• Neuro-Ophthalmology/Orbit

    Patients who present with isolated optic atrophy can be a diagnostic dilemma for the ophthalmologist. Although the etiology of optic atrophy may be elucidated by a thorough history and examination, a definite cause is not always apparent. Recent studies have evaluated the diagnostic yield of neuroimaging in patients with unexplained isolated optic atrophy.

    History

    A complete ophthalmic examination including a comprehensive history will lead to an underlying diagnosis in 92% of cases of optic atrophy (Ophthalmology. 2005;112:757-759). Patients with optic atrophy may be unable to date the onset of their visual loss. Additionally, the sudden discovery of monocular visual loss may confound the history. Optic atrophy develops several months after damage, and thus, the patient who presents with acute or subacute visual loss (days to several weeks) and optic atrophy must have a more chronic process. A detailed history, ideally before examination, can provide many diagnostic clues toward an underlying etiology of a patient’s optic atrophy. Of greatest importance are the age of the patient, onset of visual loss (sudden versus gradual, static versus progressive), past medical history, and other accompanying symptoms.

    The most common etiologies of optic neuropathy, anterior ischemic optic neuropathy (AION), and optic neuritis are also the most common causes of optic atrophy (Ophthalmology. 2005;112:757-759). Thus the patient’s age can be helpful in differentiating these potential etiologies. Sudden or subacute visual loss points toward vascular compromise or inflammation, while gradual visual loss may indicate a compressive etiology. Similarly, static loss of vision favors previous ischemia or trauma, whereas progressive visual loss may indicate continued damage from compression or nutritional deficits. Past medical history may indicate an underlying disease process such as cancer or pseudotumor cerebri that contributes to visual loss. Systemic diseases such as hypertension, diabetes, or previous myocardial infarction or stroke provide additional evidence that the patient may have vascular risk factors that explain the optic atrophy.

    Other associated symptoms may also aid in diagnosis. Focal paresthesias and weakness may indicate demyelinating disease; presence of previous painful visual loss suggests optic neuritis; and shortness of breath and/or skin rash may occur with sarcoidosis. Investigating the vision of other family members may uncover a genetic disease in the lineage such as Leber’s hereditary optic neuropathy (LHON) or dominant optic atrophy. Finally, toxic exposure, contact with animals, and vitamin deficiencies may be ascertained from social history.

    Examination

    The ophthalmologic exam can aid in determining the underlying etiology of optic atrophy. Anterior segment exam may reveal evidence of previous trauma such as iris tears. Additionally, the presence of active or previous inflammation such as keratic precipitates or active vitreous cells may point towards an infectious or inflammatory cause of optic atrophy such as sarcoid, syphilis, cat scratch disease or Lyme disease. The optic disc examination may reveal subtle clues about causes of the optic atrophy. Horizontal band (or “bow-tie”) atrophy may be present with optic chiasmal or retrochiasmal pregeniculate lesions resulting from damage to nerve fibers originating nasal to the fovea. Optociliary collateral vessels may become apparent when retinal venous outflow is compromised by an optic nerve sheath meningioma. Examination of the nerve under slit-lamp biomicroscopy is necessary to obtain a good three-dimensional view and to rule out subtle cupping that might occur in glaucoma. When one entertains a diagnosis of optic atrophy as a sequela of non-arteritic anterior ischemic optic neuropathy (NAION), then examination of the contralateral disc is essential to confirm the presence of a small, congested nerve head, which is the “disc-at-risk.”

    Ancillary Testing

    Computerized automated perimetry may detect specific patterns of visual loss helpful in the differential diagnosis. Central field deficits occur more commonly in nutritional or toxic optic neuropathies. Hemianopic field deficits suggest chiasmal or retrochiasmal damage. Additionally, formal perimetry is an important step in documenting present visual function and subsequent deterioration or improvement. Lab tests such as angiotension converting enzyme, fluorescent treponemal antibody absorption test (FTA-ABS), Lyme titer, and cat scratch titer may also prove useful, but only when history or examination has suggested the possibility of one of these diseases. Similarly, genetic testing may reveal inherited mitochondrial diseases such as LHON or dominant optic atrophy. Indiscriminate broad spectrum testing for isolated optic atrophy without cause from history or exam is not recommended. Lab tests for infectious causes of optic atrophy can produce false positive results and are of no use without clinical correlation.2,3

    Imaging

    Recently, two large academic centers reported imaging results of 91 patients referred with unexplained isolated optic atrophy. They found that 20% of these patients had compressive lesions demonstrated by magnetic resonance imaging (MRI) with fat suppression and gadolinium administration. It was recommended that patients with unexplained isolated optic atrophy may benefit from imaging to rule out a compressive cause of optic atrophy (Ophthalmology. 2005;112:757-759). The remaining 80% of patients with unexplained isolated optic atrophy may require further investigation via, for example, genetic testing, review of prior imaging or old records, and careful follow-up. Occasionally, these patients may need to be referred to a neuro-ophthalmologist for more detailed investigation.

    Summary

    A systematic approach including thorough history and exam will aid the astute ophthalmologist in determining the underlying etiology of optic atrophy in the majority of cases. Automated perimetry is a useful adjunct to localize lesions and to document the amount of visual loss sustained. Laboratory tests are useful only in situations where clinical history or exam points towards a specific diagnosis. For cases of unexplained isolated optic atrophy, imaging is appropriate. Follow-up of patients with optic atrophy will be dictated by the underlying etiology. Patients who are showing signs of progressive optic atrophy may necessitate frequent follow-up and re-imaging. If the optic atrophy is unexplained and non-progressive, follow-up can be gradually discontinued.

    References

    1. Lee AG, Chau FY, Golnik KC, Kardon RH, Wall M. The diagnostic yield of the evaluation for isolated unexplained optic atrophy.Ophthalmology. 2005;112:757-759.
    2.

    Sander A, Posselt M, Oberle K, Bredt W. Seroprevalence of antibodies to Bartonella henselae in patients with cat scratch disease and in healthy controls: evaluation and comparison of two commercial serological tests.Clin Diagn Lab Immunol. 1998;5:486-490.

    3. Bakken LL, Callister SM, Wand PJ, Schell RF. Interlaboratory comparison of test results for detection of Lyme disease by 516 participants in the Wisconsin State Laboratory of Hygiene/College of American Pathologists Proficiency Testing Program.J Clin Microbiol. 1997;35:537-543.

    Author Disclosure

    The authors state that they have no financial relationship with the manufacturer of any product discussed in this article or with the manufacturer of any competing product.