Key Features
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Anterior segment optical coherence tomography is essential in pre- and postoperative evaluation for lamellar corneal transplantations, refractive surgery, and ectasia-related disorders. It may be utilized for the diagnosis and management of ocular surface neoplasia.
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Ultrasound biomicroscopy is a valuable tool for the assessment of anterior segment tumors and corneal opacities.
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Specular microscopy is useful in evaluation of the corneal endothelium, in Fuchs’ endothelial corneal dystrophy and for preoperative planning of anterior segment surgery.
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In vivo confocal microscopy has a high sensitivity and specificity for detection of Acanthamoeba and fungal keratitis. It can be utilized in the evaluation of corneal nerve and inflammatory changes in the cornea for dry eye disease, neuropathic corneal pain, neurotrophic keratopathy, and related conditions. It also has utility in visualization of Demodex mites in the eyelids.
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Topography and wavefront imaging are critical in the evaluation and management of refractive surgery, cataract surgery, corneal transplantations, astigmatism, and corneal ectasia.
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Meibography can be used to assess structural abnormalities of meibomian glands in dry eye disease and related disorders.
Introduction
Advances in anterior segment (AS) imaging over the past decade have revolutionized clinical care by allowing topographical, anatomical, and cellular visualization of tissues. The choice of imaging modalities used depends on the tissue to be visualized and the suspected pathology. AS optical coherence tomography (AS-OCT), for example, can be used to visualize anatomical structures anterior to the iris, and the structures behind the iris are best seen with ultrasound biomicroscopy (UBM). In vivo confocal microscopy (IVCM) provides layer-by-layer images of the entire cornea at a cellular level, whereas specular microscopy can best assess the corneal endothelium. Corneal topography and wavefront imaging can visualize topography-related abnormalities. Finally, meibography demonstrates meibomian gland (MG) abnormalities that are difficult to discern with slit-lamp biomicroscopy. The detailed principles, functions, and clinical applications of AS imaging modalities are discussed below.
Anterior Segment Optical Coherence Tomography
AS-OCT is a noninvasive, noncontact imaging device that allows cross-sectional, anatomical imaging of the eye, with the use of an interference pattern of reflected light, and relies on images reconstructed from cross-sectional scans (A-scans). Since the advent of original time domain (TD) OCT, the technology has rapidly evolved with the development of the higher resolution Fourier domain (FD-OCT) (5-µm FD-OCT versus 18-µm TD-OCT resolution), and faster speed of A-scans (26,000 scans/sec FD-OCT versus 2,000 scans/sec TD-OCT), resulting in fewer motion artifacts and the capability to obtain three-dimensional images of ocular tissues. The more recent spectral domain (SD, 5 µm) and swept-source (SS, up to 2.6 µm) OCTs provide even higher-resolution images (SD, 5 µm and SS, up to 2.6 µm) and higher speed of A-scans (about 50,000 scans/sec SD-OCT versus 100,000 scans/sec SS-OCT). Although TD AS-OCT has deeper penetration due to longer wavelength, the SD-OCT and SS-OCT have better signal-to-noise ratio and allow for more structural detail. A comparison summary of the types of AS-OCT devices is provided in Table 4.2.1 .
