Structure-function relationships using confocal scanning laser ophthalmoscopy, optical coherence tomography, and scanning laser polarimetry

PURPOSE: To assess the strength of the association between retinal nerve fiber layer (RNFL) thickness and optic disc topography measured with confocal retinal tomography (HRT II; Heidelberg Engineering, Dossenheim, Germany), optical coherence tomography (StratusOCT; Carl Zeiss Meditec, Inc., Dublin, CA), and scanning laser polarimetry (GDx with variable corneal compensator, VCC; Carl Zeiss Meditec, Inc.), and visual field (VF) sensitivity and to determine whether this association is better expressed as a linear or nonlinear function. METHODS: One hundred twenty-seven patients with glaucoma or suspected glaucoma and 127 healthy eyes from enrollees in the Diagnostic Innovations in Glaucoma Study (DIGS) were tested on HRT II, StratusOCT, GDx VCC, and standard automated perimetry (SAP, with the Swedish Interactive Thresholding Algorithm [SITA]) within 3 months of each other. Linear and logarithmic associations between RNFL thickness (HRT II, StratusOCT, and GDx VCC) and neuroretinal rim area (HRT II) and SAP sensitivity expressed in decibels were determined globally and for six RNFL/optic disc regions (inferonasal, inferotemporal, temporal, superotemporal, superonasal, and nasal) and six corresponding VF regions (superior, superonasal, nasal, inferonasal, inferior, and temporal). RESULTS: The associations (R2) between global and regional RNFL/optic disc measurements and VF sensitivity ranged from <0.01 (temporal RNFL, nasal VF, and nasal RNFL, temporal VF; linear and logarithmic associations) to 0.26 (inferotemporal RNFL, superonasal VF; logarithmic association) for HRT II; from 0.02 (temporal RNFL, nasal VF; linear association) to 0.38 (inferotemporal RNFL, superonasal VF; logarithmic association) for OCT; and from 0.03 (temporal RNFL, nasal VF; linear association) to 0.21 (inferotemporal RNFL, superonasal VF; logarithmic association) for GDx. Structure-function relationships generally were strongest between the inferotemporal RNFL-optic disc sector and the superonasal visual field and were significantly stronger for StratusOCT RNFL thickness than for other instruments in this region. Global associations (linear and logarithmic) were significantly stronger using OCT compared with HRT. In most cases, logarithmic fits were not significantly better than linear fits when visual sensitivity was expressed in log units (i.e., decibels). CONCLUSIONS: These results suggest that structure-function associations are strongest with StratusOCT measurements and are similar between HRT II and GDx VCC and these associations are generally no better expressed logarithmically than linearly when healthy, suspect, and glaucomatous eyes are considered.     

Correlation between confocal scanning laser ophthalmoscopy and scanning laser polarimetry in open angle glaucoma

PURPOSE: To correlate the findings of confocal scanning laser ophthalmoscopy and scanning laser polarimetry in diagnosed cases of glaucoma with established visual field defects. METHODS: A total of 53 diagnosed cases of primary open angle glaucoma that had at least two recorded of IOP more than 21 mm Hg on Goldmann applanation tonometry, open angles on gonioscopy and glaucomatous visual field defects on automated perimetry, were examined by confocal scanning laser ophthalmoscopy (HRT-II) and scanning laser polarimetry (GDx-NFA), in random order. RESULTS: The number on GDx advanced analysis had a significant (p < 0.05) correlation with the rim area (r = -0.279; p = 0.043), cup area (r = 0.311; p = 0.023) and the vertical cup: disc ratio (r = 0.376; p = 0.006). The correlation between HRT-II stereometric parameters and GDx advanced analysis parameters was significant (p < 0.05) for more parameters targeting the inferior pole of the disc than the superior pole. Numerically, the worst values of GDx parameters were associated with a worse result on Moorfields regression analysis, but there was poor agreement between the diagnostic labels like within or outside normal limits as obtained on GDx and HRT-II. CONCLUSIONS: Nerve fiber loss as detected on GDx correlates well with topographic optic nerve head changes as measured with the HRT-II. However, automated diagnosis on the two machines showed poor agreement.     

