Factors affecting the sensitivity and specificity of the Heidelberg Retina Tomograph parameters to glaucomatous progression in disc photographs

Purpose: To evaluate the factors affecting the sensitivity and specificity of the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT) to glaucomatous progression in stereoscopic ONH photographs. Methods: The factors affecting the sensitivity and specificity of the vertical cup : disc ratio, the cup : disc area ratio, the cup volume, the rim area and a linear discriminant function to progression were analysed. These parameters were the best indicators of progression in a retrospective study of 476 eyes. The reference standard for progression was the masked evaluation of stereoscopic ONH photographs. Results: The factors having the most significant effect on the sensitivity and specificity of the stereometric ONH parameters were the reference height difference and the mean topography standard deviation (TSD), indicating image quality. Also, the change in the TSD and age showed consistent, but variably significant, influence on all parameters tested. The sensitivity and specificity improved when there was little change in the reference height, the image quality was good and stable, and the patients were younger. The sensitivity and specificity of the vertical cup : disc ratio was improved by a large disc area and high baseline cup : disc area ratio. The rim area showed a better sensitivity and specificity for progression with a small disc area and low baseline cup : disc area ratio. Conclusion: The factors affecting the sensitivity and specificity of the stereometric ONH parameters to glaucomatous progression in disc photographs are essentially the same as those affecting the measurement variability of the HRT.     

用Heidelberg视网膜断层扫描仪对正常人、大杯和青光眼视乳头形态结构的研究

目的：探讨正常人、大杯和原发性开角型青光眼（ｐｒｉｎａｒｙ ｏｐｅｎ ａｎｇｌｅ ｇｌａｕｃｏｍａ,ＰＯＡＧ）患者之间视乳头结构参数之间的差异。方法：用Ｈｅｉｄｅｌｂｅｒｇ视网膜断层扫描仪（Ｈｅｉｄｅｌｂｅｒｇ Ｒｅｔｉｎａ Ｔｏｍｏｇｒａｐｈ,ＨＲＴ）对正常人（２２例４４眼）、大杯（１７例３４眼）和ＰＯＡＧ患者（１９例３７眼）进行视乳头断层扫描,获得视乳头平均地形图图像和视乳头结构诸参数。结果：     

Comparison of optic nerve head parameters using Heidelberg Retina Tomograph 3 and spectral-domain optical coherence tomography

Background: To assess the agreement between the Heidelberg Retina Tomograph and Cirrus spectral‐domain optical coherence tomography (Cirrus HD‐OCT [Carl Zeiss Meditec, Dublin, CA, USA]) when measuring optic disc parameters. Design: Prospective, cross‐sectional study. Participants: A total of 96 glaucoma patients and 21 normal subjects were analysed. Methods: Optic nerve head measurements, including disc area, rim area, cup‐to‐disc ratio and cup volume were obtained using both the Cirrus HD‐OCT and Heidelberg Retina Tomograph 3 (Heidelberg Engineering GmbH, Heidelberg, Germany). Main Outcome Measurements: Bland–Altman plots were used to evaluate the agreement between each of the optic disc parameters. Results: Although Cirrus HD‐OCT values were smaller than Heidelberg Retina Tomograph 3 values for the disc and rim areas, overall the Cirrus HD‐OCT and Heidelberg Retina Tomograph 3 measurements were highly correlated (r = 0.657 to 0.821). As compared with Heidelberg Retina Tomograph 3, disc and rim areas tended to be minimized by Cirrus HD‐OCT, especially when there were large disc and rim areas, although there was no relationship between the discrepancy and the level of measurement of the cup‐to‐disc ratio. The optical coherence tomography overestimated the Heidelberg Retina Tomograph‐determined cup volume, especially when there were large cup volumes. Conclusions: Bland–Altman analyses revealed that with the exception of the cup‐to‐disc ratio, there was poor agreement between the Cirrus HD‐OCT and Heidelberg Retina Tomograph 3 morphometric measurements. In addition, with the exception of the cup‐to‐disc ratio, the optic nerve head measurements could not be directly compared between the Cirrus HD‐OCT and Heidelberg Retina Tomograph 3.     

