Atypical Presentation of Vitreous Inflammation in a Patient With Hypertensive Retinopathy

Abstract

Purpose: To describe an atypical presentation of vitreous inflammation in a patient with malignant hypertension. Methods: A case was evaluated. Results: A patient presenting with a hypertensive emergency was found to have decreased vision in the setting of severe optic nerve head edema, extensive hard exudates, cotton-wool spots, and Elschnig spots in both eyes secondary to malignant hypertension as well as vitreous cells bilaterally. He was admitted to the pediatric intensive care unit for intravenous medications and observation. Conclusions: This case adds to the growing body of evidence suggesting that hypertensive urgency may be accompanied by inflammation.

Introduction

Hypertension is the leading cause of cardiovascular disease and premature death worldwide. ¹ In the United States, nearly 50% of adults have hypertension. ² Because of vascular changes visible on funduscopic examination, ophthalmologists play a crucial role in the potentially life-saving management of hypertension and cardiovascular disease.

One ocular manifestation of systemic hypertension is hypertensive retinopathy, the diagnosis of which is based on the funduscopic examination. Arteriovenous nicking, copper/silver wiring, cotton-wool spots, retinal hemorrhage/edema, and optic disc swelling are commonly found signs. ³ Hypertension is also known to cause optic neuropathy, which often presents as papilledema and hemorrhage at or near the optic nerve. Severe hypertension is associated with the presence of Siegrist streaks and Elschnig spots. Hypertensive choroidopathy resulting from fibrinoid necrosis of choroidal arterioles leads to focal areas of ischemic damage to the retinal pigment epithelium. ⁴ Optical coherence tomography (OCT) and fluorescein angiography (FA) assist in the visualization of these changes.^5,6 The differential for these lesions includes inflammatory etiologies in addition to malignant hypertension or hypertensive emergency.

Although there is abundant literature regarding hypertensive retinopathy and choroidopathy, to our knowledge previous studies have not shown bilateral vitreous cells in the setting of hypertensive retinopathy. In this report, we describe a patient in a hypertensive crisis who presented with vitreous inflammation.

Case Report

A 19-year-old man with a history of Brown syndrome was referred from the pediatric intensive care unit (PICU) to the neuro-ophthalmology outpatient clinic for bilateral visual loss. He was initially evaluated by his optometrist after noticing a horizontal “black line” in the middle of the right eye’s visual field. An ophthalmic examination showed bilateral optic nerve edema, and the patient was referred to the Massachusetts Eye and Ear emergency department.

On arrival, the patient’s blood pressure was 169/98 mm Hg and the pinhole distance visual acuity (VA) was 20/400 OD and 20/30⁻² OS. A pupillary reflex could not be assessed because the pupils were still dilated from the earlier examination. The patient’s visual fields were full. The fundus examination was remarkable for severe optic nerve head edema, greater in the right eye than in the left eye; extensive hard exudates; and cotton-wool spots and Elschnig spots in both eyes. The efferent examination was unremarkable. He had 2+ vitreous cells in both eyes. The patient was then transferred to Mass General Hospital.

On arrival to Mass General Hospital, the patient’s blood pressure was 267/170 mm Hg. He was given labetalol 10 mg intravenously in the emergency department and transferred to the PICU for treatment and workup for a hypertensive emergency. Nicardipine was started with a systolic blood pressure goal of 200 mm Hg.

Magnetic resonance imaging of the brain obtained the next day showed papilledema, likely from posterior reversible encephalopathy syndrome, without compressive lesion. The blood pressure remained above goal on nicardipine, and nitroprusside was added on day 3 of the patient’s stay in the PICU. His medications were cross-titrated, with an eventual transition solely to nicardipine. On day 5, nifedipine was added to his regimen.

Five days after being transferred to the PICU, the patient reported dark vision in the left eye. His VA in both eyes had improved to 20/70⁺² OD and 20/25 OS; however, the afferent examination showed a relative afferent pupillary defect in the left eye. He was unable to read the control plate with the left eye (0/8 color plates) but successfully did so with the right eye (1/8 color plates). Optic nerve edema remained significant in both eyes (greater in the right eye than in the left eye) with unchanged fundus findings, consistent with hypertensive retinopathy.

