- Email: [email protected]
Thick corneas, large pupils, and a giant problem
Accepted Manuscript Thick corneas, large pupils, and a giant problem Francesco Pellegrini, MD, Giovanni Prosdocimo, MD, Daniela Bonsanto, MD, Rod Foroozan, MD PII:
S0039-6257(17)30157-1
DOI:
10.1016/j.survophthal.2017.06.003
Reference:
SOP 6729
To appear in:
Survey of Ophthalmology
Received Date: 11 May 2017 Revised Date:
2 June 2017
Accepted Date: 6 June 2017
Please cite this article as: Pellegrini F, Prosdocimo G, Bonsanto D, Foroozan R, Thick corneas, large pupils, and a giant problem, Survey of Ophthalmology (2017), doi: 10.1016/j.survophthal.2017.06.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Thick corneas, large pupils, and a giant problem
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Francesco Pellegrini, MD (1) Giovanni Prosdocimo, MD (1) Daniela Bonsanto, MD (1)
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Rod Foroozan, MD (2)
(1) Neuro-Ophthalmology Service, Department of Ophthalmology, “De Gironcoli” Hospital, 31015 Conegliano (TV), Italy Baylor College of Medicine, Houston, Texas, United States of America
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(2)
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address correspondence to: Francesco Pellegrini
Address: Via D. Manin 110, Conegliano (TV) Italy, tel: +39 0438 668111
+39 0438 668362
email: [email protected]
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(In keeping with the format of a clinical pathologic conference, the abstract and key words appear at the end of the article)
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Case Report
An 87-year-old woman presented to her local hospital complaining of blurred vision in
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the right eye (OD) one month after uneventful cataract surgery. Visual acuity was 10/20 OD and 6/20 in the left eye (OS). Slit lamp examination (SLE) was remarkable for moderate corneal edema OD and a nuclear cataract OS. An intraocular lens was correctly implanted in the capsular bag in OD and both eyes (OU) were otherwise quiet,
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with no signs of external or internal inflammation. Intraocular pressure (IOP) was 8 mmHg OD and 10 mmHg OS, and fundi were normal bilaterally. A diagnosis of
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pseudophakic corneal decompensation OD was made, and the patient was scheduled for an endothelial keratoplasty. Three days later she returned to the emergency room
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complaining of bilateral blurred vision since that morning. Non-contrast brain computerized tomography was negative for ischemic events. Visual acuity was 2/20 OU. There was bilateral corneal edema, IOP was 8 mmHg OU, and the fundi were normal (although difficult to examine). Both pupils were mildly dilated and sluggishly reactive to light, and she was scheduled for a consultation in neuro-ophthalmology the next week.
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What are your thoughts so far and what would you do first?
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Comments by Rod Foroozan, MD The cataract surgery was said to be uneventful and the intraocular lens (IOL) was said to
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be in the capsular bag. This would help exclude corneal decompensation from irritation due to an improperly placed IOL haptic. Funduscopic examination was difficult to
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preform presumably because of the corneal edema in each eye. It would be important to estimate the level of visual dysfunction expected from the corneal edema. There was no suggestion of a corneal dystrophy or irido-corneal endothelial (ICE)
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syndrome, which would predispose to corneal decompensation. A family history of corneal disease (Fuchs corneal dystrophy) might be helpful. I would perform corneal pachymetry and endothelial cell counts to have a more thorough understanding of the
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health of the cornea in each eye. Anterior segment optical coherence tomography
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(OCT) would be helpful to exclude a cyclodialysis cleft (particularly if the cornea was too opaque to allow for gonioscopy) that would potentially be associated with low intraocular pressure and maculopathy from choroidal folds. Imaging studies of the optic disc (retinal nerve fiber layer [RNFL]) and macula might be helpful, sometimes even if funduscopy is limited, to help exclude structural causes of a retinopathy and optic neuropathy, particularly those associated with recent anterior
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segment surgery (cystoid macular edema, choroidal detachment or folds, optic disc edema).
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Even if we find a reasonable cause for decreased vision of the right eye based on the anterior segment findings, we still need to explain the reduced visual function in the left eye, which did not undergo surgery. We are not told the preoperative visual acuity,
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which might help explain if there had been a change in the left eye as she was now 2/20
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(20/200) in each eye.
