An 88-year-old woman developed an acute onset of painless, monocular vision loss in the right eye.
She had a medical history of hypertension, hyperlipidemia, type 2 diabetes, stage 3 chronic kidney disease, gastroesophageal reflux disease, anxiety and diverticulitis.
She had presented to the emergency department 2 days prior for several days of discomfort with swallowing, increasing generalized weakness and bloody stools and had been admitted with an acute gastrointestinal (GI) bleed, symptomatic anemia and oropharyngeal dysphagia. During her inpatient admission and before ophthalmic evaluation, she had undergone several procedures with the gastroenterology service for workup of her melena, including esophagogastroduodenoscopy, colonoscopy and a video capsule endoscopy. Her labs were remarkable for a mildly elevated C-reactive protein (CRP) of 9.7 mg/L (normal range, less than 5.0 mg/L), normal platelets and hemoglobin of 8.3 with a nadir of 6.9 shortly after presentation to the ED, for which she was transfused with two units of packed red blood cells with improvement in her hemoglobin level.
Ophthalmology was consulted when the patient reported sudden vision loss on her second day of admission, which she described as a complete darkening of the inferior half of her vision in the right eye. She also reported a feeling of “pressure” in that eye. She denied any other eye pain, new floaters or flashes, any recent fevers/chills, headache, scalp tenderness, jaw claudication or new arthralgias. She endorsed increased fatigue over the past few weeks, which was thought to be related to her anemia. Her ocular history included cataract extraction with IOL implantation in the left eye 2 weeks before her hospitalization, nonproliferative diabetic retinopathy in both eyes and dry age-related macular degeneration in both eyes.
On examination, the patient’s best corrected near visual acuity with a +3.00 lens was 20/800+1 in the affected right eye and 20/30 in the fellow eye. She had a prominent afferent pupillary defect on the right. Confrontation visual field testing demonstrated an inferonasal defect in the right eye. IOPs were normal. She was able to correctly identify 2/10 color plates in the right eye compared with 8/10 color plates in the left eye on Ishihara testing. Anterior and posterior segment examination revealed a 3+ brunescent nuclear sclerotic cataract in the right eye as well as a slightly pale disc with mildly blurred disc margins. The cup-to-disc ratio was 0.3 in both eyes, with the left optic nerve being pink and sharp. Drusen were noted in the right eye in addition to retinal pigment epithelial atrophy and pigmentary changes in both eyes.
In an older woman with signs of optic neuropathy, giant cell arteritis (GCA) or arteritic anterior ischemic optic neuropathy is the most critical differential diagnosis to consider.
GCA typically affects older patients, with a peak between 70 and 80 years of age, and is more common in white patients and women. It is a vasculitic process that causes intimal proliferation and ultimately vessel occlusion in large- and medium-sized blood vessels, which can lead to ischemia of the optic nerve and/or other structures of the eye and potentially irreversible vision loss. The most frequent symptoms are headache (particularly in the temporal region), scalp tenderness, jaw claudication, and nonspecific symptoms such as fatigue, fever, weight loss and arthralgias. Other ocular symptoms may include amaurosis fugax occurring for several minutes and episodic or persistent diplopia. Ophthalmic examination findings may reveal pallid disc edema, cilioretinal artery occlusion, or central or branch retinal artery occlusion; in a clinic setting, fluorescein angiography can be performed and often shows prolonged choroidal and central retinal arterial filling times and/or patchy choroidal nonperfusion or filling defects. There is an association between GCA and polymyalgia rheumatica (PMR). PMR occurs in 40% to 60% of patients with GCA, and 16% to 21% of patients with PMR will have or develop GCA. Typically, inflammatory markers such as platelet count, erythrocyte sedimentation rate (ESR) and CRP are elevated. Although neither sensitive nor specific for GCA, elevated levels of these markers have been shown to be predictive of a greater likelihood of positive biopsies; the likelihood is 1.5 times greater with an ESR of 47 mm/h to 107 mm/h, 4.2 times greater with platelets greater than 400,000/µL and 5.3 times greater with a CRP greater than 2.45 mg/dL.
In this patient with minimally elevated inflammatory markers and negative systemic symptoms, other causes of optic neuropathy were also considered, such as posterior ischemic optic neuropathy and nonarteritic anterior ischemic optic neuropathy (NAION). NAION is a disease caused by ischemia of small vessels to the anterior optic nerve that often presents with similar findings on clinical examination. It is a more common cause of anterior ischemic optic neuropathy than GCA, accounting for 95% of cases. Patients are typically between 55 to 65 years of age with risk factors that include hypertension (present in 50% of patients), diabetes (present in 25%), hyperlipidemia, history of stroke, ischemic heart disease, smoking, systemic atherosclerosis and obstructive sleep apnea. A “disc at risk,” or an optic nerve with a small cup-to-disc ratio, may be seen in the fellow eye. NAION can also be differentiated from GCA by the absence of elevated inflammatory markers, absence of GCA systemic symptoms (including pain or headache) and absence of the fluorescein angiography findings described above. Amaurosis fugax is more suggestive of GCA rather than NAION. In addition, patients with GCA tend to be older and have more profound vision loss, on the level of counting fingers to no light perception, compared with patients with NAION. Less common findings, such as chalky white disc edema and ischemic optic neuropathy in conjunction with cilioretinal artery occlusion, have also been noted only with GCA.
Posterior ischemic optic neuropathy is also a consideration in this patient who presented with symptomatic anemia and GI bleed and developed vision loss after sedation for multiple endoscopic and colonoscopic procedures. It is the result of ischemia to the retrobulbar optic nerve, often associated with significant blood loss, hypotension and/or anemia in the setting of cardiovascular risk factors. This diagnosis presents similarly with painless, severe vision loss despite typically unremarkable funduscopic findings soon after onset. It is far less common than either GCA or NAION.
