Neuro-ophthalmic look-alikes

In every-day clinical practice, there are usually a number of disorders that could account for a particular presentation, and our job is to distinguish among them. In this chapter, however, we will focus on cases in which there are just two main diagnostic possibilities, and look at how these two conditions are distinguished. For teaching purposes, we will highlight the one best feature that differentiates the two disorders in question. The main point of this chapter is to provide the clinician with specific tips on how to distinguish between two common “lookalike” diagnoses.

Idiopathic optic neuritis vs. Leber’s hereditary optic neuropathy

Case: A 35-year-old accountant noted rapidly progressive visual loss in his left eye, described as a “bright fog”, which developed over a 10-day period. Examination revealed visual acuity of 20/400 OS, a moderate (2+) left RAPD and dense central scotoma (Figure 9.1A). The right optic disc had a normal appearance, the left optic disc was slightly swollen and just a bit hyperemic. The remainder of the fundus examination was unremarkable (Figure 9.1B). The patient was in good general health and taking no medications. He had no history of prior neurologic deficits and his family history was negative for neurologic or eye disease.

Based on this patient’s clinical presentation, what is your first diagnostic consideration?

(demyelinating) optic neuritis. A predilection for central visual loss is typical, as in the above case. In the acute stage, the optic disc is either swollen (in one-third of patients) or normal. This patient had an MRI of brain and orbits including contrast administration, which was completely normal, and then received a course of IV methylprednisolone for a presumptive diagnosis of isolated idiopathic optic neuritis. He was assured that most patients with this diagnosis experience recovery of vision to 20/40 or better. His vision, however, did not show the expected improvement and eight weeks later he noticed onset of similar visual loss in the fellow eye.

Does his clinical course change your mind about the diagnosis?

Lack of visual improvement by four to six weeks after onset is so atypical for idiopathic optic neuritis that other causes of optic neuropathy must be investigated. In this case, failure to recover vision in the affected eye, plus the early development of similar visual loss in the second eye, pointed to the alternative diagnosis of Leber’s hereditary optic neuropathy (LHON). Molecular genetic testing of this patient’s mitochondrial DNA revealed a point mutation at 11778, termed the Wallace mutation, confirming a diagnosis of LHON.

Was there a “red flag” at the time of his initial presentation?

Absence of pain at the onset of this patient’s visual loss would be highly atypical for idiopathic optic

neuritis. More than 90% of patients with idiopathic optic neuritis experience ipsilateral eye pain, usually exacerbated by eye movement and accompanied by globe tenderness. In a patient who seems to have optic neuritis but without pain, it is important to consider alternative possibilities, including ischemic optic neuropathy, neuroretinitis, compressive optic neuropathy, a variety of maculopathies and LHON. In retrospect, the normal orbital MRI should also have cast some doubt on the diagnosis of optic neuritis; abnormal optic nerve enhancement is present in approximately 90% of cases.

Discussion: Leber’s hereditary optic neuropathy

(LHON) is characterized by acute to subacute onset of painless central visual loss. The usual age at onset is between 15 and 35 years, hence the overlapping profile with idiopathic optic neuritis. LHON has a strong male preponderance (80–90%) in contrast to the female predilection in optic neu-

ritis (approximately 75%), so this patient’s gender alone is grounds for considering an alternative diagnosis, particularly LHON. Visual loss usually occurs sequentially and deteriorates over several months before stabilization. Second eye involvement occurs in most cases within weeks to months after the first eye. As in the above case, visual loss is often attributed to optic neuritis initially but when the second eye is affected the diagnosis of LHON becomes apparent.

Optic disc appearance in LHON is variable. Some patients exhibit apparent hyperemic swelling of the disc. What appear to be dilated capillaries on the disc surface actually represent a fine network of vessels referred to as circumpapillary telangiectatic microangiopathy, or, alternatively, peri-papillary microvascular angiopathy. These vessels can be distinguished from other forms of disc hyperemia by their failure to show leakage on fluorescein angiography. Accompanying the microangiopathy