At this point we have an 87-year-old woman with decreased visual function in both eyes after she had cataract surgery in the right eye only one month before. We can use a simplified table of sites of visual loss with their clinical characteristics to help sort out
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the most likely cause of decreased vision for this patient: While there are exceptions, the site of visual loss in most patients can be distinguished
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using the guidelines in this table. Problems involving the “eyeball” (ocular media and
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retina) are generally detected (“seen”) through slit lamp biomicroscopy and funduscopy. Even when problems in the retina are difficult to distinguish with funduscopy, other imaging techniques, including OCT, help uncover most retinopathies. More posteriorly, the pupillary examination and visual field testing are key. The hallmark of an optic neuropathy when the deficit is symmetric is bilaterally sluggish pupils. Disorders of the optic chiasm cause preferential loss of the temporal visual field and, when the optic chiasm is affected symmetrically bilaterally, sluggish pupils may also occur. This
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patient had progressive loss of central visual function in each eye so that posterior visual pathway disease would be unexpected.
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I would suggest automated perimetry to help determine whether there is another pattern of visual loss apart from the reduction of central sensitivity expected from corneal
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edema, cataract, or another anterior segment cause.
Both pupils were said to be sluggishly reactive to light and mildly dilated, and there was
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no suggestion of efferent dysfunction (iris sphincter tears or third nerve palsy, for example) so we should presume there is bilateral involvement of the anterior visual pathways (retina and optic nerve) or optic chiasm until proven otherwise.
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If we cannot adequately assess the optic disc and retina to discover the cause of visual loss, then I would suggest an MRI of brain and orbits with contrast and fat suppression. The non-contrast CT of brain is often not sufficient to image the soft tissue of the optic
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nerves, sella, suprasellar space, and optic chiasm.
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Case Report (Continued)
At neuro-ophthalmologic examination the patient felt otherwise well, she denied eye pain, headache, and jaw claudication. Her past history was negative for major diseases. She took beta blockers for systemic hypertension. Family history was negative for ischemic events or neoplastic diseases. Extraocular motility was full. Visual acuity in the meanwhile had dropped to no light perception (NLP) OU. IOP was 2 mmHg in OD and
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about 0 mmHg in OS with corneal edema OS worse than OD (Figure 1). Pupils were dilated with no response to light or near stimulation. Fundi could not be seen OS, while
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there was a diffuse retinal edema suggestive of central retinal artery occlusion (CRAO) OD associated with a retinal hemorrhage inferior to the optic nerve (Figure 2). Fluorescein angiography (FA) and optical coherence tomography were performed OD
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(Figure 3), while they were not feasible OS because of corneal edema and cataract. On
detectable bilaterally (Figure 4).
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intracranial magnetic resonance angiography (MRA), the ophthalmic arteries were not
Is the vision consistent with progressive corneal edema?
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What else would you consider?
Comments
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Comments by Rod Foroozan, MD
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The visual loss has now progressed in each eye and while there is corneal edema bilaterally the cornea is not opaque enough, particularly in the right eye, to cause NLP vision. Because we cannot visualize the posterior pole due to corneal edema in the left eye an ultrasound might be help to exclude chorioretinal disorder.
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MRA of the head suggested impaired ophthalmic artery flow on each side. This could be further assessed using orbital color Doppler imaging. Funduscopy is consistent with
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a CRAO in the right eye and, given no embolic material within the retinal arterioles, an arteritic cause becomes more likely. Although we can only see a portion of the right optic disc, there was pallid edema temporally, suggestive of an arteritic cause. The FA
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suggested perfusion delay and impaired choroidal filling supporting a potential arteritic
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cause.
In addition the IOP has decreased in both eyes, most likely from limited ciliary body perfusion. This would imply impairment of the long posterior ciliary circulation in
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combination with the retinal circulation in the right eye and potentially global loss of perfusion of both eyes, a form of ocular ischemic syndrome. The timing of the visual
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deficits and bilaterality go against the perfusion deficits resulting from progressive carotid occlusive disease, the most common cause of ocular ischemic syndrome. When
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multiple sites of the ocular circulation are affected, particularly when bilateral, an arteritic cause becomes more likely.
Even without systemic symptoms of giant cell arteritis, I would suggest hospitalization and treatment with systemic corticosteroids and a complete blood count, erythrocyte
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sedimentation rate (ESR), C-reactive protein, and temporal artery biopsy. I would obtain an MRI of brain and orbits with contrast and MRA of the neck. Pending these
patients with giant cell arteritis.
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Case Report (Continued)
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results, I would also suggest imaging of the aortic arch that is sometimes helpful in
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A diagnosis of bilateral rapidly progressive ocular ischemic syndrome was made. ESR was 91mm/h and C-reactive protein (CRP) was 8 mg/dL (normal less than 0.5 mg/dL). Temporal artery biopsy was positive for giant cell arteritis (GCA) (Figure 5). The patient was treated with i.v 1000 mg methylprednisolone with no effect on vision. At one month
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the corneal edema has resolved, but she was still NLP OU.
