| | High-speed Optical Coherence Tomography of Corneal OpacitiesPresented in part at: Association for Research in Vision and Ophthalmology Annual Meeting, May 2006, Fort Lauderdale, Florida. Received 13 July 2006; accepted 20 October 2006. published online 16 February 2007. PurposeTo evaluate corneal opacities with optical coherence tomography (OCT). DesignProspective observational case series. ParticipantsTwenty-three eyes of 19 patients with corneal opacities referred to a tertiary medical center. MethodsTwenty-three consecutive eyes with corneal opacities were imaged with a high-speed corneal OCT prototype (Carl Zeiss Meditec, Inc., Dublin, CA). The OCT system operates at a speed of 2000 axial scans per second and a wavelength of 1.3 μm. Slit-scanning tomography (Orbscan II, software version 3.12; Bausch & Lomb, Inc., Rochester, NY) and ultrasound pachymetry (Corneo-Gage Plus; Sonogage, Cleveland, OH) also were performed. Main Outcome MeasuresCentral cornea thickness was measured by the 3 instruments. ResultsIn eyes with central opacities (n = 17), OCT central cornea thickness measurements were statistically equivalent to ultrasound pachymetry, whereas Orbscan II measurements were significantly less than ultrasound pachymetry (difference, −132.7±143 μm; P = 0.006). The OCT and ultrasound pachymetry results were obtained for all eyes, whereas Orbscan was unable to provide readings in 4 eyes. In eyes with off-center opacities (n = 6), OCT and Orbscan II central cornea thickness measurements were statistically equivalent to ultrasound pachymetry. The OCT measurements of epithelial thickness and scar depth also were demonstrated. ConclusionsOptical coherence tomography provides consistent pachymetry mapping, whereas Orbscan II significantly underestimates corneal thickness in the presence of central corneal scars. Optical coherence tomography could be valuable in the planning of surgical treatment of corneal scars. The measurement of corneal thickness is important in the planning of LASIK, photorefractive keratectomy (PRK), phototherapeutic keratectomy (PTK), and other corneal and refractive procedures. Various techniques, including ultrasound pachymetry,1, 2 optical pachymetry,3 confocal microscopy,4 and optical low coherence reflectometry,5, 6 are used to measure central and peripheral corneal thickness by providing localized, spot measurements. Newer scanning technologies such as slit-scanning optical pachymetry,7, 8, 9, 10, 11, 12 high-frequency ultrasound imaging,13 optical coherence tomography (OCT),14 and rotating slit-scanning Scheimpflug camera,15 are capable of mapping the thickness of a wide area of the cornea. Pachymetry mapping provides several advantages over spot measurements. It can reveal abnormal patterns such as keratoconus and pellucid marginal degeneration, and it also allows preoperative planning for surgeries that concern more than just the center of the cornea, such as astigmatic keratotomy, Intacs (Addition Technology, Des Plaines, IL) intracorneal ring segment implantation, PTK, and lamellar keratoplasty. One form of pachymetric mapping is Orbscan (Bausch & Lomb, Inc., Rochester, NY) slit-scanning topography, which analyzes real images of the optical sections as viewed through a slit lamp. The anterior and posterior corneal height profiles are reconstructed from these sections using a 3-dimensional ray tracing. Several studies have noted that the accuracy and precision of Orbscan thickness are satisfactory for evaluating normal corneas.9, 10, 11 However, a major limitation of Orbscan slit-scanning technology is the tendency to underestimate corneal thickness in eyes with keratoconus16 and in eyes that have undergone PRK17, 18, 19 and LASIK.18, 19, 20, 21, 22 In these situations, scattering from corneal haze and stromal interfaces interferes with the identification of the corneal surface reflections because of the limited resolution of slit scanning.16, 17, 18 Thus, a better method of pachymetric mapping in the presence of corneal opacities is still needed. Advances in OCT technology have allowed for high-speed scanning of the anterior segment and cornea.23, 24, 25 Optical coherence tomography has been shown to measure anterior chamber depth accurately,25 to detect narrow anterior chamber angles,26 and to assess the angle after laser iridotomy in narrow-angle glaucoma.27 Finally, OCT produces rapid, reproducible