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In vivo corneal high-speed, ultra high-resolution optical coherence tomography [Case Report]

Christopoulos, Viki; Kagemann, Larry; Wollstein, Gadi; Ishikawa, Hiroshi; Gabriele, Michelle L; Wojtkowski, Maciej; Srinivasan, Vivek; Fujimoto, James G; Duker, Jay S; Dhaliwal, Deepinder K; Schuman, Joel S
OBJECTIVE: To introduce new corneal high-speed, ultra-high-resolution optical coherence tomography (hsUHR-OCT) technology that improves the evaluation of complicated and uncomplicated cataract, corneal, and refractive surgical procedures. DESIGN: This case series included a control subject and 9 eyes of 8 patients who had undergone phacoemulsification, Descemet membrane stripping endokeratoplasty, corneal implantation for keratoconus, and complicated and uncomplicated laser in situ keratomileusis. These eyes underwent imaging using a prototype ophthalmic hsUHR-OCT system. All the scans were compared with conventional slitlamp biomicroscopy. RESULTS: Cross-sectional hsUHR-OCT imaging allowed in vivo differentiation of corneal layers and existing pathologic abnormalities at ultrahigh axial image resolution. These images illustrate the various incisional and refractive interfaces created with corneal procedures. CONCLUSIONS: The magnified view of the cornea using hsUHR-OCT is helpful in conceptualizing and understanding basic and complicated clinical pathologic features; hsUHR-OCT has the potential to become a powerful, noninvasive clinical corneal imaging modality that can enhance surgical management. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00343473.
PMCID:2136433
PMID: 17698748
ISSN: 0003-9950
CID: 1886082

Optical coherence tomography and histologic measurements of nerve fiber layer thickness in normal and glaucomatous monkey eyes

Schuman, Joel S; Pedut-Kloizman, Tamar; Pakter, Helena; Wang, Nan; Guedes, Viviane; Huang, Lina; Pieroth, Liselotte; Scott, Wayne; Hee, Michael R; Fujimoto, James G; Ishikawa, Hiroshi; Bilonick, Richard A; Kagemann, Larry; Wollstein, Gadi
PURPOSE: To investigate optical coherence tomography (OCT) measurements of retinal nerve fiber layer (RNFL) thickness change associated with elevated intraocular pressure (IOP) over a period of time, and to compare in vivo OCT RNFL thickness measurements with morphologic measurements of the same tissues. METHODS: One eye of each of 12 cynomolgus monkeys was treated with argon laser to the anterior chamber angle to induce elevated IOP. OCT measurements were made weekly in the treated and the contralateral eyes of each monkey for 14 weeks after the laser insult. The monkeys were killed at the conclusion of the experiment, and comparisons were made between the terminal OCT RNFL measurements and quantitative histomorphometric assessments in the same eyes. Effects of exposure to elevated IOP on RNFL were characterized by a mixed-effects model. Linear mixed-effects models provided unbiased analysis of balanced and unbalanced repeated-measures data, detection of group effects (fixed effects), and individual subject effects (random effects), thereby making the best use of all available data. RESULTS: Increased IOP was achieved in 10 eyes. Exposure to high IOP was associated with the loss of mean RNFL thickness at a median rate of 3.77 +/- 0.08 microm/wk. On average, OCT RNFL thickness measurements were higher than histomorphologic measurements by 5.7 microm (95% confidence interval, 3.6-7.8; P = 0.003). CONCLUSIONS: Thinning of the RNFL associated with elevated IOP was demonstrated with OCT in a group of experimentally glaucomatous monkey eyes over a period. OCT measurements corresponded with histomorphometric measurements of the same tissues.
PMCID:2034325
PMID: 17652734
ISSN: 0146-0404
CID: 1886092

