Anthony N. Kuo

Refractive change after descemet stripping automated endothelial keratoplasty surgery and its correlation with graft thickness and diameter.

Purpose: The purpose of this study was to evaluate the refractive change after Descemet stripping automated endothelial keratoplasty (DSAEK) surgery and its correlation with graft thickness and diameter. Methods: We retrospectively analyzed the refractive outcomes of 45 cases of DSAEK surgery that were performed at Duke University Eye Center between August 2005 and December 2006. We divided our study groups into DSAEK triple cases and pseudophakic DSAEK cases. We measured manifest refraction preoperatively and postoperatively in each group and compared the difference between the preoperative and the postoperative spherical equivalent. We evaluated the correlation of the refractive change with graft thickness and diameter. Results: Forty-five DSAEK cases in 44 patients (27 women and 17 men) were evaluated and analyzed. Mean age of the patients at surgery was 67.6 years (15-81 years, SD 10.7 years). Forty cases were treated for Fuchs endothelial dystrophy and 5 for pseudophakic bullous keratopathy/bullous keratopathy. Seventeen cases were DSAEK triple cases and 28 pseudophakic DSAEK cases. In the DSAEK triple group, the mean change in refraction at an average of 4 months postoperatively was +1.15 D (range −0.02 to 2.87, SD 1.15). In the pseudophakic DSAEK group, the mean change in refraction at an average of 5 months postoperatively was +0.71 D (range −1.75 to 3.0, SD 1.11). The overall refractive change was +0.88 D (range −1.75 to 3.0, SD 1.02). Correlation of refractive change with graft diameter was modest (r = 0.29, P = 0.05), and a small correlation was found with respect to graft thickness (r = −0.16, P = 0.31). Conclusions: Our study of DSAEK grafts demonstrated a hyperopic refractive shift after DSAEK surgery. This observation should be taken into consideration when deciding on the appropriate intraocular lens power in DSAEK triple surgery and may also aid in anticipating refractive outcomes after pseudophakic DSAEK surgery. Further studies to follow these refractive changes over a longer follow-up period and to investigate the mechanism of this refractive change after DSAEK surgery are warranted.

Fast Acquisition and Reconstruction of Optical Coherence Tomography Images via Sparse Representation

In this paper, we present a novel technique, based on compressive sensing principles, for reconstruction and enhancement of multi-dimensional image data. Our method is a major improvement and generalization of the multi-scale sparsity based tomographic denoising (MSBTD) algorithm we recently introduced for reducing speckle noise. Our new technique exhibits several advantages over MSBTD, including its capability to simultaneously reduce noise and interpolate missing data. Unlike MSBTD, our new method does not require an a priori high-quality image from the target imaging subject and thus offers the potential to shorten clinical imaging sessions. This novel image restoration method, which we termed sparsity based simultaneous denoising and interpolation (SBSDI), utilizes sparse representation dictionaries constructed from previously collected datasets. We tested the SBSDI algorithm on retinal spectral domain optical coherence tomography images captured in the clinic. Experiments showed that the SBSDI algorithm qualitatively and quantitatively outperforms other state-of-the-art methods.

Preclinical evaluation and intraoperative human retinal imaging with a high-resolution microscope-integrated spectral domain optical coherence tomography device

Purpose: The authors have recently developed a high-resolution microscope-integrated spectral domain optical coherence tomography (MIOCT) device designed to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of this report is to describe translation of this device from preclinical testing into human intraoperative imaging. Methods: Before human imaging, surgical conditions were fully simulated for extensive preclinical MIOCT evaluation in a custom model eye system. Microscope-integrated spectral domain OCT images were then acquired in normal human volunteers and during vitreoretinal surgery in patients who consented to participate in a prospective institutional review board–approved study. Microscope-integrated spectral domain OCT images were obtained before and at pauses in surgical maneuvers and were compared based on predetermined diagnostic criteria to images obtained with a high-resolution spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same time point. Cohorts of five consecutive patients were imaged. Successful end points were predefined, including ≥80% correlation in identification of pathology between MIOCT and HHOCT in ≥80% of the patients. Results: Microscope-integrated spectral domain OCT was favorably evaluated by study surgeons and scrub nurses, all of whom responded that they would consider participating in human intraoperative imaging trials. The preclinical evaluation identified significant improvements that were made before MIOCT use during human surgery. The MIOCT transition into clinical human research was smooth. Microscope-integrated spectral domain OCT imaging in normal human volunteers demonstrated high resolution comparable to tabletop scanners. In the operating room, after an initial learning curve, surgeons successfully acquired human macular MIOCT images before and after surgical maneuvers. Microscope-integrated spectral domain OCT imaging confirmed preoperative diagnoses, such as full-thickness macular hole and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. Conclusion: This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.