maps of a wide area of the cornea and is tightly correlated with ultrasound pachymetry in the presence of clear corneas.14 However, the reproducibility and accuracy of corneal thickness measurements from Orbscan and OCT have not been reported in corneas with opacities. The purpose of this study was to evaluate the accuracy of high-speed OCT in comparison with both Orbscan scanning technology and ultrasound pachymetry in measuring corneal thickness in corneas with opacities. Patients and Methods  We prospectively measured the central corneal thickness of 23 consecutive eyes of 19 patients with corneal opacities using a high-speed corneal OCT prototype (Carl Zeiss Meditec, Inc., Dublin, CA), Orbscan II (Bausch & Lomb, Inc., Rochester, NY), and ultrasound pachymetry (Corneo-Gage Plus; Sonogage, Cleveland, OH). All patients with corneal opacities seeking treatment from one of the authors (DH) at the Doheny Eye Institute were recruited for the study, and written informed consent was obtained from all participants. The study protocol was approved by the Institutional Review Board of the University of Southern California. Pachymetry Measurements Central corneal thickness of all eyes was measured using the 3 instruments at the same visit. Because both OCT and Orbscan II are noncontact techniques, they were performed before ultrasound pachymetry to avoid any artifact caused by corneal applanation with the ultrasound pachymeter probe. The technology and procedure for the use of the high-speed corneal and anterior segment OCT (CAS-OCT) prototype has been described previously.14 The system operates at a wavelength of 1.3 μm and a speed of 2000 axial scans per second. Two types of OCT scan patterns were used: the pachymetry map and the line scan. Each method was performed 3 times before and after PTK surgery (if performed) and the measurements were averaged. The pachymetry map pattern consisted of 10-mm radial lines on 8 meridians centered on the vertex reflection. Each of the 8 cross-sectional images contained 128 axial scans (A scans). The entire process of acquiring 1024 A scans took approximately 0.5 seconds. Corneal pachymetric maps then were generated by an automated computer program.14 The central pachymetry value was obtained by averaging the corneal thickness in a 2-mm diameter area in the center of the map. The line scan pattern is a 12-mm long line scan that contains 512 A scans. Four consecutive frames were saved for each scan, for a total of 2048 A scans. The detailed line scans were obtained along both horizontal and vertical meridians crossing the corneal vertex. We developed a computer program to register and average the 4 consecutive frames to form a composite image with increased signal-to-noise ratio and reduced speckle. Then, the image was dewarped to remove the distortion resulting from index transition at the air–corneal interface.28 Epithelial thickness and scar thickness were measured perpendicular to the anterior corneal surface on the computer screen with computer cursors placed by the operator. The anterior corneal surface was located by an automated computer algorithm. The human operator uses the computer cursor to identify the deepest rim of the scar. The computer then calculates the scar thickness perpendicular to the anterior corneal surface. The possible error is no more than 1 pixel. The axial scan depth was set to 4 mm in air. Each axial scan was sampled digitally at 768 points, giving an axial pixel size of 5.2 μm in air (3.7 μm in tissue). Pachymetry maps also were acquired with the Orbscan II system. Patients were instructed to fixate on a blinking light while a slit beam scanned the cornea from limbus to limbus, producing 40 consecutive vertical slit images of the cornea. After automated analysis of the anterior and posterior corneal borders on each resulting slit image, the thickness was measured and displayed for each section of the cornea on the pachymetric maps. In addition, we selected an Orbscan II A scan for comparison with an OCT A scan obtained at a similar location from the same cornea. We exported 1 slit image from each patient and identified the anterior and posterior corneal edges with automatic edge processing software (Orbscan II Anterior Segment Analysis System, version 2.1 A Z). The Orbscan II slit image samples 640 pixels over a 16-mm axial distance (Orbscan II User’s Manual), providing