| Types | Time-Domain OCT (TD-OCT) | Fourier-Domain OCT FD-OCT) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Spectral-Domain OCT (SD-OCT) | Swept-Source OCT (SS-OCT) | |||||||||||
| Subtypes/Examples | Visante | Heidelberg Slit-Lamp OCT | RTVue | iVue | Avanti XR | Cirrus | Spectralis | Envisu_C Class | 3D-OCT | Casia | Triton | Plex Elite 9000 |
| Manufacturer | Carl Zeiss Meditec, Dublin, CA | Heidelberg Engineering, Heidelberg, Germany | Optovue Inc., Fremont, CA | Optovue Inc., Fremont, CA | Optovue Inc., Fremont, CA | Carl Zeiss Meditec, Dublin, CA | Heidelberg Engineering | Bioptigen, Bioptigen Inc., Research Triangle Park, NC | Topcon Medical Systems, Oakland, NJ | Tomey, Nagoya, Japan | Topcon Medical Systems, Oakland, NJ | Carl Zeiss Meditec, Dublin, CA |
| Light source | Beam | Broadband light sources (Spectrometer) | Swept-source laser | |||||||||
| Wavelength (nm) | 1310 | 1310 | 840 | 840 | 840 | 840 | 820 | 1310 | 850 | 1310 | 1050 | 1060 |
| Depth (mm) | 6 | 7 | 2–2.3 | 2–2.3 | 3 | 2 | 1.9 | 1.6–2.4 | 3–6 | 6 | 12 | 3 |
| Resolution (µm) (axial × transverse) | 18 × 60 | 25 × 20-100 | 5 × 15 | 5 × 15 | 3-5 × 15-25 | 5 × 15 | 3.9 × 14 | 2.4-7.5 | 6 × 20 | 10 × 30 | 2.6 × 20 | 5.5 × 20 |
| Imaging speed (A-scans/sec) | 2,000 | 200 | 26,000 | 26,000 | 70,000 | 27,000-68,000 | 40,000 | 32,000 | 50,000 | 30,000 | 100,000 | 100,000 |
| Image size (mm) | 6 × 16 | 15 × 7 | 13 × 9 | 13 × 9 | 12 × 9 | – | – | 20 × 2.5 | 12 × 9 | 16 × 16 | 16 × 16 | 12 × 12 |
Application of the “en face” technique provides a layer-by-layer horizontal sectioning of the tissue. These sections allow for identification of microstructural information throughout the scanned area that is not available with standard AS-OCT scans. Moreover, AS-OCT angiography (OCTA), which has recently been described, allows for visualization and quantification of vessel density in the cornea, iris, and sclera ( Fig. 4.2.1 ).
Clinical Applications
Tear Film Evaluation
Tear meniscus height, depth, area, radius of curvature, and volume can be measured using AS-OCT ( Fig. 4.2.2 ). Thus, AS-OCT is a valuable noninvasive tool for the evaluation of the tear film abnormalities.
Refractive Surgery and Ectasia-Related Disorders
AS-OCT scans of the healthy corneas show corneal layers as seen in Fig. 4.2.3, A , and allow for the evaluation of flap thickness and stromal bed after refractive surgery. Thus AS-OCT measurements of preoperative corneal thickness and postoperative residual stroma thickness may help in risk stratification of patients by an ectasia scoring system. Similarly, corneal thinning can be measured by using AS-OCT for screening, risk-assessment, and diagnosis of patients with ectasia-related disorders by assessment of area and range of thinning (see Fig. 4.2.3B ). Postoperative AS-OCT can further be used to monitor complications, such as interface fluid or haze, and flap dislocation. Patients with prior refractive correction, who require cataract surgery may benefit from additional data obtained using AS-OCT for the latest biometry formulas to improve surgical outcomes.
Penetrating and Endothelial Keratoplasty–Related Procedures
AS-OCT can provide valuable information both intraoperatively and postoperatively for penetrating corneal grafts and endothelial keratoplasty detachment. Endothelial grafts can be visualized on AS-OCT for orientation, position and interface fluid intraoperatively, and for detachment postoperatively using warning signs, such as interface fluid and poor margins. Intraoperative AS-OCT can assess dissection depth in deep anterior lamellar keratoplasty (DALK) and identify graft orientation and the need for repositioning for Descemet’s membrane endothelial keratoplasty (DMEK) and Descemet’s membrane stripping automated endothelial keratoplasty (DSAEK). Postoperative graft adherence/detachment status in DMAEK and DSAEK also may be seen ( Fig. 4.2.3C ). Moreover, keratoprosthesis (KPro) offers a useful alterative for patients with severe corneal pathology, ( Fig. 4.2.3D ), identifying corneal thinning and melting under the front plate.
