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Functional and structural investigations that assess the integrity of the visual system are of utmost importance for diagnosing and monitoring ophthalmic or neurological disorders that affect vision. These investigations complement the ophthalmic and fundus examinations, allowing precise quantitative baseline and serial assessments. Structural investigations include fundus imaging, fluorescein angiography (FA), optical coherence tomography (OCT) imaging, and orbital ultrasound. Functional investigations include assessment of the visual field with perimetry and electrodiagnostic studies, such as electroretinography (ERG) or visual evoked potentials (VEPs), to assess function of the retina and optic nerve, respectively.
Ocular imaging modalities complement the fundus examination and allow enhanced assessment and documentation of anatomical changes within the visual pathways. Photography, FA, and orbital ultrasound have long served as the principal modalities for retinal and optic nerve imaging. More recently, OCT has emerged as a major breakthrough in ocular imaging, permitting a more detailed characterization of retinal and optic nerve pathologies.
Fundus imaging, which includes modalities used to capture two-dimensional (2D) images, serves as an indispensable method to recognize and record abnormalities evident on fundus examination, leading to an improved ability to diagnose, treat, and monitor retinal and neurological disease.
Standard fundus cameras, which are typically found in ophthalmology clinics, require pupillary dilation to capture images of the macula (central retina), optic disc, and retinal periphery. Dilation is needed to overcome the technical limitations of these cameras, which require the incident light beam projected on the fundus to follow a different optical path through the cornea and lens than the reflected imaging beam in order to avoid reflections from the cornea and lens. Newer nonmydriatic cameras have become available that capture high-quality images of the central retina or optic nerve in patients with pupils as small as 3–4 mm ( Fig. 43.1 , A–C ). Two-dimensional retinal images may also be obtained with scanning laser ophthalmoscopy (SLO), which generates an image based on the amount of light reflected by a single wavelength of infrared laser. Newer cameras utilizing multiple scanning lasers and pseudo-coloration (e.g., Optos plc, Dunfermline, Scotland, UK) are capable of capturing ultra-widefield retinal views of up to 200 degrees; they have particular utility for assessing disorders that affect the retinal periphery (see Fig. 43.1 , D ).
Fundus photography is primarily used to document and allow scrutiny of the ocular fundus, relying on the discernment of disease pathology by an experienced specialist who interprets the images, similar to the interpretation of a fundus examination performed during ophthalmoscopy. Although not yet routinely used, automated image analysis methods to detect abnormalities in retinal images have also been developed ( ).
In the context of waning proficiency with direct ophthalmoscopy, due to limited training, interest has recently been spurred in the development of nonmydriatic fundus cameras in settings such as emergency departments and neurology offices ( ). Nonmydriatic fundus photography offers significant advantages over direct ophthalmoscopy: it offers a much wider field of view (45 vs. 5 degrees), circumvents the technical barriers of direct ophthalmoscopy, and yields images that can be used to monitor a patient’s visual or neurological disorder—images that can be shared with consulting specialists or the patients themselves to educate them regarding their condition. Disadvantages include limited availability, lack of portability of tabletop devices, and cost.
Recent technological advances have facilitated the development of handheld nonmydriatic fundus cameras that yield a relatively wide field of view and may be used in critically ill patients, but cost and availability limit their use. Fundus photography devices that attach to the built-in cameras of smartphones have also generated considerable interest, offering many of the advantages of fundus photography and great portability. However, they can be difficult to use, especially without pupillary dilation, and image quality tends to be considerably inferior to that from tabletop cameras.
There has been growing interest in the use of fundus photography to research neurological disorders. Changes in retinal vascular caliber associated with cerebrovascular disease and cognitive impairment can be analyzed with fundus photography. These findings raise the possibility that routine fundus photography may eventually play a role in the early identification of medical and neurological conditions ( ).
Autofluorescence imaging records the light emitted by native fluorophores in the retina after excitation by light of a blue or green wavelength. The principal naturally occurring fluorophore is lipofuscin, contained within cytoplasmic granules of retinal pigment epithelial cells. Images may be captured by a properly equipped fundus camera, an SLO-OCT machine, or a wide-field SLO. A normal fundus autofluorescence (FAF) image shows a low-intensity background autofluorescence with reduced intensity in the foveal region related to the absorption of blue light by macular luteal pigment ( Fig. 43.2 , A ). The optic nerves and blood vessels, which contain no fluorophores, appear very dark. Changes in the normal pattern of FAF most often occur in retinal diseases that disrupt retinal pigment epithelium (RPE) cells (see Fig. 43.2 , B ). Autofluorescence imaging is also useful for identifying optic disc drusen at or slightly below the surface of the optic nerve head (see Fig. 43.2 , B and C ).
OCT is an imaging modality, often described as the light equivalent of ultrasound, which utilizes the backscatter of near-infrared light and the concept of low-coherence interferometry to generate a cross-sectional image of biological tissue ( ). The first clinical OCT device designed for retinal imaging became available in 1996, and OCT imaging of retinal disease had been widely adopted by the early 2000s. Collection of adjacent cross-sectional images with very high spatial resolution makes OCT essentially a three-dimensional (3D) imaging modality ( Fig. 43.3 , A ). The retinal layers are evident as alternating bands of hyper- or hyporeflective signal depending upon the cellular characteristics of that layer (see Fig. 43.3 , B ), and the thickness of individual retinal layers can be assessed through automated image segmentation algorithms (see Fig. 43.3 , C ). Older-generation time-domain OCT devices had a limited axial spatial resolution of approximately 10 μm, but newer-generation spectral-domain OCT devices have a resolution below 5 μm because of higher image acquisition speeds (up to 80,000 A-scans per second) that reduce motion artifact and allow better characterization of deeper retinal layers. OCT cross-sectional images of the retina (see Fig 43.3, A–C ) or optic nerve (see Fig. 43.3 , D and E ) demonstrate retinal and optic nerve pathology in exquisite detail. In addition, growing evidence suggests that optic nerve and retinal changes measured longitudinally with serial OCT studies are important biomarkers for several neurological disorders.
