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Delhi Journal of Ophthalmology
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Systematic Approach to a Case of Disc Pallor
Digvijay Singh, Rohit Saxena, Pradeep Sharma, Vimla Menon
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Disc pallor is often the sequel of various optic nerve disorders and signifies partial or total optic
atrophy. It may be present with symptoms or signs ranging from subtle visual dysfunction to
total blindness or may even be an incidental finding during routine ophthalmological checkup.
Discovering the cause of such a case can baffle neurologists and ophthalmologists alike. We
describe a systematic clinically oriented approach to a case of disc pallor to help arrive at a
diagnosis.
Introduction
Clinical Approach
An ophthalmologist is frequently faced with optic disc pallor
on fundoscopy and may be perplexed regarding how to
approach the case and identify the etiology behind this clinical
presentation. In this paper, we describe an approach to disc
pallor and clues to discover its etiology.
The clinical approach to a case of disc pallor is akin to
solving a jigsaw puzzle. With every piece put in its place, the
picture becomes clearer. The systematic process of arriving
at a diagnosis should begin with clues from the demographic
profile of the patient, followed by a directed clinical history.
This should precede an ocular and systemic examination
guided by the history. Investigations including neuro-imaging
would finally establish the etiology[2,3,4]. The protocol
and clinical interpretations are discussed in the appropriate
headings below.
Disc pallor is the manifestation of partial or total optic atrophy
and is a consequence of loss of nerve fibers. Optic atrophy
has classically been described into primary and secondary
types. Primary optic atrophy is secondary to a lesion affecting
the visual pathway from the optic nerve head to the lateral
geniculate body. The disc in such cases is flat and pale with
clearly demarcated margins. Disc edema precedes secondary
optic atrophy which presents with a dirty white to grey looking
disc with poorly delineated margins.
The etiology of unexplained disc pallor can be revealed by
appropriate investigations in a large majority of cases. This
was demonstrated in a multicentre study where of all cases
of optic atrophy only 8% remained unexplained. Further
directed investigations including neuro-imaging led to am
etiological diagnosis in another 20% of these cases. The
authors had recommended use of neuro-imaging in all cases
of unexplained optic atrophy[1].
The need for a definitive diagnosis in any case of disc pallor
stems from the fact that optic nerve diseases behave in a very
varied manner while carry different treatments and outcomes.
Some disorders such as optic neuritis are self limiting but may
be recurrent whereas others like toxic neuropathies are partially
reversible. Hereditary optic atrophies may be progressive and
with rare exception, do not show improvement. An Ischemic
optic neuropathy such as arteritic AION can rapidly involve
the fellow eye if not treated on time. Damage to nerve in toxic
optic neuropathy can be halted by removing the offending
agent.
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Demographic profile
The age, gender and race of a patient is often the first clue to
the diagnosis, but has to be interpreted with caution.
Age
The age is probably the most important of the demographic
parameters while short listing possible etiologies of disc
pallor. A brief list of various disorders and the presenting age
is below but one has to understand that there are no watertight
compartments and significant overlap of diagnosis exists
between each age group. Glaucoma can present with disc
pallor at any age and has been deliberately omitted from the
list and further discussion. The table depicts the causes for
disc pallor categorized by age group of presentation.
Gender
This guides us in favoring one diagnosis over another but one
has to be aware that there is no clear segregation of optic nerve
afflictions on gender. Male: LHON, Traumatic neuropathy,
some tapeto-retinal degenerations, toxic neuropathy(
lead,arsenic heavy metal occupational exposure, methyl
alcohol), Nutritional deficiency(chronic alcoholism).Female:
multiple sclerosis, meningioma, autoimmune/collagen
vascular diseases, Sheehan syndrome, ecclampsia,
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Delhi Journal of Ophthalmology
Systematic Approch to a Case of Disc Pallor
Race
The type of optic neuropathy and severity may demonstrate
a ethnic variation. For example, blacks were found to have
lower incidence of ischemic optic neuropathy than whites
and had lower incidence of severe visual loss secondary to
idiopathic intracranial hypertension than whites.5 Caucasians
are more likely to be afflicted with multiple sclerosis and
optic neuritis than Asians or Hispanics. Overall optic atrophy
is more prevalent in African-Americans (0.3%) than whites
(0.05%).
