Painless central gray spot in a teenager

Case: A 17-year-old student developed a painless “grayish spot” in the central vision of his left eye. Over the next few days the spot progressed to look like a “backward black C” and then remained stable. He had been otherwise in good health. Examination 10 days after onset showed visual acuity of 20/20 OD and 20/200 OS, with moderate dyschromatopsia and a large central scotoma in the left eye (Figure 7.1A). Pupils constricted briskly to light with a small left RAPD. Fundus examination revealed a normal right optic disc and moderate swelling of the left disc (Figure 7.1B). He was thought to have optic neuritis, prompting an MR scan of brain and orbits that was normal.

B

Figure 7.1 Visual findings in a 17-year-old student with acute monocular visual loss. (A) Goldmann perimetry in the left eye shows a large central scotoma. (B) The left optic disc is diffusely swollen and the retinal veins mildly venous distended.

What clinical features suggest a diagnosis other than idiopathic (demyelinating) optic neuritis in this patient?

Absence of eye pain is unusual in optic neuritis. In addition, there is extensive central visual loss in the involved eye but only a small RAPD. This discrepancy between the visual loss (severe) and RAPD (mild) suggests that, although the optic disc is swollen, the visual loss is due, at least in part, to retinal rather than optic nerve dysfunction. Closer inspection of the left fundus revealed very fine, spoke-like exudates centering around the macula (Figure 7.2). The presence of this subtle macular star indicates a diagnosis of neuroretinitis rather than optic neuritis. There is also a serous detachment involving the macula which is more difficult to appreciate than the star, accounting for the central scotoma.

What is the most likely cause of this patient’s neuroretinitis, and how would you test for it?

The most common cause of neuroretinitis is cat scratch disease, and the diagnosis is established by serologic testing for antibodies to the infectious organism. The patient owned a young cat who

scratched him often. The Bartonella henselae IgG titer was elevated at 1:512 (normal <1:64) and IgM titer mildly elevated at 1:16 (normal <1:16), consistent with a recent infection. The patient was treated with a 10 day course of ciprofloxacin for cat-scratch neuroretinitis. At follow-up six months later, vision in his left eye had markedly improved to 20/30 with just a small shallow central scotoma.

Discussion: Initially designated as “stellate maculopathy”, it was subsequently recognized that the macular exudates that define this condition represent leakage of protein and lipid, not from the macula, but from inflamed disc capillaries. This fluid then spreads into the peri-papillary subretinal space and outer plexiform layer, where resorption of the serous component leaves lipid exudates that are subsequently ingested by macrophages. The star pattern of exudates reflects the loose, radial configuration of the outer plexiform layer in the macula.

Neuroretinitis usually affects children and young adults, but the age range is broad. Males and females are affected equally. Neuroretinitis has been reported in association with a variety of infectious agents, the most common of which is cat

Table 7.1 Etiologies of neuroretinitis

Bartonella species (mostly B. henselae) Spirochetes

syphilis (secondary or tertiary) Lyme disease (Stage II) leptospirosis

Viral or post-viral mumps chicken pox herpes simplex herpes zoster HIV

hepatitis B Coxsackie B influenza A Epstein Barr virus

Cytomegalovirus

Tuberculosis

Toxoplasmosis Nematodes

Toxocara canis

diffuse unilateral subacute neuroretinitis (DUSN)

Histoplasmosis capsulatum

Rocky mountain spotted fever

Salmonella

Post-vaccination rabies

Non-infectious uveitis sarcoidosis

inflammatory bowel disease periarteritis nodosa

Uncertain mechanism

Parry–Romberg syndrome (progressive facial hemiatrophy)

idiopathic retinal vasculitis and aneurysms (IRVAN syndrome)

tubulointerstitial nephritis and uveitis (TINU syndrome)

scratch disease (see Table 7.1). Cases in which no infectious etiology is identified are designated as idiopathic neuroretinitis. Regardless of etiology, approximately 50 % of all affected individuals experience an antecedent flu-like illness. In patients with cat-scratch neuroretinitis these prodromal symptoms usually include sore throat, headache, myal-

gias and lymphadenopathy. Visual loss typically takes the form of unilateral blurring of central vision, which is usually painless but occasionally accompanied by a mild ache that is not exacerbated by eye movement.

Visual acuity is reduced during the acute phase, and visual field testing usually shows a central or ceco-central scotoma that corresponds to the serous retinal detachment. To the extent that visual loss in this condition is related to retinal rather than optic nerve dysfunction, the magnitude and constancy of an RAPD in neuroretinitis is less than in optic neuritis, making this a useful differential feature. In some cases there is also a degree of optic nerve dysfunction and in these cases the RAPD is more substantial.

The fundus appearance of neuroretinitis depends, in large part, on the timing of the examination. The earliest finding is disc edema that may be diffuse or segmental and is sometimes accompanied by peri-papillary nerve fiber layer hemorrhages. The disc edema in this condition is typically associated with peri-papillary serous retinal detachment extending to the macula. In addition to the characteristic changes involving the disc and macula, small yellow-white chorioretinal spots are sometimes identified. Over time, usually 9 to 12 days after onset, the serous portion of the exudation is absorbed, leaving the lipid portion which then emerges as the characteristic macular star figure (Figure 7.3). The star is initially sharply defined and spoke-like; over time the exudate develops a more globby appearance and eventually, after a number of months, disappears completely, often leaving residual subfoveal RPE defects in the macula that remain as a helpful clue to the nature of the original episode. The disc may eventually return to normal or may show pallor and gliotic changes.

Most patients with neuroretinitis enjoy excellent recovery of vision without intervention, and a repeat event either in the previously affected or the fellow eye is unusual. Patients in whom cat scratch disease is identified or suspected are often treated with antibiotics, as in the above case, but there is

no evidence that such treatment improves the natural history of the condition. There appears to be a small subset of patients, however, with a somewhat different clinical picture in whom the prognosis is more guarded. These patients experience repeated attacks with residual visual loss each time which causes substantial cumulative damage. This variant, termed idiopathic recurrent neuroretinitis, may be suspected during the initial episode by virtue of a large relative afferent pupillary defect, disc-related field loss and poor visual recovery. Such patients should be considered to be at risk for a future similar event and should be counseled accordingly. In patients who have experienced recurrent episodes, prophylactic immunosuppressive treatment may be considered.

The diagnosis of neuroretinitis is a clinical one, based on the presence of a macular star figure in conjunction with other typical clinical features. It is important to keep in mind that other conditions can be associated with a macular star, namely malignant hypertension, increased intracranial pressure (papilledema), ischemic optic neuropathy and diabetic papillopathy. In distinguishing among these

mechanisms, it is helpful to note whether the condition affects one or both eyes. Bilateral simultaneous neuroretinitis is unusual, whereas the fundus changes in malignant hypertension and increased intracranial pressure are typically bilateral and relatively symmetric (see Chapter 1, Headache and bilateral disc edema).

It is important to distinguish patients with neuroretinitis from those with optic neuritis because of the very different neurologic prognosis in the two conditions. Patients who experience an attack of optic neuritis are at increased risk for the future development of MS (see Chapter 12, Prednisone for demyelinating optic neuritis), whereas those with neuroretinitis are not. This difference in prognosis is presumably related to differences in pathophysiology in these two conditions. In demyelinating optic neuritis the target tissue of the inflammatory response is the myelin sheath, whereas in neuroretinitis the target is the optic disc vasculature. When the patient is seen after the development of the macular star, diagnosis and prognosis should be straightforward. In the acute stage, the lack of pain and absent or small RAPD relative to the degree of