening in conjunction with the NAION diagnosis were concerning for hypotension and this was communicated to the patient’s primary care provider and nephrologist. Subsequently, the dose of hydralazine was reduced from 100 mg tid to 25 mg bid and nifedipine from 60 mg bid to 30 mg daily; the other medications were unchanged. A 24-hour blood pressure monitor was ordered and demonstrated daytime systolic measurements of 93-150 mmHg and diastolic measurements of 44-72 mmHg. The nocturnal systolic readings were 134-163 mmHg and diastolic readings were 63-85 mmHg diastolic on this new medication regimen.

At his three-month follow-up he presented without visual complaints. His acuity remained 20/20 in each eye with inferior restriction on confrontation fields in the right eye and full in the left eye. There was a trace right afferent pupillary defect and improving optic nerve edema (Figure 4). However, the left optic nerve was now markedly edematous superiorly, with peripapillary hemorrhage and a small peripapillary cotton wool spot located superonasally (Figure 4). OCT imaging confirmed reduction in nerve fiber layer thickness OD and increased thickness OS compared to the prior images (Figure 5). Unfortunately, formal visual field testing was unreliable in the left eye with 56% false positive errors and 32% false negative errors.

Figure 4. (Left) Disc photos at three month follow-up show improving disc edema OD. (Right) superior disc edema OS.

 

 

With the evolution to bilateral involvement, it was critical to consider arteritic ischemic optic neuropathy, even in the absence of traditional symptoms. Cotton wool spots have rarely been reported with NAION, which further reinforced this concern. The patient had denied all symptomatology of giant cell arteritis and on exam, his bilateral temporal arteries were pulsatile. Reassuringly, his biomarkers were normal with an ESR of 29 mm/hr and CRP of 4.31 mg/L and platelet counts were within normal range.  Additional hematological testing was completed to rule out hypercoagulability and viscosity disease (Table 1). Neuroimaging was obtained with an MRI and MRA that were only significant for chronic microvascular ischemia. Therefore, the diagnosis of incipient NAION OS was made.

Hypotension was most likely the etiology of his bilateral sequential NAION particularly as his blood pressure remained erratic with daytime readings of 120-130 mmHg/75-80 mmHg, markedly lower upon awakening, ranging 109-117/51-57 mmHg with symptomatic lightheadedness. This development was communicated with the medical providers and subsequently torsemide was discontinued.

One month later, the left eye acuity worsened to 20/200 and there was a 1+ left afferent pupillary defect with markedly more disc edema to involve the nerve entirely (Figure 6). Over the course of multiple visits, the right optic nerve edema continued to improve leaving mild superior disc pallor with a final acuity of 20/25, dense inferior altitudinal field loss and significant nerve fiber layer thinning of the superior half of the nerve. The left optic nerve edema lessened at subsequent visits; the final acuity was 20/200 with overall peripheral loss and a 2+ left afferent pupillary defect. Interestingly, the left eye also developed subretinal fluid throughout the macula with residual outer retinal disruption which eventually resolved (Figure 7). Primary care and nephrology adjusted his hypertensive medications multiple times, which proved challenging given hypertensive episodes after medication reductions.

 

 

 

DISCUSSION

Nonarteritic anterior ischemic optic neuropathy (NAION) accounts for over three quarters of all anterior ischemic optic neuropathy cases and is the most common optic nerve disorder in patients over 50 years old.¹ The classic presentation constitutes reduced perfusion to the optic nerve resulting in unilateral disc edema with a hemorrhagic component, correlating with vision reduction, visual field loss in an altitudinal pattern, and an afferent pupillary defect.^2,3 The disc edema can worsen within the first few weeks due to compounding edema, typically resolves within six weeks, and is followed by disc pallor in the involved area. The range of vision loss is vast, from normal acuity to profound vision loss with significant visual field loss as well. The Ischemic Optic Neuropathy Decompression Trial found that in patients with vision worse than 20/64, almost half regained at least three lines of acuity within the first six months.⁴ Unfortunately, no treatment is available for NAION nor to prevent recurrence. Differentiating between arteritic and nonarteritic ischemic neuropathy and systemic risk factor management is essential.

The pathogenesis is not well understood but agreed to be multifactorial including reduced perfusion to the anterior optic nerve and an anatomically small disc size. Autoregulation of the posterior ciliary arteries can be disrupted by arteriosclerosis, hypertension, or vasoactive substances released from the ischemic tissue.³ This is often compounded by hypotensive episodes, anemia, and even blood loss. As this edema ensues, the crowded disc anatomy allows for a compartment syndrome of axonal and capillary bed compression due to swelling within the confined space at the optic nerve head, further disrupting the microcirculation of the nerve, worsening the ischemic edema.^2,3 The classic ‘disc at risk’ appearance is named such in that the structural crowding of a small disc is unable to tolerate this edema.