Clinical History
•
•
•
Chief complaints
Blurring or decrease of vision, pain on eyeball movement,
inability to see part of visual field
Clinical picture and interpretation
• Onset Acute onset (over hours to days) is seen in optic
neuritis, ischemic optic neuropathies and traumatic optic
neuropathy. Sub-acute onset (over few days) is seen
in non demyelinating inflammatory neuropathy and
compressive neuropathy. Insidious onset is characteristic
of toxic and nutritional deficiency neuropathy as well as
hereditary neuropathies.
• Course If the symptoms had self resolved without any
intervention or recurrent episodes of decrease of vision
are present, a previous demyelinating pathology should
be suspected. On the other hand a residual poor vision
after an episode or progressive deterioration or protracted
course should point towards any of the other pathologies.
• Laterality Unilateral disease is found in typical
optic neuritis, ischemic neuropathy (Non-arteritic),
traumatic neuropathy and compressive lesions. Bilateral
presentation (though may be asymmetrical) is observed
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• •
•
•
in toxic/nutritional deficient neuropathy, hereditary
neuropathy, atypical optic neuritis and arteritic anterior
ischemic optic neuropathy.
Ocular history such as red eye episodes, painful eye
movements(retrobulbar optic neuritis), diplopia and
proptosis
Systemic history such as fever, jaw claudication,
palpitations, breathlessness and symptoms suggestive
of systemic illness like diabetes, hypertension,
hyperthyroidism, recent viral infection, tuberculosis
etcetera.
History of CNS disease in form of headache, meningitis,
seizures, projectile vomiting, Transient ischemic
attacks, motor weakness, paraesthesia and other sensory
symptoms etcetera.
History of trauma
Occupational and social history with special emphasis
on alcohol/drug intake, smoking, diet and unsafe sexual
practices.
Family history is important to diagnose hereditary
neuropathy.
History of previous medications guides us regarding the
possibility of toxic neuropathy.
Ocular Examination
A complete and thorough ophthalmic examination is
mandatory. The neuro-ophthalmology specific ocular
examination includes• Visual acuity Typically disc pallor secondary to optic
neuritis, LHON, Nutritional deficiency optic neuropathy,
NAAION and inflammatory neuropathies presents
with a visual acuity of around 20/200. Hereditary optic
neuropathies (AD/AR), AAION, post papilledema and
traumatic optic neuropathies on the other hand present
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Delhi Journal of Ophthalmology
•
•
•
•
•




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with a poor visual acuity and even absence of light
perception. Toxic optic neuropathies have a variable and
unpredictable visual acuity.
Visual fields Confrontation visual fields can give a
quick assessment of any large scotomas or hemi field or
altitudinal defects. A carefully done confrontation field
test and a tangent screen test with a red target provide a
fairly accurate result.
Color desaturation test The patient may be shown a
red capped bottle and asked to compare the red color
separately with both eyes. The eye with disc pallor would
give a washed out red or pink appearance in contrast to
the bright red color seen by the fellow eye.
Pupils A relative afferent papillary defect is
characteristically found in cases of disc pallor though it
is absent in bilateral symmetrically affected cases. RAPD
can be quantitatively assessed using neutral density filters
for comparison of any future worsening of neuropathy.
Macula/Posterior pole One needs to look for presence
of exudates in the form of a star or fan or sequel thereof.
Occasionally an optic disc pit may be associated with
central serous choroidoretinopathy or a choroidal
neovascular membrane.
Disc[6]
Size This may be measured by various techniques using
a direct ophthalmoscope (use 50 cone of Welch Allen
ophthalmoscope), indirect ophthalmoscope or on slit
lamp biomicroscopy (When using a 90D lens multiply
the height of the slit measured in mm by 1.3 when it
is focused and just equal to the disc to get disc size in
mm). The importance of disc size comes when a case of
optic disc hypoplasia is confused with a disc pallor post
neuropathy.
Shape : The disc normally appears round or oval. Any
variation from this should alert towards a congenital
anomaly or traumatic avulsion.
Color : The disc is normally salmon pink in color
though the actual color varies from race to race. A disc is
described as pale if it loses the pink hue to turn towards
a whitish yellow color or a lemon tint. It is described as
hyperemic if it becomes reddish pink (a sign of increased
vascularity). There are methods described in literature to
objectively or subjectively assess and document the color
of the disc. These involve recording ophthalmoscopic
appearances and digital stereoscopic disc images
followed by analyzing them. One should establish their
own protocol and document progression of disc pallor
during follow up visits. A word of precaution which
merits mention is that the 90D lens may make the disc
look falsely healthier(less pale) due to its the yellow tint.