a 25-μm axial pixel size. Ultrasound pachymetry also was performed by an ophthalmic technician during each visit with the Corneo-Gage Plus high-frequency (50 MHz) probe (Sonogage, Cleveland, OH). After topical anesthesia was applied to the eye, the tip of the pachymeter’s probe was held perpendicular to the central surface of the cornea, and 3 thickness measurements then were obtained and averaged. Statistical Analysis The differences between central pachymetry values obtained with the 3 different instruments were analyzed with the paired 2-sided t test. A P value less than 0.05 was considered statistically significant (Excel; Microsoft, Seattle, WA). Pearson correlation coefficients (r) also were calculated (Excel; Microsoft, Seattle, WA). Results Twenty-three eyes of 19 patients (10 men, 9 women) with corneal opacities were evaluated (Table 1). The average age of the patients was 58±16 years (range, 27–77 years). Thirty percent (7/23) of the corneal opacities were scars secondary to infectious keratitis; 30% (7/23) of the scars were the result of Salzmann nodular degeneration; 13% (3/23) were secondary to corneal dystrophies; and 27% (6/23) were scars from other causes. Seventy-four percent (17/23) of the corneal opacities involved the central 2-mm diameter of the cornea, whereas the other 26% (6/23) were off center (outside the central 2-mm diameter). Comparison of Optical Coherence Tomography and Orbscan Pachymetry A scans from the OCT system and the Orbscan II system were acquired from similar locations in an eye with a corneal opacity. In the OCT A scans, the signal peaks at the air–tear interface and the cornea–aqueous interface were distinct and clearly identified (Fig 1a). In the Orbscan II A scans, the stromal signal was stronger, and the anterior and posterior surface reflections merged with stromal reflections without forming distinct peaks (Fig 1b). In eyes with central opacities (n = 17), the average corneal thickness was 533±108 μm by ultrasound pachymetry, 384±107 μm by Orbscan II, and 547±122 μm by OCT. There was a difference of −132±143 μm (mean±standard deviation; P = 0.006) between the Orbscan II and ultrasound thickness measurements, whereas the difference was 13.6±38 μm (P = 0.16) between OCT and ultrasound measurements. Ultrasound readings correlated well with OCT measurements but not the Orbscan measurements (Pearson correlation r = 0.954 and 0.169, respectively). This is illustrated in Figure 2A. Orbscan II was unable to measure corneal topography and corneal thickness in 4 eyes because of severe surface irregularities (Table 1: patients 11, 15, and 18 [both eyes]). The OCT pachymetric maps and cross-sectional scans were obtained in all patients. In eyes with off-center opacities (n = 6), the central cornea thickness was 559±32 μm by ultrasound pachymetry, 563±36 μm by Orbscan II, and 557±31 μm by OCT. There was a difference of 4.0±7.8 μm (P = 0.25) between Orbscan II and ultrasound, whereas the difference was −1.0±8.7 μm (P = 0.72) between OCT and ultrasound. Ultrasound readings correlated well with both OCT and Orbscan measurements (Pearson correlation r = 0.954 and 0.977, respectively). This is illustrated in Figure 2B. Case Report A 27-year-old myopic Asian woman was referred for consideration of PTK or PRK for a corneal opacity of her right eye (Table 1, patient 3). The patient experienced a corneal ulcer associated with overnight contact lens wear 7 months previously. The infection was treated successfully with antibiotics, but a scar formed. On examination, her uncorrected visual acuity was 20/400 in the right eye, which corrected to 20/50 with −9.75 +0.55 ×0.80. Slit-lamp examination revealed a dense central 3-mm subepithelial scar with 10% thinning (Fig 3A). There was also a small satellite scar in the mid periphery, superior to the subepithelial lesion. Central cornea thickness was measured as 475 μm by ultrasound, 325 μm by Orbscan II (Fig 3B), and 487 μm by OCT pachymetry map (Fig 3C). The detailed OCT line scans (Fig 3D, E) showed the maximum opacity depth to be 165 μm and the maximum epithelial thickness to be 96 μm. The OCT data was used to plan the PTK depth (Fig 3E). Corneal thickness, opacity depth, opacity width, high myopic refraction, and epithelial thickness were all considered as well. The VISX S4 laser (VISX, Santa Clara, CA) was programmed to perform a circular PTK ablation 