Not uncommonly, patients present with complaints of visual loss in which the neuro-ophthalmic history and examination fail to provide a ready diagnosis. In fact, the final common pathway for unexplained visual loss and suspected nonorganic disorders is typically the neuro-ophthalmologist. Such patients may have no evident structural abnormalities of the eye, and the patient’s complaints and history may not suggest any of the afferent visual disorders discussed in the previous chapters. This chapter discusses a variety of disorders that should be considered in patients who have unexplained visual loss.
Patients with unexplained visual loss may have subtle, undiagnosed ocular disease as the cause of their visual complaint. The neuro-ophthalmologist must therefore maintain an open mind during the entire examination, devoting as much attention to the slitlamp and retinal examinations as is given to testing the visual fields. The neurologist may need the help of an ophthalmology colleague, especially in patients with unexplained afferent visual complaints. This chapter discusses anterior segment and retinal disorders that mimic neuro-ophthalmic disorders.
Tear film disorders, such as dry eye syndrome, commonly cause transient visual blurring that may range in duration from seconds to hours in one or both eyes (see Table 1–3). Dry eye syndrome is very common in women older than 40 years, but is also associated with collagen vascular disease (Sjögren syndrome and many others), medications, systemic disorders (such as sarcoidosis), and neurological conditions (eg, progressive supranuclear palsy [PSP], Parkinson disease, facial nerve palsies). Patients frequently describe blurring that begins 2 to 3 minutes into a task requiring concentration, such as reading or driving. Sometimes the blurred vision clears momentarily with a blink. The patient’s visual acuity may vary widely between examinations. A foreign body sensation and conjunctival injection are often present, but may not be prominent. Tear film disorders resulting in inadequate tear coverage can actually cause excessive tearing, but this reflex tearing consists of watery tears that fail to adhere to the ocular surface. Meibomian gland dysfunction and blepharitis can cause destabilization of the tear film and further exacerbate dry eye syndrome (Box 6–1).
BOX 6–1. TEAR FILM
The importance of the tear film in maintaining clear vision is not always appreciated by physicians. In addition to providing nutrients to the cornea, the tear film provides a smooth surface over the corneal curvature to optimize the optics of the eye. Tear film dysfunction is a very frequent cause of blurred vision, eye pain, red eyes, and tearing.
The tear film is complex, consisting of three distinct layers: (1) an inner mucous layer that adheres to the ocular surface, (2) an aqueous layer in the middle that is the thickest layer, (3) an outer lipid layer that retards evaporation. This arrangement allows the tear film to distribute evenly over the ocular surface, pulled up as a sheet with each blink. Deficiencies in any of the three layers can cause the tear film to break up too soon or evaporate too quickly. Tear film dysfunction can result in overproduction of the aqueous component, which fails to adhere to the eye and simply accumulates until it falls over the lower eyelid. (Patients often question why artificial tears are recommended when their complaint is “too much tearing”). Tear film stability is also weakened by debris in the tear film, such as the products of chronic blepharitis.
Evidence of ocular surface disease at the slitlamp includes punctuate staining (with topical fluorescein or rose bengal) of the exposed area of the cornea, rapid tear breakup time (observing the fluorescein-stained tear film fall apart prematurely after a blink), deficient tear meniscus (normal adherence of tears along the lower lid margin is minimal or absent), and injection of the conjunctiva in the exposed area between the lids.
Patients with intermittent, variable blur and ocular pain/foreign body sensation or other signs of ocular surface disease may benefit from a trial of artificial tears (at least four times a day for several weeks) before (or concurrent with) further neuro-ophthalmic investigation. Ointment at night, punctal plugs, Restasis, and other measures may be helpful if indicated.
Irregularities of the corneal epithelium can cause intermittent blurring of vision, similar to tear film disorders. Epithelial defects and punctate keratopathies are usually obvious with the slitlamp examination, especially when the cornea is stained with topical fluorescein. Corneal epithelial dystrophies such as map-dot-fingerprint dystrophy may be subtle, and can escape notice if the slitlamp examination is cursory (Figure 6–1).
Corneal epithelial basement membrane dystrophy.
This common disorder disrupts the normally smooth optical surface of the cornea/tear film with ridges of epithelial irregularity. This may have a geographic appearance like a map, appear as dots on the surface of the cornea, or have irregular parallel ridges that resemble a fingerprint (hence, the alternative descriptive name: map, dot, fingerprint dystrophy). The map-like appearance and dots are evident on this clinical photograph of the cornea of a patient who presented with unexplained intermittent blurred vision.
The slitlamp examination, augmented with fluorescein or rose bengal staining, is the primary means of diagnosing ocular surface disorders. Schirmer testing is a helpful adjunct to measure basal tear secretion.
