28 Optic Nerve

310 ANKYLOSING SPONDYLITIS AND

REITER’S DISEASE 720.0

James P. Dunn, Jr., MD

Baltimore, Maryland

Sanjay R. Kedhar, MD

Baltimore, Maryland

●The prognosis depends on the number and severity of attacks of uveitis.

●Most clinicians believe that prompt, aggressive corticosteroid therapy for each attack reduces the risk of chronic uveitis and macular edema.

Ankylosing spondylitis (AS) and Reiter’s disease are two of the seronegative spondyloarthropathies, disorders characterized by chronic inflammation of the peripheral and axial joints, familial occurrence, and extra-articular involvement of the skin, genitals, and eyes.

ETIOLOGY/INCIDENCE

AS usually affects young adults aged 16 to 40. Men are affected slightly more often than women and often have more severe involvement.

●Four to eight percent of the Caucasian US population is positive for HLA-B27. The prevalence is somewhat lower in other ethnic groups.

●There is a 2% cumulative lifetime incidence of uveitis in HLA-B27-positive patients. The mechanism by which HLAB27 confers increased susceptibility to systemic and ocular disease is unclear. The HLA-B27 gene product may crossreact with foreign antigens (‘molecular mimicry’).

Clinical signs and symptoms

AS is characterized by chronic inflammation of the cartilaginous joints of the axial skeleton, including the sacroiliac joints, intervertebral spaces, and apophyseal and costovertebral articulations. Early symptoms include low back pain, which improves with activity. Fusion of the axial skeleton (‘bamboo spine’) can occur in untreated patients, causing marked impairment in mobility. The arthritis can also involve the shoulders, hips, knees, and feet; cervical arthropathy and heel pain (plantar fasciitis) are common symptoms. Extra-articular manifestations include cardiac conduction defects, aortic regurgitation, IgA nephropathy, amyloidosis, apical lobe fibrosis, and cauda equina syndrome. The classic ocular manifestation of AS is acute, unilateral, recurrent, nongranulomatous iridocyclitis, with attacks repeatedly affecting one eye or alternating between the eyes. Symptoms include pain, redness, and photophobia. Intervals between episodes can be months to years. After repeated attacks, chronic iridocyclitis can develop, more com-

Ureaplasma urealyticum, or Campylobacter spp. may trigger attacks of Reiter’s disease.

●Uveitis develops in 20% to 40% of patients with AS and in approximately 25% of those with Reiter’s disease.

●Of patients with HLA-B27-associated anterior uveitis, 24% to 69% have ankylosing spondylitis and 15% have Reiter’s disease.

●In patients with systemic and ocular disease, the systemic disease is undiagnosed in more than 50% at the time of uveitis consultation; more than 80% of patients experience rheumatologic symptoms before the initial episode of uveitis.

●There is a 10-fold increased risk of AS and iridocyclitis in first-degree relatives who are positive for HLA-B27.

COURSE/PROGNOSIS

●The average attack of iridocyclitis in AS and Reiter’s disease lasts about 6 weeks, with considerable variation.

at the time of an acute attack is usually normal or low (due to ciliary body dysfunction), but may increase with treatment as aqueous production normalizes and the hypertensive effects of corticosteroid therapy or peripheral anterior synechiae become manifest.

Reiter’s disease consists of the triad of nongonococcal urethritis, asymmetric polyarticular arthritis of the large joints, and conjunctivitis or anterior uveitis. AS can occur in patients with Reiter’s disease. Other characteristic features include keratoderma blennorrhagicum, a psoriatic skin disease, in approximately 25% of patients, and balanitis circinata. Fasciitis and tendonitis, often manifesting as heel pain, can occur. Reiter’s disease is more common in men. Ocular manifestations of Reiter’s disease include acute, recurrent, unilateral, nongranulomatous iridocyclitis; bilateral, mucopurulent conjunctivitis; and subepithelial or anterior stromal corneal infiltrates. As with AS-related iridocyclitis, intraocular pressure may be normal or low at the time of an acute attack but may increase with treatment.

Nerve Optic • 28 SECTION

Neuropathies Optic Compressive • 311 CHAPTER

Nerve Optic • 28 SECTION

COMPLICATIONS

All orbital surgeries are fraught with the possibility of iatrogenic damage to the optic nerve. The surgical field must have complete hemostasis at the conclusion of the operation. Bleeding into the closed orbital space can also cause a compressive optic neuropathy. Significant swelling occurs after any orbital surgery. Patients routinely receive high dose systemic corticosteroids (oral or intravenous) during the perioperative period to decrease orbital swelling.

