CASE 2: VISION LOSS

HISTORY TAKING

GENERAL DATA 65 years old

Male

CHIEF COMPLAINT Vision loss

HISTORY OF 6 months PTA: Ten-pound unintentional weight loss

PRESENT ILLNESS 2 months PTA: Started on a new medication for cholesterol and experienced sore achy muscles. ESR
workup found to be elevated at 116
1 week PTA: Vision in R eye (OD) became blurred and completely black for 1-2 minutes during
dinner; Second similar episode in the same eye while reading the newspaper
Noted nagging right temporal headache (severe at times), occasional jaw claudication, fatigue

PAST OCULAR Corneal abrasion 3 years ago in the Right eye (OD) due to trauma
HISTORY (-) Prior eye surgeries
(-) Amblyopia, Strabismus

OCULAR None
MEDICATIONS

PAST MEDICAL Medical: Hypertension (good control), Hyperlipidemia

HISTORY Surgical: Knee surgery few years ago
Allergies: None
Medications: Hydrochlorothiazide, Lisinopril, Simvastatin

FAMILY MEDICAL (-) Macular degeneration, Glaucoma, Blindness

HISTORY

SOCIAL HISTORY Current smoker, 1 pack per day x 40 years

REVIEW OF SYSTEM Mild chronic cough (longstanding)

Denies recent illness or any other CNS, heart, lung, GI, skin or joint symptoms

PHYSICAL EXAMINATION

TEST RESULT INTERPRETATION

VISUAL ACUITY OD: 20/20 OD : Normal visual acuity

TEST OS: 20/25 +1 OS : Patient read all letters on 20/25 line and
one letter on the next line.

PUPIL REACTION OD- negative RAPD Pupillary reaction is unremarkable OU

TEST OS- negative RAPD

EOM MOTILITY OD- full EOM are intact OU

TEST 0S- full

CONFRONTATION OD- full to finger counting Visual fields intact OU

TEST OS- full to finger counting

APPLANATION OD- 14 mmHg IOP is within normal range (12-22 mmHg) OU

TONOMETRY OS- 13 mmHg

SLIT LAMP Lids, lashes, conjunctiva, sclera: unremarkable, OU Lids, lashes, conjunctiva, sclera, cornea,
Cornea: clear Anterior chamber, iris and vitreous chamber are
 Iris: (-) neovascularization unremarkable.
Lens: grade 1 nuclear cataract, OU No neovascularization.
Vitreous: clear Lens : NS tr or 1+ Nucleus clearer than anterior/
posterior sections.

FUNDUS Dilated fundus Dilated fundus examination is unremarkable.

EXAMINATION Clear view
CDR 0.2 with sharp optic disc margins
Flat macula with normal foveal light reflex
Normal vessels and peripheral retina, OU

ADDITIONAL QUESTIONS :
● Any episodes of temporary vision loss on contralateral eye?
● Are there any experiences of pain or weakness in the shoulder and hips?
○ Presence of possible rheumatic pain.

PERTINENT DATA

PERTINENT POSITIVE PERTINENT NEGATIVE

65 yo (-) Prior eye surgeries

Male (-) Amblyopia, Strabismus
Hypertension and hyperlipidemia (under medications: (-) Ocular medications
Hydrochlorothiazide, Lisinopril, Simvastatin) (-) Allergies
Vision loss, OD for 1-2 minutes (-) Family history of macular degeneration, Glaucoma,
Right temporal headache Blindness
Occasional jaw claudication (-) RAPD
Fatigue Intact extraocular muscles
ESR elevated at 116 Intact visual fields
Unintentional weight loss Normal IOP
Smoker, 1 pack per day x 40 years Fundus examination normal
No preauricular or submandibular lymph node enlargement

INITIAL IMPRESSION: Transient monocular visual loss

 DIFFERENTIAL DIAGNOSIS

Most Probable Diagnosis: GIANT CELL ARTERITIS

● Giant cell arteritis, historically referred to as temporal arteritis, is an inflammation of medium- and large-sized arteries.
● It characteristically involves one or more branches of the carotid artery, particularly the temporal artery.
● It is a systemic disease that can involve arteries in multiple locations, particularly the aorta and its main branches.

RULE IN RULE OUT

● 65 years old ● Age >60 years old

● Sudden unilateral blindness ● Female > Male
● Nagging right temporal headache ● Edema of the optic disc
● Jaw claudication ● Optic nerve is hyperemic with marginal bleeding
● Fatigue
● Weight loss
● Sore achy muscles
● Elevated ESR

JUSTIFICATION
● occurs almost exclusively in individuals >50 years
● more common in women than in men and is rare in blacks
● most commonly characterized clinically by the complex of fever, anemia, high ESR, and headaches in a patient over
the age of 50 years.

