Ординатура / Офтальмология / Английские материалы / Neuro-Ophthalmology_Kidd, Newman, Biousse_2008

in the nonaffected eye. At fluorescein angiography, there is leakage from the vessels on the surface of the disc but never leakage at the macula. Occasionally slight leakage from peripapillary vessels is seen.

The disorder is self-limiting; the disc swelling resolves over 6 to 8 weeks, and the macular lesions evolve over 7 to 10 days then remain static for several weeks before receding slowly over 6 to 12 months.

Most patients recover completely, whereas others are left with slight visual distortion from the macula, in association with defects of retinal pigment epithelium at that site. Rarely, patients exhibit a poor visual recovery and develop optic disc pallor.

There is a subgroup of patients who have a relapsing condition. This is uncommon but associated with a less favorable visual outcome. Attacks may affect the same eye or both. Corticosteroids appear not to be helpful but immunosuppression may be so.32

Fifty percent of patients provide a history of antecedence viral-type symptoms.

A modest CSF lymphocyte pleocytosis may be seen, but serologic evidence for viral infection is not often found in blood or in CSF.33,34

Other conditions may mimic neuroretinitis: a macular infiltrate may be seen in papilledema, and anterior ischemic optic neuropathy and disc infiltration by tumor. In these cases, the macular lesions would leak fluorescein, however, so these conditions can readily be thus distinguished from neuroretinitis. There is no association between neuroretinitis and the subsequent development of multiple sclerosis (MS),35 although a recent series of 25 cases included 3 who had already been diagnosed with MS, all of whom were taking interferon.36

Patients with bacterial pathogens noted previously almost invariably have symptoms of the underlying disorder (Table 7–3). Thus, those with cat scratch disease may have myalgia, malaise, fever, and lymphadenopathy, and those with Lyme disease may have arthritis, skin lesions such as erythema chronicum migrans, and the various other neurologic and ophthalmic manifestations of the infection (Table 7–3).

Treatment

In general, those with viral or idiopathic disorders will recover well and spontaneously. There is no clear evidence that use of corticosteroids enhances or accelerates recovery. Those with serologic evidence for a causative infection should have this treated. Patients with B. henselae have been treated with doxycycline,

A few cases that have been biopsied to investigate the possibility of an optic nerve sheath meningioma have shown a lymphocytic infiltration, in others granulomas are seen, and in others fibrous tissue, suggesting that the pathogenesis, although certainly inflammatory, is not consistent.

SINUS MUCOCELE AND PYOCELE

A mucocele is a noninfective complication of sinusitis in which sinus mucosa containing mucus and other secretions pass through the thin bony wall of the sinus into the extra-axial space. When this arises from the ethmoid or sphenoid sinuses, neuro-ophthalmic syndromes may ensue. A pyocele or fungal infection of the sinuses may also cause an optic neuropathy and orbital apex syndrome in the same way.

Ethmoid Sinus

Those arising from the anterior ethmoid air cells may erode into the orbit producing a painful proptosis and lateral rectus restriction. Those that arise form the posterior air cells may also produce proptosis, but if the lesion is more posteriorly placed it may compress the optic nerve at the orbital apex (Fig. 7–3) or through the orbital canal by erosion. The optic neuropathy that results may be painless and slowly progressive but may also present with a painful subacute or sudden visual loss, which is misconstrued as an acute optic neuritis. It may even relapse and remit and appear to be steroid-responsive.

If even more posteriorly placed, the lesion may involve the cavernous sinus leading to ophthalmoparesis. Mucoceles that arise from the Onodi cells are particularly likely to be associated with an optic neuropathy in view of their close proximity to the orbital apex.43

Figure 7–3 Mucoceles of (A) the ethmoid and (B) the sphenoid sinuses causing optic nerve compression.

Sphenoid Sinus

Those arising from the sphenoid sinus may spread upward to the cavernous sinus leading to ophthalmoparesis and trigeminal pain and sensory loss or to the parasellar region and even into the pituitary. The chiasm may be involved or one or both of the optic nerves or tracts. Just as with ethmoid sinus mucoceles or pyoceles, the optic neuropathy may be progressive or subacute.

In two recent series of isolated sinus disease associated with acute bacterial sinusitis, aspergillus sinusitis, and sinus mucocele,44,45 optic neuropathy arose in 10 of 73 patients of one series, and ophthalmoparesis with or without trigeminal involvement arose in 10, in which a sixth nerve neuropathy was the most common. In the second series of 50 cases, 24 had “visual changes” and only one an eye movement disorder.