Extracranial optic canal decompression can be complicated by meningitis, cerebrospinal fluid leaks, pneumocephalus, sinusitis, esotropia, and symptomatic diplopia. The most feared complication is carotid bleeding. If attention is paid to the anatomic landmarks in the sphenoid sinus, the internal carotid artery may be avoided.

COMMENTS

Compressive optic neuropathies should be suspected in any patient with progressive vision loss associated with a relative afferent pupillary defect or with a relative afferent pupillary defect and proptosis, injection, or ophthalmoplegia. These patients require a complete evaluation including visual acuity, color vision, pupillary assessment, ocular motility evaluation, and visual field testing. Careful attention must be paid to the visual field of the contralateral eye for superotemporal quadrant field defects that are suggestive of a junctional scotoma and an anterior chiasmal mass. The optic nerve head may have a normal appearance or demonstrate atrophy, edema, shunt vessels, and large cupping. Patients may or may not have ophthalmoplegia, injection, chemosis, strabismus, proptosis, pain, resistance to retropulsion, bruits, and periorbital changes.

If patients are suspected of having a compressive optic neuropathy, they must undergo a neuroimaging study of the brain and orbits. Magnetic resonance imaging with gadolinium enhancement and fat suppression is the modality of choice.

After treatment, all patients with compressive optic neuropathy should be followed with sequential tests of visual acuity and perimetry. Afferent pupillary defects are best followed with neutral density filters.

REFERENCES

Goldberg RA, Steinsapir KD: Extracranial optic canal decompression: indications and technique. Ophthal Plast Reconstr Surg 12:163–170, 1996.

Graham SM, Brown CL, Carter KD, et al: Medial and lateral orbital wall surgery for balanced decompression in thyroid eye disease. Laryngoscope 113:1206–1209, 2003.

Li KK, Lucarelli MJ, Bilyk JR, Joseph MP, et al: Optic nerve decompression for compressive neuropathy secondary to neoplasia. Arch Otolaryngol Head Neck Surg 123:425–429, 1997.

Saeed P, Rootman J, Nugent RA, et al: Optic nerve sheath meningioma. Ophthalmology 110:2019–2030, 2003.

Schaefer SD, Soliemanzadeh P, Della Rocca DA, et al: Endoscopic and transconjunctival orbital decompression for thyroid-related orbital apex compression. Laryngoscope 113:508–513, 2003.

Turbin RE, Thompson CR, Kennerdell JS, et al: A long-term visual outcome comparison in patients with optic nerve sheath meningioma managed with observation, surgery, radiotherapy, or surgery and radiotherapy. Ophthalmology 109:890–899, discussion 899–900, 2002.

312 CONGENITAL PIT OF THE OPTIC

DISC 377.4

Fion D. Bremner BSc, MBBS, PhD, FRCOphth

London, England

ETIOLOGY/INCIDENCE

Congenital pits in the optic nerve head are developmental anomalies found in 1 : 11,000 of the normal population (males = females). They are usually single, unilateral (85%) and occur most commonly in the temporal sector of larger than normal discs. Light microscopy shows herniation of dysplastic retinal tissue through a defect in the lamina cribrosa. There are no associations with other developmental anomalies, although cilioretinal arteries are present in over 50% of cases. Autosomal dominant inheritance has been described, but most cases are sporadic and the underlying genetic defect and pathogenesis are unknown.

COURSE/PROGNOSIS

Many optic pits remain asymptomatic throughout life. However, 25–75% of patients with this condition present in the third to fourth decades of life with visual loss due to serous detachment of the macula. The source of the fluid is unknown. The precipitant is probably vitreous traction, and the risk is greatest if the pit is temporal. Spontaneous anatomical reattachment occurs in 25% of cases but visual function often remains subnormal.

DIAGNOSIS

Visual acuity is usually unaffected in patients with uncomplicated optic pits, but threshold perimetry may reveal nonprogressive visual field defects, particularly arcuate scotomata. Maculopathy causes central blurring and metamorphopsia, with a drop in acuity to 6/9–6/60; there is serous elevation of the retina extending from the optic pit to the fovea, sometimes accompanied by a partial thickness macular hole (Figure 312.1). On fluorescein angiography pits show early hypofluorescence and late hyperfluorescence (staining) without leakage of dye towards the macula. Ocular coherence tomography (OCT) confirms that the fluid is mainly within a schitic cavity, accumulating under the retina only after formation of an outer leaf hole under the fovea. Rarely, an inner leaf cyst progresses to a hole and rhegmatogenous retinal detachment.

Differential diagnosis

Of pit:

●Disc coloboma;

●Glaucomatous excavation (especially normal tension glaucoma).

Of maculopathy:

●Central serous retinopathy (CSR).