6.0 mm in diameter with a 0.5-mm transition zone. A transepithelial ablation of 135 μm depth was carried out first. Carboxymethylcellulose 0.5% artificial tear (Refresh Plus; Allergan, Irvine, CA) then was applied to the cornea as a smoothing agent. Further ablation of 70 μm was carried out with reapplication of the smoothing agent after a few micrometers of ablation. An exact ablation depth cannot be known because of the unknown blocking action of the smoothing agent, but the total depth was probably between 135 and 205 μm. If a 50% blocking efficiency is assumed, the estimated ablation depth was 170 μm, which is close to the opacity depth of 165 μm measured on OCT. Next, mitomycin C (0.02%) was applied for 1 minute on the central cornea using a 7-mm diameter cellulose sponge and then rinsed off with approximately 10 ml balanced salt solution. Three months after surgery, her uncorrected visual acuity was 20/40, which corrected to 20/30 with a +2.00 sphere. Slit-lamp examination showed mild corneal haze at the periphery of the ablation zone. The central cornea was clear (Fig 4A). The corneal thickness after the PTK was 284 μm by ultrasound, 304 μm by Orbscan II, and 290 μm by OCT (Fig 4B). The PTK ablation thinned the cornea by 197 μm as measured by OCT and 191 μm as measured by ultrasound. This was slightly more than expected, but within the range of variation introduced with the use of masking agent. According to the Orbscan II, the ablation thinned the cornea only by 21 μm, which differed markedly from the laser setting and other measurements. Optical Coherence Tomography Images from Other Patients Slit-lamp photographs and OCT cross-sectional images are presented for the following conditions: Salzmann nodular degeneration (Table 1, patient 4; Fig 5A, B); recurrent granular corneal dystrophy after penetrating keratoplasty (Table 1, patient 7; Fig 5C, D); and corneal scar after acanthamoeba infection (Table 1, patient 5; Fig 5E, F). The detailed OCT line scans are labeled with spot measurements of maximum epithelial thickness, maximum scar depth, and minimum corneal thickness. Discussion Optical coherence tomography is a noncontact cross-sectional imaging system with high axial resolution.29, 30 Ophthalmic OCT was developed initially for retinal imaging31 and used a near-infrared 0.8-μm wavelength. Recent advances in OCT technology have allowed for high-speed scanning of the cornea and anterior segment.23, 24, 25 This new technology uses a longer wavelength of 1.3 μm, bringing 2 advantages to anterior segment imaging. First, because light at a 1.3-μm wavelength is absorbed by water, retinal exposure is much lower, allowing the use of approximately 20 times more power without exceeding the retinal exposure limit.32 The higher power, in turn, permits a much faster scanning speed while maintaining image quality.23, 26, 33 Second, light at a longer wavelength light scatters less in opaque tissues, allowing for deeper penetration. This permits imaging through the limbus to visualize angle structures, such as the scleral spur and angle recess,23, 26, 33, 34, 35 and imaging through corneal opacities to visualize the cornea and other anterior segment structure. Together, the improvements in speed and penetration allowed us to map corneal thickness and to measure opacity depth in this case series. Our CAS-OCT prototype is similar to the commercially available Zeiss Visante OCT Anterior Segment Imaging System (Carl Zeiss Meditec, Jena, Germany/Dublin, CA). We found OCT to be very helpful in managing corneal opacities. This comparative study with ultrasound pachymetry and our experience in excimer laser PTK gave us confidence in the accuracy of OCT measurements of pachymetry and opacity depth. We now routinely use OCT to assess the feasibility of ablative treatment such as PTK, mechanical scraping and peeling, and a combination of the 2 options. In general, we consider ablative treatment if the scar within the optical zone can be removed while maintaining a minimal corneal thickness of 300 μm (including the epithelium). Of course, we must also consider the resulting hyperopic shift, the possibility of inducing regular or irregular astigmatism, and the feasibility of subsequent spectacles, rigid gas permeable lenses, or PRK treatments to achieve improved vision overall. In the case example highlighted, we aimed for the complete removal of