The systemic risk factors for NAION include atherosclerosis, sleep apnea, renal failure, diabetes, hypertension and nocturnal hypotension.² The crowded optic nerve with a small or absent physiological cup is documented in 82% of patients with NAION and considered to be the most significant ocular risk factor.² Optic disc drusen further crowds the optic nerve and should also be considered and ruled out in any small optic nerve.

The recurrence rate of NAION in the affected eye is uncommon likely due to atrophic loss of tissue resulting in decompression of the nerve.^2,5 Diabetes and worse baseline visual acuity considered to be risk factors.⁵ The lifetime risk of contralateral involvement in NAION has been reported as 30-40% and approximately 15% within 5-years from the initial episode.^5,6 Bilateral simultaneous cases are unlikely unless hypovolemic or perioperative, most associated with coronary-artery bypass grafting occurring in less than 1% of grafting surgeries.⁷ Hemodialysis is well documented to cause sequential NAION due to intradialytic hypotension, typically accompanied by anemia, resulting in poor perfusion and poor-quality blood, an ischemic duo.⁸ Sequential NAION has been reported with sildenafil use and even COVID-19 infection.^9,10

In this patient, the left optic nerve likely initially suffered an incipient NAION – the clinical features of disc edema without visual loss – that developed into a classic NAION with substantial vision loss. This distinct clinical entity is important to understand as asymptomatic unilateral disc edema can raise concern for alternative pathologies including non-ischemic central retinal vein occlusion or inflammatory optic neuropathy. Of patients with incipient NAION, 55% of the fellow eyes had a classic NAION, and 25% of the incipient eyes had progressed to classic NAION at six weeks. The risk of ipsilateral recurrence of incipient NAION is 20%, markedly higher than in classic NAION at 6.4%.¹¹ There is no documented systemic disease that is associated with progression from incipient to classic NAION.¹²

In bilateral NAION, the visual outcome in terms of acuity and visual field loss is similar between the initial and subsequent eye. In the Ischemic Optic Neuropathy Decompression Trial Follow-up Study approximately half of the patients’ acuity was within three lines of each other; only 30% of patients had an acuity difference greater than six lines.⁵ Given risk factor management is usually initiated or modified after the first NAION episode, it may be insightful to think the second eye should be of a milder nature and while that has been supported in the literature, there is also data to argue there is no predictive ability from the initial to subsequent NAION outcome.^5,13

The systemic profile of this patient is significant for multiple predisposing vascular risk factors including renal disease and OSA; there are no medication culprits, nor inciting events such as dialysis or surgery to cause his bilateral sequential presentation. Unfortunately, this patient suffered more significant vision loss with the second event likely due to persistent hypotension despite blood pressure medication reduction after the initial event. After the initial symptomatic right eye event, the dose of hydralazine was changed from 100 mg tid to 25 mg bid and nifedipine from 60 mg bid to 30 mg daily. Despite this significant reduction in treatment, symptomatic episodes of hypotension persisted hovering around 100/60 mmHg. Following the left eye involvement, further medication reductions were required including reducing labetalol from 200 mg tid to bid and torsemide 10 mg every morning to every other day. Being that he required additional lessening of his blood pressure medications after the initial event, it is feasible continued hypotension remained the main cause of the second eye involvement. Nocturnal diastolic arterial hypotension has been suggested as a cause of ipsilateral recurrence of NAION.¹¹ This patient had substantial peripheral vision loss in the right eye, but worse visual acuity loss in the left eye, with a left afferent pupillary defect. Initial measures to remediate risk factors are not always successful at impacting visual outcome in a sequential NAION.¹⁴

This case also highlights another unique presentation in the left eye – subretinal fluid in the macula region. Submacular fluid has been documented with NAION in the literature ranging from 3.49%  to 10.5% of patients without specific risk factors identified.^15,16 The typical course of resolution has been shown to be approximately one month.¹⁷ The suspected pathophysiology is fluid from the peripapillary choroid extends subretinally and can extend to the macula, likely with axoplasmic flow stasis contributing.¹⁵ Alternatively, local release of vascular endothelial growth factor may occur as a cause of the vasogenic disc edema and subsequently result in subretinal fluid.¹⁸  The visual acuity can be impacted by this edema, and often as the edema resolves, the vision improves.