The diagnosis is made with imaging (Fig. 7–3), and treatment is with surgery in which the mucocele is drained and removed. This may be carried out as an open procedure at craniotomy or as an endoscopic technique. The prognosis for visual recovery in general depends on the latency between onset of symptoms and treatment46; these authors contend that visual recovery from optic neuropathy is poor, whereas recovery from ocular motor palsies may occur even months after onset of symptoms.

Systemic Inflammatory Disorders

SARCOIDOSIS

Sarcoidosis is an inflammatory disorder of unknown etiology in which there is inflammation accompanied by an infiltration of granulomatous tissues. The prevalence is 10 to 40 105 and is more common in African Americans than Caucasians. Most organs may be involved; those most often involved include the lungs, skin, joints, and eyes. The central nervous system is affected in 10% of cases, with the development of meningeal-based inflammatory lesions leading most commonly to cranial neuropathies, but mass lesions in the brain and spinal canal occur in around 20% of cases. Intraparenchymal masses may arise very rarely, and involvement of the muscles and peripheral nerves, although uncommon, has been noted.47

Ocular Complications

Twenty-five percent to 80% of patients develop ocular complications at some point during the course of the disease, and oftentimes it is the presenting symptom of the disease. One series of 183 patients with sarcoidosis attending the Johns Hopkins Medical Institutions48 identified 47 patients (26%) who had developed ophthalmic complications attributable to the systemic disease. Seventy-four percent showed signs of uveitis, of whom the majority had an anterior involvement, 28% had involvement of the lacrimal glands, and 17% had conjunctival involvement. A band keratopathy was seen in three patients (6%), and there was one patient each with scleral involvement and an optic neuropathy. Uveitis was less common in a series from Finland49 in which 79 of 281 patients (28%) were

with substantial visual symptoms, their presence is helpful in differentiating a sarcoid uveitis from other causes.

Most ophthalmic manifestations of sarcoid respond well and rapidly to topical or systemic steroid administration. The chronic insidious panuveitis, however, does not and is associated with posterior synechiae, cataract formation, and glaucoma, leading to persistent visual impairment in around 25% of cases. Immunosuppression with azathioprine, methotrexate, cyclosporine A, and mycophenolate alone or in combination works well; more recently TNFa antagonists have also been shown to work in cases refractory to immunosuppression.56

Optic Neuropathy

Optic neuropathy in sarcoidosis arose in 5% of cases in one published series,57 although another series of 649 patients had only one case58 and a third had no cases in 285 patients with systemic sarcoidosis.59

A review of the early literature on optic nerve involvement by sarcoidosis revealed 57 published cases, the majority as single case reports or small series. Subsequent investigation revealed the cause of the optic neuropathy to be compression because of an intracerebral mass lesion in 9 cases and to hydrocephalus in 6 cases. In 6 cases, the optic neuropathy was attributed to complications of posterior uveitis. The remaining 35 cases showed evidence for a primary optic neuropathy; of these 11 presented as anterior involvement with disc granuloma (this was asymptomatic in 1 case), and in the remaining 24 cases, 9 were bilateral (4 were sequential involving the nerves, the remainder had chiasmal involvement), and 8 were associated with disc swelling in the acute phase. In only 4 of the 15 unilateral cases and none of the bilateral cases was pain a feature. In general, the clinical syndrome closely resembled that of other inflammatory optic neuropathies, because the condition developed subacutely, over days, with blurred vision and the appearance of a central scotoma. The nadir acuity was lower than that seen in demyelinating optic neuritis; 65% had an acuity in the worse affected eye of 6/60 (20/200) or lower. In 4 cases, it was NPL (no perception of light) (28%). In only 1 case did spontaneous improvement occur60; however, a recovery of function was observed to be appreciable in association with systemic corticosteroids in the

majority of cases. Some patients may undergo a worsening in acuity after steroid withdrawal.61,62

In our own series of patients with optic nerve involvement, 24 cases have been seen, of whom 12 were female and 11 were Afro-Caribbean. The mean age was 41 (20 to 71) years. Four cases had previously been diagnosed as having systemic sarcoidosis, and a further 4 cases had had symptoms likely to represent an earlier manifestation of the disease. Half had unilateral optic neuropathies (6 were associated with periorbital pain or pain on eye movement); of the bilateral cases, 3 occurred simultaneously, in the remainder the second eye was usually involved within 3 months of the first. Six were painful. Thirteen cases showed disc swelling in the acute phase. The nadir acuity was lower than that of a demyelinating optic neuritis (57% had acuity in the worse affected eye of 6/60 [20/200] or lower, and 3 had no perception of light). The clinical syndrome was of a subacute optic neuropathy with a central field defect in the majority of cases. Two further cases had compressive optic neuropathies associated with

Figure 7–5 Sarcoidosis. A, T2-weighted coronal magnetic resonance imaging showing high signal within the right optic nerve. B, Enhancement on T1-weighted sequences in a patient with systemic sarcoidosis who developed a recurrent painful optic neuropathy on the right side.

neurosarcoid mass lesions. Nine had evidence of uveitis. Of 16 cases who had undergone MRI, 7 showed enhancement of the optic nerve or sheath (Fig. 7–5), 2 showed granulomatous masses in close relation to the optic nerve, and 9 showed no abnormality. MRI of the brain and spinal cord showed abnormalities other than the optic nerve involvement in 12 cases.

