A 76-year-old, German, Caucasian female, with past medical history of relapsing-remitting MS (in remission for more than three decades), chronic obstructive pulmonary disease, hypertension, and heavy cigarette smoker, consulted to the emergency department in 2016 referring increased glare and sudden fall of visual acuity (VA) on both eyes (OU) since a couple of days. Ophthalmological background was left eye (LE) amblyopia and retrobulbar optic neuritis in the LE in 1986 and in the right eye (RE) in 1987, which along with the findings in Magnetic Resonance Imaging (MRI) of the brain led to the diagnosis of MS. Both episodes were treated with Azathioprine but, since then, did not receive additional therapy. The patient denied additional neurological symptoms for the last 30 years. She had cataract surgery with intraocular lens (IOL) implantation in OU in 2012. She noted decreased vision in the RE around six months before consulting in 2016, and diagnoses of anterior uveitis and vitreous hemorrhage (VH) in the right eye (RE) were done elsewhere. However, the patient did not continue to attend the treating ophthalmologist and thus did not receive specific management. She consulted the emergency department two days after noticing a sudden and greater decrease in VA in OU.
Examination approach: VA in the RE was Counting Fingers and 0.32 in the LE (Snellen decimal scale), which did not improve with spectacles. Intraocular pressure (IOP) was 19 mmHg in the RE and 22 mmHg in the LE. Slit lamp examination revealed in OU marked inflammation in anterior chamber (cells 3+) and granulomatous endothelial precipitates. In addition, posterior synechia and precipitates on the IOL front surface were observed in the LE. Vitreous turbidity, vitreous cells and snowballs, and retinal vessels with mild sheathing and adjacent hemorrhages were found in OU.
B-scan Macular Optical Coherence Tomography (OCT) from the RE revealed inflammatory cells in vitreous humor, epiretinal membrane, and preserved foveal architecture, with parafoveal retinal thickening (mild macular edema), without cysts or serous detachment (Figure 1(a)). In the LE, inflammatory cells in vitreous humor, epiretinal membrane without traction, and preserved foveal architecture without cysts or serous detachment were revealed (Figure 1(b)). Fluorescein angiography showed on the RE blockage of choroidal fluorescence secondary to vitreous opacities, pronounced ischemic areas in inferotemporal arcade, collateral vessel formation, and leakage near the optic nerve head and along the retinal veins (periphlebitis) (Figure 2(a)). In the LE, blockage of choroidal fluorescence secondary to vitreous opacities, leakage in foveal area (macular edema (ME)) and along the retinal vessels, and staining of nasal retinal veins (periphlebitis) were shown (Figures 2(b) and 2(c)).
Neurological approach proved intact cranial nerves function, no paresis, no pyramidal tract signs, and adequate reflexes. MRI of the orbit exhibited no evidence of retrobulbar optic neuritis. Skull MRI revealed no evidence of acute inflammatory cerebral foci.
Paraclinical tests helped ruling out differential diagnosis. Sarcoidosis was excluded by normal serum angiotensin converting enzyme, and there were no relevant abnormalities on chest x-ray. Other diseases possibly associated with ocular signs were not likely on absence of systemic clinical findings, negative ANA, and ANCA, normal HbA1c (5,2%), and no heart rhythm abnormalities. Infectious etiologies such Syphilis, Bartonellosis, and Lyme disease were also ruled out. Regarding ischemic causes, Carotid Doppler showed no plaques, dissection, or stenosis. Furthermore, the absence of malignant suspicious lymphocytes (dysplasic, pleomorphic lymphocytes with elevated nucleus-cytoplasm ratio) in a vitreous sample from RE excluded ocular lymphoma (Masquerade syndrome). PCR tests in that sample were negative for Herpes simplex, Varicella Zoster, Cytomegalovirus, and Mycobacterium Tuberculosis. Eventually, given the exclusion of other possible etiologies, diagnosis was a bilateral anterior uveitis and intermediate uveitis with occlusive vasculitis and mild macular edema, attributable to a MS relapse.
Intravenous methylprednisolone, 250 mg q.i.d. for 5 days, was administered. Topical prednisolone was indicated, initially every hour, and then tapered gradually over around two months. Cyclopentolate b.i.d. was used for several weeks. This scheme led to improvement of the findings, but Dorzolamide/Timolol b.i.d. and Brimonidine t.i.d. had to be used to control IOP increase.
At discharge, 5 days after the admission, VA from the RE was 0.1 and 0.32 on the LE, which did not improve with optical correction. IOP was normal in OU. Oral steroid taper schedule and hypotensive eye drops were prescribed. On the third month's control, even under daily oral steroids, bilateral vasculitis persisted. Consequently, interferon beta-1a (Rebif ) was initiated (44 mcg, 3 times per week, subcutaneously). On the sixth month's visit, CME was found in OU, despite the fact that she was receiving interferon beta-1a and 7.5 mg oral prednisolone. Bilateral subtenon injections of triamcinolone were performed. Two months later, CME persisted and a dexamethasone intravitreal implant (Ozurdex ) was injected in the RE and three months later in the LE as well.
Due to side effects with interferon beta-1a (Flu-like symptoms and depression), eight months after it was started, she was switched to peginterferon beta1-a (Plegridy ) 125 mcg injected subcutaneously every 2 weeks. A stable response to treatment was achieved, without inflammatory or neovascularization signs and improvement of CME for a couple of months. Nevertheless, due to persistence of ischemic findings in the retina (ischemic areas, collateral vessel formation, and mild macular edema reappearance) evidenced in fluorescein angiography image control, which possibly triggered recurrence of macular edema, despite having an adequate control of the inflammatory component, pan-retinal photocoagulation was performed in OU, in three sessions between 7 and 8 months after the initial consult, with satisfactory evolution. CDVA at the last check-up visit was 0.4 in the RE and 0.5 in the LE.