CONCLUSION

While the classic presentation of NAION is well documented, it is important to know that bilateral presentations can occur. Being that hypotension was likely the primary cause for this patient’s bilateral sequential NAION, it serves as a reminder that patients with this diagnosis need to have interdisciplinary care involved to ensure they are managing their risk factors adequately. Communication with his primary care doctor, cardiologist, and nephrologist were critical to demonstrate his eye findings and correlation with systemic status as well as advocate for further management at the time the second eye was involved. In this patient’s case, four medication adjustments were required prior to reaching an appropriate regimen that managed his hypertension without causing hypotension. This case is unique because it highlights sequential NAION related to overtreated hypertension and secondary submacular fluid.

REFERENCES

1. Foster RC, Bhatti MT, Crum OM, Lesser ER, Hodge DO, Chen JJ. Reexamining the Incidence of Nonarteritic Anterior Ischemic Optic Neuropathy: A Rochester Epidemiology Project Study. J Neuro-Ophthalmol. 2024 Jul;00:1-5.
2. Biousse V, Newman N. Ischemic Optic Neuropathies. N Engl J Med. 2015 Jun; 372:2428-36.
3. Hayreh SS. Factors Influencing Blood Flow in the Optic Nerve Head. J Glaucoma. 1997 Jul;6:412-425.
4. Characteristics of patients with non arteritic anterior ischemic optic neuropathy eligible for the Ischemic Optic Neuropathy Decompression Trial. Arch Ophthalmol. 1996 Nov;114:1366-74.
5. Newman NJ, Scherer R, Langenberg P, Kelman S, Feldon S, Kaufman D, Dickersin K. Ischemic Optic Neuropathy Decompression Trial Research G: The fellow eye in NAION: report from the ischemic optic neuropathy decompression trial follow-up study. Am J Ophthalmol. 2002 Sep;134(3):317–328.
6. Beri M, Klugman MR, Kohler JA, Hayreh SS. Anterior ischemic optic neuropathy. VII. Incidence of bilaterality and various influencing factors. Ophthalmol. 1987 Aug;94:1020–1028.
7. Newman NJ. Perioperative visual loss after nonocular surgeries. Am J Ophthalmol. 2008 Apr;145:604-10.
8. Donaldson L, Freund P, Aslahi R, Margolin E. Dialysis-Associated Nonarteritic Anterior Ischemic Optic Neuropathy: A Case Series and Review. J Neuro-Ophthalmol. 2002 Mar;42(1):p e116-e123.
9. Moschos MM, Margetis I. Bilateral Simultaneous Anterior Ischemic Optic Neuropathy Associated with Sildenafil. Case Rep Ophthalmol. 2011 Mar; 2(2): 262–265.
10. Sanoria A,Jain, Arora R, Bharti N. Bilateral Sequential Non-Arteritic Optic Neuropathy Post-COVID-19. Indian J Ophthalmol. 2022 Feb; 70(2): 676–679.
11. Hayreh SS, Podhajsky PA, Zimmerman B. Ipsilateral recurrence of nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 2001 Nov;132:734–42.
12. Hayreh SS, Zimmerman MB. Incipient Nonarteritic Anterior Ischemic Optic Neuropathy. Ophthalmol. 2007 Sep; 114:1763-1772.
13. Hayreh SS, Zimmerman MB. Bilateral Nonarteritic Anterior Ischemic Optic Neuropathy: Comparison of Visual Outcome in the Two Eyes. J Neuroophthalmol. 2013 Dec;33(4):338-43.
14. Keren S, Zanolli M, Dotan G. Visual outcome following bilateral non-arteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis. BMC Ophthalmol. 2017 Aug;17:155.
15. Hedges TR III, Vuong LN, Gonzalez-Garcia AO, Mendoza-Santiesteban CE, Amaro-Quierza ML. Subretinal Fluid From Anterior Ischemic Optic Neuropathy Demonstrated by Optical Coherence Tomography. Arch Ophthalmol. 2008 Jun;126(6):812-815.
16. Donmez O, Kocaoglu G, Yaman A, Bajin MS, Saatci AO. Macular Evaluation With Spectral Domain Type Optic Coherence Tomography in Eyes with Acute Nonarteritic Ischemic Optic Neuropathy at the Presentation Visit. Open Ophthalmol J. 2017 Jan;11:17–23.
17. Molaie AM, Pramil V, Hedges TR III, Tomb LC, Vuong LN. Vitreoretinal Findings in Nonarteritic Ischemic Optic Neuropathy. J Neuroophthalmol 42(1):p e124-e129, Mar 2022.
18. Dave VP, Pappuru RR. An unusual presentation of non-arteritic ischemic optic neuropathy with subretinal fluid treated with intravitreal bevacizumab. Indian J Ophthalmol. 2016 Jan;64:87-8.