Alternative Diagnosis: RETINAL MIGRAINE

● transient vasospasm of the posterior cerebral artery that supplies the visual cortex.
● repeated attacks of the monocular visual disturbance, including scintillations, scotomata or blindness, associated with
migraine headache

RULE IN RULE OUT

 ● Headache ● Age <40 years old
● Hypertension ● Female > Male
● Transient unilateral visual loss ● Presence of series of flashes of bright light
(fortification spectra)
● Nausea
● Vertigo
● Paresis of the ocular muscles

● Transient visual loss and headache were present in this patient

● The presence of elevated ESR, jaw claudication and weight loss makes the diagnosis only an alternative

Must-not-miss Diagnosis: CENTRAL RETINAL ARTERY OCCLUSION (CRAO)

● Central Retinal Artery Occlusion or CRAO , is one of only two "absolute" emergencies in ophthalmology.
● It manifests as sudden painless loss of vision. Visual loss is severe, and remaining vision just after the episode is
usually in the area of count fingers and hand motions.
● Some patients report a prodrome of temporary "wipeout" of vision several times in a span of days to weeks before the
actual CRAO. This "wipeout" is very brief and lasts for a few seconds. At this time the patient's vision appears white or
gray with all details gone temporarily.
● CRAO is usually related to systemic vascular disease like hypertension, arteriosclerosis, collagen disease, hematologic
disorders.

RULE IN RULE OUT

● Painless vision loss ● Cherry red spot in the center of the macula
● Sudden acute vision loss (hallmark)
● Mono-ocular blurring of vision (Right Eye) ● Whitening of the retina/pale color
● Risk factor: Hypertension and hyperlipidemia ● Presence of RAPD

● CRAO can be considered in patients with transient vision loss.

● It characterizes sudden painless onset.
● It is considered as an ocular emergency which causes irreversible damage.
● The presence of hyperlipidemia and hypertension were also considered.
● Presence of cherry red-spot in fundoscopic finding is one of the hallmarks of CRAO but is not present in the patient.

SUMMARY OF DIFFERENTIAL DIAGNOSIS

Pertinent data of the patient Giant cell arteritis Retinal migraine Central retinal artery
occlusion (CRAO)

Age -65 yrs (+) (-) (+)

Sex- male (-) (-) (+)

Females > males

Chief complain - vision loss (+) (+) (+)

Sudden unilateral vision loss Transient unilateral vision Painless loss of vision
loss

History - hypertension , (-) (+) (+)

hyperlipidemia , smoking Hypertension is a risk factor

Nagging right temporal (+) (+) (-)

headache ( severe at times )

Jaw claudication , elevated (+) (-) (+)

ESR , weight loss Very specific Only if CRAO is due to GCA

DISCUSSION OF THE MOST PROBABLE DIAGNOSIS:

GIANT CELL ARTERITIS
INTRODUCTION ● Also known as Horton disease, cranial arteritis, and temporal arteritis.
● Categorized as a vasculitis of large- and medium-sized vessels because it can involve the
aorta and great vessels.
● Vessels most often involved are the arteries of the scalp and head, especially the arteries
over the temples.

EPIDEMIOLOGY ● Aging - greatest risk factor for developing GCA

○ Affecting individuals older than 50 years.
○ Mean age at onset is about 70, with a range of 50 to > 90.
● Women are affected more often.
● About 40 to 60% of patients with giant cell arteritis have symptoms of polymyalgia
rheumatica.
● Ethnicity - highest incidence figures are found in Scandinavian countries and among
Americans of Scandinavian descent.

ETIOLOGY ● Idiopathic
○ Most common idiopathic systemic vasculitis
● Potential trigger: environmental factors
○ Because of seasonal variations and because incidence is higher in large
conurbations
● Genetic abnormalities (i.e.HLA-DR4 mutations)

PATHOPHYSIOLOGY

Legend:
● Blue box - pathophysiology
● Yellow box - mechanism
● Green box - signs/symptoms / laboratory findings

