Ординатура / Офтальмология / Английские материалы / Ocular Periphery and Disorders_Dartt, Bex, Amore_2011

dispersed collagen fibrils. On confocal microscopy, Bowman’s layer is imaged poorly without the aid of anatomical landmarks such as the highly reflective subbasal nerve plexus due to an average thickness of only 15 mm.

In the corneal stroma, which typically is about 500-mm thick, keratocyte nuclei appear hyperreflective against a dark background. Confocal images exhibit poor reflectivity of stromal keratocyte cytoplasm, cell boundaries, and collagen substance. In the anterior stroma keratocyte nuclei appear as distinct, bright, and oval-round in random orientation. In the mid-stroma, keratocytes exhibit a more regular oval shape transitioning to elongated spindleshaped as the scan approaches the posterior stroma. Additionally, hyperreflective nerve fibers are sporadically seen coursing within the anterior and mid-stroma, but they are absent in the posterior stroma (Figures 5 and 6).

Descemet’s membrane thickens throughout life. It is the basement membrane of the inner layer of endothelial cells. Because of the lack of cellularity and thinness, it is poorly captured by confocal microscopy.

Figure 5 Anterior stroma.

Corneal endothelial cells are single layered, normally characterized by a regular hexagonal hyperreflective cell body, void of nuclei, and surrounded by hyporeflective borders (Figure 7).

Pachymetry

Confocal microscopy can be used to determine corneal thickness through a function known as confocal microscopy through focusing (CMTF) on the TSCM. This is accomplished by focusing in the Z-axis and determining the amount of light backscattering which in turn is plotted as an intensity profile curve. The differences in scattering of the various corneal layers allows for determination of each layer’s location. Overall, this method for determination of corneal thickness offers good repeatability, especially for determination of thin layers such as the epithelium and Bowman’s membrane. Nontandem models such as the Nidek Confoscan 4 utilize a contact ring at the limbus.

Applications in Pathology

The treatment of infectious keratitis can be challenging. The golden standard for diagnosis of infectious keratitis is light microscopic examination and culture of corneal scrapings. However, confocal microscopy is a very useful tool in helping with diagnostic quandaries. Confocal microscopy is particularly helpful when Acanthamoeba or fungal elements are suspects as etiologies. Bacteria (2 mm) can theoretically be visualized; however, given their small size (near the typical resolution for confocal microscopy), clinical distinction is not possible. Fungal infections generally image as hyperreflective, elongated, filaments, or budding yeasts (Figures 8 and 9). In its cystic form, Acanthamoeba appears as a highly reflective, round, or ovoid double-wall structure with a diameter of 10–25 mm (Figure 10). Radial keratoneuritis may appear as irregularly enlarged nerve fibers.

Figure 8 Fusarium keratitis.

Figure 9 Fusarium keratitis.

Figure 10 Acanthaeomba.

Other applications

Confocal microscopy has also been used to research and clinically evaluate the effects of refractive surgery on the cornea, evaluation of corneal deposits and stromal

Figure 11 Iridocorneal endothelial syndrome (ICE). Note the epithelial-like endothelial cells with hyperreflective nuclei, which is characteristic of ICE syndrome in which the endothelium grows across the angle and iris. Notice irregular rows and shape of the endothelial cells.

Figure 12 Posterior polymorphous membranous dystrophy (PPMD). Note the hyporeflective vesicular changes which are characteristic of PPMD in which the endothelium has areas of large and irregularly shaped cells.

dystrophies, endothelial pathology, as well as evaluation of corneal ectatic disorders (Figures 11 and 12).

Anterior Segment OCT

Historical Overview

David Huang and colleagues developed OCT in the early 1990s. Joseph Izatt and colleagues first demonstrated corneal and anterior segment OCT in 1994. Over the next decade, the majority of developments in OCT technology focused on retinal imaging. The use of longer wavelengths, telecentric transverse scanning, and very high-speed axial scanning with a grating-based rapid scanning optical delay (RSOD) mechanism in the

reference arm allowed for improved imaging of the anterior segment. In October 2005, the Food and Drug Administration in the United States approved the Zeiss Visante anterior segment OCT, the first commercially available OCT device designed for the anterior segment.