Discussion
GCA is a medium-to-large vessel vasculitis with potentially sight- and life- threatening complications.2 The arteritis has a predilection for temporal, vertebral, ophthalmic, and posterior ciliary arteries, 16 thus explaining the high frequency of visual loss observed in this disorder. In 1990 the American College of Rheumatology (ACR) developed
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diagnostic classification criteria for GCA,
8
concluding that if a patient met 3 of the
following 5 criteria, a diagnosis of GCA could be made: 1) age 50 years or older, 2)
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new-onset of localized headache, 3) temporal artery tenderness or decreased temporal artery pulse, 4) ESR ≥ 50 mm/h, 5) biopsy specimen findings consistent with a diagnosis of GCA. Since 1990, however, our understanding of the pathogenesis,
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diagnosis, and treatment of GCA has improved, and the validity of the ACR criteria has been questioned. Murchison and colleagues13 found that 25% of patients with biopsy-
Moreover, approximately 20% of
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proven GCA would not have sufficient clinical ACR criteria for the correct diagnosis. patients with GCA present with occult GCA,6
meaning that a patient may suffer profound visual loss, even bilaterally, without other
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typical signs and symptoms of GCA such as jaw claudication, temporal headache, etc. While anterior ischemic optic neuropathy is the most common (80-90%) cause of visual loss in GCA, 11 visual dysfunction may occur on the basis of choroidal ischemia, retinal
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artery occlusion, posterior ischemic optic neuropathy, and occipital lobe stroke as well.15
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Giant cell arteritis, because of the inflammatory occlusion of the common carotid, internal carotid, or ophthalmic arteries,1,3,9 has the potential to cause ocular ischemic syndrome, a progressive disorder that results from hypoperfusion of the eye. The pathogenesis of the occlusion is usually atherosclerosis, but other causes can also be associated with carotid occlusion. Independently from the cause, these patients develop venous stasis retinopathy, red eye, mild uveitis, progressive cataract, and initially low intraocular pressure, in various combinations.
Acute ocular hypotony is a rare
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complication of GCA14 that results from decreased production of aqueous humor caused by insufficient arterial blood flow to the ciliary body through the long posterior ciliary
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arteries, and it can be present even without other signs of ocular ischemia.7 In rare cases, vessel inflammation caused by GCA may produce reduced blood flow to the entire orbit, thus causing a clinical syndrome that suggests orbital pseudotumor or orbital cellulitis
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and is characterized by proptosis, chemosis of the conjunctiva, limitation of eye movement, and reduced visual acuity.10 It is not clear why in the present case corneal
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edema developed before marked ocular hypotony, although the thickened corneas may have been a cause of IOP overestimation at least initially.
The endothelium is in the
main responsible for maintaining the relatively low level of stromal hydration and
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consequently of corneal transparency. This function is assured by the activity of “ionic pumps” that mediate the transfer of ions such as sodium, potassium, and magnesium from the corneal stroma to the aqueous humor. In order for this active process to work
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properly, metabolic energy is required to maintain the normal corneal thickness and
cells.12
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transparency.4,5 Numerous mitochondria are present within the cytoplasm of endothelial Reduced blood flow to the anterior segment may thus have altered the
“endothelial pump” function and caused corneal edema. The latter, theoretically, may also have been favored by a decreased number of endothelial cells in the elderly and a more pronounced reduction of endothelial cells in the operated eye. In conclusion, ophthalmologists should be aware of the many uncommon presentation of this common
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disease of the elderly. Giant cell arteritis should always be suspected in unilateral or
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bilateral ocular ischemic syndrome in patients older than 50.
References
(1) Casson RJ, Fleming FK, Shaikh A, et al. Bilateral ocular ischemic syndrome
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secondary to giant cell arteritis. Arch Ophthalmol 2001;119:306–307.
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(2) Frohman L, Wong ABC, Matheos K, Leon-Alvarado LG, Danesh-Meyer HV. New developments in giant cell arteritis. Surv Ophthalmol. 2016;61:400-421. (3) Hamed LM, Guy JR, Moster ML et al. Giant cell arteritis in the ocular ischemic syndrome. Am J Ophthalmol. 1992;113:702-705 (4) Harris J. Symposium on the cornea. Introduction: factors influencing corneal hydration. Invest Ophthalmol Vis Sci. 1962;1:151.