For tear-film disorders, the use of artificial tears, punctal plugs, or cyclosporine ophthalmic emulsion (Restasis) can be curative in many patients. Artificial tears can also be helpful to some extent in patients with corneal surface abnormalities. Therefore, in patients in whom an ocular surface disorder is suspected, a trial of artificial tears may be indicated prior to initiation of an extensive neuro-ophthalmic evaluation.
Irregular corneal astigmatism may be a cause of unexplained decreased visual acuity or monocular diplopia. This condition may result from contact lens wear, ocular surgery, or intrinsic disease of the cornea such as keratoconus (Figure 6–2). Patients with this diagnosis typically complain of blurred rather than dim vision. Visual field testing tends to be normal or show an overall slight depression. Often patients have seen many eye doctors, and have been given a variety of contact lens or eyeglasses prescriptions. Irregular corneal astigmatism is often first identified as an irregular reflex during retinoscopy. This is one case in which the pinhole acuity may exceed the best-corrected visual acuity. Keratometry and corneal topography are useful diagnostic tools for characterizing irregular corneal astigmatism. Placement of a diagnostic rigid contact lens will ameliorate corneal surface or contour abnormalities, and contact lens over-refraction will establish the true visual potential of the eye.
Keratoconus as a cause of unexplained visual loss.
A 37-year-old woman with a complaint of gradual visual loss in her left eye had a best-corrected visual acuity of 20/60 in the right eye and 20/400 in the left eye. The patient was referred for a neuro-ophthalmic evaluation for suspected optic neuritis. The examination revealed an irregular reflex on retinoscopy, no relative afferent pupillary defect, and a normal fundus examination. (A) Automated perimetry revealed diffuse depression of the visual field in both eyes, but with a normal pattern deviation. (B) Corneal topography showed marked irregular astigmatism consistent with the suspected diagnosis of keratoconus. The irregular astigmatism was confirmed as the cause of her visual loss by a diagnostic trial of rigid contact lenses, with an over-refraction yielding visual acuities of 20/25 in each eye.
Another frequent masquerader of neuro-ophthalmic disease is cataract. Patients complain of the gradual onset of blurred (rather than dim) vision. Lens opacities do not cause focal visual field defects. The visual field is usually normal, or demonstrates a diffuse depression. Cataract may also cause monocular diplopia.
The opalescent nuclear sclerotic cataract is frequently unrecognized at the slitlamp, because it lacks the brunescent (yellow-brown) color of a typical nuclear sclerotic cataract, and often occurs in relatively young patients (aged 40–60 years). This type of cataract is also more frequent in myopic individuals (see Figure 1–3).
Posterior subcapsular cataract can cause variable visual blurring from glare, depending on lighting conditions. Subcapsular cataract may be more evident in the red reflex with the ophthalmoscope, retinoscope, or slitlamp (retro-illumination) than with direct illumination. Cortical water clefts that are located at the posterior pole of the lens can also cause significant visual problems. Both subcapsular and cortical water cleft cataracts can cause a disproportionate amount of visual loss when compared to their appearance with the slitlamp, due to their location near the optical nodal point of the eye.
The slitlamp and the potential acuity meter (PAM) are important diagnostic tools when cataract is suspected to be the cause of a visual complaint. The PAM is a device that projects an acuity chart onto the retina as a narrow beam, which can be maneuvered around any anterior segment opacities. Additional findings consistent with cataract as the cause of visual loss include the lack of a relative afferent pupillary defect (RAPD), a myopic shift in refraction, and a normal (or slightly depressed) visual field.
Every patient with subnormal visual acuity should have a refraction to determine the best corrected visual acuity. A surprising number of patients with simple refractive errors are referred with suspected neuro-ophthalmic diagnoses. As discussed in Chapter 2, performing retinoscopy in the course of a manifest refraction has other benefits, as it may reveal irregular corneal astigmatism or cataract.
Latent hyperopia should be suspected in patients in their 30s or 40s who complain of variable blurred vision, “eye strain” headaches, or difficulty reading. Such patients may have undercorrected hyperopia, which remains asymptomatic until their accommodative potential is reduced to a critical level in the early stages of presbyopia. Latent hyperopes must maintain constant accommodation to see clearly, and transient blurring of vision occurs with momentary lapses in this ocular marathon. Diplopia can occur when excessive focusing effort (accommodation) results in convergence spasm. A cycloplegic refraction may be required for confirmation of suspected latent hyperopia. A hyperopic change in the patient’s corrective lenses is curative. Overcorrected myopic patients can present with symptoms similar to undercorrected hyperopes, because both require excessive accommodative effort to see clearly.