Robust automatic segmentation of corneal layer boundaries in SDOCT images using graph theory and dynamic programming.

Segmentation of anatomical structures in corneal images is crucial for the diagnosis and study of anterior segment diseases. However, manual segmentation is a time-consuming and subjective process. This paper presents an automatic approach for segmenting corneal layer boundaries in Spectral Domain Optical Coherence Tomography images using graph theory and dynamic programming. Our approach is robust to the low-SNR and different artifact types that can appear in clinical corneal images. We show that our method segments three corneal layer boundaries in normal adult eyes more accurately compared to an expert grader than a second grader—even in the presence of significant imaging outliers.

3D refraction correction and extraction of clinical parameters from spectral domain optical coherence tomography of the cornea

Capable of three-dimensional imaging of the cornea with micrometer-scale resolution, spectral domain-optical coherence tomography (SDOCT) offers potential advantages over Placido ring and Scheimpflug photography based systems for accurate extraction of quantitative keratometric parameters. In this work, an SDOCT scanning protocol and motion correction algorithm were implemented to minimize the effects of patient motion during data acquisition. Procedures are described for correction of image data artifacts resulting from 3D refraction of SDOCT light in the cornea and from non-idealities of the scanning system geometry performed as a pre-requisite for accurate parameter extraction. Zernike polynomial 3D reconstruction and a recursive half searching algorithm (RHSA) were implemented to extract clinical keratometric parameters including anterior and posterior radii of curvature, central cornea optical power, central corneal thickness, and thickness maps of the cornea. Accuracy and repeatability of the extracted parameters obtained using a commercial 859nm SDOCT retinal imaging system with a corneal adapter were assessed using a rigid gas permeable (RGP) contact lens as a phantom target. Extraction of these parameters was performed in vivo in 3 patients and compared to commercial Placido topography and Scheimpflug photography systems. The repeatability of SDOCT central corneal power measured in vivo was 0.18 Diopters, and the difference observed between the systems averaged 0.1 Diopters between SDOCT and Scheimpflug photography, and 0.6 Diopters between SDOCT and Placido topography.

Characterization of genomic structure and polymorphisms in the human carbamyl phosphate synthetase I gene

Human carbamyl phosphate synthetase I (CPSI) is an essential hepatic enzyme that initiates the urea cycle. Deficiency of this enzyme usually results in lethal hyperammonemia. CPSI is encoded by the CPSI gene located on chromosome 2q35. In the present study, we report the coding sequence and define the intron-exon structure of the human CPSI gene. These data are compared to the previously defined rat CPSI gene structure. This work was generated from direct sequence determination of human genomic DNA (35 introns) and comparison to public domain sequence of anonymous BACs (2 introns). The human CPSI gene spans >120kb of genomic DNA. CPSI has 38 exons and 37 introns, and all adhere to the consensus splicing sequences. Comparison of the human and rat CPSI genes reveals that the nucleotide sequences, amino acid sequences, and intron-exon organizations are highly similar. We report the primers and conditions for screening the human CPSI exonic and bordering intronic sequences. We also screened 100 individuals for polymorphisms in the human CPSI gene and identified 14 polymorphisms in the CPSI message. The knowledge of the CPSI gene structure and the 14 polymorphisms presented in this study will greatly facilitate future molecular studies involving the CPSI gene and the enzyme it encodes.

Distribution of refractive error in healthy infants

PURPOSE Few data exist regarding the upper limits of refractive error distributions in healthy infants; the data that do exist are biased because they were selected from the records of pediatric ophthalmology practices. We sought to obtain these data to validate examination failure criteria for vision screening. METHODS We reviewed records from all children age birth to 5 years seen at the Tennessee Lions Eye Center at Vanderbilt Childrens Hospital with a billing diagnosis of nasolacrimal duct obstruction and no comorbid ocular diagnoses except for refractive error. This was to avoid referral bias for any condition that could have influenced refractive error. All patients received a complete eye examination and cycloplegic refraction. Cumulative probability distribution (CPD) plots and means for spherical and cylindrical refractive error and anisometropia were prepared. RESULTS One hundred thirty patients were studied; mean age was 15.5 +/- 9.9 months (range, 2 days to 66 months). The mean refractive error (spherical equivalent) was +1.4 D +/- 1.1 D. CPD plot analysis showed 95% of hyperopia to be < +3.25 D. Two children had myopia </=-1.00 D. The mean astigmatism was +0.2 D +/- 0.4 D, and 74% of patients had no astigmatism. Seven children had astigmatism > +1.00 D in one eye. CPD plot analysis showed 95% of astigmatism to be < +1.50 D and 95% of meridional anisometropia to be < 1.50 D. Six children had anisometropia >/=1.50 D, and 3 children had anisometropia > 3.00 D. CONCLUSIONS At least 95% of children have hyperopia < +3.25 D, astigmatism < +1.50 D, and anisometropia < 1.50 D. This information will prove useful in identifying the natural history and prevalence of amblyogenic factors identified during preschool vision screening.