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(5) Harris J, Nordquist L. The hydration of the cornea. I. The transport of water from the cornea. Am J Ophthalmol. 1995;40:100.
manifestations. Am J Ophthalmol.1998;125:521-526.
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(6) Hayreh SS, Podhajsky PA, Zimmerman B. Occult giant cell arteritis: ocular
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(7) Huna-Baron R, Mizrachi IB, Glovinsky Y. Intraocular pressure is low in eyes with giant cell arteritis. J Neuroophthalmol. 2006;26:273-275.
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(8) Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990;33:1122-1228.
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(9) Hwang JM, Girkin CA, Perry JD et al. Bilateral ocular ischemic syndrome secondary to giant cell arteritis progressing despite corticosteroid treatment. Am J
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Ophthalmol.1999;127.102-104.
(10) Lee AG, Tang RA, Feldon SE, et al. Orbital presentation of giant cell arteritis.
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Graefes Arch Clin Exp Ophthalmol 2001;239:509–513. (11) Liu GT, Glaser JS, Schatz NJ et al. Visual morbidity in giant cell arteritis: clinical characteristics and prognosis for vision. Ophthalmology.1994;101:1779-1785 (12) Marshall J, Grindle CF. Fine structure of the cornea and its development. Trans Ophthalmol Soc UK. 1978; 98:320-328.
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(13) Murchison AP, Gilbert ME, Bilyk JR, et al. Validity of the American College of Rheumatology criteria for the diagnosis of giant cell arteritis. Am J Ophthalmol.
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2012;154:722-729. (14) Radda TM, Bardach H, Riss B. Acute ocular hypotony: a rare complication of
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temporal arteritis. Ophthalmologica.1981;182:148–152.
(15) Slavin ML, Barondes MJ. Visual loss caused by choroidal ischemia preceding ischemic
optic
Ophthalmol.1994;117:81-86.
neuropathy
in
giant
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anterior
cell
arteritis.
Am
J
(16) Wilkinson IMS, Russell RWR. Arteries of the head and neck in giant cell
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arteritis. A pathological study to show the pattern of arterial involvement. Arch
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Neurol. 1972;27:378-391.
Abstract
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An 87-year-old woman presented 1 month after uneventful cataract surgery with ipsilateral corneal edema. She was diagnosed with pseudophakic bullous keratopathy
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and scheduled for endothelial transplantation. However, a few days later, she presented with bilateral corneal edema, dilated pupils and further reduction of visual acuity. Neuro-Ophthalmic evaluation disclosed a bilateral ocular ischemic syndrome causing Temporal artery biopsy was consistent with GCA. Corneal
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complete visual loss.
decompensation should be considered as a rare presentation of GCA, that
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ophthalmologists should suspect in any case of unilateral or bilateral ocular ischemic
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syndrome.
Keywords: ocular ischemic syndrome; central retina artery occlusion; giant cell arteritis;
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ocular hypotony; choroidal ischemia; corneal edema.
Figure 1. Top row. External view of patient’s eye. Note bilateral dilated pupils and no signs of inflammation. Bottom row. Slit lamp photographs show bilateral corneal edema (more evident in the left eye) with a nuclear cataract in the left eye.
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Figure 2. Fundus photography of the right eye shows retinal whitening associated with a
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hemorrhage inferiorly to the optic nerve.
Figure 3. Fluorescein angiography of the right eye shows a delay in choroidal perfusion
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both in (a) early and (b) late frame (27 seconds and 5 minutes respectively). On Optical
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Coherence Tomography (c), the macula is thickened as a result of ischemic edema.
Figure 4. Magnetic Resonance Angiography (MRA) of the patient shows absence of
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flow of ophthalmic arteries bilaterally.
Figure 5. Histopathology of patient’s temporal artery biopsy specimens with H&E
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staining. A. Appearance of the artery specimen: lumen is occluded and no longer visible.
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B. A multinucleated giant cell (arrow).
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Table 1
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__________________________________________________________________ Clinical Findings
Eyeball
“You will see it”
Optic nerve
Relative afferent pupillary defect if asymmetric and
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Site
sluggish pupils if symmetric. Central and/or nerve fiber bundle visual field defects
Preferential involvement of the temporal visual field
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Optic chiasm Optic tract
Relative afferent pupillary defect and homonymous hemianopia
Normal pupils and homonymous hemianopia
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Cerebral cortex
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______________________________________________________________________ Reprinted with permission from Turnbull AM, Trikha S, Gibson D, Evans AR, Foroozan R. Surv Ophthalmol. 2013;58:86-91.