How it Works

Anterior segment OST (AS-OCT) is a noncontact imaging technique based on Michelson low coherence inferometry. In conventional interferometry with long coherence length (laser interferometry), interference of light occurs over a distance of meters. In OCT, this interference is shortened to a distance of micrometers. Light in an OCT system is broken into two arms – a sample arm (containing the item of interest) and a reference arm (usually a mirror). The combination of reflected light from the sample arm and reference light from the reference arm gives rise to an interference pattern, but only if light from both arms have traveled the same optical distance (same meaning a difference of less than a coherence length). By scanning the mirror in the reference arm, a reflectivity profile of the sample can be obtained (time domain OCT). Areas of the sample that reflect with greater intensity will create greater interference than areas that do not. Any light that is outside the short coherence length will not interfere. This reflectivity profile, called an A-scan, contains information about the spatial dimensions and location of structures within the item of interest (Figure 13). This is analogous to B-scan ultrasonography; however, OCT uses light as compared to sound waves. OCT was initially used for retinal evaluation, where images are optimized with an 820-nm light. AS-OCT evolved from retinal OCT. For the Visante AS-OCT, Zeiss uses a longer wavelength (1310 nm) that allows for greater penetration through tissues that scatter light intensely such as the sclera and limbus, which in turn permits visualization of anterior segment structures such as the angle, ciliary body, and ciliary sulcus. Approximately 90% of the 1310-nm light is absorbed prior to reaching the retina allowing for the AS OCT to be used as a higher power than retinal OCT. This results in realtime imaging and decreased motion artifacts. Currently, there are three commercially available anterior segment OCT devices: the Visante OCT (Visante OCT, Carl Zeiss Meditech Inc, Dublin, CA, USA), the Slit Lamp OCT (SL-OCT, Heidelberg Engineering GmbH, Heidelberg, Germany), and the Optovue (RTVue with Cornea-Anterior Module, Freemont, CA, USA). The Visante OCT provides high-resolution corneal scans, anterior segment scans (anterior-chamber depth, anterior-chamber angle, angle- to-angle distance), and pachymetry maps. It is reported to have an axial resolution of 18 mm and a transverse resolution of 60 mm. The SL-OCT is essentially a slit lamp biomicroscope-mounted OCT device allowing similar

SLD

Detector

Reference

Demodulator AD Computer

Figure 13 Schematics of the basic fiber-optic OCT system. Light from a superluminescent diode (SLD) is launched into a single mode-optical fiber. The light is equally split at the coupler into the sample and reference arms. Sample and reference reflections are recombined at the coupler and the interference pattern is converted to an electrical signal by the detector. The signal is demodulated and converted from analog to digital (AD) form for computer signal and image processing. To scan the reflections from various depths in the sample, the reference mirror is scanned over the equivalent range of delay. This produces a scan of sample reflectivity versus depth, also called an axial scan. From Steinert, R. E. and Huang, D. (2008). Anterior Segment Optical Coherence Tomography. Thorofare, NJ: SLACK Incorporated. Reprinted with permission from SLACK Incorporated.

measurements as the Visante OCT. The potential advantage of the SL-OCT is its attachment to the biomicroscope. The SL-OCT has a reported axial resolution of 25 mm and a transverse resolution of 20–100 mm. The speed of acquisition is 4 –8 frame s 1 for the Visante OCT and 1 frame s 1 for the SL-OCT. The Optovue OCT employs an interchangeable lens system for anterior-segment images. Its principal advantage is the use of spectral domain OCT technology, with a substantially higher resolution. However, scans are limited in width, so only a portion of the cornea can be imaged at one time, and the retina-optimized wavelength does not allow useful imaging of the angle.

Clinical Applications

Anterior segment OCT is a powerful tool for the clinician. It can be used to measure corneal thickness, pachymetry maps, total corneal power, corneal backscatter, angle configuration, anterior-segment tumors, anterior-segment depth, lens vault, corneal opacities, and corneal refractive implants. The following discussion pertains to applications of the Visante OCT.

