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Woman presents with acute onset monocular visual distortion
There was mild retinal venous sheathing focally along the inferior arcade in the left eye and in the mid-periphery in both eyes.
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A 27-year-old woman with a history of Crohn’s disease complained of new onset visual distortions, which started 3 days prior. She described seeing a wavy area in the inferotemporal region of her visual field in the left eye. She also felt that colors appeared washed out bilaterally. She denied having similar symptoms in the past.
She did not take any medications. She denied any family history of ocular diseases. She denied smoking, alcohol or illicit drug use.
Figure 1. Fundus photograph of patient on presentation. Right eye (a). Left eye (b). Peripheral venous sheathing right eye (c). Peripheral venous sheathing left eye (d).
Images: Ho J, Hedges TR
Examination
On examination, best corrected central visual acuity was 20/20 in both eyes. Pupils were equal and round, without an afferent pupillary defect. Color vision tested by Ishihara plates was full bilaterally. IOP by applanation was 16 mm Hg in both eyes. Visual field testing and extraocular movements were full bilaterally.
Anterior segment exam of both eyes was normal in appearance without any anterior chamber cell or flare. Posterior segment exam showed trace vitreous cells. There was mild retinal venous sheathing focally along the inferior arcade in the left eye and in the mid-periphery in both eyes (Figure 1). There was no significant arteritis.
What is your diagnosis?
Retinal periphlebitis
The differential diagnosis for the fundus findings of retinal periphlebitis includes multiple sclerosis, sarcoidosis, Eales disease, Crohn’s disease, tuberculosis, HIV, Behçet’s disease and birdshot chorioretinopathy.
Differential diagnosis
Multiple sclerosis (MS) may present with retinal periphlebitis in approximately 11.5% of patients. It is usually a bilateral process, with mild vitreous inflammation and peripheral focal areas of venous sheathing. There may be round dot-like opacities that have the diameter of a medium-sized vein and are located in the vitreous immediately anterior to the retina. Visual acuity is usually grossly unaffected unless the region of vasculitis involves the area of the arcades. However, patients may present with vague complaints of blurred vision. Fluorescein angiography is helpful in making the diagnosis of retinal periphlebitis, revealing normal artery and vein transit times with mid-phase peripheral venous leakage and late-phase staining. Visual field testing is often unrevealing. The etiology is thought to be secondary to segmental infiltration of the perivenous areas by lymphoplasmacytic cells.
Sarcoidosis may rarely present with retinal periphlebitis. It is usually non-occlusive, with segmental perivenous cuffing. However, it may also present more diffusely, with extensive venous sheathing, perivenous exudates (commonly known as “candle wax drippings”) and intraretinal hemorrhages. Small, round chorioretinal lesions in the periphery can also be seen. Cystoid macular edema affects 19% to 72% of patients. In severe cases, retinal ischemia with secondary choroidal neovascular membranes may occur.
Eales disease is an idiopathic, usually bilateral vasculitis, occurring in young patients with three overlapping stages of venous vasculitis, peripheral vascular nonperfusion and peripheral retinal neovascularization. Patients may complain of floaters or decreased vision from recurrent retinal and vitreous hemorrhages. The anterior chamber may show inflammation with possible keratic precipitates. Fundus examination reveals peripheral vascular tortuosity and possible retinal neovascularization. Although it is an idiopathic condition, many patients test positive for Mycobacterium tuberculosis.
Tuberculosis may cause intraocular inflammation in a variety of ways. It may present as bilateral iridocyclitis with mutton-fat keratic precipitates. Other times it may cause retinal periphlebitis. Often, both arteries and veins are involved. Snowballs and snow banking in the vitreous may be seen. Cystoid macular edema may also be present.
HIV may rarely cause retinal periphlebitis. The associated retinal vasculitis usually affects both arteries and veins, with significant macular ischemia. Patients often lose significant vision in the presence of severe retinal ischemia. In patients with coexisting cytomegalovirus, infection may present with frosted-branch retinal phlebitis.
Behçet’s disease classically presents with retinal vasculitis with intraretinal infiltrates and adjacent hemorrhages. Anterior segment findings may include inflammation with a sterile hypopyon. Leakage on fluorescein angiography tends to be diffuse. Patients also often have associated oral and genital ulcers, which may develop after onset of intraocular inflammation.
Birdshot chorioretinopathy may present with periphlebitis, often accompanied by vitritis. Other retinal findings include creamy, circular chorioretinal lesions around the vascular arcades and peripapillary area. It is strongly associated with HLA-A29 positivity.
Crohn’s inflammatory bowel disease may rarely present with retinal periphlebitis. It is worth mentioning because our patient had this condition. Most cases of Crohn’s retinal vasculitis have bilateral obliterative vasculitis, mainly involving the arteries, leading to retinal ischemia. Secondary proliferative neovascularization may occur as a result.
Figure 2. Fluorescein angiography of the left eye. Mid-phase hyperfluorescence focally around vein in inferior arcade (a). Late-phase staining along same region (b). Right eye peripheral venous staining (c). Left eye peripheral venous staining (d).