Objective monitoring of papilloedema using confocal scanning laser ophthalmoscopy

Idiopathic intracranial hypertension can cause severe optic nerve damage with irreversible visual loss. Heidelberg retina tomography is a sensitive and reproducible tool that can be used in the monitoring of optic disc swelling due to IIH. We demonstrate that the three-dimensional images produced are easy to interpret, indicate progression or resolution and improve the timing of intervention in multidisciplinary settings by facilitating communication between specialists.     

Relationships between standard automated perimetry, HRT confocal scanning laser ophthalmoscopy, and GDx VCC scanning laser polarimetry

PURPOSE: This study was designed to determine and compare the relationships between visual function measured with standard automated perimetry (SAP) and structure, either as neuroretinal rim area measured with confocal scanning laser ophthalmoscopy (CSLO), or as retinal nerve fiber layer thickness determined by scanning laser polarimetry with variable corneal compensation (SLP-VCC). METHODS: Forty-six healthy subjects and 76 glaucoma patients were examined with SAP, with CSLO by means of the commercially available Heidelberg Retina Tomograph I (HRT), and with SLP-VCC by means of the commercially available GDx VCC. The relationships between SAP, expressed either in the typically used decibel scale or as number of abnormal points in the total deviation probability plot, and CSLO and between SAP and SLP-VCC were described with linear and logarithmic regression analysis for global data and six individual sectors. The relationship between measurements with CSLO and SLP-VCC was fit with linear regression analysis. RESULTS: The relationships between SAP and CSLO and between SAP and SLP-VCC appeared curvilinear for all sectors except the temporal one between SAP and SLP-VCC. For CSLO, a logarithmic fit was significantly better than a linear one for the global data and in the superotemporal and inferonasal sectors. For SLP-VCC, a curvilinear fit was better for the global data and in the superotemporal, superonasal, and inferonasal sectors. CSLO data correlated linearly with SLP-VCC data in all sectors, except temporally. CONCLUSIONS: CSLO and SLP-VCC showed a very similar curvilinear relationship with SAP. The observed curvilinear relationships confirm earlier reports that these imaging devices appear to detect glaucomatous loss earlier than SAP.     

激光共聚焦扫描检眼镜在青光眼早期诊断中的应用

激光共聚焦扫描检眼镜 (confocal scanning laser ophthalm oscopy,CSLO)是近年来出现的一种新型眼底检查设备。它可对视盘及其周围结构的形态进行客观、定量、三维地测量 ,对眼底血管及血流进行检查和测定。目前已成为眼科诊断的重要辅助设备。本文即对 CSL O在青光眼中的一部分应用做一综述。1　海德堡视网膜断层扫描的应用青光眼损害是不可逆的 ,青光眼的早期诊断是改善其预后的一个重要途径。而青光眼尤其是开角型青光眼首先发生眼底形态学改变 ,当视功能损害超过 4 0 %时才出现视野缺损。因此通过对视盘形态学测量和动态观察可提高…     

High resolution fundus imaging by confocal scanning laser ophthalmoscopy in the mouse

We evaluated fundus imaging using a modified confocal scanning laser ophthalmoscope (cSLO) in mice. Examinations were performed in conscious, untrained mice. The largest field of view measured 1,520 x 1,520 mu, with a significant interindividual variability, itself correlated to biometric variability. The composite field of view extended up to the ora serrata. The reflectance imaging associated light reflection from nerve fiber bundles and vessel walls, and absorption by hemoglobin and melanin. Light absorption by the pigment epithelium indeed increased the contrast of the nerve fiber layer, but impaired viewing of the choroid. Due to the confocal mode, fluorescence angiograms with clear separation of retinal and choroidal fluorescence could be obtained even in albino mice. Micrometric-scale transverse resolution and several planes of optical sectioning within the retina were obtained. This permitted for instance tridimensional, subcellular viewing of gfp-expressing retinal microglial cells in CX(3)CR1 mice. We concluded that cSLO is a promising tool for noninvasive, multimodal intravital microscopy of the fundus in the mouse.     