Retinal diseases can cause visual loss that may mimic optic nerve disorders. Most of the time retinal disorders are visible with the ophthalmoscope, but occasionally the retinal findings are scant. Usually, the RAPD in monocular retinal disorders is less than the RAPD that would be present from an optic neuropathy causing similar visual field loss. The pattern of visual field loss is helpful in some patients, but retinal vascular occlusions can produce visual field defects that are similar to optic nerve disease (Figure 6–3).
Retinal artery occlusion.
A 71-year-old man described the sudden loss of the superior visual field in his right eye. (A) The visual field was somewhat altitudinal, raising the possibility of anterior ischemic optic neuropathy. (B) However, the fundus examination showed no evidence of optic disc edema. Instead, retinal edema can be seen in the distribution of the inferior arcade vessels, diagnostic of a hemiretinal arterial occlusion. Note also the nonocclusive embolus (Hollenhorst plaque) lodged at the bifurcation in the superior temporal artery.
Central vision loss, and hence loss of visual acuity, occurs with macular disease. The Amsler grid is helpful in detecting metamorphopsia, a symptom that suggests macular rather than optic nerve disease. Photo-stress testing can also help distinguish between macular and optic nerve disorders, as discussed in Chapter 2. The introduction of optical coherence tomography (OCT), as discussed in detail in Chapter 1, has greatly improved our ability to diagnosis otherwise subtle macular disease that can mimic optic neuropathies. Intravenous fluorescein angiography (IVFA) and electroretinography (full-field or multifocal ERG) are needed in some cases of unexplained visual loss to look further for occult retinopathies. A few selected retinal disorders that often escape detection on examination or that may be confused with optic neuropathies are discussed in this section.
Branch retinal artery occlusions (BRAO) cause acute visual loss and focal visual field defects that can be similar to optic nerve disorders. Acutely, ophthalmoscopy reveals a whitish area of edematous ischemic retina, and often emboli can be seen in the retinal arterioles (see Figure 6–3). However, the retinal edema typically clears in days to weeks, leaving only subtle changes in the caliber of the affected retinal arterioles. Similarly, the retinal edema and “cherry red spot” from a central retinal artery occlusion (CRAO) (Figure 6–4A) soon resolve, leaving retinal arteriolar narrowing and mild diffuse optic nerve pallor. Distinguishing a long-standing CRAO from a primary optic neuropathy is often difficult, and CRAO should be considered in the differential diagnosis of visual loss and optic disc pallor. Intravenous fluorescein angiography is helpful in diagnosing both BRAO and CRAO, especially acutely. The electroretinogram (ERG) is diagnostic in central retinal artery occlusion, demonstrating preservation of the a-wave and loss of the b-wave from infarction of the inner retinal layers (see Figure 6–4B). Embolic retinal vascular occlusions are discussed in more detail in Chapter 14.
Central retinal artery occlusion.
(A) A 62-year-old woman with a history of a previous stroke had sudden visual loss in her left eye. Her evaluation led to a diagnosis of embolic central retinal artery occlusion (CRAO). The funduscopic examination in the affected eye (pictured) shows narrowing of the retinal arterioles; pale retina, especially in the macular area; and the cherry-red spot centrally. The cream-colored edematous nerve fiber layer is most evident where the nerve fiber layer is thickest, in the macula between the vascular arcades. Because of the anatomic peculiarities of the foveola, there are no axons to obscure the normal red color of the uninvolved choroidal circulation, which stands out against the pale surrounding macula, giving rise to the infamous cherry-red spot. When the retinal edema subsides (in days to weeks), the diagnosis will not be as obvious. (B) Electroretinogram (ERG) in a patient with a CRAO. A CRAO affects the inner retina, but the photoreceptors in the outer retina are supplied by the choroid, and so their function is preserved. This is evident in the ERG pictured, with preservation of the a-wave generated by the intact outer retina, but loss of the b-wave from ischemia of the inner retina. (Normal b-wave is shown for comparison; see Figure 2–28B).
Central retinal vein occlusions (CRVO) and branch retinal vein occlusions (BRVO) cause marked retinal hemorrhages that are impressive and difficult to miss initially. Disc edema may also occur acutely, but the presence of peripheral retinal hemorrhages distinguishes a retinal vein occlusion from a primary optic neuropathy. After several months the retinal hemorrhages clear, leaving only a few markers of the event. Sometimes venous collateral vessels on the optic disc and slight disc pallor remain, mimicking the findings in optic nerve sheath meningioma.