Two cases improved spontaneously without steroid treatment. Twenty-two cases were treated with high-dose steroids, 9 of whom showed a worsening of acuity on stopping or reducing the steroid dose. Nine patients were treated additionally with azathioprine and two with methotrexate. Visual outcome was good in 11 patients given steroids within 1 week of visual loss, and a delay in treatment beyond 4 weeks was associated with a good response to treatment in only 3 out of 7 cases. Mean follow-up was 17 months (10 weeks to 70 months); 7 out of 36 eyes followed had a final acuity of worse than 6/12.

In another recent series,63 24 cases were presented of whom 17 had not previously been diagnosed with systemic sarcoidosis. Sufficient paraclinical data to support a diagnosis were obtained in all cases with a raised serum angiotensin converting enzyme (ACE) (an isolated feature in only 1 case), chest x-ray (CXR), gallium scan, and urinary calcium excretion. In these 17 patients, the gallium scan was abnormal in all 10 cases in which it was performed, the serum ACE was elevated in 11 of 13 cases, and the CXR abnormal in 9 of 14 cases.

Seventy-five percent had bilateral visual symptoms. The field defects included a wide range including central and paracentral scotomata, peripheral depression, arcuate defects, and chiasmal and tract defects. Forty-two percent showed evidence for current or previous uveitis. The discs were swollen only in 29% of cases, and periphlebitis and other fundal abnormalities were seen in around 15% of cases. Neuroimaging was abnormal in 70% and normal in those with isolated optic disc granulomata. Fourteen of 16 patients who underwent a spinal fluid examination showed abnormalities such as raised protein or lymphocytosis. Treatment and its response to it were not included in the report.

Hence, sarcoidosis may affect the anterior visual pathways in a number of ways. First and most commonly, a primary inflammatory optic neuropathy may

and optic nerve granuloma and ischemic complications of uveitis may also be associated with signs of optic neuropathy.

CHRONIC RELAPSING INFLAMMATORY OPTIC NEUROPATHY

From the neuro-ophthalmology departments of the National Hospital and St. Thomas’ Hospital we identified 15 patients in whom bilateral optic neuropathies (Fig. 7–8) arose that improved with corticosteroid administration but relapsed after cessation of treatment. These patients were not found to have an underlying systemic inflammatory or vasculitic disease or MS, and we felt that they formed a separate disease entity, which Dr. Elizabeth Graham called chronic relapsing inflammatory optic neuropathy (CRION).64

In the majority of cases, pain was a prominent feature before the onset of visual loss, even with relapse. The degree of visual loss is in general more severe than that seen in demyelinating optic neuritis, and the response to steroids is often dramatic, with restoration of vision from blindness within 2 to 3 days; furthermore, vision may improve with steroid administration even though months have elapsed since the onset of the optic neuropathy. On relapse, all but two cases showed further improvements in vision, and vision was subsequently maintained with immunosuppression, but in two cases relapse was associated with an irreversible visual loss.

Investigations revealed high signal within optic nerves (Fig. 7–9), often associated with enhancement, and no brain lesion. Blood investigations were normal as noted earlier, and spinal fluid examinations revealed modest elevations of protein in four of the patients and no cellular response. Oligoclonal bands were not seen.

We felt that the disorder was one of granulomatous inflammation for two reasons: first, the characteristics of the clinical syndrome with a painful

subacute optic neuropathy that responded quickly to steroids, with relapse after steroid withdrawal,61,62 which is typical of that seen in sarcoidosis (it is known

that in this condition symptoms may improve months after onset if steroids are withheld, and it is most uncommon for spontaneous improvement without treatment to take place60; and second, there are pathologic data from biopsied cases in which an optic nerve sheath meningioma was suspected, but a granulomatous

Figure 7–8 Chronic relapsing inflammatory optic neuropathy (CRION). Bilateral optic disc swelling in a patient with a subacute painful bilateral optic neuropathy that was steroid responsive and subsequently recurred.