Optic disc measurements in myopia with optical coherence tomography and confocal scanning laser ophthalmoscopy

PURPOSE: To evaluate the relationships between optic disc measurements, obtained by an optical coherence tomograph and a confocal scanning laser ophthalmoscope, and myopia. METHODS: One hundred thirty-three eyes from 133 healthy subjects with mean spherical equivalent -6.0 +/- 4.2 D (range, -13.13 to +3.25 D) were analyzed. Optic disc measurements including disc area, rim area, cup area, cup-to-disc area, and vertical and horizontal ratios were obtained with an optical coherence tomograph (StratusOCT; Carl Zeiss Meditec Inc., Dublin, CA) and a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph, HRT 3; Heidelberg Engineering, GmbH, Dossenheim, Germany). The modified axial length method derived from prior published work was used to correct the OCT measurements for ocular magnification. Bland-Altman plots were used to evaluate the agreement for each optic disc parameter. Associations between optic disc area and axial length/spherical equivalent were evaluated by linear regression analysis. RESULTS: Disc area increased with the axial length/negative spherical equivalent in the HRT and the corrected OCT measurements although opposite directions of associations were found when the OCT measurements were not corrected for magnification. The difference of the corrected OCT and HRT disc area (corrected OCT disc area minus HRT disc area) was correlated with the axial length (r = 0.195, P = 0.025). When the ametropia was limited to -8.0 to +4.0 D, the correlations became insignificant in the HRT. Using the corrected OCT measurements, disc area, rim area, and cup area, cup-to-disc area, and cup-to-disc horizontal and vertical ratios were significantly larger than those measured by the HRT, with a span of 95% limits of agreement at 1.99, 1.33, and 1.86 mm(2) for the areas, 0.34, 0.53, and 0.58 for the ratios, respectively. CONCLUSIONS: While optic disc area generally increased with the axial length and myopic refraction, the HRT measurements demonstrated that optic disc size was largely independent of axial length and refractive error between -8 and +4 D. OCT may overestimate optic disc size in myopic eyes and results in poor agreement between the two instruments.     

In vivo confocal imaging of the retina in animal models using scanning laser ophthalmoscopy

Scanning-laser ophthalmoscopy is a technique for confocal imaging of the eye in vivo. The use of lasers of different wavelengths allows to obtain information about specific tissues and layers due to their reflection and transmission characteristics. In addition, fluorescent dyes excitable in the blue and infrared range offer a unique access to the vascular structures associated with each layer. In animal models, a further enhancement in specificity can be obtained by GFP expression under control of tissue-specific promotors. Important fields of application are studies in retinal degenerations and the follow-up of therapeutic intervention.     

Agreement of measurement of parapapillary atrophy with confocal scanning laser ophthalmoscopy and planimetry of photographs

PURPOSE: To evaluate whether parapapillary atrophy can be measured interactively using confocal scanning laser ophthalmoscopy. METHODS: For 36 patients with open-angle glaucoma or suspected of having glaucoma, confocal scanning laser ophthalmoscopy of the optic nerve head was performed using the Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany). Alpha and beta zones of parapapillary atrophy were plotted independently by two examiners on HRT images before and after reviewing optic disc photographs. These data were compared with planimetric measurements obtained from analyzing the disc photographs. RESULTS: Before viewing the disc photographs, assessment using the HRT images correlated better with the beta zone than alpha zone planimetric measurements. If the HRT images were evaluated while simultaneously viewing disc photographs, correlation coefficients increased for both examiners 1 and 2. Interobserver and intraobserver reliability were 0.431 and 0.802, respectively, for alpha zone, and 0.882 and 0.948, respectively, for beta zone. CONCLUSION: Parapapillary atrophy can be estimated with confocal scanning laser ophthalmoscopy. Correlation with planimetric measurements is best if conventional optic disc photographs are simultaneously viewed. Intraobserver and interobserver reliability are higher for beta zone than for alpha zone.     

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography,scanning laser polarimetry and confocal scanning laser ophthalmoscopy

Purpose

The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters.

Methods

Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models.

Results

Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02–6.80, P=0.04), SLPECC inferior RNFLT (per −1 μm, HR=1.38, 95% CI: 1.02–2.2, P=0.02), and TDOCT inferior RNFLT (per −1 μm, HR=1.11, 95% CI: 1.04–1.2, P=0.001) had significant HRs for SAP progression.

Conclusion

Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes.     