Glaucoma detection with matrix and standard achromatic perimetry

Burgansky-Eliash, Zvia; Wollstein, Gadi; Patel, Avni; Bilonick, Richard A; Ishikawa, Hiroshi; Kagemann, Larry; Dilworth, William D; Schuman, Joel S
BACKGROUND: Matrix perimetry is a new iteration of frequency-doubling technology (FDT) which uses a smaller target size in the standard achromatic perimetry presentation pattern. AIM: To compare the performance of matrix and Swedish interactive thresholding algorithm (SITA) perimetry in detecting glaucoma diagnosed by structural assessment. DESIGN: Prospective cross-sectional study. METHODS: 76 eyes from 15 healthy subjects and 61 consecutive glaucoma suspects and patients with glaucoma were included. All patients underwent optic nerve head (ONH) photography, SITA and matrix perimetries, and optical coherence tomography (OCT) within a 6-month period. Glaucoma diagnosis was established by either glaucomatous optic neuropathy or OCT by assessing retinal nerve fibre layer (RNFL) thickness. Mean deviation (MD), pattern standard deviation (PSD), glaucoma hemifield test and cluster of abnormal testing locations were recorded from matrix and SITA perimetries. RESULTS: Similar correlations were observed with matrix and SITA perimetry MD and PSD with either cup-to-disc ratio or OCT mean RNFL. The area under the receiver operating characteristic (AROC) curves of MD and PSD for discriminating between healthy and glaucomatous eyes ranged from 0.69 to 0.81 for matrix perimetry and from 0.75 to 0.77 for SITA perimetry. There were no significant differences among any corresponding matrix and SITA perimetry AROCs. CONCLUSIONS: Matrix and SITA perimetries had similar capabilities for distinguishing between healthy and glaucomatous eyes regardless of whether the diagnosis was established by ONH or OCT-RNFL assessment.
PMCID:1955642
PMID: 17215267
ISSN: 0007-1161
CID: 1886102

Peripapillary nerve fiber layer thickness profile determined with high speed, ultrahigh resolution optical coherence tomography high-density scanning

Gabriele, Michelle L; Ishikawa, Hiroshi; Wollstein, Gadi; Bilonick, Richard A; Kagemann, Larry; Wojtkowski, Maciej; Srinivasan, Vivek J; Fujimoto, James G; Duker, Jay S; Schuman, Joel S
PURPOSE: To determine the retinal nerve fiber layer (RNFL) thickness profile in the peripapillary region of healthy eyes. METHODS: Three-dimensional, Fourier/spectral domain optical coherence tomography (OCT) data were obtained as raster scan data (512 x 180 axial scans in a 6 x 6-mm region centered on the optic nerve head [ONH]) with high-speed, ultrahigh-resolution OCT (hsUHR-OCT) from 12 healthy subjects. RNFL thickness was measured on this three-dimensional data set with an in-house software program. The disc margin was defined subjectively in each image and RNFL thickness profiles relative to distance from the disc center were computed for quadrants and clock hours. A mixed-effects model was used to characterize the slope of the profiles. RESULTS: Thickness profiles in the superior, inferior, and temporal quadrants showed an initial increase in RNFL thickness, an area of peak thickness, and a linear decrease as radial distance from the disc center increased. The nasal quadrant showed a constant linear decay without the initial RNFL thickening. A mixed-effects model showed that the slopes of the inferior, superior, and nasal quadrants differed significantly from the temporal slope (P = 0.0012, P = 0.0003, and P = 0.0004, respectively). CONCLUSIONS: RNFL thickness is generally inversely related to the distance from the ONH center in the peripapillary region of healthy subjects, as determined by hsUHR-OCT. However, several areas showed an initial increase in RNFL, followed by a peak and a gradual decrease.
PMCID:1950319
PMID: 17591885
ISSN: 0146-0404
CID: 1886112

Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography

Kagemann, Larry; Wollstein, Gadi; Wojtkowski, Maciej; Ishikawa, Hiroshi; Townsend, Kelly A; Gabriele, Michelle L; Srinivasan, Vivek J; Fujimoto, James G; Schuman, Joel S
We use Fourier domain optical coherence tomography (OCT) data to assess retinal blood oxygen saturation. Three-dimensional disk-centered retinal tissue volumes were assessed in 17 normal healthy subjects. After removing DC and low-frequency a-scan components, an OCT fundus image was created by integrating total reflectance into a single reflectance value. Thirty fringe patterns were sampled; 10 each from the edge of an artery, adjacent tissue, and the edge of a vein, respectively. A-scans were recalculated, zeroing the DC term in the power spectrum, and used for analysis. Optical density ratios (ODRs) were calculated as ODR(Art)=ln(Tissue(855)Art(855))ln(Tissue(805)Art(805)) and ODR(Vein)=ln(Tissue(855)Vein(855))ln(Tissue(805)Vein(805)) with Tissue, Art, and Vein representing total a-scan reflectance at the 805- or 855-nm centered bandwidth. Arterial and venous ODRs were compared by the Wilcoxon signed rank test. Arterial ODRs were significantly greater than venous ODRs (1.007+/-2.611 and -1.434+/-4.310, respectively; p=0.0217) (mean+/-standard deviation). A difference between arterial and venous blood saturation was detected. This suggests that retinal oximetry may possibly be added as a metabolic measurement in structural imaging devices.
PMCID:2916162
PMID: 17867801
ISSN: 1083-3668
CID: 1886122