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S0039-6257(17)30157-1
DOI:
10.1016/j.survophthal.2017.06.003
Reference:
SOP 6729
To appear in:
Survey of Ophthalmology
Received Date: 11 May 2017 Revised Date:
2 June 2017
Accepted Date: 6 June 2017
Please cite this article as: Pellegrini F, Prosdocimo G, Bonsanto D, Foroozan R, Thick corneas, large pupils, and a giant problem, Survey of Ophthalmology (2017), doi: 10.1016/j.survophthal.2017.06.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Thick corneas, large pupils, and a giant problem
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Francesco Pellegrini, MD (1) Giovanni Prosdocimo, MD (1) Daniela Bonsanto, MD (1)
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Rod Foroozan, MD (2)
(1) Neuro-Ophthalmology Service, Department of Ophthalmology, “De Gironcoli” Hospital, 31015 Conegliano (TV), Italy Baylor College of Medicine, Houston, Texas, United States of America
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(2)
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address correspondence to: Francesco Pellegrini
Address: Via D. Manin 110, Conegliano (TV) Italy, tel: +39 0438 668111
+39 0438 668362
email: [email protected]
ACCEPTED MANUSCRIPT
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(In keeping with the format of a clinical pathologic conference, the abstract and key words appear at the end of the article)
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Case Report
An 87-year-old woman presented to her local hospital complaining of blurred vision in
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the right eye (OD) one month after uneventful cataract surgery. Visual acuity was 10/20 OD and 6/20 in the left eye (OS). Slit lamp examination (SLE) was remarkable for moderate corneal edema OD and a nuclear cataract OS. An intraocular lens was correctly implanted in the capsular bag in OD and both eyes (OU) were otherwise quiet,
TE D
with no signs of external or internal inflammation. Intraocular pressure (IOP) was 8 mmHg OD and 10 mmHg OS, and fundi were normal bilaterally. A diagnosis of
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pseudophakic corneal decompensation OD was made, and the patient was scheduled for an endothelial keratoplasty. Three days later she returned to the emergency room
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complaining of bilateral blurred vision since that morning. Non-contrast brain computerized tomography was negative for ischemic events. Visual acuity was 2/20 OU. There was bilateral corneal edema, IOP was 8 mmHg OU, and the fundi were normal (although difficult to examine). Both pupils were mildly dilated and sluggishly reactive to light, and she was scheduled for a consultation in neuro-ophthalmology the next week.
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What are your thoughts so far and what would you do first?
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Comments by Rod Foroozan, MD The cataract surgery was said to be uneventful and the intraocular lens (IOL) was said to
SC
be in the capsular bag. This would help exclude corneal decompensation from irritation due to an improperly placed IOL haptic. Funduscopic examination was difficult to
M AN U
preform presumably because of the corneal edema in each eye. It would be important to estimate the level of visual dysfunction expected from the corneal edema. There was no suggestion of a corneal dystrophy or irido-corneal endothelial (ICE)
TE D
syndrome, which would predispose to corneal decompensation. A family history of corneal disease (Fuchs corneal dystrophy) might be helpful. I would perform corneal pachymetry and endothelial cell counts to have a more thorough understanding of the
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health of the cornea in each eye. Anterior segment optical coherence tomography
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(OCT) would be helpful to exclude a cyclodialysis cleft (particularly if the cornea was too opaque to allow for gonioscopy) that would potentially be associated with low intraocular pressure and maculopathy from choroidal folds. Imaging studies of the optic disc (retinal nerve fiber layer [RNFL]) and macula might be helpful, sometimes even if funduscopy is limited, to help exclude structural causes of a retinopathy and optic neuropathy, particularly those associated with recent anterior
ACCEPTED MANUSCRIPT
segment surgery (cystoid macular edema, choroidal detachment or folds, optic disc edema).
RI PT
Even if we find a reasonable cause for decreased vision of the right eye based on the anterior segment findings, we still need to explain the reduced visual function in the left eye, which did not undergo surgery. We are not told the preoperative visual acuity,
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which might help explain if there had been a change in the left eye as she was now 2/20
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(20/200) in each eye.