Study on Stereometric Parameters of Optic Nerve Head of Normal,Big—cup

Purpose: To investigate the difference of stereometric parameters of optic nerve head between the normal subjects and patients with big-cupped disk and primary open angle glaucoma (POAG).Methods: Twenty-two cases (44 eyes) of normal subjects, 17 cases (34 eyes) of patients with big-cupped disk and 19 cases (37 eyes) of patients with POAG underwent Heidelberg Retina Tomograph (HRT) examination to get topography images and stereometric parameters of optic nerve head.Results: The stereometric parameters of optic nerve head of the normal, patients with big-cupped disk and POAG were 1) disk area (mm2): 1. 995± 0. 501, 2. 407±0. 661 and 2. 248±0.498; 2) cup area (mm2): 0.573±0.264, 1. 095±0. 673 and 1. 340±0. 516; 3) cup/disk ratio: 0. 25±0. 095, 0. 428±0. 176 and 0. 589±0.195; 4) rim area (mm2): 1.461±0.328, 1.312±0.418 and 0. 905± 0.409; 5)cup volume (mm3): 0. 108±0. 073, 0. 347±0. 346 and 0. 550 ±0. 394; 6) rim volume (mm3): 0. 421±0. 111, 0. 378±0. 225 and 0. 224±0. 189; 7) mean cup dept     

用Heidelberg视网膜断层扫描仪对正常眼压性青光眼与正常人视盘形态结构的对比研究

目的 比较正常人(本文所指正常人指非青光眼者)和正常眼压性青光眼(Normal Tension Glaucoma，NTG)视盘形态结构参数之间的差异，以指导正常眼压青光眼的早期诊断。方法 用Heidelberg视网膜断层扫描仪(Heidelberg Retina Tomograph Ⅱ，HRTⅡ)对正常人40例(80眼)及NTG30例(60眼)的视乳头进行断层扫描，获得视乳头平均地形图像和视乳头结构诸参数。结果 正常人与NTG视乳头结构各参数中视盘面积、视杯面积、杯盘比、盘沿面积、视杯容积、平均视杯深度、最大视杯深度、平均视神经纤维层厚度及视神经纤维层横截面积存在明显差异。结论 HRT能在活体对视乳头结构进行准确分析，视盘面积可能是青光眼的一个易感因素，对NTG早期诊断具有帮助。     

Assessment of optic disc parameters among healthy adult Malays by Heidelberg Retinal Tomograph II

Background: This study aims to assess the optic disc characteristics in healthy adult Malays and to correlate them with age, gender and refractive errors. Design: Cross‐sectional study. Participants: A total of 200 voluntary participants (106 women and 94 men) among Malay students aged 20 to 37 years at Health Campus, Universiti Sains Malaysia. Methods: The relationship between Heidelberg Retinal Tomograph parameters with age, gender and refractive error were analysed with correlation tests and multiple linear regression analyses. Main Outcome Measures: Twelve parameters, that is, disc area, rim area, cup area, cup to disc area, cup volume, rim volume, height variation contour, cup shape measure, mean cup depth, maximum cup depth, mean retinal nerve fibre layer thickness and retinal nerve fibre layer cross‐sectional area. Results: Disc area, rim area and cup : disc area ratio averaged 2.24 ± 0.52 (mean ± standard deviation), 1.64 ± 0.32 and 0.25 ± 0.12 mm², respectively. Five parameters (disc area, cup area, cup volume, cup : disc area ratio and mean retinal nerve fibre layer thickness) showed statistically significant difference between men and women. Age was negatively and significantly correlated with rim area with coefficient r = ?0.21, P = 0.003. All optic disc parameters were significantly correlated (P < 0.05) with disc area, except cup shape measure. Conclusions: One or more of optic disc parameters were affected significantly by age, gender and disc area in healthy adult Malays' eyes. These factors need to be considered during the evaluation of optic disc.     