Ocular Surface Tumors
Although conjunctival and corneal tumors can be observed clinically by using slit-lamp biomicroscopy, their exact location, depth, extent, and anatomic relationship to surrounding structures can be assessed further by using AS-OCT ( Fig. 4.2.4 ). AS-OCT can complement UBM in imaging and is superior to UBM for imaging ocular surface tumors. For example, squamous cell neoplasia presents as a localized area of hyperreflective thickened epithelium with an abrupt transition between the normal and thickened area; a lymphoma manifests as a hyporeflective, homogeneous subepithelial mass; a melanoma presents as a hyperreflective subepithelial mass; and nevi present with cysts in a subepithelial mass.
Cataract Surgery and Intraocular Lens Implantation
Pre- and postoperative AS-OCT imaging helps assess the anterior chamber (AC) in evaluation of phakic intraocular lenses. Preoperative AS-OCT can determine the AC angle, width, and lens rise, whereas postoperative AS-OCT can evaluate surgical wounds and assess for complications, including angle-closure glaucoma and corneal decompensation. Further, as detailed above, AS-OCT may aid in biometry in patients who have previously undergone LASIK surgery.
Keratitis
Keratitis may be diagnosed clinically, but the areas of necrosis and infiltration may be better assessed by using AS-OCT, particularly in opaque corneas. Because AS-OCT allows for quantitative measurement of corneal thickness, it serves as an additional aide in detection and treatment of keratitis and corneal ulcers. Localization of stromal necrosis and radial hyperreflective stromal bands in Acanthamoeba keratitis can further be translated for rapid diagnosis and reduction of perforation rates as a result of earlier intervention.
Miscellaneous Uses
AS-OCT has several other applications, such as grading of cells in anterior uveitis and visualization of intracorneal implants. Further, it is useful in screening corneas from eye banks for corneal abnormalities, such as prior LASIK surgery.
Limitations
AS-OCT has limited ability to visualize structures posterior to iris as a result of pigmentation, whereas UBM is more useful clinically.
Clinical Applications
Tear Film Evaluation
Tear meniscus height, depth, area, radius of curvature, and volume can be measured using AS-OCT ( Fig. 4.2.2 ). Thus, AS-OCT is a valuable noninvasive tool for the evaluation of the tear film abnormalities.
Refractive Surgery and Ectasia-Related Disorders
AS-OCT scans of the healthy corneas show corneal layers as seen in Fig. 4.2.3, A , and allow for the evaluation of flap thickness and stromal bed after refractive surgery. Thus AS-OCT measurements of preoperative corneal thickness and postoperative residual stroma thickness may help in risk stratification of patients by an ectasia scoring system. Similarly, corneal thinning can be measured by using AS-OCT for screening, risk-assessment, and diagnosis of patients with ectasia-related disorders by assessment of area and range of thinning (see Fig. 4.2.3B ). Postoperative AS-OCT can further be used to monitor complications, such as interface fluid or haze, and flap dislocation. Patients with prior refractive correction, who require cataract surgery may benefit from additional data obtained using AS-OCT for the latest biometry formulas to improve surgical outcomes.
Penetrating and Endothelial Keratoplasty–Related Procedures
AS-OCT can provide valuable information both intraoperatively and postoperatively for penetrating corneal grafts and endothelial keratoplasty detachment. Endothelial grafts can be visualized on AS-OCT for orientation, position and interface fluid intraoperatively, and for detachment postoperatively using warning signs, such as interface fluid and poor margins. Intraoperative AS-OCT can assess dissection depth in deep anterior lamellar keratoplasty (DALK) and identify graft orientation and the need for repositioning for Descemet’s membrane endothelial keratoplasty (DMEK) and Descemet’s membrane stripping automated endothelial keratoplasty (DSAEK). Postoperative graft adherence/detachment status in DMAEK and DSAEK also may be seen ( Fig. 4.2.3C ). Moreover, keratoprosthesis (KPro) offers a useful alterative for patients with severe corneal pathology, ( Fig. 4.2.3D ), identifying corneal thinning and melting under the front plate.
