Faculty Bibliography

OBJECTIVE: To evaluate the current published literature on the use of optic nerve head (ONH) and retinal nerve fiber layer (RNFL) measurement devices in diagnosing open-angle glaucoma and detecting progression. METHODS: A search of peer-reviewed literature was conducted on February 15, 2006 in PubMed and the Cochrane Library for the period January 2003 to February 2006. The search was limited to studies of adults in English-language journals and yielded 442 citations. The panel reviewed the abstracts of these articles and selected 159 articles of possible clinical relevance for review. Of these 159 full-text articles, 82 were determined to be relevant for the first author and methodologist to review and rate according to the quality of evidence. RESULTS: There were no studies classified as having the highest level of evidence (level I). The ONH and RNFL imaging instruments reviewed in this assessment were determined to be highly effective in distinguishing eyes with glaucomatous visual field (VF) loss from normal eyes without VF loss, based on level II evidence. In addition, some studies demonstrated that parameters from ONH or RNFL imaging predicted the development of VF defects among glaucoma suspects. Studies on detecting glaucoma progression showed that although there was often agreement on progression between the structural and functional (VF) tests, a significant proportion of glaucoma patients progressed by either the structural or the functional test alone. CONCLUSIONS: The ONH and RNFL imaging devices provide quantitative information for the clinician. Based on studies that have compared the various available technologies directly, there is no single imaging device that outperforms the others in distinguishing patients with glaucoma from controls. Ongoing advances in imaging and related software, as well as the impracticalities associated with obtaining and assessing optic nerve stereophotographs, have made imaging increasingly important in many practice settings. The information obtained from imaging devices is useful in clinical practice when analyzed in conjunction with other relevant parameters that define glaucoma diagnosis and progression.

OBJECTIVE: To evaluate published literature to assess whether central corneal thickness (CCT) is a risk factor for the presence, development, or progression of glaucomatous optic nerve damage related to primary open-angle glaucoma (POAG). METHODS: A PubMed literature search limited to English language articles conducted on November 15, 2004 retrieved 195 articles. The authors reviewed these abstracts and selected 57 to review in full text to determine relevance to the assessment questions. A further 24 studies of interest were identified from periodic updates to the literature search, surveillance of the literature, and reference lists of reviewed articles. From the 81 published reports identified, the first author applied specified selection criteria that yielded 37 articles for methodological review because of relevance to the assessment questions. The articles were rated according to the strength of evidence by the panel methodologist. A level I rating was assigned to well-designed properly conducted randomized clinical trials or similar quality-validated cohort studies with appropriate reference standards. A level II rating was assigned to well-designed case-control studies, exploratory cohort studies, and other nonrandomized clinical studies lacking consistently applied reference standards. A level III rating was reserved for poorly designed case-control studies, case series, and papers consisting only of expert opinion without supporting evidence. In addition, each study was graded as positive if it supported a statistical association of CCT with the risk of having or developing glaucomatous optic nerve damage or as negative if no such association was found. RESULTS: There is strong and consistent level I and level II evidence that CCT is a risk factor for progression from ocular hypertension to POAG. Studies that were rated as providing the highest quality of evidence revealed mixed results with respect to glaucoma prevalence. One population-based study (level II) showed a positive association, another larger study (level I) revealed an association of marginal significance, and 3 studies (all level I) found no association of CCT with POAG prevalence. CONCLUSIONS: There is strong evidence that measuring CCT is an important component of a complete ocular examination, particularly for patients being evaluated for the risk of developing POAG. Therefore, CCT measurement should be included in the examination of all patients with ocular hypertension. Although the evidence supporting the necessity of measuring CCT as part of screening for POAG or as a risk factor for glaucoma progression is not as strong, intraocular pressure (IOP) is the only modifiable risk factor in the treatment of glaucoma, and CCT has the potential to significantly impact IOP measurement by applanation tonometry in all patients.

A 42-year-old man with Hunter syndrome developed bilateral visual field loss. Visual field testing demon-strated bilateral ring scotomata that corresponded to areas of thinning seen on standard resolution optical coherence tomography. High-speed, ultrahigh resolution optical coherence tomography, capable of 3.5-micron axial resolution, showed a loss of photoreceptors outside the fovea and cystoid spaces within the inner nuclear, ganglion cell, and outer nuclear layers. These results were consistent with histopathologic features that have been reported previously in patients with Hunter syndrome. Optical coherence tomography could be used as a diagnostic modality to monitor patients with Hunter syndrome and to detect subclinical forms of disease.

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.

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.

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.

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.

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.

OBJECTIVES: To compare structural changes in the retina seen on high-speed ultra-high-resolution optical coherence tomography (hsUHR-OCT) with multifocal electroretinography (mfERG) and automated visual fields in patients receiving hydroxychloroquine. METHODS: Fifteen patients receiving hydroxychloroquine were evaluated clinically with hsUHR-OCT, mfERG, and automated visual fields. Six age-matched subjects were imaged with hsUHR-OCT and served as controls. RESULTS: Distinctive discontinuity of the perifoveal photoreceptor inner segment/outer segment junction and thinning of the outer nuclear layer were seen with hsUHR-OCT in patients with mild retinal toxic effects. Progression to complete loss of the inner segment/outer segment junction and hyperscattering at the outer segment level were seen in more advanced cases. The mfERG abnormalities correlated with the hsUHR-OCT findings. Asymptomatic patients had normal hsUHR-OCT and mfERG results. CONCLUSION: Distinctive abnormalities in the perifoveal photoreceptor inner segment/outer segment junction were seen on hsUHR-OCT in patients receiving hydroxychloroquine who also were symptomatic and had abnormalities on automated visual fields and mfERG.