Cup : Disc Ratio: This shows great variability and can
range from no visible cupping to 0.6 and beyond in
Systematic Approch to a Case of Disc Pallor
the normal subjects. A deep excavated cup is of more
significance compared to a large shallow cup. The size of
a cup can also be measured similar to that described for
the disc above. Both direct and indirect ophthalmoscopy
underestimates the cupping in comparison to slit lamp
biomicroscopy.
 Neuroretinal rim : This is a congregation of nerve fibers
from the retina converging upon the disc to form the
optic nerve. A pale disc secondary to a neuro-ophthalmic
disease often has a uniform thin neuroretinal rim but there
is no focal notching or loss in contrast to glaucoma.
 Disc Margins : These should be well defined. In disc
edema they are usually blurred in the INST sequence.
Often one may notice a pallid disc edema in circulatory
compromise of the disc. LHON may present with
pseudoedema.
 Disc Vascularity : Kestenbaum count is the number of
capillaries observed on the disc. The normal number is 10
while optic atrophy will have a count of less than 6.
 Peripapilla : Presence of peripapillary atrophy (alpha
zone and beta zone) needs to be documented.
 Retinal nerve fibre layer : The presence of any RNFL
defects should be noted. This is best examined with a red
free green filter.
The appearance of the disc can give a clue about the possible
etiology[7]. Some diagnostic categories and the corresponding
disc appearance are as follows:
Ischemic Optic Neuropathy
1. Retinal arterial attenuation and sheathing
2. Pallid disc edema
3. Superior or inferior disc pallor
4. Disc hemorrhages
5. Fellow eye may show small disc with absent cup( disc at
risk)
Optic Neuritis
1. Typical : Normal disc or mild temporal pallor (Unilateral)
2. Atypical: Pallid disc edema or diffuse or bilateral disc
pallor with arterial attenuation and disc hemorrhages.
Figure 1: Bowtie optic atrophy
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Systematic Approch to a Case of Disc Pallor
Figure 2: Post papilledemic optic atrophy
Figure 3: Primary optic atrophy
Figure 4: Hemi atrophy post AION
Infectious/Infiltrative neuropathy
1. Usually following an episode of unilateral or bilateral
disc edema with macular star
2. Disc pallor is typically subtle and diffuse
Toxic/Nutritional Optic Neuropathy
1. Temporal Disc pallor
2. Usually symmetric bilateral but may show significant
asymmetry in early stages.
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Delhi Journal of Ophthalmology
Hereditary optic neuropathy (AD/Non Leber’s)
1. Disc pallor is usually subtle, mostly temporal and
occasionally diffuse
2. Non-glaucomatous cupping with peripapillary atrophy
and/or arterial attenuation is noted.
Lebers Hereditary optic neuropathy
1. Sequential bilateral presentation
2. Temporal disc pallor with RNFL defects in papillomacular
bundle
3. Non-glaucomatous cupping with arterial attenuation
4. Fellow eye may show disc at risk picture and during acute
vision loss stage may demonstrate pseudoedema with
disc hemorrhages and peripaillary telangectasias.
Optic Chiasm/Tract lesion
1. Bilateral involvement
2. Bow tie atrophy of contralateral disc (Superior and
inferior sparing)
Compressive neuropathy
1. Unilateral or bilateral disc edema and/or disc pallor
2. Painless progressive disc pallor on follow up
3. Optico-ciliary shunts/disc collaterals
Radiation neuropathy
1. Rapidly developing disc pallor (4 wks)
2. Usually disc edema not noted at any stage
3.Associated with radiation retinopathy (diabetic
retinopathy like findings)
Traumatic neuropathy
1. Anterior lesions show early ophthalmoscopic findings
such as in optic nerve avulsion and disc edema with early
onset disc pallor(3-4 weeks)
2. Posterior lesions show late onset disc pallor with no other
fundus change
Papilledema
1. A dirty grey-white optic pallor with ill defined disc details
and margins are the typical signs of a secondary optic
atrophy following long standing pailledema.