Keratoconus is a bilateral corneal ectasia characterized by progressive thinning and inferior protrusion. Diagnosis of this and other ectasias (e.g., pellucid marginal degeneration) is critical when evaluating patients for possible refractive surgery. Form fruste keratoconus is subclinical and can often be difficult to diagnose. Anterior segment OCT is a valuable tool in evaluating these patients

to aid in proper diagnosis. As both the Orbscan and Pentacam are based on slit-scanning principles, they tend to underestimate corneal thickness in keratoconic eyes. OCT has a higher resolution as compared to these other imaging modalities and therefore accurately maps the corneal thickness of normal, postoperative, and opacified corneas. The pachymetry map allows for accurate pachymetry readings over broad areas of the cornea

allowing for detection of subclinical thinning suggestive of corneal ectatic disorders (Figures 14 and 15).

The Visante OCT can obtain high-resolution images of the cornea. The flap tool measures laser-assisted in situ keratomileusis (LASIK) flap thickness and residual stromal bed (RSB) in up to seven locations. This application allows for evaluation of LASIK flaps in uncomplicated and ectatic cases. RSB measurements are invaluable in providing

information regarding the potential safety of performing an enhancement when lifting the flap. Additionally, the flap tool can be useful when evaluating a patient with postLASIK keraecastia (Figure 16(a)–16(d)). Likewise, OCT is useful in evaluations of refractive corneal inlays and intacs intracorneal ring segments (Figures 17(a)–17(c) and 18).

Assessment of the depth of corneal ulcers is another valuable application of AS-OCT. Involved tissue appears hyperintense on OCT images. The clinician is able to follow the progression of keratitis by imaging the depth of involvement, the density of the infiltrate, and evaluating

for possible corneal thinning (Figures 19(a)–19(e) and 20(a)–20(e)). Penetrating (full thickness) and lamellar (partial thickness) corneal transplantation has been the focus of several technologic and surgical advancements over the past several years. The development of posterior lamellar keratoplasty (Descemet stripping endothelial keratoplasty, or DSEK), and femtosecond laser-enabled keratoplasty have dramatically changed corneal transplantation techniques. AS-OCT evaluation of these patients preand postoperatively is helpful in surgical planning and clinical follow-up (Figures 21–23).

S/W version: 1.1.0.Research.1991 Patient ID: Gender: male Age: 51 High res. corneal quad

180°

−3.76 mm

474 m

231 m

OD OS

0°

3.37 mm

410 m

257 m

Accurate measurement of corneal opacities is another clinical application of AS-OCT. Compared to ultrasonic pachymetry, ultrasound imaging, optical pachymetry, confocal microscopy, and optical low-coherence reflectometry, OCT has been shown to accurately map pachymetry in both normal and opacified corneas. This accuracy aids in clinical decision making with respect to ablative treatments such as phototherapeutic keratectomy, mechanical scraping and peeling, or their combination.

Peripheral corneal pathologies, such as peripheral corneal and scleral melts, are also amenable to OCT scans. The longer wavelength (1310 nm) allows for full thickness imaging of the cornea and sclera through overlying opacities such as infiltrate, pannus (flap of tissue), and calcium plaques. Measurement of the depth of involvement and thickness of remaining tissue is useful for clinical and surgical planning (Figure 24(a)–24(c)).

Beyond corneal applications, AS-OCT can also be utilized for glaucoma evaluations. Determination of angle configuration, visualization of normal angle structures (Figure 25(a)–25(c)), iris configuration (pupillary block configuration, preand postiridotomy (procedure

to create a hole in the iris to enhance the drainage passages blocked by a portion of the iris), plateau iris configuration, preand postiridoplasty, a surgical procedure where the position of the peripheral iris is changed), and evaluation of peripheral anterior synechiae closure (condition where the peripheral iris adheres to the cornea) (Figure 26(a)–26(c)) are among the many applications of AS-OCT pertaining to glaucoma.

Conclusion

Confocal microscopy and optical coherence tomography imaging allow clinicians and researchers to evaluate the structure of the cornea and anterior segment at levels beyond slit lamp biomicroscopy. Each technology has its own advantages and drawbacks, with their applications generally complementing each other. Quantitative and qualitative measures of normal and pathologic states greatly improve the clinician’s ability to follow and treat.