While the patient was in the PICU, he was evaluated for secondary causes of hypertension by the consulting nephrology service. His thyroid-stimulating hormone, cortisol, basic metabolic panel, complete blood cell count, renin and aldosterone, random urine catecholamines, plasma metanephrines, urinary analysis, ultrasound kidney and bladder with Doppler, and computed tomographic angiogram of the abdomen and pelvis were all within normal limits.

Given the lack of clear precipitating etiologies, additional assessment was done, including 24-hour urine collection for metanephrine and catecholamines, 24-hour urine 5-hydroxyindoleacetic acid, serum serotonin, and chromogranin A. Inconsistencies were found in the catecholamine/metanephrine screens; therefore, the pediatric endocrinology and pediatric nephrology services recommended the laboratory studies be repeated and plasma metanephrine be obtained. The chromogranin A screen was within normal limits. Clinical suspicion for paraganglioma led to a recommendation of further imaging studies, including a positron emission tomography scan, which was negative for paraganglioma. The patient was discharged on the 15th day of hospitalization and was followed for further workup of hypertension as an outpatient by the Mass General Hospital pediatric nephrology team.

The patient’s follow-up examination 21 days after presentation was notable for a 2+ afferent pupillary defect. In addition, he had a distance pinhole VA of 20/80 OD and 20/40 OS with marked bilateral dyschromatopsia. Humphrey visual field testing showed generalized reduction bilaterally, and the Goldmann visual field examination was notable for mild constriction of the visual fields, with a right-sided central scotoma and a left-sided constricted visual field with an island of central vision.

At that follow-up, FA showed leakage of dye from the optic nerve head bilaterally and focal areas of hypofluorescence around both optic nerve heads (Figure 1, A-F). The optic nerves were swollen bilaterally, with 360 degrees of blurring of the disc margins (Figure 2, A and B). Exiting the disc were grade III Friesen-like obstructions of the vessels. Diffuse hard exudates, cotton-wool spots, and Elschnig spots were noted bilaterally (Figure 2, C and D), and mild splinter hemes in the left eye surrounded the optic nerve head (Figure 2D). In addition, 2+ vitreous cells persisted in both eyes, without apparent vitreous haze or anterior chamber inflammation. OCT showed an increase in the retinal nerve fiber layer thickness from 308 µm to 338 µm. The thickness of the ganglion cell complex was also reduced in both eyes, suggestive of optic nerve axonal damage.

Figure 1.

Twenty-one days after presentation, FA photographs of the patient’s right eye and left eye sequenced at 1 minute, 4 minutes, and 12 minutes show normal right-sided choroidal filling with a diffusely dilated disc and a capillary bed with moderate leakage throughout the peripapillary area (A, C, and E). (B, D, and F) Left-sided imaging shows a dilated disc capillary bed with increased disc leakage over time.

Abbreviation: FA, fluorescein angiography.

Figure 2.

Twenty-one days after presentation, a dilated funduscopic examination of the right eye (A and C) and the left eye (B and D) shows bilateral optic nerve head edema, whitened vessels, marked retinal exudates, and subretinal fluid. (E and F) Fluorescein angiography shows leakage of fluid.

The patient’s examination at his last follow-up visit (147 days after initial presentation) was notable for a left-sided relative afferent pupillary defect. The distance pinhole VA was 20/30 OD and 20/20 OS. Automated visual fields showed a marked generalized reduction in sensitivity in the left eye with an improved pattern deviation plot for the right eye. Goldmann visual fields showed very similar peripheral field loss in the right eye and slightly improved visual fields in the left eye. A dilated funduscopic examination showed numerous, widespread pigmented Elschnig spots and several bilateral sclerotic long-segment choroidal vessels (Figure 3, A and B). The optic nerves were mildly swollen and somewhat pale bilaterally (Figure 3, C and D). Hard exudates remained in the macula. There were 2+ (old) cells in the vitreous bilaterally. OCT findings, which showed ganglion cell segmentation (Figure 3, E and F), were unchanged from the patient’s imaging study performed 126 days earlier.