OCT imaging is an indispensable component of the diagnosis and monitoring of retinal disorders in which pathology is evident by morphological changes in the retina. It is also extremely valuable to distinguish cases of subtle macular pathology from other causes of visual loss, such as retrobulbar optic neuropathy.
The retinal arterioles originating from the central retinal artery give rise to capillary networks supplying the inner retinal layers, including the retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL), and most of the inner nuclear layer ( ). The outer retinal layers, which include the photoreceptors, receive oxygen through diffusion from the retinal choriocapillaris, which is supplied by posterior ciliary arteries originating from the ophthalmic artery. Thus an acute central or branch retinal artery occlusion results in cytotoxic edema in the inner retinal layers that is evident as hyperreflective signal change and thickening ( Fig. 43.4, A and B ). In areas with permanent injury, atrophy ensues over weeks, with loss of thickness of the retinal layers extending beyond the GCL into the inner nuclear layer, which includes the bipolar cell soma (see Fig. 43.4 , C ). The outer retinal layers that receive oxygen through diffusion from the retinal choroid are preserved in an isolated occlusion of a central or branch retinal artery. In contrast to the optic atrophy that ensues following occlusion of a central retinal artery, optic atrophy from primary optic neuropathies is characterized by selective thinning of the retinal nerve’s fiber layer and GCL without involvement of the deeper inner retinal layers.
Cystoid macular edema may result from retinal pathology (e.g., neovascularization from age-related macular degeneration [AMD], diabetic retinopathy, retinal vein occlusion, epiretinal membrane, retinitis pigmentosa [RP]) or from edema originating at the optic disc (e.g., papilledema, anterior ischemic optic neuropathy, neuroretinitis). Macular edema is also a rare complication of fingolimod use for the treatment of multiple sclerosis (MS), occurring in about 2 per 1000 patients ( ). Macular edema, which may be somewhat difficult to appreciate on fundal examination, is easily detected on OCT, where it appears as hyporeflective intraretinal cystoid spaces with retinal thickening (see Fig. 43.4 , D ). Lipid exudates are evident as hyperreflective foci.
Central serous chorioretinopathy (CSCR) is a cause of acute or subacute painless loss or distortion of central vision originating from subfoveal neurosensory retinal detachment or pigment epithelial detachment. Men are affected more frequently than women, most often between 30 and 50 years of age ( ). The cause is not fully understood, but increasing evidence suggests that hyperpermeability of the choriocapillaris endothelium results in secondary dysfunction of the retina pigment epithelium and accumulation of fluid beneath the neurosensory retina or retina pigment epithelium. CSCR is more likely to develop in patients treated with exogenous corticosteroids, those with type-A behavioral traits, or in patients experiencing an acute stress ( ). It may also worsen following administration of corticosteroids if another type of inflammatory choroiditis is suspected or if it is mistaken for optic neuritis. OCT demonstrates a sensorineural retinal detachment and in the majority of cases also demonstrates a component of pigment epithelial detachment (see Fig. 43.4 , E ).
Geographic atrophy (GA) consists of outer retinal atrophy within the macula and is a feature of late-stage AMD as well as inherited maculopathies such as ABCA-4–related retinopathy (Stargardt disease). In AMD, GA results in central visual loss, with OCT showing attenuation of the outer nuclear layer (ONL), external limiting membrane (ELM), ellipsoid zone (EZ), retinal pigment epithelium (RPE), and choriocapillaris accompanied by subretinal drusenoid deposits (see Fig. 43.4 , F ; ).
RP refers to a group of inherited retinopathies that cause progressive visual loss as a result of degeneration of rod and cone photoreceptors. Patients typically develop peripheral visual loss and nyctalopia during early stages, followed by gradual development of central visual loss. Fundus changes may include peripheral “bone spicule” pigment accumulation, atrophy of the RPE, and retinal arteriolar attenuation. OCT imaging assists in the diagnosis, as fundus features may be nonspecific or bland early in the disease course. Characteristic OCT findings include attenuation of the RPE, EZ, ELM, ONL, and OPL, often progressing from the outer to the central macula over time (see Fig. 43.4 , G ; ).
Acute zonal occult outer retinopathy (AZOOR) is a retinal disease presenting with rapid onset of a visual scotoma due to loss of retinal function with minimal changes on fundus examination. Visual loss is typically accompanied by photopsias due to photoreceptor dysfunction. Variants of AZOOR include the acute idiopathic blind spot enlargement syndrome (AIBSES). This disease may relate to the retinal white dot syndromes, a group of inflammatory disorders of the choroid, RPE, and outer retina. OCT is particularly useful, as the fundus examination shows minimal if any changes initially, and the first changes are detected with alterations of the EZ on OCT (see Fig. 43.4 , H and I ). ERG localizes the dysfunction to the RPE-photoreceptor layers. Over time, patients develop visible atrophic changes in the RPE, and OCT demonstrates thinning of the photoreceptor layers, RPE, and choroid. In the AIBSES these structural changes occur in the peripapillary region.
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