2. The disc may show an excavated appearance.
Systemic Examination
A detailed systemic examination forms an important part of
any neuro-ophthalmology workup. The key factors looked for
are:
1. General demeanor to look for nutritional deficiency or
chronic illness
2. Pulse to look for any cardiovascular signs.
3. Blood pressure, specifically for ischemic optic neuropathy
4. Conjunctival pallor for anemia which may provide
evidence of nutritional deficiency
5. Icterus to rule out systemic illness causing jaundice
and neuropathy such as hepatitis, syphilis, viral
infections,leptospira, malignancy etc. Also to suspect
toxic neuropathy.
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Delhi Journal of Ophthalmology
6. Lymphadenopathy, seen in diseases such as tuberculosis,
Collagen vascular diseases, syphilis, viral infections,
malignancy etc.
7. Specific systems including cardiovascular, respiratory,
gastrointestinal, skin and musculoskeletal to rule out
ischemic heart disease, arrhythmias, major vessel
obstructions, tuberculosis, sarcoidosis, malignancy,
collagen vascular diseases, viral exanthems, syphilis etc.
8. Central and peripheral nervous system examination to
look for any associated neurological diseases including
but not limited to meningitis, encephalitis, multiple
sclerosis, neuromyelitis optica, Friedriech ataxia and
malignancy.
On the basis of the history, ocular and systemic examination,
one should create a list of differential diagnosis and proceed
towards investigations.
Ocular Investigations
The ocular investigations should be done at baseline and
appropriate follow up visits. The follow up protocol can
be tailored by each institution on the basis of patient load
and human resource availability. We recommend these
investigations on first visit and at 1 month follow up to
establish a baseline. Then, they may be repeated once at 3
months and 6 monthly thereon. The investigations that should
be done in a case of disc pallor include
1. Color vision (Ishihara or HRR plates). Note both the
number and type of unread plates.
2. Contrast sensitivity: Pelli Robinson or FACT
3. Visual fields: Both Goldmann/Humphrey visual fields.
4. Color and red free fundus photograph centered on the
disc.
5. Flourescein fundus angiogram needs to be undertaken
only if specific indication.
6. Optical coherence tomography of the optic disc to
document nerve head and retinal nerve fiber status.
7. Electrophysiology: Visual evoked reponse (Preferably
pattern, if possible or else flash), Electroretinogram
and Electrooculogram to look for any associated retinal
dysfunction.
Systemic Investigations
The systemic investigative lineup for a case of disc pallor
may be divided into first line investigations and second line
or specific testing.
First line tests
1. Hemogram with peripheral smear, Complete blood count
with differential count
2. Liver function test
3. ESR
4. Mantoux test
5. Chest X-ray
6. MRI of Head and Orbit with thin cuts and fat suppression
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Systematic Approch to a Case of Disc Pallor
7. VDRL (syphilis serology)
8. Lumbar puncture
Specific tests based on suspected cause
1. Sarcoidosis: Serum ACE, serum Calcium levels, Gallium
scan
2. Collagen Vascular disease: Immunology workup; ANCA,
Anti-dsDNA, RF, Complement levels
3. Tuberculosis: Sputum smear AFB, Quantiferon Gold
assay, Lymph node FNAC/biopsy
4. Nutritional deficiency neuropathy: Serum B12 and Folate
levels
5. Toxic neuropathy: Heavy metal screening
6. Post infectious optic neuritis: TORCH titers
7. Hereditary neuropathy : LHON mutation testing
(preferably full mitochondrial sequencing or at least the
common primary mutations)
8. Paraneoplastic syndrome: Antibody profile such as
CRMP5 for small cell CA of lung
9. Thyroid eye disease: Serum T3, T4 and TSH levels.
10. Devic’s disease: MRI spine, Anti NMO antibody titer.
11. AAION: Temporal artery biopsy, CRP levels
Conclusion
A systematic approach to a case of disc pallor will result in
a definite diagnosis in majority of the cases without undue
loss of time or resources. Nonetheless, there are still cases
which remain unexplained and for them, the ophthalmologist,
on his part can keep a close follow up initially to ensure a
non progressive condition. While visual prognosis remains
guarded for patients with disc pallor at present, the future
holds promise with the advent of stem cell therapy, potential
for optic nerve transplantation and fast progressing technology
for artificial vision.
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4. Brazis PW, Masdeu JC, Biller J(eds).Localization in clinical
neurology. Lippincott Williams & Wilkins. 2007:131-69.
5. Mansoui AM, Hamed LM. Racial variation of optic nerve
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