Andrew J. Tatham

Assessment of choroidal thickness and volume during the water drinking test by swept-source optical coherence tomography.

OBJECTIVE To evaluate changes in peripapillary and macular choroidal thickness and volume after the water-drinking test (WDT) using swept-source optical coherence tomography (SS OCT). DESIGN Prospective, cross-sectional, observational study. PARTICIPANTS Fifty-six eyes of 28 healthy volunteers. METHODS Participants underwent a 3-dimensional optic disc and macula scanning protocol with a prototype SS OCT (Topcon, Inc., Tokyo, Japan) at baseline and 15, 30, 45, and 120 minutes after the start of the WDT. The WDT consisted of drinking 1000 ml of water within 5 minutes. Objective measurements of the choroid were obtained with automated segmentation of the choroidal boundaries. MAIN OUTCOME MEASURES Choroidal thickness and volume. RESULTS Mean age ± standard deviation of participants was 35.6 ± 9.1 years. Intraocular pressure (IOP) increased from 14.9 ± 2.7 mmHg at baseline to a peak of 16.8 ± 3.0 mmHg 15 minutes after the WDT (P < 0.001). Mean baseline choroidal thickness and volume were 181.3 ± 50.8 μm and 6.19 ± 1.80 mm(3), respectively, at the optic disc and 217.4 ± 43.6 μm and 7.83 ± 1.55 mm(3), respectively, at the macula. After the WDT, peripapillary and macular choroidal thickness increased by a maximum of 5.7% (P<0.001) and 4.3% (P<0.001), respectively. Choroidal volumes increased by 6.4% (P<0.001) and 3.9% (P<0.001), respectively. There was no association between change in IOP and peripapillary (P = 0.27) or macular (P = 0.09) choroidal thickness. CONCLUSIONS Using automated segmentation of SS OCT measurements, significant increases in choroidal thickness and volume are observed after the WDT in healthy subjects.

Association Between Progressive Retinal Nerve Fiber Layer Loss and Longitudinal Change in Quality of Life in Glaucoma

IMPORTANCE Evaluation of structural optic nerve damage is a fundamental part of diagnosis and management of glaucoma. However, the relationship between structural measurements and disability associated with the disease is not well characterized. Quantification of this relationship may help validate structural measurements as markers directly relevant to quality of life. OBJECTIVE To evaluate the relationship between rates of retinal nerve fiber layer (RNFL) loss and longitudinal changes in quality of life in glaucoma. DESIGN, SETTING, AND PARTICIPANTS Observational cohort study including 260 eyes of 130 patients with glaucoma followed up for a mean (SD) of 3.5 (0.7) years. All patients had repeatable visual field defects on standard automated perimetry (SAP) at baseline. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was performed annually, and spectral-domain optical coherence tomography and SAP were performed at 6-month intervals. A joint model was used to investigate the association between change in NEI VFQ-25 Rasch-calibrated scores and change in RNFL thickness, adjusting for confounding socioeconomic and clinical variables. MAIN OUTCOMES AND MEASURES Association between change in binocular RNFL thickness (RNFL thickness in the better eye at each point) and change in NEI VFQ-25 scores. RESULTS Progressive binocular RNFL thickness loss was associated with worsening of NEI VFQ-25 scores over time. In a multivariable model adjusting for baseline disease severity and the rate of change in binocular SAP sensitivity, each 1-μm-per-year loss of RNFL thickness was associated with a decrease of 1.3 units (95% CI, 1.02-1.56) per year in NEI VFQ-25 scores (P < .001). After adjusting for the contribution from SAP, 26% (95% CI, 12%-39%) of the variability of change in NEI VFQ-25 scores was associated uniquely with change in binocular RNFL thickness. The P value remained less than .001 after adjusting for potential confounding factors. CONCLUSIONS AND RELEVANCE Progressive binocular RNFL thickness loss was associated with longitudinal loss in quality of life, even after adjustment for progressive visual field loss. These findings suggest that rates of binocular RNFL change are valid markers for the degree of neural loss in glaucoma with significant relationship to glaucoma-associated disability.