Differential imaging in scanning laser ophthalmoscopy

Differential imaging may be useful for understanding pathologies of the choroid. We use a prototype scanning laser ophthalmoscope capable of simultaneous multiple wavelength imaging to record fundus images. The advantages of simultaneous acquisition compared to serial acquisition are, reduced image capture times, and image registration is not required.The system is run under non-confocal conditions in using slit apertures with a width of up to 600 m. The laser lines launched into the SLO were the 633 nm line of a HeNe- laser, and the 815 nm line from a tunable (740 nm to 840 nm) cw Ti:Sapphire-laser. The difference in absorption at these two wavelengths is used to produce a differential image. We compare conventional imaging with differential spectral imaging for viewing the choroidal vessels. Qualitative results show the contrast of choroidal vessels in differential imaging is improved compared with normal imaging in the region of the optic disk and for the level of pigmentation in the subjects examined.     

Comparison of confocal scanning laser ophthalmoscopy, scanning laser polarimetry and optical coherence tomography to discriminate ocular hypertension and glaucoma at an early stage

Background The aim was to compare the ability of confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence tomography (OCT) to discriminate eyes with ocular hypertension (OHT), glaucoma-suspect eyes (GS) or early glaucomatous eyes (EG) from normal eyes. Methods Ocular hypertension, GS, and EG were defined as normal disc with intraocular pressure >21 mmHg, glaucomatous disc without visual field loss, and glaucomatous disc accompanying the early glaucomatous visual filed loss respectively. Ninety-three normal eyes, 26 OHT, 55 GS, and 67 EG were enrolled. Optic disc configuration was analyzed by CSLO (version 3.04), whereas retinal nerve fiber layer thickness was analyzed by SLP (GDx-VCC; version 5.3.2) and OCT-1 (version A6X1) in each individual. The measurements were compared in the four groups of patients. Receiver operating characteristic curve (ROC) and area under the curve (AUC) discriminating OHT, GS or EG from normal eyes were compared for the three instruments. Results Most parameters in GS and EG eyes showed significant differences compared with normal eyes. However, there were few significant differences between normal and OHT eyes. No significant differences were observed in AUCs between SLP and OCT. In EG eyes, the greatest AUC parameter in OCT (inferior—120; 0.932) had a higher AUC than that in CSLO (vertical cup/disc ratio; 0.845; P=0.017). In GS, the greatest AUC parameter in OCT (average retinal nerve fiber layer [RNFL] thickness; 0.869; P=0.002) and SLP (nerve fiber indicator [NFI]; 0.875; P=0.002) had higher AUC than that in CSLO (vertical cup/disc ratio; 0.720). Conclusions Three instruments were useful in identifying GS and EG eyes. For glaucomatous eyes with or without early visual field defects, SLP and OCT performed similarly or had better discriminating abilities compared with CSLO.     

Visualization of retinal pigment epithelial cells in vivo using digital high-resolution confocal scanning laser ophthalmoscopy

PURPOSE: To visualize retinal pigment epithelial cells in vivo by fundus autofluorescence imaging using a confocal scanning laser ophthalmoscope. DESIGN: Experimental study and observational case report. METHODS: Digital in vivo autofluorescence images were recorded with a confocal scanning laser ophthalmoscope (excitation, 488 nm; emission, >500 nm) and compared with confocal scanning laser ophthalmoscope and fluorescence microscopic recordings from human donor eyes. RESULTS: A uniform pattern of the polygonal retinal pigment epithelial cell layer was visualized in vivo outside of absorbing retinal vessels and macular pigment. Autofluorescence intensities of individual cells showed marked variation. The pattern corresponded to in vitro findings. Visualization is based on the topographic distribution of autofluorescent lipofuscin granules and melanin granules in apical retinal pigment epithelium cytoplasm. CONCLUSIONS: High-resolution autofluorescence imaging may be useful to determine morphologic and lipofuscin-dependent alterations in retinal diseases and may be applicable for monitoring effects of therapeutic interventions targeting the retinal pigment epithelium.     

Screening for glaucoma with Moorfields regression analysis and glaucoma probability score in confocal scanning laser ophthalmoscopy

Objective

To compare the validity of Moorfields regression analysis (MRA) and glaucoma probability score (GPS) of the confocal scanning laser ophthalmoscopy (Heidelberg retina tomograph 3; HRT3) in detecting glaucomatous optic nerve damage in a screening population.