Peripapillary schisis in glaucoma patients with narrow angles and increased intraocular pressure [Case Report]

Kahook, Malik Y; Noecker, Robert J; Ishikawa, Hiroshi; Wollstein, Gadi; Kagemann, Larry; Wojtkowski, Maciej; Duker, Jay S; Srinivasan, Vivek J; Fujimoto, James G; Schuman, Joel S
PURPOSE: To describe two cases of peripapillary retinal schisis in patients with glaucoma without evidence of optic nerve pits, pseudopits, or X-linked retinoschisis. DESIGN: Two observational case reports and literature review. METHODS: Imaging of the peripapillary nerve fiber layer and schisis cavities was completed in two patients, and one patient was followed over time. RESULTS: The first patient, diagnosed with narrow angle glaucoma, was noted to have peripapillary schisis in the right eye with matching changes on visual field and optical coherence tomographic (OCT) results. Follow-up examination revealed that the schisis disappeared in the right eye while appearing in the left. The findings were verified with high-speed ultra-high-resolution OCT performed in both eyes. The second case involved a patient with anatomically narrow angles, high intraocular pressure (IOP), and peripapillary schisis extending into the macula. CONCLUSIONS: Peripapillary retinoschisis may represent a unique sequelae of intraocular fluctuations in patients with uncontrolled glaucoma. Further studies are needed to better understand this disease process.
PMCID:1941763
PMID: 17386284
ISSN: 0002-9394
CID: 1886142

Evaluating short-term pain after steroid injection

Wollstein, Ronit; Chaimsky, Gershon; Carlson, Lois; Watson, H K; Wollstein, Gadi; Saleh, Jaber
Steroids are injected into joints for various indications. All steroid preparations relieve pain similarly over the long term. Therefore, decisions about which preparation to use are often arbitrary. We evaluated methylprednisolone acetate and a combination of betamethasone diproprionate and betamethasone sodium phosphate for short-term pain and the predictive value of short-term pain. Eighty-five patients were injected in prospective double-blind randomized fashion. Pain was evaluated by visual analog scale (1 = no pain, 10 = severe pain) at baseline, 3 days, and 3 weeks. No patient had joint pain immediately after injection. Three days after injection, mean (SD) pain levels were 5.1 (2.9) for methylprednisolone and 5.2 (2.6) for betamethasone (P = .97); 3 weeks after injection, they were 4.0 (2.8) and 3.7 (2.5), respectively (P = .57). Short-term pain increased from baseline for both preparations and decreased from 3 days to 3 weeks. Pain at 3 days and 3 weeks was positively correlated. This study does not support a difference in short-term pain between preparations. The significant correlation between short- and long-term pain may justify early decisions regarding treatment, especially in patients with high levels of initial pain.
PMID: 17461394
ISSN: 1078-4519
CID: 2297802

Glaucoma detection with the Heidelberg retina tomograph 3

Burgansky-Eliash, Zvia; Wollstein, Gadi; Bilonick, Richard A; Ishikawa, Hiroshi; Kagemann, Larry; Schuman, Joel S
PURPOSE: To compare the ability of the Heidelberg retina tomograph version 3 (HRT 3) and HRT version 2 (HRT 2) to discriminate between healthy and glaucomatous eyes. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Seventy-one eyes of 71 healthy volunteers and 50 eyes of 50 glaucoma patients were studied. The average visual field mean deviation of the glaucoma group was -6.03+/-5.78 dB. INTERVENTION: All participants had comprehensive ocular examinations, perimetry, and HRT scanning within 6 months. HRT 2 data were analyzed using HRT 3 software without modifying the disc margin. MAIN OUTCOME MEASURES: Discrimination capabilities between healthy and glaucomatous eyes were determined by areas under the receiver operating characteristics (AROCs) curves. Comparisons between corresponding AROCs obtained by HRT 2 and HRT 3 analyses were performed using the nonparametric DeLong method. Agreement between classifications as defined by the different analysis methods was quantified by kappa analysis. RESULTS: The individual stereometric parameters with the best discrimination were linear cup/disc ratio (AROC = 0.897; 95% confidence interval [CI], 0.836-0.958) for standard HRT 3 analysis and horizontal retinal nerve fiber layer curvature (0.905) for HRT 3 glaucoma probability score (GPS) analysis. Areas under the receiver operating characteristics for discrimination between glaucomatous and healthy eyes of the overall classification by HRT 2 Moorfields regression analysis (MRA), HRT 3 MRA, and GPS were 0.927 (95% CI, 0.877-0.977), 0.934 (0.888-0.980), and 0.880 (0.812-0.948), respectively. The difference between the 3 AROCs was not significant (P = 0.44). The agreement between HRT 2 and HRT 3 overall MRA classification was good (kappa = 0.70; CI, 0.59-0.80) with HRT 3 tending to report more abnormalities than HRT 2 analysis. The agreement between overall HRT 3 MRA and overall GPS was kappa = 0.58 (CI, 0.45-0.70). CONCLUSIONS: The glaucoma discriminating ability of the new HRT 3 software is similar to that of the previous generation HRT 2. The GPS analysis showed promising results in differentiating between healthy and glaucomatous eyes without the need for subjective operator input.
PMCID:1945822
PMID: 17141321
ISSN: 1549-4713
CID: 1886182