Test-retest variation in macular thickness measurements with the Heidelberg Retina Tomograph

Purpose: The aim was to evaluate the test-retest variation of macular thickness measurements using the Heidelberg Retina Tomograph (HRT3) Retina Module and compare it with the Stratus optical coherence tomography (OCT). As no normative data has been published for the HRT Retina Module, a secondary purpose was to obtain reference values for this technique. Methods: Thirty healthy subjects and nine patients with macular oedema were examined. The healthy subjects underwent five examinations by two experienced examiners at two different occasions. The patients with maculopathy were examined twice by one examiner on one occasion. All measurements were made with both the HRT3 and the Stratus OCT and the macular thickness measurements were used for calculations of the test-retest variation. Results: In healthy subjects the coefficient of variation (CV) ranged from 4.5 to 8.8 per cent with the HRT3 and from 0.6 to 1.5 per cent with the Stratus OCT. In the nine patients with macular oedema, the HRT CV ranged from 7.9 to16.6 per cent and for OCT from 1.1 to 2.5 per cent. The intra-class correlation in the central area for intra-observer/intra-visit in healthy subjects was 0.78 with the HRT3 and 0.93 with the Stratus OCT. Corresponding values for the patients with macular oedema were 0.64 with the HRT3 and 1.0 with the Stratus OCT. Mean macular thickness was significantly larger in all areas measured with the HRT3 compared with the Stratus OCT. No significant correlations were found between the thickness values from the different instruments. Conclusion: In this study, macular thickness was measured with two different techniques. The HRT3 showed lower repeatability and reproducibility as well as a higher CV compared with the Stratus OCT in both healthy subjects and patients with macular oedema. This difference might be of clinical relevance, even though the nine patients with maculopathy in the current study showed abnormal results with both methods.     

Clinical and experimental findings in Acanthamoeba keratitis with Heidelberg Retina Tomograph III-RCM.

PURPOSE: To observe Acanthamoeba cysts and trophozoites in the corneal tissue of patients and rabbits with Acanthamoeba keratitis (AK), using the Heidelberg Retina Tomograph III Rostock-cornea-module (HRTIII-RCM). METHODS: Eight eyes of seven patients with clinical and laboratory diagnosis of AK, presenting to the Beijing Institute of Ophthalmology between July and December 2006, were included in this study. The laboratory diagnosis in all cases was established by a cytological analysis and culture of the corneal scraping. The scanning with HRTIII-RCM was performed on all the patients. Acanthamoeba cysts and trophozoites in the corneas of three rabbits were observed with the HRTIII-RCM after a suspension of trophozoites was injected into the corneal stromal layer of the rabbits. RESULTS: Acanthamoeba cysts or trophozoites were observed with the HRTIII-RCM in the corneas of all the patients. The size and shape of Acanthamoeba in the tissue of the rabbit corneas was consistent with that in the patients' eyes. The Acanthamoeba cyst presented a round high-contrast particle, 15-20 microm in diameter, with a double wall. In contrast, the trophozoite presented an irregular high-contrast particle, without an apparent wall, 25-40 microm in diameter and with a round conspicuous nucleus. CONCLUSIONS: HRTIII-RCM is a useful non-invasive clinical technique to help to diagnose and monitor the response of AK to therapy.     

Reproducibility of volumetric macular measurements in diabetic patients with the Heidelberg Retina Tomograph

Aims: To quantify diabetic macular edema by confocal scanning laser ophthalmoscopy and assess its usefulness by determining the reproducibility of topographic measurements at the macula. Methods: The volumes above reference plane bound by a 2 mm diameter circle centred on the fovea were measured by two observers. The reference plane was adjusted to the lowest point of the height variation of the contour line. The reproducibility of this technique was assessed in 20 eyes of 20 diabetic patients of which 8 eyes had macular edema. Three HRT scans of each eye were obtained. The measurements of volume above reference plane of each scan were repeated three times. Results: For all diabetic eyes, the intra scan coefficients of variability measured 14.71% to 21.21%, the inter scan coefficient of variability was 30.46%. The average standard deviations were 0.053 mm³ for one examination per scan, 0.047 mm³ for two examinations per scan and 0.044 mm³ for three examinations per scan. Linear regression demonstrated an increase in standard deviation with greater volumetric measurements (p < 0.001). We found good correlation (r = 0.959, p < 0.001) and strong agreement between the two observer's findings for all 20 eyes. For the 8 eyes with macular edema, the coefficients of variability were similar to those calculated for all 20 eyes. The average SD for one examination per scan were 0.078 mm³, 0.069 mm³ for two examinations per scan and 0.062 mm³for three examinations per scan. We found good correlation (r = 0.945, p < 0.001) and strong agreement between the two observer's findings in eyes with edema. Conclusion: The reproducibility of this technique has been demonstrated in diabetic eyes. This may have useful clinical applications for the quantification of diabetic macular edema and monitoring of laser therapy. This revised version was published online in July 2006 with corrections to the Cover Date.     