After initial evaluation, the patient was started on treatment with intravenous steroids (1 g of IV methylprednisolone) given concern for GCA. The standard dose is 3 to 5 days of IV steroids based on the severity of disease, followed by oral prednisone 1 mg/kg for a minimum of 4 weeks, which is gradually tapered down. Most patients will remain on oral steroids for at least 1 year. Given the side effects of high-dose steroids, in this patient with multiple medical comorbidities and cardiovascular risk factors (hypertension, hyperlipidemia, diabetes), ongoing workup for GI bleed and clinically significant anemia requiring blood transfusion, it was felt that a nonarteritic optic neuropathy could be the cause of her symptoms. Therefore, the decision was made to hold off on further doses of IV methylprednisolone after the initial dose was given and to continue on oral prednisone until a definitive diagnosis of GCA could be made.
Temporal artery biopsy is considered to be the gold standard for diagnosis of GCA. The classic histological picture of GCA is a transmural inflammatory infiltrate associated with marked disruption of the internal elastic lamina and the presence of giant cells. Our patient underwent a temporal artery biopsy the following day, which ultimately revealed active giant cell arteritis with partial/complete disruption of the internal elastic lamina, the presence of an inflammatory infiltrate with mononuclear or granulomatous features involving the media/adventitia, and the presence of intimal hyperplasia, medial fibrosis and inflammation involving the adventitia/peri-vasa vasorum.
Other diagnostic modalities for the evaluation of GCA include color-duplex ultrasonography, which can be used to assess vascular inflammation of the temporal artery and often reveals a suggestive “halo sign” or hypoechoic ring around the arterial lumen. Although this type of testing is noninvasive, it is user-dependent and has been found to have a wide range of sensitivity and specificity, limiting its utility. MRI of the brain and orbits with and without gadolinium contrast can also be used to aid in the preliminary diagnosis of inflammatory vs. ischemic optic neuropathies (as enhancement of the optic nerve is present with inflammatory etiologies but is absent with ischemia). This can be particularly helpful in cases of GCA when acute phase reactants (such as platelet count or ESR, the latter of which is not used at our institution) are normal or only mildly elevated. In our patient, MRI was limited by motion artifact.
Occult GCA (also known as silent or atypical GCA) is defined as ocular involvement by GCA without any systemic signs and symptoms of GCA and with or without elevated inflammatory markers. In 1962, Simmons and Cogan reported that these symptoms may be absent or minimal with only retrospective significance and that they may not appear until after the ocular phase of the disease manifests. A more recent study of biopsy-confirmed cases of GCA found that 21% of patients with vision loss did not report systemic symptoms and that ESR and CRP levels may be elevated but tend to be lower in these patients than in those with classic GCA (P < .0001 and P = .0133, respectively).
Cases of occult GCA have been described in the literature with symptoms varying from a few days of intermittent blurred vision or a gradual progression of blurring to blindness (no light perception) reported 30 minutes after the onset of visual symptoms. Vision loss and amaurosis fugax are the most common complaints, and diplopia and eye pain are less frequently reported. On repeat history, patients often recall mild systemic symptoms, such as headache, that they may have initially dismissed as insignificant or unrelated. Examination findings, such as anterior ischemic optic neuropathy, central retinal artery occlusion, cilioretinal artery occlusion and posterior ischemic optic neuropathy, present with similar incidences regardless of the presence of systemic signs and symptoms. By far, the most common finding in patients with occult GCA is anterior ischemic optic neuropathy. The criteria above can be used to help differentiate this from NAION.
The diagnosis of occult GCA should be considered in all cases of sudden vision loss, retinal artery or vein occlusion, ophthalmoplegia or diplopia that cannot be otherwise explained, or other ocular symptoms without a clear diagnosis. Patients with either classic or occult GCA have been found to retain their existing vision when treated adequately with systemic steroids and when no further vision loss occurs within the first week after starting treatment. For this reason, maintaining a high index of suspicion for GCA, obtaining a temporal artery biopsy and inflammatory markers, and initiating steroids early despite the absence of systemic symptoms are crucial.
After the positive temporal artery biopsy confirmed the diagnosis of GCA, the patient was ultimately treated with a total 3-day course of IV steroids. Further history was also elicited from her daughter by phone, who reported that the patient had complained of headaches and jaw pain before presenting to the hospital. After discussion, the patient admitted to minimizing her symptoms out of concern that they would worry her children.
At the time of hospital discharge, the patient’s visual acuity in the affected right eye was counting fingers at 4 feet superiorly. Visual acuity, color vision and visual fields in the left eye remained stable. One week later, the patient was seen for outpatient neuro-ophthalmology follow-up. She continued on 60 mg of oral prednisone, and her visual acuity remained counting fingers in the right eye with persistent afferent pupillary defect, inferior visual field loss and right optic nerve pallor. Her left eye remained stable. She was given a prescription for polycarbonate lenses and monocular precautions.
Giant cell arteritis is an aggressive, progressive and vision-threatening disease if untreated. Prompt diagnosis and management are critical to prevent vision loss, which can cause profound morbidity in the older population typically affected by this disease. Whenever possible, history should try to be corroborated from family members as these patients may not be optimal historians. Even in the setting of minimally elevated inflammatory markers and minimal symptoms, GCA should be considered and ruled out in older patients who present with severely decreased vision and evidence of optic neuropathy or retinal ischemia. Occult GCA presents without typical systemic symptoms, but the consequences of missing this diagnosis can be devastating.
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