FIGURE 312.1. Congenital optic disc pit (black arrow) with serous detachment of the macula (white arrow).

TREATMENT

Uncomplicated optic pits require no treatment although prophylaxis against maculopathy has been suggested. Various measures have been tried to restore vision in patients with associated maculopathy.

Laser

Linear photocoagulation between pit and macula (to ‘wall off’ the subretinal fluid and prevent extension under the fovea) used to be the standard treatment but proved ineffective, probably because the fluid is mainly within a schitic cavity and not subretinal.

Surgical

Two approaches have been described, vitrectomy with gas tamponade and macular buckling. Both procedures have produced good long-term outcomes in published series.

COMPLICATIONS

Of maculopathy:

●Intraschitic haemorrhage;

●Macular cyst;

●Macular hole;

●Rhegmatogenous detachment.

Of treatments:

●Rhegmatogenous detachment;

●Cataract;

●Glaucoma.

COMMENTS

Congenital optic pits are not uncommon but are frequently overlooked. Associated serous detachment of the macula is easily misdiagnosed as CSR unless the disc is also examined carefully. The distinction is clinically important since, unlike CSR, optic pit-associated maculopathy is rarely self-limiting and without surgical treatment carries a poor prognosis for spontaneous visual recovery.

REFERENCES

Kranenburg EW: Crater-like holes in the optic disc and central serous retinopathy. Arch Ophthalmol 64:912–924, 1960.

Lincoff H, Schiff W, Krivoy D, Ritch R: Optical coherence tomography of optic pit maculopathy. Am J Ophthalmol 122:264–266, 1996.

McDonald HR, Schatz H, Johnson RN: Treatment of retinal detachment associated with optic nerve pits. Int Ophthalmol Clin 32:35–42, 1992.

Sobol WM, Blodi CF, Folk JC, Weingeist: Long-term visual outcome in patients with optic nerve pit and serous retinal detachment of the macula. Ophthalmology 97(11):1539–1542, 1990.

Stefko ST, Campochiaro P, Wang P, et al: Dominant inheritance of optic pits. Am J Ophthalmol 124(1): 112–113, 1997.

313DRUG-INDUCED OPTIC ATROPHY

377.34

Roberto Guerra, MD

Modena, Italy

Gian Maria Cavallini, MD

Modena, Italy

Drug-induced optic atrophy is a toxic optic neuropathy ranging from partially or totally reversible forms to irreversible blindness. The condition is usually bilateral. Visual acuity may range from 20/20 to light perception, with most patients showing a visual acuity in the range of 20/200 at the time of the first examination.

ETIOLOGY/INCIDENCE

Relatively little is known about the pathogenesis of druginduced neuropathies, but clinical signs and symptoms and the results of optic nerve conduction studies indicate that most of these neuropathies are characterized by the selective symmetric involvement of maculopapillary axons, ganglion cells, or both.

Toxic optic neuropathies seem to be directly related to the dosage and duration of treatment.

Agents that may cause optic atrophy include amiodarone, barbiturates, carmustine, chloramphenicol, chloroquine, cisplatin, corticosteroids, 2′,3′-dideoxyinosine (ddI), digoxin, disulfiram, ergotamine, ethambutol, fluoroquinolones, heavy metal compounds, halogenated 8-hydroxyquinolines, hexachlorophene, hexamethonium, iodide compounds, isoniazid, lithium carbonate, methotrexate, metronidazole, monoamine oxidase inhibitors, nitrosoureas, oral contraceptives, penicillamine, perhexiline, phenothiazines, streptomycin, tamoxifen, tryparsamide and vincristine.

Optic atrophy has been associated with vigabatrin use. Cimetidine and linezolid-associated optic neuropathies as well sildenafil-associated nonarteritic anterior ischemic neuropathy have been reported.

Optic neuropathy has been reported as a rare complication with the use of several vaccines, including rabies; smallpox; trivalent measles, mumps, and rubella; diphtheria; and bacille Calmette–Guérin.

The cocaine-exposed newborn may have optic nerve abnormalities and delayed visual maturation.

Atrophy Optic Induced-Drug • 313 CHAPTER

Nerve Optic • 28 SECTION

Neuropathies Optic Inflammatory • 314 CHAPTER

Nerve Optic • 28 SECTION

DIAGNOSIS

Clinical signs and symptoms (see Table 315.1)

These conditions present as acute optic neuropathies but unlike demyelinating optic neuritis they are more often bilateral and can be more painful. Optic disc swelling, often with haemorrhage and a cellular infiltrate of the vitreous, is usually present and other signs of a systemic vasculitis or multi-system inflammatory disorder may be seen. Spontaneous improvement in vision does not occur or vision may worsen after a standard treatment course of corticosteroids.