Ocular Surface Tumors
Although conjunctival and corneal tumors can be observed clinically by using slit-lamp biomicroscopy, their exact location, depth, extent, and anatomic relationship to surrounding structures can be assessed further by using AS-OCT ( Fig. 4.2.4 ). AS-OCT can complement UBM in imaging and is superior to UBM for imaging ocular surface tumors. For example, squamous cell neoplasia presents as a localized area of hyperreflective thickened epithelium with an abrupt transition between the normal and thickened area; a lymphoma manifests as a hyporeflective, homogeneous subepithelial mass; a melanoma presents as a hyperreflective subepithelial mass; and nevi present with cysts in a subepithelial mass.
Cataract Surgery and Intraocular Lens Implantation
Pre- and postoperative AS-OCT imaging helps assess the anterior chamber (AC) in evaluation of phakic intraocular lenses. Preoperative AS-OCT can determine the AC angle, width, and lens rise, whereas postoperative AS-OCT can evaluate surgical wounds and assess for complications, including angle-closure glaucoma and corneal decompensation. Further, as detailed above, AS-OCT may aid in biometry in patients who have previously undergone LASIK surgery.
Keratitis
Keratitis may be diagnosed clinically, but the areas of necrosis and infiltration may be better assessed by using AS-OCT, particularly in opaque corneas. Because AS-OCT allows for quantitative measurement of corneal thickness, it serves as an additional aide in detection and treatment of keratitis and corneal ulcers. Localization of stromal necrosis and radial hyperreflective stromal bands in Acanthamoeba keratitis can further be translated for rapid diagnosis and reduction of perforation rates as a result of earlier intervention.
Miscellaneous Uses
AS-OCT has several other applications, such as grading of cells in anterior uveitis and visualization of intracorneal implants. Further, it is useful in screening corneas from eye banks for corneal abnormalities, such as prior LASIK surgery.
Tear Film Evaluation
Tear meniscus height, depth, area, radius of curvature, and volume can be measured using AS-OCT ( Fig. 4.2.2 ). Thus, AS-OCT is a valuable noninvasive tool for the evaluation of the tear film abnormalities.
Refractive Surgery and Ectasia-Related Disorders
AS-OCT scans of the healthy corneas show corneal layers as seen in Fig. 4.2.3, A , and allow for the evaluation of flap thickness and stromal bed after refractive surgery. Thus AS-OCT measurements of preoperative corneal thickness and postoperative residual stroma thickness may help in risk stratification of patients by an ectasia scoring system. Similarly, corneal thinning can be measured by using AS-OCT for screening, risk-assessment, and diagnosis of patients with ectasia-related disorders by assessment of area and range of thinning (see Fig. 4.2.3B ). Postoperative AS-OCT can further be used to monitor complications, such as interface fluid or haze, and flap dislocation. Patients with prior refractive correction, who require cataract surgery may benefit from additional data obtained using AS-OCT for the latest biometry formulas to improve surgical outcomes.
Penetrating and Endothelial Keratoplasty–Related Procedures
AS-OCT can provide valuable information both intraoperatively and postoperatively for penetrating corneal grafts and endothelial keratoplasty detachment. Endothelial grafts can be visualized on AS-OCT for orientation, position and interface fluid intraoperatively, and for detachment postoperatively using warning signs, such as interface fluid and poor margins. Intraoperative AS-OCT can assess dissection depth in deep anterior lamellar keratoplasty (DALK) and identify graft orientation and the need for repositioning for Descemet’s membrane endothelial keratoplasty (DMEK) and Descemet’s membrane stripping automated endothelial keratoplasty (DSAEK). Postoperative graft adherence/detachment status in DMAEK and DSAEK also may be seen ( Fig. 4.2.3C ). Moreover, keratoprosthesis (KPro) offers a useful alterative for patients with severe corneal pathology, ( Fig. 4.2.3D ), identifying corneal thinning and melting under the front plate.