Comparison of visual field defects using matrix perimetry and standard achromatic perimetry

Patel, Avni; Wollstein, Gadi; Ishikawa, Hiroshi; Schuman, Joel S
PURPOSE: To compare visual field (VF) defects found by Swedish interactive thresholding Algorithm (SITA) perimetry and Matrix perimetry, a new VF device that utilizes frequency doubling technology in a 24-2 test pattern. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Fifty eyes from 50 subjects with SITA field defects were recruited for an observational study. METHODS: Swedish Interactive Threshold Algorithm and Matrix VF testing were performed on patients from a glaucoma practice. To evaluate the learning effect on the performance of the VF, we tested subsets of each group who had previous experience with standard automated perimetry (SAP). MAIN OUTCOME MEASURES: Test duration, mean threshold, mean deviation (MD), pattern standard deviation (PSD), glaucoma hemifield test, and number of abnormal points on the pattern deviation plot were evaluated for each device. RESULTS: Test duration was significantly shorter for Matrix (SITA, 357.0+/-85.6 seconds; Matrix, 319.5+/-16.5 seconds; P = 0.0002, paired t-test). Thirty-six percent of eyes with SITA VF defects showed a normal Matrix field. In 30 of 32 eyes (94%) where both devices showed VF defects, the defects were congruent. Mean threshold value was significantly lower with Matrix compared to SITA (P<0.0001, paired t-test), as was MD (-5.34+/-5.42 dB, -4.14+/-5.29 dB, respectively; P = 0.03, paired t-test). There was no significant difference in PSD between the 2 devices (P = 0.78, paired t-test). Matrix delineated significantly smaller (P = 0.005, Wilcoxon's test) and deeper (P<0.001, Wilcoxon's test) defects than those found with SITA. Similar results were observed in the subgroups with prior SAP experience. CONCLUSIONS: The Matrix examination did not detect 36% of abnormal SITA fields. Matrix field defects were smaller and deeper than those appearing in SITA perimetry.
PMCID:1945823
PMID: 17123623
ISSN: 1549-4713
CID: 1886192

Translation histogram based hierarchical algorithm for 3-d optic nerve head modeling

Xu, Juan; Ishikawa, Hiroshi; Wollstein, Gadi; Schuman, Joel S
This paper describes a translation histogram based, hierarchical algorithm for automated three-dimensional (3-D) optic nerve head (ONH) modeling from stereoscopic ONH photographs. Recovering the depths in featureless region is still one of the problems in previous studies of 3-D ONH reconstruction. The proposed algorithm hierarchically optimized and modeled the peripheral ONH surface to solve this problem. The algorithm has various steps consisting of disparity detection, hierarchical surface modeling, weighted fusing, and depth calibration. Dual-registration algorithm is firstly applied to precisely detect the matching points which are then converted into disparities. The peripheral ONH surface is initialized and refined through hierarchical modeling and optimization from the disparities. The final 3-D ONH model is generated by fusing the modeled peripheral ONH surface and the depths measured from dual-registration together with the interpolation. The true depth is obtained after calibration of eye lens through the axial length information. The experimental results showed the proposed algorithm could successfully generate 3-D ONH model, and get good consistency with human expert in cup-to-disc (C/D) ratio evaluation. The algorithm indicates the potential usefulness for 3-D ONH modeling and evaluation.
PMCID:2912148
PMID: 18003577
ISSN: 1557-170x
CID: 1886212