Diagnostic accuracy of Heidelberg Retina Tomograph III classifications in a Turkish primary open‐angle glaucoma population

Purpose: This study aimed to evaluate the diagnostic accuracy of Moorfields regression analysis (MRA) and the glaucoma probability score (GPS) in primary open‐angle glaucoma (POAG) and to measure the level of agreement between the two algorithms in classifying eyes as normal or abnormal in a Turkish population. Methods: We prospectively selected 184 healthy subjects and 158 subjects with POAG, who underwent an ophthalmological examination, visual field analysis and imaging with the Heidelberg Retina Tomograph II, using HRT III software, Version 3.0. The diagnostic accuracies of the two classifications were measured when the borderline was taken as either normal (highest specificity criteria) or abnormal (highest sensitivity criteria). The agreement between them was calculated using the unweighted kappa (κ) coefficient. Results: Optic nerve head topographic parameters showed statistically significant differences between the control and POAG groups (p < 0.001). The parameters with the highest area under the receiver operating characteristic curves were global GPS (0.86), cup : disc area (0.85), rim : disc area (0.85) and vertical cup : disc (0.85). According to the highest specificity criteria, MRA had a sensitivity of 67.7% and a specificity of 95.1%, whereas the GPS had a sensitivity of 70.9% and a specificity of 88.0%. According to the highest sensitivity criteria, MRA had a sensitivity of 81.0% and a specificity of 75.0%, whereas the GPS had a sensitivity of 89.2% and a specificity of 57.6%. A moderate agreement of 68% (233 eyes) with a κ coefficient of 0.51 was found between MRA and the GPS. Conclusions: The GPS automated classification showed similar sensitivity to MRA, but considerably lower specificity, when applied in a Turkish population.     

Agreement in identification of glaucomatous progression between the optic disc photography and Heidelberg retina tomography in young glaucomatous patients

AIM:To evaluate concordance between the clinical assessment of glaucomatous progression of the optic disc photography and progression identified by Heidelberg Retina Tomograph (HRT) in patients with suspected primary juvenile open angle glaucoma (JOAG).METHODS:Optic disc photographs and corresponding HRT Ⅱ series were reviewed. Optic disc changes between first and final photographs were noted as well as progression identified by HRT topographic change analysis (TCA) and rim area regression line (RARL) Agreement between progression indentified by photography and HRT methods was assessed. Progression, determined from optic disc photographs by consensus assessment was used as the reference standard.RESULTS: A total of 31 patients (59 eyes) with suspected JOAG were studied. Agreement for progression/no progression between TCA and photography was obtained in 4 progressing eyes and 38 stable eyes (71.19%, k=0.11). Agreement for progression/no progression between RARL and photography was detected in 5 progressing eyes and in 34 stable eyes (66.10%, k=0.15). The number of HRT per patient was statistically higher in the progressing group (P=0.034).CONCLUSION:Agreement for detection of longitudinal changes between photography and HRT analysis was poor. One way to improve the chance of discovery of the progression could be increasing the number of HRT examinations.     

Heidelberg Retina Tomograph (HRT3) in Population-based Epidemiology: Normative Values and Criteria for Glaucomatous Optic Neuropathy

Purpose: To establish normative values for Heidelberg Retina Tomograph (HRT3) variables and to develop HRT3-based criteria for glaucomatous optic neuropathy for epidemiological research in a white population.

Methods: Consecutive participants in the Rotterdam Study were examined with HRT and simultaneous stereoscopic fundus photography (ImageNet) in addition to other ophthalmic examinations including intraocular pressure (IOP) measurements and perimetry. Normative values for all HRT3 variables were determined in participants who met all the following criteria: no glaucomatous visual field loss (GVFL), an IOP of 21mmHg or less, no IOP lowering treatment, and a negative family history of glaucoma. Sensitivity was determined in participants with glaucomatous visual field loss at a fixed high specificity of 97.5% ? a value commonly used in population-based epidemiology.