Assessment of choroidal thickness in healthy and glaucomatous eyes using swept source optical coherence tomography.

Purpose To evaluate choroidal thickness (CT) in healthy and glaucomatous eyes using Swept Source Optical Coherence Tomography (SS-OCT). Methods A cross-sectional observational study of 216 eyes of 140 subjects with glaucoma and 106 eyes of 67 healthy subjects enrolled in the Diagnostic Innovations in Glaucoma Study. CT was assessed from wide-field (12×9 mm) SS-OCT scans. The association between CT and potential confounding variables including age, gender, axial length, intraocular pressure, central corneal thickness and ocular perfusion pressure was examined using univariable and multivariable regression analyses. Results Overall CT was thinner in glaucomatous eyes with a mean (± standard deviation) of 157.7±48.5 µm in glaucoma compared to 179.9±36.1 µm in healthy eyes (P<0.001). The choroid was thinner in both the peripapillary and macular regions in glaucoma compared to controls. Mean peripapillary CT was 154.1±44.1 µm and 134.0±56.9 µm (P<0.001) and macular CT 199.3±46.1 µm and 176.2±57.5 µm (P<0.001) for healthy and glaucomatous eyes respectively. However, older age (P<0.001) and longer axial length (P<0.001) were also associated with thinner choroid and when differences in age and axial length between glaucomatous and healthy subjects were accounted for, glaucoma was not significantly associated with CT. There was also no association between glaucoma severity and CT. Conclusions Glaucoma was not associated with CT measured using SS-OCT; however, older age and longer axial length were associated with thinner choroid so should be considered when interpreting CT measurements.

Predicting progression in glaucoma suspects with longitudinal estimates of retinal ganglion cell counts.

PURPOSE We evaluated the ability of baseline and longitudinal estimates of retinal ganglion cell (RGC) counts in predicting progression in eyes suspected of having glaucoma. METHODS The study included 288 glaucoma suspect eyes of 288 patients followed for an average of 3.8 ± 1.0 years. Participants had normal standard automated perimetry (SAP) at baseline. Retinal nerve fiber layer thickness assessment was performed with optical coherence tomography (OCT). Progression was defined as development of repeatable abnormal SAP or glaucomatous progressive optic disc changes. Estimates of RGC counts were obtained by combining data from SAP and OCT according to a previously described method. Joint longitudinal survival models were used to evaluate the ability of baseline and rates of change in estimated RGC counts for predicting progression over time, adjusting for confounding variables. RESULTS A total of 48 eyes (17%) showed progression during follow-up. The mean rate of change in estimated RGC counts was -18,987 cells/y in progressors versus -8,808 cells/y for nonprogressors (P < 0.001). Baseline RGC counts and slopes of RGC loss were significantly predictive of progression, with HRs of 1.56 per 100,000 cells lower (95% confidence interval [CI], 1.18-2.08; P = 0.002) and 2.68 per 10,000 cells/y faster loss (95% CI, 1.22-5.90; P = 0.014), respectively. The longitudinal model including estimates of RGC counts performed significantly better than models including only structural or functional indexes separately. CONCLUSIONS Baseline and longitudinal estimates of RGC counts may be helpful in predicting progression and performed significantly better than conventional approaches for risk stratification of glaucoma suspects.

Assessment of optic nerve head drusen using enhanced depth imaging and swept source optical coherence tomography.

Background: Optic nerve head drusen (ONHD) are calcific deposits buried or at the surface of the optic disc. Although ONHD may be associated with progressive visual field defects, the mechanism of drusen-related field loss is poorly understood. Methods for detecting and imaging disc drusen include B-scan ultrasonography, fundus autofluorescence, and optical coherence tomography (OCT). These modalities are useful for drusen detection but are limited by low resolution or poor penetration of deep structures. This review was designed to assess the potential role of new OCT technologies in imaging ONHD. Evidence Acquisition: Critical appraisal of published literature and comparison of new imaging devices to established technology. Results: The new imaging modalities of enhanced depth imaging optical coherence tomography (EDI-OCT) and swept source optical coherence tomography (SS-OCT) are able to provide unprecedented in vivo detail of ONHD. Using these devices it is now possible to quantify optic disc drusen dimensions and assess integrity of neighboring retinal structures, including the retinal nerve fiber layer. Conclusions: EDI-OCT and SS-OCT have the potential to allow better detection of longitudinal changes in drusen and neural retina and improve our understanding of drusen-related visual field loss.