CLINICAL Manifestations of GCA

MANIFESTATIONS ● Symptoms may begin gradually over several weeks or abruptly
● Symptoms due to involvement of cranial vessels
 ○ Headache
■ Most common symptom: Severe, throbbing headache (temporal,
occipital, frontal, or diffuse) and may be accompanied by scalp pain
elicited by touching the scalp or combing the hair.
○ Jaw claudication (pain on chewing)
■ Jaw claudication and diplopia are associated with a higher risk of
blindness.
○ Scalp tenderness
○ Visual disturbances
■ Include diplopia, scotomas, ptosis, blurred vision, and loss of vision
(which is an ominous sign).
■ Brief periods of partial or complete vision loss (amaurosis fugax) in one
eye may be rapidly followed by permanent irreversible loss of vision. If
untreated, the other eye may also be affected
○ Abnormalities of temporal artery( pain, nodules, absence of pulse)
● Symptoms due to involvement of great vessels (aorta and branches of aorta)
○ Claudication of extremities (especially arm)
● Symptoms due to systemic inflammation
○ Fever (usually low-grade), night sweats, fatigue, malaise and unexpected weight
loss
● Polymyalgia rheumatica
○ Mainly proximal myalgia and stiffness of the neck and shoulder and pelvic girdle
■ Diagnosis of GCA is more likely if patients also have symptoms of
polymyalgia rheumatica
Other ocular manifestations of GCA
● Central retinal artery occlusion
● Cilioretinal artery occlusion
● Retinal cotton-wool spots
● Ophthalmic artery occlusion
● Diffuse ocular ischemia

LABORATORY ● Indicators of systemic inflammation:

FINDINGS
○ Elevation in the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
level, but both may be normal.

■ ESR markedly raised (80–100 mm in the first hour)

■ CRP moderately raised (25–50 mg/dL)

○ Normochromic normocytic anemia

○ Leukocytosis
○ Thrombocytosis
○ Increase in acute-phase proteins in serum albumin electrophoresis

DIAGNOSTIC PROCEDURES

A. Laboratory Diagnosis

Test Definition Expected Finding Notes

Erythrocyte Measures how quickly the red Markedly raised (80-100 mm in the first ESR and CRP can
Sedimentation Rate blood cells fall to the bottom of hour) sometimes be normal.
(ESR) the tube. One of the most useful Elevation does not
marker of giant cell arteritis correlate with severity.

Normal value: 1-5 mm/h Non Concordance

between ESR and CRP
C-Reactive Protein Hepatic in origin that usually rises Moderately raised can occur. The use of
(CRP) before ESR in most disease both tests provides a
states. Marker of inflammation slightly greater
sensitivity than used
Normal value: <5mg/L alone
Complete blood Normal values: Increased platelet count Leukocyte and
count Hemoglobin = 11.7 (thrombocytosis) differential counts are
Platelet count = 150000 - generally normal
350000 Anemia has been shown to have a
good negative predictive value for
severe ischemic complications

Temporal artery GOLD STANDARD for
biopsy diagnosis of Giant Cell Arteritis
The frontal branch of the
superficial temporal artery is
preoperatively identified by
visualization, palpation or Doppler
ultrasonography and marked with
a pen or a dye
Recommended for patients 55
years old and older in a later
stage of diagnostic protocol
(1) Intimal proliferation with resulting May not be positive in
luminal stenosis all patients due to
(2) Disruption of the internal elastic patchy histologic
lamina by a mononuclear cell infiltrate findings.
(3) Invasion and necrosis of the media
progressing to involvement of the entire Positive yield is
vessel wall with an inflammatory increased by obtaining
infiltrate consisting predominantly of a biopsy segment of 3-5
mononuclear cells cm together with serial
(4) Giant cell formation with sectioning of biopsy
granulomata within the mononuclear specimens
cell infiltrate

Fluorodeoxyglucose Evaluate the vasculitic process Large vessel arteritis Is not useful in
Positron Emission within large vessels such as the vasculitis limited to the
Tomography thoracic aorta temporal arteries
(FDG-PET/CT) because of the small
diameter of these
vessels and the high
levels of FDG uptake in
the brain

Color Duplex Reported helpful in the diagnosis Hypoechoic halo around the temporal Halo sign may not be
Ultrasonography of and has been increasingly used artery lumen evident in early
temporal artery by some physicians Non-compressible arteries inflammatory changes
Stenosis
Vessel Occlusion

Cerebral Not the procedure of choice Granulomatous inflammation in the wall At cost of potent
Angiography of medium-size and large arteries and complications
preferentially affects extracranial
branches of the carotid artery