Ocular Surface Tumors
Although conjunctival and corneal tumors can be observed clinically by using slit-lamp biomicroscopy, their exact location, depth, extent, and anatomic relationship to surrounding structures can be assessed further by using AS-OCT ( Fig. 4.2.4 ). AS-OCT can complement UBM in imaging and is superior to UBM for imaging ocular surface tumors. For example, squamous cell neoplasia presents as a localized area of hyperreflective thickened epithelium with an abrupt transition between the normal and thickened area; a lymphoma manifests as a hyporeflective, homogeneous subepithelial mass; a melanoma presents as a hyperreflective subepithelial mass; and nevi present with cysts in a subepithelial mass.
Cataract Surgery and Intraocular Lens Implantation
Pre- and postoperative AS-OCT imaging helps assess the anterior chamber (AC) in evaluation of phakic intraocular lenses. Preoperative AS-OCT can determine the AC angle, width, and lens rise, whereas postoperative AS-OCT can evaluate surgical wounds and assess for complications, including angle-closure glaucoma and corneal decompensation. Further, as detailed above, AS-OCT may aid in biometry in patients who have previously undergone LASIK surgery.
Keratitis
Keratitis may be diagnosed clinically, but the areas of necrosis and infiltration may be better assessed by using AS-OCT, particularly in opaque corneas. Because AS-OCT allows for quantitative measurement of corneal thickness, it serves as an additional aide in detection and treatment of keratitis and corneal ulcers. Localization of stromal necrosis and radial hyperreflective stromal bands in Acanthamoeba keratitis can further be translated for rapid diagnosis and reduction of perforation rates as a result of earlier intervention.
Specular Microscopy
Specular microscopy allows for imaging and analysis of the corneal endothelium. It works on the basic principle of light reflection using a mirror: the angle of incidence is equal to that of reflection. As light passes through a media with higher index of refraction, most of it is reflected; this reflected light is captured by a detection lens. The endothelial cells can be imaged because their refractive index is greater than that of the aqueous humor. The light source can be a stationary or moving slit or spot; wider slit allows greater field, but reduced contrast and resolution. Specular microscopy can be contact or noncontact and automated or manual, or both. The types of specular microscopes are shown in Table 4.2.2 .
| Contact Specular Microscopes | Noncontact Specular Microscopes |
|---|---|
| CL-1000xz (HAI Labs Inc., Lexington, MA) | CL-1000nc (HAI Labs Inc., Lexington, MA) |
| CELLCHEK Series (Konan Medical USA, Inc., Irvine, CA) | |
| CellCheck D (eyebank) (Konan Medical USA, Inc., Irvine, CA) | |
| CEM-530 (Nidek Fremont, CA) | |
| EM-3000 (Tomey, Inc., Phoenix, AZ) | |
| SP-1P (TopCon Medical, Inc., Tokyo, Japan) |
Specular microscopy provides pachymetric measurements and endothelial cell analysis (density and morphology), including endothelial cell density, mean cell area, coefficient of variation (standard deviation divided by mean area of cells), and percentage of hexagonality or pleomorphism (percentage of cells with variation from normal hexagonal shape). Coefficient of variation and pleomorphism are the more sensitive indicators of endothelial dysfunction and stress, as even at low endothelial density (<500 cells/mm 2 ) the endothelial function may remain uncompromised.
The fixed-frame method allows for cell quantification within a fixed area ( Fig. 4.2.5A ), and the variable-frame method allows the observer to make an accurate boundary around the edges of the cells. In contrast, the center method requires the centers of contiguous cells to be marked manually, hence peripheral cells are not counted as they do not have adjoining cells. Moreover, the center-flex method requires delineating the boundary of an area, followed by marking of cell centers.
Clinical Applications
The normal corneal endothelium comprises hexagonal and similar size cells (see Fig. 4.2.5A ). The cell density decreases with aging (0.5% per year). Examples of cell abnormalities include guttae (excrescences of the Descemet’s membrane). Contact lens wear can cause transient or chronic changes to the endothelial cell morphology.