At this point we have an 87-year-old woman with decreased visual function in both eyes after she had cataract surgery in the right eye only one month before. We can use a simplified table of sites of visual loss with their clinical characteristics to help sort out
TE D
the most likely cause of decreased vision for this patient: While there are exceptions, the site of visual loss in most patients can be distinguished
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using the guidelines in this table. Problems involving the “eyeball” (ocular media and
AC C
retina) are generally detected (“seen”) through slit lamp biomicroscopy and funduscopy. Even when problems in the retina are difficult to distinguish with funduscopy, other imaging techniques, including OCT, help uncover most retinopathies. More posteriorly, the pupillary examination and visual field testing are key. The hallmark of an optic neuropathy when the deficit is symmetric is bilaterally sluggish pupils. Disorders of the optic chiasm cause preferential loss of the temporal visual field and, when the optic chiasm is affected symmetrically bilaterally, sluggish pupils may also occur. This
ACCEPTED MANUSCRIPT
patient had progressive loss of central visual function in each eye so that posterior visual pathway disease would be unexpected.
RI PT
I would suggest automated perimetry to help determine whether there is another pattern of visual loss apart from the reduction of central sensitivity expected from corneal
SC
edema, cataract, or another anterior segment cause.
Both pupils were said to be sluggishly reactive to light and mildly dilated, and there was
M AN U
no suggestion of efferent dysfunction (iris sphincter tears or third nerve palsy, for example) so we should presume there is bilateral involvement of the anterior visual pathways (retina and optic nerve) or optic chiasm until proven otherwise.
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If we cannot adequately assess the optic disc and retina to discover the cause of visual loss, then I would suggest an MRI of brain and orbits with contrast and fat suppression. The non-contrast CT of brain is often not sufficient to image the soft tissue of the optic
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nerves, sella, suprasellar space, and optic chiasm.
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Case Report (Continued)
At neuro-ophthalmologic examination the patient felt otherwise well, she denied eye pain, headache, and jaw claudication. Her past history was negative for major diseases. She took beta blockers for systemic hypertension. Family history was negative for ischemic events or neoplastic diseases. Extraocular motility was full. Visual acuity in the meanwhile had dropped to no light perception (NLP) OU. IOP was 2 mmHg in OD and
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about 0 mmHg in OS with corneal edema OS worse than OD (Figure 1). Pupils were dilated with no response to light or near stimulation. Fundi could not be seen OS, while
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there was a diffuse retinal edema suggestive of central retinal artery occlusion (CRAO) OD associated with a retinal hemorrhage inferior to the optic nerve (Figure 2). Fluorescein angiography (FA) and optical coherence tomography were performed OD
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(Figure 3), while they were not feasible OS because of corneal edema and cataract. On
detectable bilaterally (Figure 4).
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intracranial magnetic resonance angiography (MRA), the ophthalmic arteries were not
Is the vision consistent with progressive corneal edema?
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What else would you consider?
Comments
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Comments by Rod Foroozan, MD
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The visual loss has now progressed in each eye and while there is corneal edema bilaterally the cornea is not opaque enough, particularly in the right eye, to cause NLP vision. Because we cannot visualize the posterior pole due to corneal edema in the left eye an ultrasound might be help to exclude chorioretinal disorder.
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MRA of the head suggested impaired ophthalmic artery flow on each side. This could be further assessed using orbital color Doppler imaging. Funduscopy is consistent with
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a CRAO in the right eye and, given no embolic material within the retinal arterioles, an arteritic cause becomes more likely. Although we can only see a portion of the right optic disc, there was pallid edema temporally, suggestive of an arteritic cause. The FA
SC
suggested perfusion delay and impaired choroidal filling supporting a potential arteritic
M AN U
cause.
In addition the IOP has decreased in both eyes, most likely from limited ciliary body perfusion. This would imply impairment of the long posterior ciliary circulation in
TE D
combination with the retinal circulation in the right eye and potentially global loss of perfusion of both eyes, a form of ocular ischemic syndrome. The timing of the visual
EP
deficits and bilaterality go against the perfusion deficits resulting from progressive carotid occlusive disease, the most common cause of ocular ischemic syndrome. When
AC C
multiple sites of the ocular circulation are affected, particularly when bilateral, an arteritic cause becomes more likely.
Even without systemic symptoms of giant cell arteritis, I would suggest hospitalization and treatment with systemic corticosteroids and a complete blood count, erythrocyte
ACCEPTED MANUSCRIPT
sedimentation rate (ESR), C-reactive protein, and temporal artery biopsy. I would obtain an MRI of brain and orbits with contrast and MRA of the neck. Pending these
patients with giant cell arteritis.
SC
Case Report (Continued)
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results, I would also suggest imaging of the aortic arch that is sometimes helpful in
M AN U
A diagnosis of bilateral rapidly progressive ocular ischemic syndrome was made. ESR was 91mm/h and C-reactive protein (CRP) was 8 mg/dL (normal less than 0.5 mg/dL). Temporal artery biopsy was positive for giant cell arteritis (GCA) (Figure 5). The patient was treated with i.v 1000 mg methylprednisolone with no effect on vision. At one month
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the corneal edema has resolved, but she was still NLP OU.