Diagnostic ability of retinal nerve fiber layer imaging by swept source optical coherence tomography in glaucoma

PURPOSE To evaluate the diagnostic accuracies of swept-source optical coherence tomography (OCT) wide-angle and peripapillary retinal nerve fiber layer (RNFL) thickness measurements for glaucoma detection. DESIGN Cross-sectional case-control study. METHODS In this study we enrolled 144 glaucomatous eyes of 106 subjects and 66 eyes of 42 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Glaucoma was defined by the presence of repeatable abnormal standard automated perimetry results and/or progressive glaucomatous optic disc change on masked grading of stereophotographs. Wide-angle and peripapillary RNFL thicknesses were assessed using swept-source OCT. Peripapillary RNFL thickness was also evaluated using spectral-domain OCT. Areas under the receiver operating characteristic (ROC) curves were calculated to evaluate the ability of the different swept-source OCT and spectral-domain OCT parameters to discriminate between glaucomatous and healthy eyes. RESULTS Mean (± standard deviation) average spectral-domain OCT wide-angle RNFL thicknesses were 50.5 ± 5.8 μm and 35.0 ± 9.6 μm in healthy and glaucomatous eyes, respectively (P < 0.001). Corresponding values for swept-source OCT peripapillary RNFL thicknesses were 103.5 ± 12.3 μm and 72.9 ± 16.5 μm, respectively (P < 0.001). Areas under the ROC curves of swept-source OCT wide-angle and peripapillary RNFL thickness were 0.88 and 0.89, respectively. Swept-source OCT performed similar to average peripapillary RNFL thickness obtained by spectral-domain OCT (area under the ROC curve of 0.90). CONCLUSION Swept-source OCT wide-angle and peripapillary RNFL thickness measurements performed well for detecting glaucomatous damage. The diagnostic accuracies of the swept-source OCT and spectral-domain OCT RNFL imaging protocols evaluated in this study were similar.

Relationship between ganglion cell layer thickness and estimated retinal ganglion cell counts in the glaucomatous macula

PURPOSE To investigate the relationship between macular ganglion cell-inner plexiform layer (mGCIPL) thickness and estimated macular retinal ganglion cell (RGC) counts in glaucoma. DESIGN Observational cohort study. PARTICIPANTS Cross-sectional study of 77 healthy, 154 glaucoma suspect, and 159 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study. METHODS All eyes underwent 24-2 standard automated perimetry (SAP) and optic nerve and macular imaging using high-definition optical coherence tomography (OCT). The total number of RGCs was estimated using a previously described model that uses SAP and OCT circumpapillary retinal nerve fiber layer (cpRNFL) measurements. The number of macular RGCs was estimated from the temporal cpRNFL and SAP test points within the central 10°. MAIN OUTCOME MEASURES The correlation between mGCIPL thickness and estimates of macular RGC counts. RESULTS The average estimated macular RGC count in glaucomatous eyes was 306 010 ± 109 449 cells, which was significantly lower than the estimate of 520 678 ± 106 843 cells in healthy eyes (P < 0.001). Glaucomatous eyes had 41% fewer estimated macular RGCs than healthy eyes and suspects had 21% fewer estimated macular RGCs. There was strong correlation between estimated macular RGC counts and mGCIPL thickness (R(2) = 0.67; P < 0.001). Macular RGC counts performed better than average mGCIPL thickness in discriminating healthy and glaucomatous eyes with receiver operating characteristic curve areas of 0.873 and 0.775, respectively (P = 0.015). CONCLUSIONS The strong association between estimated macular RGC counts and mGCIPL thickness and the better diagnostic performance of the macular RGC counts compared with mGCIPL thickness provides further evidence that estimates of RGC number from cpRNFL thickness and SAP sensitivity can be used to assess neural losses in glaucoma.