B. Clinical Diagnosis

1. ACR criteria (1990) 2. Revised ACR criteria -

Score Criteria Score Criteria

1 Age at onset ≥50 years Entry

2 A new headache N/A Age at onset ≥50 years

3 Temporal artery abnormality such as N/A Absence of exclusion criteria

tenderness to palpation or decreased
 pulsation Domain I

4 Erythrocyte sedimentation rate ≥50 mm/h 1 New onset localized headache

5 Abnormal artery biopsy showing vasculitis with 1 Sudden onset of visual disturbances
mononuclear cell or granulomatous
inflammation, usually with giant cell infiltrates 2 Polymyalgia Rheumatica

● 3 of 5 points are required for diagnosis 1 Jaw claudication

2 Abnormal temporal artery

Domain II

1 Unexplained fever or anemia

1 ESR ≥50 mm/hr

2 Compatible pathology

● In the presence of 3 points or more out of 11 with at

least one point belonging to domain I along with all entry
criteria, the diagnosis of Giant cell arteritis can be
established
● Exclusion criteria: ENT and eye inflammation, kidney,
skin and peripheral nervous system involvement, lung
infiltration, lymphadenopathies, stiff neck and digital
gangrene or ulceration
● No other etiologies can better explain any one of the
criteria
● Enlarged and/or pulseless temporal artery: 1.p./tender
temporal artery: 1.p
● It must be ignored in the presence of PMR
● Vascular and/or perivascular fibrinoid necrosis along
with leukocyte infiltration: 1.p. /and granuloma: 1.p

Patient’s Score based on Revised ACR criteria:

● Entry Criteria:
○ Age = 65 years old
○ Absence of exclusion criteria
● Domain I:
○ 1 = New onset localized headache
○ 1 = Sudden onset of visual disturbances
○ 1 = Jaw claudication
● Domain 2:
○ 1 = ESR of 116 mm/hr

MANAGEMENT

TREATMENT Goal of treatment: to reduce symptoms and to prevent visual loss

Gold Standard for the treatment of Giant Cell Arteritis: GLUCOCORTICOIDS

Mechanism of Action (glucocorticoids)

● Glucocorticoids are carried via the transporter glucocorticoid binding protein (GBP)
● It binds to the glucocorticoid receptor complex (GRC) which is to HSP90 and HSP70 (2 heat shock
proteins) which are located in the cytoplasm. This activates the receptor and dissociates the 2
protein from the complex
● The activated glucocorticoid complex is then allowed to to translocate into the nucleus where it
binds the glucocorticoid response element
● This then activates the complex and alter the gene transcription
○ It upregulates gene lipocortion which inhibits phospholipase 2 enzyme and prevents the
liberation of arachidonic acid from the membrane phospholipid which reduce
 prostaglandin and thromboxane a2 production
MEDICATIONS:
● GLUCOCORTICOIDS
○ IV methylprednisolone, 500 mg to 1 g/ day fro 3 days followed by oral prednisolone 1-2
mg/kg/day
○ After 3 days- oral dose is reduced to 50-60 mg ( not less than 0.75 mg/kg) fo 4 weeks or
until symptom resolution and ESR/CRP is normal
○ Typical subsequent regimen
■ Reducing daily dose by 10mg/kg Q2 weeks until 20 mg/day is reached
■ Tapering afterwards titrated against ESR/CRP symptoms
● BIPHOSPHATE & CALCIUM OR VIT. D SUPPLEMENT (WEEKLY)
○ Justification
■ GCA therapy requires both long term and short term and high dose of
glucocorticoid therapy. An oral glucocorticoid treatment- >5 mg prednisone
daily can lead to bone density reduction and raid dose-dependent increase in
the risk of fracture:
● PROTON PUMP INHIBITORS (PPI)
○ Omeprazole, lansoprazole
○ Justification:
■ Gastrointestinal protection is recommended especially if concomitant risk
factors are present (NSAID use and old age)
● ORAL ASPIRIN THERAPY
○ 81 mg/day
○ Justification:
■ Antiplatelet therapy may reduce the risk of ischemic events (stroke or
blindness)

SUPPORTIVE MONITORING
● Full blood count, ESR/CRP, urea and electrolytes, random glucose and blood pressure
○ Checked each visit
○ Frequency of follow up:
■ Weeks 0,1,3, 6, then months 3, 6, 9, 12 in the 1st year
■ Extra visits in the events of relapse or AE
● Every 1-2 years, chest xray or more sophisticated imaging to exclude aortic aneurysm; assess
bone mineral density

RELAPSE
● Treated aggressively with increase steroid dose
● IV methylprednisolone if visual disturbance occur

FUTURE THERAPIES
● Tocilizumab (subcutaneous)
● Abatacept