Discussion
GCA is a medium-to-large vessel vasculitis with potentially sight- and life- threatening complications.2 The arteritis has a predilection for temporal, vertebral, ophthalmic, and posterior ciliary arteries, 16 thus explaining the high frequency of visual loss observed in this disorder. In 1990 the American College of Rheumatology (ACR) developed
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diagnostic classification criteria for GCA,
8
concluding that if a patient met 3 of the
following 5 criteria, a diagnosis of GCA could be made: 1) age 50 years or older, 2)
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new-onset of localized headache, 3) temporal artery tenderness or decreased temporal artery pulse, 4) ESR ≥ 50 mm/h, 5) biopsy specimen findings consistent with a diagnosis of GCA. Since 1990, however, our understanding of the pathogenesis,
SC
diagnosis, and treatment of GCA has improved, and the validity of the ACR criteria has been questioned. Murchison and colleagues13 found that 25% of patients with biopsy-
Moreover, approximately 20% of
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proven GCA would not have sufficient clinical ACR criteria for the correct diagnosis. patients with GCA present with occult GCA,6
meaning that a patient may suffer profound visual loss, even bilaterally, without other
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typical signs and symptoms of GCA such as jaw claudication, temporal headache, etc. While anterior ischemic optic neuropathy is the most common (80-90%) cause of visual loss in GCA, 11 visual dysfunction may occur on the basis of choroidal ischemia, retinal
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artery occlusion, posterior ischemic optic neuropathy, and occipital lobe stroke as well.15
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Giant cell arteritis, because of the inflammatory occlusion of the common carotid, internal carotid, or ophthalmic arteries,1,3,9 has the potential to cause ocular ischemic syndrome, a progressive disorder that results from hypoperfusion of the eye. The pathogenesis of the occlusion is usually atherosclerosis, but other causes can also be associated with carotid occlusion. Independently from the cause, these patients develop venous stasis retinopathy, red eye, mild uveitis, progressive cataract, and initially low intraocular pressure, in various combinations.
Acute ocular hypotony is a rare
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complication of GCA14 that results from decreased production of aqueous humor caused by insufficient arterial blood flow to the ciliary body through the long posterior ciliary
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arteries, and it can be present even without other signs of ocular ischemia.7 In rare cases, vessel inflammation caused by GCA may produce reduced blood flow to the entire orbit, thus causing a clinical syndrome that suggests orbital pseudotumor or orbital cellulitis
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and is characterized by proptosis, chemosis of the conjunctiva, limitation of eye movement, and reduced visual acuity.10 It is not clear why in the present case corneal
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edema developed before marked ocular hypotony, although the thickened corneas may have been a cause of IOP overestimation at least initially.
The endothelium is in the
main responsible for maintaining the relatively low level of stromal hydration and
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consequently of corneal transparency. This function is assured by the activity of “ionic pumps” that mediate the transfer of ions such as sodium, potassium, and magnesium from the corneal stroma to the aqueous humor. In order for this active process to work
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properly, metabolic energy is required to maintain the normal corneal thickness and
cells.12
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transparency.4,5 Numerous mitochondria are present within the cytoplasm of endothelial Reduced blood flow to the anterior segment may thus have altered the
“endothelial pump” function and caused corneal edema. The latter, theoretically, may also have been favored by a decreased number of endothelial cells in the elderly and a more pronounced reduction of endothelial cells in the operated eye. In conclusion, ophthalmologists should be aware of the many uncommon presentation of this common
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disease of the elderly. Giant cell arteritis should always be suspected in unilateral or
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bilateral ocular ischemic syndrome in patients older than 50.
References
(1) Casson RJ, Fleming FK, Shaikh A, et al. Bilateral ocular ischemic syndrome
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secondary to giant cell arteritis. Arch Ophthalmol 2001;119:306–307.
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(2) Frohman L, Wong ABC, Matheos K, Leon-Alvarado LG, Danesh-Meyer HV. New developments in giant cell arteritis. Surv Ophthalmol. 2016;61:400-421. (3) Hamed LM, Guy JR, Moster ML et al. Giant cell arteritis in the ocular ischemic syndrome. Am J Ophthalmol. 1992;113:702-705 (4) Harris J. Symposium on the cornea. Introduction: factors influencing corneal hydration. Invest Ophthalmol Vis Sci. 1962;1:151.