Results: A total of 2516 participants were included in this study of whom 66 had glaucomatous visual field loss in at least one eye and 1680 fulfilled the criteria for contributing to the normative values. The HRT3 linear cup-disc ratio (LCDR) variable, adjusted for disc area, showed the highest sensitivity, 35%, at the required specificity of 97.5%. The 97.5th percentile of the LCDR was 0.67 for small discs (up to 1.5mm²), 0.73 for medium-sized discs and 0.79 for large discs (above 2.0mm²). The HRT3 Glaucoma Probability Score and previously published linear discriminant functions showed a lower sensitivity than LCDR at this specificity.

Conclusions: At the high specificity of 97.5% as is commonly used in population-based epidemiology, the sensitivity of the HRT3 is low ? albeit not lower than that of the vertical cup-disc ratio as assessed with simultaneous stereoscopic fundus photography and analyzed with the ImageNet software. The LCDR variable, stratified for disc area, seems to be the most suitable variable to develop criteria for glaucomatous optic neuropathy for epidemiological purposes.     

Optic disc classification by the Heidelberg Retina Tomograph and by physicians with varying experience of glaucoma

Purpose

To compare the diagnostic accuracy of the Heidelberg Retina Tomograph''s (HRT) Moorfields regression analysis (MRA) and glaucoma probability score (GPS) with that of subjective grading of optic disc photographs performed by ophthalmologists with varying experience of glaucoma and by ophthalmology residents.

Methods

Digitized disc photographs and HRT images from 97 glaucoma patients with visual field defects and 138 healthy individuals were classified as either within normal limits (WNL), borderline (BL), or outside normal limits (ONL). Sensitivity and specificity were compared for MRA, GPS, and the physicians. Analyses were also made according to disc size and for advanced visual field loss.

Results

Forty-five physicians participated. When BL results were regarded as normal, sensitivity was significantly higher (P<5%) for both MRA and GPS compared with the average physician, 87%, 79%, and 62%, respectively. Specificity ranged from 86% for MRA to 97% for general ophthalmologists, but the differences were not significant. In eyes with small discs, sensitivity was 75% for MRA, 60% for the average doctor, and 25% for GPS; in eyes with large discs, sensitivity was 100% for both GPS and MRA, but only 68% for physicians.

Conclusion

Our results suggest that sensitivity of MRA is superior to that of the average physician, but not that of glaucoma experts. MRA correctly classified all eyes with advanced glaucoma and showed the best sensitivity in eyes with small optic discs.     

Heidelberg Retina Tomograph II Findings of Acanthamoeba Keratitis

Purpose: Heidelberg retina tomograph II (HRTII) examination was performed with cornea module in one patient with Acanthamoeba keratitis (AK) to provide images detailing characteristic findings of the disease. Methods: A 34-year-old woman presented with clinical signs and symptoms of AK. HRTII with cornea module was performed and the patient underwent laboratory investigations. Results: HRTII examination with cornea module revealed numerous 20–26-μ m diameter high-contrast round particles within the corneal epithelium and anterior stroma, resembling Acanthamoeba cysts. Stellate cells as well as ovoid irregular objects, possibly inflammatory cells, trophozoites, altered cysts, or activated keratocytes, were also present in the area of stromal infiltrates. Laboratory investigations confirmed the diagnosis of AK. Conclusions: HRTII cornea module can be helpful in the diagnosis of AK by identifying acanthamoeba cyst-like structures in the cornea. This technique also has potential uses in monitoring the efficiency of anti-infective treatment.     