Vasculitis can affect the retinal arteries or veins. In many patients, the consequences are catastrophic and obvious on examination. However, mild or focal disease can produce loss of visual acuity and visual field defects without profound visible changes in the retina (Figure 6–5). Retinal vasculitis is associated with a variety of systemic conditions, many of which can also cause central nervous system (CNS) disease. In addition to vasculitis, a number of other CNS and systemic diseases may present with vision loss and prominent retinal findings. Acute posterior multifocal placoid pigment epitheliopathy (AMPPE) is characterized by large extramacular lesions, and can be associated with cerebral vasculitis and stoke in some patients. Microangiopathy of the brain, retina, and inner ear (Susac syndrome) presents with branch retinal artery occlusions and CNS microinfarction. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cause of stroke in young adults, with retinal findings including retinal arteriolar narrowing and sheathing, cotton-wool spots, and ischemic optic neuropathy.
Syphilitic macular vasculitis.
A 45-year-old man presented with decreased vision in his right eye. Serologic evaluation revealed active syphilis. (A) The initial automated visual field showed a superior paracentral visual field defect in the right eye; the left eye was normal. (B) The fundus examination demonstrated a normal optic disc and only very subtle changes in the macular vasculature. (C) Intravenous fluorescein angiography was performed because the visual field did not implicate an optic nerve disorder, demonstrating focal retinal vasculitis. The visual field defect cleared after treatment for neurosyphilis.
Age-related macular degeneration (ARMD) is common and often coexists with optic nerve disease such as anterior ischemic optic neuropathy in the older population. Visual field loss that can be attributed to ARMD should precisely match the shape and severity of the visible macular lesion (see Figure 3–7). Similar to optic neuritis, central serous chorioretinopathy causes central scotomas in young patients. Often an RAPD is small or absent. The fundus findings may be subtle, but OCT (or IVFA) is diagnostic (Figure 6–6). Epiretinal membranes tend to cause metamorphopsia rather than discreet scotomas, and are usually evident on careful ophthalmoscopy (Figure 6–7). Vitreomacular traction (VMT) and macular holes can cause decreased visual acuity and tiny central visual field defects—so small that the foveal threshold may be the only abnormal point with automated perimetry. Even with biomicroscopy using the 90-diopter lens or retinal contact lens, macular changes in the various stages of macular holes may be subtle, but fortunately OCT is diagnostic (Figure 6–8). Cystoid macular edema (CME) can occur as a consequence of many retinal and ocular disorders, and is not always evident with ophthalmoscopy. OCT is diagnostic of CME (Figure 6–9), and IVFA (showing late petaloid staining of the macular region) is needed only in atypical cases. CME can occur with diabetes, uveitis, and retinitis pigmentosa. CME can be associated with mild optic disc edema following intraocular surgery (known as Irvine-Gass syndrome).
Central serous chorioretinopathy.
A 35-year-old woman complained of a painless decline in the vision of her left eye over 3 days. The visual acuity was 20/80. The relative afferent pupillary defect was only 0.3 log units—the first hint that this was not an optic neuritis. (A) Automated perimetry revealed a central scotoma. The shallow central depression is not evident in the grayscale, but can be seen in the total deviation probability plot. (B) The fundus examination suggested submacular fluid. The subtle retinal findings could easily be missed if the examiner (prematurely convinced of a diagnosis of optic neuritis) neglected a careful macular examination. (C) The diagnosis is confirmed by intravenous fluorescein angiography. Note the extent of the submacular fluid (arrows), and the punctate window defect in the retinal pigment epithelium, which is the source of the fluid.
A 54-year-old man was referred to the neuroophthalmology service for a complaint of progressive blurred vision in his left eye over 6 months, with a visual acuity of 20/30. Further history revealed that the vision in the eye was not just blurred but distorted—straight edges (his venetian blinds) were crooked in the middle. An Amsler grid showed central metamorphopsia (the patient’s Amsler grid is shown in Figure 2–9C). (A) Fundus photographs. The right eye is normal. In the left eye, the foveal reflex is blunted, but pathologic changes are not obvious. (B) Optical coherence tomography (OCT) retinal thickness map. The color-coded retinal thickness map shows elevation of the left macula, with a normal right macula. (C) OCT cross section through fovea demonstrates an epiretinal membrane (arrow), pulling and distorting the macula—which is the cause of the patient’s metamorphopsia.
A 73-year-old woman had successful cataract surgery in the right eye, but was disappointed as the best corrected visual acuity was 20/40. Automated perimetry was normal, with the exception of a decreased foveal threshold in the right eye. The fundus examination did not reveal the diagnosis, but optical coherence tomography (OCT) clearly shows vitreomacular traction (VMT) in the right eye, with distortion of the foveola (top). Note the normal OCT contour of the unaffected left eye (with unattached vitreous surface seen in the OCT cross section, bottom). VMT is often not evident on the funduscopic examination, and even intravenous fluorescein angiography is usually unrevealing. This diagnosis was often missed before the era of OCT imaging. Many patients at this stage of traction will progress to develop a macular hole, though some can have spontaneous release of the vitreous with restoration of normal foveolar architecture and improvement in visual acuity.