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(5) Harris J, Nordquist L. The hydration of the cornea. I. The transport of water from the cornea. Am J Ophthalmol. 1995;40:100.
manifestations. Am J Ophthalmol.1998;125:521-526.
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(6) Hayreh SS, Podhajsky PA, Zimmerman B. Occult giant cell arteritis: ocular
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(7) Huna-Baron R, Mizrachi IB, Glovinsky Y. Intraocular pressure is low in eyes with giant cell arteritis. J Neuroophthalmol. 2006;26:273-275.
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(8) Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990;33:1122-1228.
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(9) Hwang JM, Girkin CA, Perry JD et al. Bilateral ocular ischemic syndrome secondary to giant cell arteritis progressing despite corticosteroid treatment. Am J
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Ophthalmol.1999;127.102-104.
(10) Lee AG, Tang RA, Feldon SE, et al. Orbital presentation of giant cell arteritis.
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Graefes Arch Clin Exp Ophthalmol 2001;239:509–513. (11) Liu GT, Glaser JS, Schatz NJ et al. Visual morbidity in giant cell arteritis: clinical characteristics and prognosis for vision. Ophthalmology.1994;101:1779-1785 (12) Marshall J, Grindle CF. Fine structure of the cornea and its development. Trans Ophthalmol Soc UK. 1978; 98:320-328.
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(13) Murchison AP, Gilbert ME, Bilyk JR, et al. Validity of the American College of Rheumatology criteria for the diagnosis of giant cell arteritis. Am J Ophthalmol.
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2012;154:722-729. (14) Radda TM, Bardach H, Riss B. Acute ocular hypotony: a rare complication of
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temporal arteritis. Ophthalmologica.1981;182:148–152.
(15) Slavin ML, Barondes MJ. Visual loss caused by choroidal ischemia preceding ischemic
optic
Ophthalmol.1994;117:81-86.
neuropathy
in
giant
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anterior
cell
arteritis.
Am
J
(16) Wilkinson IMS, Russell RWR. Arteries of the head and neck in giant cell
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arteritis. A pathological study to show the pattern of arterial involvement. Arch
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Neurol. 1972;27:378-391.
Abstract
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An 87-year-old woman presented 1 month after uneventful cataract surgery with ipsilateral corneal edema. She was diagnosed with pseudophakic bullous keratopathy
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and scheduled for endothelial transplantation. However, a few days later, she presented with bilateral corneal edema, dilated pupils and further reduction of visual acuity. Neuro-Ophthalmic evaluation disclosed a bilateral ocular ischemic syndrome causing Temporal artery biopsy was consistent with GCA. Corneal
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complete visual loss.
decompensation should be considered as a rare presentation of GCA, that
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ophthalmologists should suspect in any case of unilateral or bilateral ocular ischemic
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syndrome.
Keywords: ocular ischemic syndrome; central retina artery occlusion; giant cell arteritis;
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ocular hypotony; choroidal ischemia; corneal edema.
Figure 1. Top row. External view of patient’s eye. Note bilateral dilated pupils and no signs of inflammation. Bottom row. Slit lamp photographs show bilateral corneal edema (more evident in the left eye) with a nuclear cataract in the left eye.
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Figure 2. Fundus photography of the right eye shows retinal whitening associated with a
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hemorrhage inferiorly to the optic nerve.
Figure 3. Fluorescein angiography of the right eye shows a delay in choroidal perfusion
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both in (a) early and (b) late frame (27 seconds and 5 minutes respectively). On Optical
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Coherence Tomography (c), the macula is thickened as a result of ischemic edema.
Figure 4. Magnetic Resonance Angiography (MRA) of the patient shows absence of
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flow of ophthalmic arteries bilaterally.
Figure 5. Histopathology of patient’s temporal artery biopsy specimens with H&E
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staining. A. Appearance of the artery specimen: lumen is occluded and no longer visible.
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B. A multinucleated giant cell (arrow).
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Table 1
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__________________________________________________________________ Clinical Findings
Eyeball
“You will see it”
Optic nerve
Relative afferent pupillary defect if asymmetric and
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Site
sluggish pupils if symmetric. Central and/or nerve fiber bundle visual field defects
Preferential involvement of the temporal visual field
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Optic chiasm Optic tract
Relative afferent pupillary defect and homonymous hemianopia
Normal pupils and homonymous hemianopia
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Cerebral cortex
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______________________________________________________________________ Reprinted with permission from Turnbull AM, Trikha S, Gibson D, Evans AR, Foroozan R. Surv Ophthalmol. 2013;58:86-91.
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