Man presents with constant headache, worsening vision

Both eyes showed flamed-shaped hemorrhages and macular exudates on fundus examination.

Issue: February 10, 2009

ByMatthew Lazzara, MD

ByCaroline R. Baumal, MD

Jeffrey Chang

Vivek Chaturvedi

A 36-year-old Brazilian man presented to the New England Eye Center with his first episode of a constant headache and worsening vision in both eyes over the course of 1 month.

He initially saw a practitioner of traditional Chinese medicine and was given unknown herbal medications. Over the course of 1 month, the patient then noted progressive worsening of his vision, left greater than right, at both distance and near.

His medical and ocular histories were unremarkable, and he denied use of prescription medications or illicit drugs. The patient’s family history was significant only for treated hypertension in his father. Review of systems was negative for fatigue, rash, cough, shortness of breath, gastrointestinal symptoms and joint pain.

Examination

On examination, visual acuity in the right eye was 20/80, improving to 20/70 with pinhole, and in the left eye count fingers at 6 feet, improving to 20/400 with pinhole. The patient’s pupils were round and reactive with no relative afferent pupillary defect. Extraocular movements were full, and confrontational visual fields revealed no defects. Applanation tonometry readings were 12 mm Hg in both eyes.

Anterior segment examination was unremarkable in either eye. Dilated fundus exam of the right eye showed four quadrants of flame-shaped hemorrhages, nerve fiber layer infarcts, obscuration of the optic disc margins and macular exudates with subretinal fluid in the posterior pole (Figure 1a). Similarly, in the left eye, exam revealed flame-shaped hemorrhages and cotton-wool spots in all fours quadrants along with optic disc edema, posterior pole subretinal fluid and macular exudates (Figure 1b).

Color fundus photograph, right eye.

Color fundus photograph, left eye. Both photographs demonstrate four quadrants of flame-shaped hemorrhages, nerve fiber layer infarcts, obscuration of the optic disc margins and macular exudates with subretinal fluid in the posterior pole.

Images: Lazzara M, Baumal CR

What is your diagnosis?

Headache, worsening vision

Malignant hypertension is a rare syndrome defined clinically as severe hypertension with secondary retinal, choroidal and optic nerve changes.

Discussion

The actual pathogenesis involves changes in the vascular pathways as a result of, or in response to, the extreme pressures, which leads to obstruction of arterioles and breakdown of the blood-retinal barrier. As opposed to chronic hypertensive retinopathy, ocular symptoms are common and include headache, scotoma, diplopia, dimness in vision and photopsias.

While somewhat dependent on baseline levels, the blood pressure associated with these more dramatic changes generally include a systolic pressure greater than 200 mm Hg and/or a diastolic pressure greater than 140 mm Hg. Systemic causes include renal disease, adrenal disease, pheochromocytoma, coarctation of the aorta and pregnancy.

The most prominent changes on fundus exam include retinal arteriolar spasm, superficial retinal hemorrhages, cotton-wool spots, serous retinal detachment and optic disc edema. The clinical narrowing of arterioles – whether true or “pseudo-narrowing,” as demonstrated by Hayreh – is often dramatic relative to engorged venous vessels obstructed at the site of nerve head swelling. Kimura and others found prominent pericytic degeneration on examination of postmortem retinal capillaries via electron microscope.

This loss of wall integrity of the capillaries is likely what leads to periarteriolar intraretinal transudates – tan/white retinal lesions pinpoint to one-quarter disc-diameter in size in the posterior retina. In his rhesus monkey model of renovascular malignant arterial hypertension, Hayreh found that these lesions, along with superficial retinal hemorrhages, were the first changes clinically evident. Cotton-wool spots represent infarction of the nerve fiber layer causing permanent defects, although they clinically resolve within 3 to 6 weeks.

Hypertensive choroidopathy includes retinal pigment epithelium (RPE) changes and delayed choroidal filling seen on fluorescein angiography from compensatory vasoconstriction of the choroidal vessels. This leads to marked secondary retinal edema and subretinal fluid from both an incompetent RPE and a pressure gradient pushing fluid into the outer retina. Specific findings include Elschnig’s spots, punctate tan/white lesions of necrotic and/or atrophied RPE that leak fluid on fluorescein angiogram and indocyanine green. Siegrist’s streaks are similar pigmentary changes running parallel to choroidal arteries.

