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Delhi Journal of Ophthalmology Preferred Practice Pattern 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. DJO 28 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, Vol. 21, No. 3, January-March, 2011 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 Vol. 21, No. 3, January-March, 2011 • • • • 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 DJO 29 Delhi Journal of Ophthalmology • • • • • DJO 30 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 Vol. 21, No. 3, January-March, 2011 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. Vol. 21, No. 3, January-March, 2011 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. DJO 31 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 DJO 32 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. References 1. Lee AG, Chau FY, Golnik KC, Cardon RH, Wall M. The diagnostic yield of the evaluation for isolated unexplained optic atrophy. Ophthalmology 2005:112:757-59. 2. Behbehani R. Clinical approach to optic neuropathies. Clin Ophthalmol. 2007:1(3):233-46. 3. Lee AG, Brazis PW (eds). Clinical pathways in NeuroOphthalmology: An Evidence based approach. Thieme Medical Publishers. 2003:1-35. 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 disease. Neuro-Ophthalmology.1991:11:319-23. 6. Teymoorian S. Examination of the optic nerve at the slit lamp biomicroscope with a handheld lens. http://eyewiki.aao.org. Accessed on 2nd January 2011. 7. O’Neill EC, Danesh-Meyer HV, Connell PP et al. The optic nerve head in acquired optic neuropathies. Nat rev neurol. 2010:6(3):221-36. Vol. 21, No. 3, January-March, 2011