Corneal Dystrophies
Specular microscopy is a valuable tool to diagnose different endothelial disorders, such as Fuchs’ endothelial corneal dystrophy (FECD), posterior polymorphous dystrophy (PPMD), or iridocorneal endothelial (ICE) syndrome. In FECD, the mosaic endothelium presents dark areas (guttae) (see Fig. 4.2.5B ). Bilateral involvement, with donut-shaped vesicles and clearly defined black rings anterior to the cells may be seen in PPMD; whereas in ICE syndrome, many pentagonal cells are seen with intracellular dark areas. In advanced ICE disease, a “reversal appearance” occurs with black areas and white margins.
Intraocular Surgery Evaluation
Permanent corneal edema occurs at low epithelial cell density (300–700 cells/mm 2 ) or presence of other morphological abnormalities (coefficient of variation >40% or <50% hexagonal cells). Loss of cells with ocular surgery is estimated to be between 0 and 30%; preoperative assessment of the patients’ endothelium to assess cell density may reduce postoperative complications.
Donor Cornea Evaluation
Specular microscopy is particularly important in assessment of donor corneas to assess for sufficient endothelial cell density and donor quality.
Limitations
One of the limitations of specular microscopy is that it is difficult to image endothelial cells through edematous or opaque corneas. In these cases, confocal microscopy provides superior image quality.
Clinical Applications
The normal corneal endothelium comprises hexagonal and similar size cells (see Fig. 4.2.5A ). The cell density decreases with aging (0.5% per year). Examples of cell abnormalities include guttae (excrescences of the Descemet’s membrane). Contact lens wear can cause transient or chronic changes to the endothelial cell morphology.
Corneal Dystrophies
Specular microscopy is a valuable tool to diagnose different endothelial disorders, such as Fuchs’ endothelial corneal dystrophy (FECD), posterior polymorphous dystrophy (PPMD), or iridocorneal endothelial (ICE) syndrome. In FECD, the mosaic endothelium presents dark areas (guttae) (see Fig. 4.2.5B ). Bilateral involvement, with donut-shaped vesicles and clearly defined black rings anterior to the cells may be seen in PPMD; whereas in ICE syndrome, many pentagonal cells are seen with intracellular dark areas. In advanced ICE disease, a “reversal appearance” occurs with black areas and white margins.
Intraocular Surgery Evaluation
Permanent corneal edema occurs at low epithelial cell density (300–700 cells/mm 2 ) or presence of other morphological abnormalities (coefficient of variation >40% or <50% hexagonal cells). Loss of cells with ocular surgery is estimated to be between 0 and 30%; preoperative assessment of the patients’ endothelium to assess cell density may reduce postoperative complications.
Donor Cornea Evaluation
Specular microscopy is particularly important in assessment of donor corneas to assess for sufficient endothelial cell density and donor quality.
Intraocular Surgery Evaluation
Permanent corneal edema occurs at low epithelial cell density (300–700 cells/mm 2 ) or presence of other morphological abnormalities (coefficient of variation >40% or <50% hexagonal cells). Loss of cells with ocular surgery is estimated to be between 0 and 30%; preoperative assessment of the patients’ endothelium to assess cell density may reduce postoperative complications.
Ultrasound Biomicroscopy
UBM uses high frequency (20–100 MHz) ultrasound waves and is useful for the evaluation of deeper structures in the eye and in opaque corneas. Echoes from tissues at different depths are recorded at different time intervals and can be used to construct the image. In general, higher frequency waves have lesser penetration, and lower frequency waves have lower penetration. Most UBMs in use today have scan rate of 35–50 MHz, giving an axial resolution of 42 µm, and a depth of 4–5 mm.
Clinical Applications
Using UBM, surface epithelium, Bowman’s layer, and Descemet’s membrane can be identified as reflective structures, while the endothelium cannot be identified. As a result of penetration of sound through the pigmented epithelium, UBM can visualize the structures posterior to the iris, which is not possible with an AS-OCT. Hence, posterior chamber structures, including lens zonules, ciliary body, and anterior choroid, can be visualized ( Fig. 4.2.6 ).