Diagnostic ability of macular ganglion cell inner plexiform layer measurements in glaucoma using swept source and spectral domain optical coherence tomography.

Purpose To evaluate the diagnostic ability of macular ganglion cell and inner plexiform layer measurements in glaucoma, obtained using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) and to compare to circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. Methods The study included 106 glaucomatous eyes of 80 subjects and 41 eyes of 22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under the receiver operating characteristic curves (AUCs) were calculated to determine ability to differentiate glaucomatous and healthy eyes and between early glaucomatous and healthy eyes. Results Mean (± standard deviation) mGCIPL and mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT compared to using SD-OCT. Fixed and proportional biases were detected between SS-OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS-OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired using SS-OCT and SD-OCT tended to be higher (0.83 and 0.85, respectively) than for average mGCC (0.82 and 0.78, respectively), and mGCIPL (0.73 and 0.75, respectively) but these differences did not consistently reach statistical significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT) had the highest AUC (0.86) among macular measurements. Conclusion Assessment of mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous damage, but measurements are not interchangeable for patient management decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT were similar to that of cpRNFL for glaucoma detection.

Estimated Retinal Ganglion Cell Counts in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects

PURPOSE To estimate retinal ganglion cell (RGC) losses associated with visible glaucomatous localized retinal nerve fiber layer (RNFL) defects. DESIGN Observational cross-sectional study. METHODS A multicenter study of 198 normal eyes (138 subjects) and 66 glaucomatous eyes (55 subjects) recruited from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. All eyes underwent standard automated perimetry (SAP), spectral-domain optical coherence tomography, and fundus stereophotography within 6 months. Glaucomatous eyes were included if localized RNFL defects were detected by masked grading of stereophotographs. The number of RGCs in each sector of a structure-function map was estimated using a previously published model combining RGC estimates from SAP and spectral-domain optical coherence tomography. The estimated percentage loss of RGCs (combined structure-function index) was calculated. RESULTS In glaucomatous eyes, there were 136 sectors with visible RNFL defects and 524 sectors without visible RNFL defects. The most common sectors with visible RNFL defects were inferior and inferotemporal sectors, followed by superior and supertemporal sectors. Eyes with visible RNFL defects had a mean estimated RGC count of 657,172 cells versus 968 883 cells in healthy eyes (P < .001). The average combined structure-function index in sectors with a visible RNFL defect (59 ± 21%) was significantly higher than in sectors without a visible RNFL defect in glaucomatous eyes (15 ± 29%; P < .001) and higher than in healthy eyes (1 ± 13%; P < .001). CONCLUSIONS Although visible localized RNFL defects often are considered an early sign of glaucoma, this study indicates that they are likely to be associated with large neuronal losses.

Strategies for improving early detection of glaucoma: the combined structure-function index

The early detection of glaucoma is important in order to enable appropriate monitoring and treatment, and to minimize the risk of irreversible visual field loss. Although advances in ocular imaging offer the potential for earlier diagnosis, the best method is likely to involve a combination of information from structural and functional tests. Recent studies have shown it is possible to estimate the number of retinal ganglion cells from optical coherence tomography and standard automated perimetry, and to then pool the results to produce a combined structure–function index (CSFI). The CSFI represents the estimated percentage of retinal ganglion cells lost compared to an age-matched healthy eye. Previous studies have suggested that the CSFI is better able to detect glaucoma than isolated measures of structure and function, and that it performs well even in preperimetric glaucoma. The purpose of this review is to describe new strategies, such as the CSFI, that have the potential to improve the early detection of glaucoma. We also describe how our ability to detect early glaucoma may be further enhanced by incorporating demographic risk factors, clinical examination findings, and imaging and functional test results into intuitive models that provide estimates of disease probability.