Figure 3. MRI FLAIR images showing focal periventricular hyperintensities. Saggital section (a). Coronal section (b).
Diagnosis and management
Fluorescein angiography showed normal retinal artery and vein transition times with mid-phase perivascular hyperfluorescence and late phase perivascular staining bilaterally (Figure 2). Laboratory testing for tuberculosis (PPD), sarcoidosis (ACE and chest X-ray) and HIV were negative. The patient also complained of vague systemic symptoms including numbness and tingling of her extremities. An MRI with FLAIR imaging was obtained and showed periventricular regions of white matter hyperintensities suggestive of MS (Figure 3). The patient was started on glatiramer and prednisone, with resolution of the retinal vasculitis over 1 month.
She returned 8 months later with complaints of sudden onset diplopia on left gaze for 1 week duration. Her visual acuity was 20/20 bilaterally, with no afferent pupillary defect or visual field deficits found. Maddox rod testing revealed an 18 D esotropia, worse with left gaze, consistent with a left sixth nerve palsy. MRI revealed a lesion in the left facial colliculus. A short course of IV prednisone with oral taper was started with resolution of the sixth nerve palsy.
Six years after her initial presentation, the patient developed mild complaints of blurred vision in her right eye. Her vision remained 20/20 in each eye. There was a trace afferent pupillary defect in the right eye. Visual field examination was full bilaterally. Color plates were full bilaterally but slower on the right. Fundus examination did not show evidence of optic nerve swelling or pallor. There was also no evidence of retinal vasculitis. Retinal nerve fiber layer and ganglion cell analysis with optical coherence tomography was within normal limits bilaterally. Pattern visual evoked potential (VEP) testing revealed delays at P100 for 15 minute, 30 minute and 60 minute checks on the right, consistent with optic neuritis in the right eye. No delays were seen in the left eye. She was not affected much by the symptoms, so she was observed without a course of steroids.
Discussion
MS has a number of different ocular manifestations, including optic neuritis, retinal vasculitis and rarely cranial nerve palsies. Optic neuritis is the most common ocular manifestation. It has been reported that up to 50% of patients with MS will develop an episode of optic neuritis. It is typically unilateral, with associated pain on eye movement, color desaturation and afferent pupillary defect. However, there may be times when the presentation is much more subtle and visual acuity is relatively preserved, without pain on eye movement, an afferent pupillary defect or color desaturation. In these situations, ancillary testing such as contrast letter acuity are more sensitive than traditional Snellen acuity in picking up decreased vision.
Balcer et al found that pattern VEP latency was shown to correlate with decreased low-contrast letter acuity. In fact, pattern VEP has been shown to be even more sensitive than contrast letter acuity. Gundogan et al compared OCT RNFL thickness to P100 latencies on VEP in MS patients without evidence of optic neuritis and found that temporal RNFL thickness is significantly less compared with normal controls. However, they found that while 53.8% of patients in the study had P100 delay in latency, only 30.7% of patients had a decreased RNFL thickness. This finding points to the importance of VEP to follow patients with MS to detect early signs of optic neuritis.
Retinal vasculitis may be found in 11.5% of patients with MS. The majority of cases involve peripheral retinal veins. Given that the lesions are peripheral in location, many cases are often asymptomatic. Some cases may involve the retinal arteries and be associated with retinal ischemia and choroidal neovascularization. Mackenzie et al demonstrated a case of MS-associated retinal vasculitis with vision-threatening macular edema that resolved with retrobulbar triamcinolone. Friedman et al demonstrated a case of MS-associated retinal vasculitis found to have choroidal neovascular membrane. The patient was treated with peripheral panretinal photocoagulation with resolution of the neovascularization.
While internuclear ophthalmoplegia is more commonly found in MS, isolated cranial nerve palsies are a rare finding because MS primarily affects oligodendrocytes rather than Schwann cells. In cases of cranial nerve palsies, the lesion is typically located at the cranial nerve fascicles. It represents 0.5% of cases as the only presenting sign of MS. Sixth nerve palsy is most common of the cranial nerve palsies. Barr et al reported three cases of sixth nerve palsy as the presenting sign of MS. While two of the cases revealed hyperintensities in the lower pontine tegmentum on MRI FLAIR imaging, one case had a normal MRI.
References:
Balcer LJ, et al. Neurology. 2003;doi:10.1212/01.WNL.0000094315.19931.90.Barr D, et al. J Neurol. 2000;doi:10.1007/s004150070114.
Friedman SM. Retina. 2005;25(2):218-219.
Gundogan FC, et al. Invest Ophthalmol Vis Sci. 2007;doi:10.1167/iovs.07-0834.
Mackenzie PJ, et al. Retina. 2002;22(1):133-134.
Narayanan D, et al. Mult Scler. 2014;doi:10.1177/1352458514523498.
Rose JW, et al. J Clin Neuroophthalmol. 1992;12(1):17-20.
For more information:
Joseph Ho, MD, and Thomas R. Hedges III, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.Edited by Gregory D. Lee, MD, and Nora W. Muakkassa, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.