Figure 3.

One hundred forty-six days after initial presentation, a dilated funduscopic examination of the right eye (A and C) and the left eye (B and D) shows numerous, widespread pigmented Elschnig spots; several sclerotic long-segment choroidal vessels are present in both eyes. The optic nerves were mildly swollen and somewhat pale in both eyes. Hard exudates remain in the macula in both eyes. (E and F) Optical coherence tomographic imaging of the right eye and left eye with ganglion cell segmentation shows decreased overall thickness of the ganglion cell complex, with an average measurement of 49 µm and 78 µm, respectively.

Conclusions

This 19-year-old man presented with a history of subacute-onset bilateral visual loss and marked bilateral optic nerve edema with retinal findings most consistent with a diagnosis of hypertensive retinopathy and optic neuropathy. His ophthalmologic examination featured 2+ vitreous cells bilaterally without other signs of active intraocular inflammation (ie, no anterior chamber cells and flare, no vitreous haze, and no active retinochoroidal lesions). In addition, vitreous cells were seen in the emergency department on the day of initial presentation.

Few entities can simultaneously cause systemic hypertension and intraocular inflammation. Systemic lupus erythematous and polyarteritis nodosa are among these entities; however, they most commonly cause scleritis or retinochoroidal vasculopathy rather than uveitis. Two less likely differential diagnoses are Fabry disease and tubulointerstitial nephritis and uveitis syndrome. In Fabry disease, ocular manifestations frequently include cornea verticillata, conjunctival changes, and nonspecific retinal vessel tortuosity. Although hypertension may occur with Fabry disease, it is not a characteristic feature and is typically secondary to chronic kidney damage. ⁷ Given the mild retinal vessel tortuosity in our case and the absence of corneal abnormalities and other associated systemic symptoms, Fabry disease is considered unlikely. Tubulointerstitial nephritis and uveitis syndrome can present with vitreous cells and optic disc swelling in patients with acute kidney inflammation, although the typical presentation involves bilateral anterior uveitis. ⁸ Our patient did not have kidney disease, making this syndrome less likely.

Given the peculiar finding of bilateral vitreous cells in the setting of hypertensive retinopathy, we performed a literature search and found no articles reporting a clear association between arterial hypertension/hypertensive retinopathy and vitreous inflammation. In one study, ⁹ patients whose fundus examination showed marked hypertensive changes had a higher fluorescein concentration than healthy individuals on ocular fluorophotometry in the posterior vitreous and anterior chamber, even in the absence of fluorescein leakage on FA. This indicates that hypertension can accelerate the extravasation of intravascular contents, possibly through an alteration of the blood–retinal barrier.

Another mechanism that may explain our patient’s presentation is that the vitreous cells observed during the fundus examination could have been residual red blood cells associated with retinal hemorrhages in the setting of a hypertensive crisis. A study by Dana et al ¹⁰ supports this theory. Vitreous inflammation in our patient’s case may have been caused by ocular ischemia, and it is known that the reverse process—ocular ischemia caused by ocular inflammation—can occur in diseases such as giant cell arteritis. ¹¹ In a cohort of patients with serous retinal detachment (RD), Noma et al ¹² suggested that an increase in the presence of vitreous inflammatory factors and a decrease in anti-inflammatory factors led to ocular ischemia. This is an unlikely mechanism in our patient, however, because good perfusion was observed on retinal FA. In addition, he had no RD.

Our patient’s history of a progressive-onset bilateral decrease in vision, which was initially worse in the right eye than the left eye, followed by a subsequent acute decrease in vision in the left eye while he was hospitalized in the PICU, suggests he might have had a secondary hypertensive optic neuropathy with left-eye ischemic optic neuropathy, also in the context of hypertensive retinopathy, that ultimately limited the visual recovery. Some of the reduced central acuity was likely caused by the retinal and subretinal edema, especially in the right eye.

In conclusion, this case demonstrates that vitreous inflammation can accompany severe hypertensive retinopathy in the absence of autoimmune pathology. The underlying mechanism is likely vascular insufficiency and leakage.