In a similar manner, vasoconstriction of the posterior ciliary arteries supplying the anterior optic nerve leads to disc swelling via disruption of axoplasmic flow — a form of anterior ischemic optic neuropathy. It is felt that this finding correlates more closely with the duration of elevated blood pressure rather than its degree.

Management

Once end-organ damage from malignant hypertension is evident (encephalopathy/cerebrovascular accident, acute congestive heart failure/myocardial infarction, hematuria), management includes slow, meticulous lowering of blood pressure in a monitored setting, generally the ICU. Early, astute diagnosis is critical, as nearly 90% of untreated patients will die within 1 year. With treatment, survival has been reported as high as 90% at 40 to 52 months. Specific ophthalmologic interventions are not indicated, and most patients’ vision returns to normal. Permanent vision loss, if it occurs, is most likely the result of optic nerve damage or RPE changes after a retinal detachment.

Our patient’s blood pressure was found to be 220/160 mm Hg in the eye clinic, and he was immediately transferred to the emergency department for care of this hypertensive emergency. His blood pressure was controlled on labetalol and lisinopril. His workup included a urine toxicology screen, which was negative. Urinalysis revealed 3+ proteinuria and blood without red blood cell casts. Magnetic resonance angiography (MRA) of the renal arteries showed 30% to 50% stenosis bilaterally – not enough to cause this degree of hypertension and likely subsequent changes from severe blood pressure elevation. A renal biopsy was performed because of renal failure of unknown etiology with a normal MRA. A diagnosis of IgA nephropathy was made after renal biopsy confirmed diffuse, global glomerulosclerosis and severe vasculopathy with 3+ IgA staining. On further questioning, the patient revealed a history of recurrent hematuria while in his 20s.

IgA nephropathy has been found to be the most frequent cause of idiopathic (primary) glomerulosclerosis in the developed world. The classic presentation is hematuria after an upper respiratory infection, but it more commonly presents as asymptomatic hematuria and rarely as malignant hypertension. Nearly 50% of patients will progress to end-stage renal disease. Most ocular findings are attributable to hypertension and renal disease; however, there have been case reports suggesting an association with scleritis.

This patient has been seen twice in clinic since his initial presentation and has shown slow improvement in visual acuity, with a best corrected visual acuity of 20/70 in the right eye and 20/50 in the left eye at 6 weeks follow-up. Further improvement is expected, as some subretinal fluid and edema remain evident on optical coherence tomography.

References:

Colville D, Savige J, Branley P, Wilson D. Ocular abnormalities in thin basement membrane disease. Br J Ophthalmol. 1997;81(5):373-377.

Hayreh SS, Servais GE, Virdi PS. Fundus lesions in malignant hypertension. V. Hypertensive optic neuropathy. Ophthalmology. 1986;93(1):74-87.

Kimura T, Mozota A, Fujimoto N, Tsuyama Y. Light and electron microscopic studies on human retinal vessels of patients with sclerosis and hypertension. Int Ophthalmol. 2005;26(4-5):151-158.

Nomoto Y, Sakai H, Endoh M, Tomino Y. Scleritis and IgA nephropathy. Arch Intern Med. 1980;140(6):783-785.

Rogers AH. Hypertensive retinopathy. In: Yanoff M, Duker JS, eds. Ophthalmology. 2nd ed. St. Louis: Mosby; 2004:849-853.

Suzuki M, Minamoto A, Yamane K, et al. Malignant hypertensive retinopathy studied with optical coherence tomography. Retina. 2005;25(3):383-384.

van den Born BJ, Honnebier UP, Koopmans RP, van Montfrans GA. Microangiopathic hemolysis and renal failure in malignant hypertension. Hypertension. 2005;45(2):246-251.

Matthew Lazzara, MD, and Caroline R. Baumal, MD, can be reached at Tufts Medical Center, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.

Edited by Jeffrey Chang, MD, and Vivek Chaturvedi, MD. Drs. Chang and Chaturvedi can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Chang and Chaturvedi have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.