opacity and emmetropia. We achieved fairly good results, although there was approximately 20% overablation. In retrospect, it might have been more effective to use a greater margin of undercorrection, given the uncertainty of the laser ablation rate through the epithelium, scar, and masking agent. The use of masking agents in PTK introduces the greatest variable in ablation planning. Therefore, intraoperative slit-lamp examination of the opacity is still useful in determining the end point of ablation during the smoothing stage of PTK. In addition, transepithelial PTK ablation is an excellent method of smoothing out small-scale corneal surface irregularities, especially small depressions (nodular scars can be scraped and peeled off and do not required transepithelial ablation). Optical coherence tomography provides measurements of the epithelial hyperplasia in areas with topographic depressions. These measurements can be used to determine the upper boundary of the transepithelial ablation to reduce surface irregularity. Although masking agents and transepithelial ablation are useful in removing small-scale corneal irregularities, large-scale irregularities may be addressed better through topography-guided ablation.36 We did not perform any topography-guided ablation in this study because it is not approved by the Food and Drug Administration in the United States, and we did not have access to an investigational laser system. In comparison with OCT, the ultrasound probe provides a useful confirmation of central pachymetry, but it is difficult to map out the variations in corneal thickness with the point measurements from the probe. Slit-scanning technology such as the Orbscan II also provides pachymetric mapping, but it is not as accurate as OCT or ultrasound pachymetry in the presence of central opacification. In this study, Orbscan II underestimated the corneal thickness as much as 63% in areas of opacity (Table 1, patient 11) in comparison with ultrasound pachymetry. The difference between corneal thickness measurements from Orbscan II and ultrasound pachymetry was highly significant (P = 0.006). This is consistent with previous studies showing that Orbscan underestimates pachymetry in the presence of corneal haze.17, 19 Scattering from corneal haze and stromal opacities interferes with the identification of the corneal surface reflections because of the limited resolution of the slit scanning.37 In contrast, the higher resolution of OCT allows corneal boundaries to be defined clearly by distinct signal peaks, free of interference from stromal reflections (Fig 1). The high resolution also makes OCT measurements more robust than slit-scanning results. For example, OCT was able to provide a pachymetry map in all cases, whereas Orbscan II was unable to construct a map or to determine cornea thickness in 4 patients (17%) because of an irregular corneal surface. Recently, another method for measuring corneal thickness became available commercially. The Pentacam (Oculus, Wetzlar, Germany) uses a rotating Scheimpflug camera to image the anterior segment of the eye.38 It is specifically designed to calculate a 3-dimensional model of the anterior segment, including data for corneal topography, complete corneal pachymetry, and densitometry of lens opacity. Pentacam recently was shown to be an excellent noncontact method for measuring central corneal thickness, and in healthy eyes, the results correlate highly with measurements from ultrasound pachymetry.15, 39 We do not have any data that compares OCT with the Pentacam. 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Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California.  Correspondence to David Huang, MD, PhD, Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California,1450 San Pablo Street, DEI 5702, Los Angeles, CA 99033.
Supported by the National Institutes of Health, Bethesda, Maryland (grant no. P30 EY03040), and Carl Zeiss Meditec, Inc., Dublin, California. Dr Huang receives patent royalties for optical coherence tomography technology. Drs Huang, Li, and Tang receive research grant support from Carl Zeiss Meditec. The other authors do not have proprietary interests in the article’s topic. PII: S0161-6420(06)01471-0 doi:10.1016/j.ophtha.2006.10.033 © 2007 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. | |
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