Design

Population-based, cross-sectional study.

Participants

Subjects at high risk for development of open-angle glaucoma (OAG).

Methods

All subjects underwent confocal scanning ophthalmoscopy (Heidelberg retina tomograph; HRTII) testing, visual fields testing with frequency-doubling technology perimetry (FDT), and a standard ophthalmologic examination. All HRTII images were reprocessed with HRT3. Based on an ophthalmologic examination and FDT results, eyes were classified into 4 categories: normal, possible glaucoma, probable glaucoma, and definitive glaucoma. Main outcome measures included sensitivity and specificity of HRTII/MRA, HRT3/MRA, HRT3/GPS, and combination HRT3/MRA/GPS.

Results

The left eyes of 221 of 291 subjects were included; 4 (1.8%) eyes were classified as definitively having glaucoma. Depending on the reference standard diagnosis as well as on the borderline test-positive definition of the HRTII-3, sensitivity and specificity varied between 36.4% and 100%. For HRTII/MRA, 88.2% to 96.5%, 54.5% to 100%, and 74.5% to 93.6%; for HRT3/MRA, 61.9% to 100% and 64.3% to 85.2%; for HRT3/GPS, 85.7% to 100%; and for combination HRT3/MRA/GPS, 73.4% to 78.2%.

Conclusions

In this pilot study, the MRA of the HRT3 appears to be more sensitive but less specific than the MRA in the HRTII version. The GPS, although somewhat less specific than MRA (and some discs are nonclassifiable by this technique), had greater sensitivity and as a screening method may have the additional advantage of being contour-line independent.     

Retinal imaging with adaptive optics scanning laser ophthalmoscopy in unexplained central ring scotoma

Adaptive optics scanning laser ophthalmoscopy allows for noninvasive, in vivo visualization of retinal abnormalities at a cellular level. We herein describe for the first time, to our knowledge, the utility of high-resolution retinal imaging in studying the photoreceptor mosaic in an otherwise unexplained visual disturbance. Imaging of the cone mosaic was performed in a 64-year-old man with a unilateral ringlike paracentral distortion that could not be explained using common clinical imaging instruments. Adaptive optics scanning laser ophthalmoscopy findings revealed a parafoveal circular abnormality of the cone mosaic approximately 3 degrees in diameter that corresponded to the ring of visual disturbance. Visualization of the cone mosaic with adaptive optics scanning laser ophthalmoscopy can reveal photoreceptor damage that may not be detectable with standard imaging devices. Optical axial sectioning of the retina may help in identifying and localizing abnormalities within the retinal layers.     

Comparison of optic nerve head measurements obtained by optical coherence tomography and confocal scanning laser ophthalmoscopy

PURPOSE: To evaluate the relationship between optic nerve head (ONH) measurements generated by optical coherence tomography (OCT; versions 2 and 3) and confocal scanning laser ophthalmoscopy (CSLO) and to compare the association between OCT and CSLO ONH measurements with glaucoma disease status, as determined by clinical evaluation and perimetry. DESIGN: Cross-sectional study. METHODS: In a prospective study in the glaucoma service of an academic department of ophthalmology, 159 eyes (97 subjects) and 77 eyes (44 subjects) were recruited in two separate periods. All subjects were scanned with a CSLO device. Subjects tested within the first period of recruitment were scanned with OCT version 2 and in the second period with OCT version 3. The main outcome measure was the correlation between automatic and manually defined OCT ONH measurements and the correlation of CSLO and OCT ONH measurements between devices and with glaucoma disease status. RESULTS: A high correlation was found between ONH measurements obtained by the automatic determination of ONH margin and those obtained by manual tracing of the disk margin (r =.93 to.98). Optical coherence tomography and CSLO ONH measurements were highly correlated. Optical coherence tomography-measured mean disk area was significantly larger than that measured by CSLO, as were all other disk size-related parameters. The areas under the receiver operator characteristic (AROC) curves for the associations between CSLO and OCT ONH measurements and clinical diagnosis were found to be similar and in the range of 0.47 to 0.79 for both devices. CONCLUSIONS: Automated OCT ONH measurements correlate highly with those obtained by manual tracing of disk margin. Optical coherence tomography and CSLO ONH analyses are highly correlated and have similar associations with glaucoma disease status.