Simultaneous swept source optical coherence tomography of the anterior segment and retina using coherence revival

We report on an implementation of coherence revival-based heterodyne swept source optical coherence tomography that is capable of simultaneously imaging the anterior and posterior eye. A polarization-encoded sample arm was used to efficiently focus orthogonal polarizations on the anterior segment and retina. Depth encoding was achieved using coherence revival, which allows for multiple depths within a sample to be simultaneously imaged and frequency encoded by carefully controlling the optical pathlength of each sample path. This design is a significant step toward whole-eye optical coherence tomography (OCT), which would enable customized ray-traced modeling of patient eyes to improve refractive surgical interventions and eliminate optical artifacts in retinal OCT diagnostics. We demonstrated the feasibility of this system for in vivo imaging by simultaneously acquiring images of the anterior segments and retinas in healthy human volunteers.

Air bubble-associated endothelial trauma in descemet stripping automated endothelial keratoplasty.

PURPOSE To evaluate endothelial cell trauma by anterior chamber (AC) air bubbles in Descemet stripping automated endothelial keratoplasty (DSAEK). DESIGN Laboratory investigation. METHODS Twelve human donor corneas (6 pairs) were sectioned using an automated microkeratome system (Moria ALTK System, Antony, France). One cornea of each pair was mounted on a Moria artificial AC, and an air bubble was injected to fill 40% of the AC. The apparatus was rotated 180 degrees for a total of 50 times to simulate air bubble trauma. The fellow corneas were used as controls. Each endothelial graft was stained with 0.25% Trypan blue for 90 seconds followed by 0.2% alizarin red for 2 minutes, and digital photomicrographs were obtained. Abnormally staining areas indicative of graft injury were removed digitally from the total graft area. The proportion of uninjured corneal endothelium was calculated, and differences were analyzed. RESULTS In this ex vivo model of air bubble trauma, the proportion of viable graft endothelium after air bubble injury was 79.8 +/- 0.04% (n = 6). The proportion of viable endothelium in the control group was 89.9 +/- 0.02% (n = 6). The statistically significant mean difference of 10.1% (P = .03) is indicative of greater endothelial injury after air bubble trauma. CONCLUSIONS Using this model, a moderate but significant amount of endothelial cell damage was associated with air bubble trauma compared with the control group. Air bubble trauma may account partially for the loss of endothelial cell density after DSAEK surgery and may impact graft survival.

Optical Coherence Tomography Accurately Measures Corneal Power Change from Laser Refractive Surgery

PURPOSE To determine the ability of motion-corrected optical coherence tomography (OCT) to measure the corneal refractive power change due to LASIK. DESIGN Evaluation of a diagnostic test or technology in a cohort. SUBJECTS A total of 70 eyes from 37 subjects undergoing LASIK were measured preoperatively. A total of 39 eyes from 22 subjects were measured postoperatively and completed the study. METHODS Consecutive patients undergoing LASIK at the Duke Eye Center who consented to participate were imaged with Placido-ring topography, Scheimpflug photography, and OCT on the day of their surgery. Patients were then reimaged with the same imaging systems at the postoperative month 3 visit. Change in preoperative to postoperative corneal refractive power as measured by each of the imaging modalities was compared with the preoperative to postoperative change in manifest refraction (MRx) using the t test with generalized estimating equations. MAIN OUTCOME MEASURES Corneal refractive power change due to LASIK as measured by Placido-ring topography, Scheimpflug photography, and OCT compared with the MRx change vertexed to the corneal plane. The change in MRx should correspond to the change in the corneal refractive power from LASIK and was considered the reference measurement. RESULTS In 22 individuals (39 eyes) returning after LASIK, we found no significant difference between the clinically measured pre- to post-LASIK change in MRx and both Scheimpflug photography (P = 0.714) and OCT (P = 0.216). In contrast, keratometry values from Placido-ring topography were found to be significantly different from the measured refractive change (P < 0.001). In addition, of the 3 imaging modalities, OCT recorded the smallest mean absolute difference from the reference measurement with the least amount of variability. CONCLUSIONS Motion-corrected OCT more accurately measures the change in corneal refractive power due to laser refractive surgery than other currently available clinical devices. By offering accurate corneal refractive power measurements in normal and surgically modified subjects, OCT offers a compelling alternative to current clinical devices for determining corneal refractive power.