Laboratory findings (see Table 315.1)

All patients should have gadolinium-enhanced orbital and brain magnetic resonance imaging (MRI) which will rule out a compressive lesion and may show optic nerve sheath or meningeal enhancement consistent with sarcoidosis. The brain imaging should be reviewed for asymptomatic lesions consistent with demyelination which may help to differentiate demyelinating optic neuritis from the other inflammatory optic neuropathies where lesions would not be expected. Spinal cord MRI should be performed if neuromyelitis optica is suspected. Genetic testing for Leber’s mutation may be helpful in appropriate patients. Serological and other tests to investigate for the presence of sarcoidosis or a systemic vasculitis should be performed. A positive antinuclear antibody test may, however, be seen in up to 3% of patients with typical demyelinating optic neuritis.

An infectious cause, such as syphilis, Lyme disease, HIV, or tuberculosis should be excluded in appropriate patients. A cerebrospinal fluid examination is very useful in identifying infections, particularly if there is hypercellularity. The protein level is usually raised in the inflammatory optic neuropathies. There may be no oligoclonal bands or matched oligoclonal bands in both CSF and serum indicating systemic production of immunoglobulins. In demyelinating optic neuritis there may be no oligoclonal bands of immunoglobulins, or intrathecal synthesis of immunoglobulins (unmatched bands compared with serum).

Differential diagnosis

●Demyelinating optic neuritis.

●Compressive optic neuropathy.

●Infectious optic neuropathy.

●Anterior ischemic optic neuropathy.

●Leber’s hereditary optic neuropathy.

●Toxic optic neuropathy.

●Nutritional optic neuropathy.

PROPHYLAXIS

Prolonged immunosuppression is usually required to prevent relapses.

TREATMENT (see Table 315.1)

These conditions are rare and in most cases randomized trials of treatment have not been performed. Treatment advice is therefore based on Class III evidence. Systemic medical treatment is required in most cases.

Treatment of a suspected inflammatory optic neuropathy should be with 1g/day intravenous methylprednisolone for 3

days followed by 1 mg/kg/day of oral prednisolone. This should be tapered at 10 mg/month after symptoms have improved and an alternate-day regimen considered. When 20 mg/day equivalent is reached then the withdrawal should be more made more slowly. If a relapse occurs on reducing the dose then high-dose prednisolone should be re-instigated, or a pulse of intravenous methylprednisolone given in severe cases, and a corticosteroidsparing agent such as azathioprine, methotrexate or ciclosporin started before reducing the prednisolone dose again. Gastric protection and measures to try to prevent corticoste- roid-induced osteoporosis need to be employed, according to local guidelines.

The specific treatment of some of the inflammatory optic neuropathies, according to the evidence that is available, is considered below.

Autoimmune and vasculitic optic neuritis

In optic neuritis associated with vasculitis (e.g. in systemic lupus eythematosus) the early addition of intravenous cyclophosphamide has been reported to be of benefit in some cases to restore vision.

Behçet’s disease

Optic neuropathy is rare in Behçet’s disease and is often seen in combination with retinal vasculitis. Treatment should commence with intravenous methylprednisolone followed by a tapering dose of prednisolone as described above, with the early addition of ciclosporin in treatment-resistant cases.

Neuromyelitis optica

The initial treatment of neuromyelitis optica should be as outlined above with early addition of azathioprine in most cases. Where there is a poor initial response to treatment then plasma exchange should be performed as there is evidence of humeral factors being involved in the pathogenesis of the condition and Class I trial evidence supporting this line of therapy. Rituximal may be useful for maintenance therapy in refractory cases.

Neuroretinitis

The visual loss in neuroretinitis usually recovers spontaneously and the disease does not usually recur. In a subgroup of patients, vision is not recovered without corticosteroids; long-term immunosuppression with azathioprine is required to prevent relapses. If an underlying infectious cause is found then treatment with appropriate antibiotic medication may hasten visual recovery.

Sarcoidosis

The addition of weekly methotrexate to oral prednisolone has been reported to both improve vision and reduce the cortico- steroid-dose requirement in sarcoid-associated optic neuropathy. In a refractory case, infliximab may be considered.

COMPLICATIONS

Corticosteroids

In the short term, high-dose corticosteroids can cause insomnia, mild mood changes, stomach upsets, facial flushing, acne, edema and weight gain. Serious side effects reported following their use include psychosis, acute pancreatitis, avascular necrosis of the femoral head and deaths in two children from chicken pox. In the long term corticosteroids can precipitate hypertension, diabetes mellitus, cataracts and osteoporosis. Measures to