Retinal tomographic measurements in optic disc pit

Background: The aim was to assess the Heidelberg Retina Tomograph II measurements in optic disc pit. Methods: The study included 10 patients with a unilateral optic disc pit. The patients had no other ocular conditions except refractive errors. Normal fellow eyes of the patients were used as a control group. Optic nerve head topographic analyses were performed using a confocal scanning laser ophthalmoscope, Heidelberg Retina Tomograph II (HRT II). Results: The topographic parameters of the eyes with optic disc pit and normal fellow eyes were as follows, respectively: disc area (3.77 ± 1.50 and 3.07 ± 0.83 mm²), cup area (1.99 ± 1.71 and 1.09 ± 0.54 mm²), rim area (1.67 ± 0.55 and 1.87 ± 0.75 mm²), cup volume (0.94 ± 1.24 and 0.34 ± 0.27 mm³), rim volume (0.51 ± 0.40 and 0.55 ± 0.19 mm³), mean cup depth (0.44 ± 0.20 and 0.31 ± 0.11 mm) and mean retinal nerve fibre layer thickness (0.25 ± 0.20 and 0.28 ± 0.59 mm). Eyes with an optic disc pit were found to have significantly larger disc area compared to fellow eyes (p = 0.038). All the other parameters showed no statistically significant interocular differences (p > 0.05). Conclusion: Our study demonstrates that the optic disc pit affects only the disc area measurement in HRT II. Other changes in optic nerve head morphometric parameters were insignificant. The clinician must be careful in the evaluation of HRT II results with respect to optic disc area in a disc with a pit.     

Heidelberg retina tomograph parameters of the optic disc in eyes with progressive retinal nerve fibre layer defects

Purpose: To determine the Heidelberg retina tomograph (HRT) parameters that identify glaucomatous changes in optic nerve head (ONH) topography associated with progression of retinal nerve fibre layer (RNFL) defects. Methods: A total of 68 eyes with open‐angle glaucoma were included in this retrospective study: 34 eyes showed progression of an RNFL defect during the follow‐up period and 34 eyes did not. Successful RNFL photographs and scanning laser tomography examinations with the HRT were taken in all patients at each of three visits. The change in HRT parameter values during follow‐up was calculated. Results: Progression of the RNFL defect was statistically significantly correlated (p = 0.049) with only one topographic ONH parameter, the cup shape measure. The best combination of two parameters (p = 0.009) included the maximum cup depth and the linear cup : disc area ratio; the best combination of three parameters (p = 0.007) included the maximum cup depth, the linear cup : disc area ratio and the horizontal cup : disc area ratio. Sensitivity and specificity values were 52.9% and 73.5%, respectively, for the cup shape measure, 70.6% and 73.5%, respectively, for the two‐parameter combination, and 76.5% and 79.4%, respectively, for the three‐parameter combination. The areas under the receiver operating characteristic curve were 0.617, 0.724 and 0.753, respectively. Conclusions: The results indicate that the HRT parameters may be used to detect small ONH changes associated with progression of the RNFL defect. With the exception of the cup shape measure, the parameters which provide the best correlation with progression differ from those considered optimal for recognizing the presence or absence of glaucoma.     

应用海德堡视网膜断层成像仪（HRT）研究年龄对正常人视网膜神经纤维层的影响

目的;探讨正常人视网膜神经纤维层（RNFL）是否随年龄发生变化。方法：本研究采用新型的共焦扫描激光眼底镜－海德堡视网膜断层成像系统（Heidelberg Retina Tomograph,HRT),对年龄在12－64岁的57位正常人57只眼后极部视网膜进行扫描,分颞侧、鼻侧、上方和下方四个区域和全视盘测定盘沿体积和沿视盘边缘的RNFL厚度,以年龄为自变量作相关与回归分析。结果：视盘全周平均RNFL厚度、盘沿体积与年龄成负相关（P＜0．01）;颞侧RNFL厚度、盘沿体积与年龄无显著相关性（P＞0．05）;鼻侧、上方和下方RNFL厚度、盘沿体积与年龄呈负相关（P＜0．01,P＜0．05,P＜0．01）。结论：随年龄的增长,视网神经纤维层有变薄的趋势。     

Enhanced visualization of acute macular neuroretinopathy by Heidelberg Retina Tomography

We report Heidelberg Retina Tomography (HRT) findings in a case of bilateral acute macular neuroretinopathy in a 22-year-old man. In addition to fundus photography, fluorescein and indocyanine green angiography, and visual field testing, HRT scans of the macula were performed early in the disease and at a follow up of 2 months. We found typical paracentral scotomata in visual field testing corresponding to sharply delineated, hyporeflective areas of the macula as visualized in HRT II scans. Those lesions were almost invisible on regular fundus photographs. Angiography results were unremarkable. The lesion size decreased over time. The visibility of the lesions was markedly enhanced by HRT scans, thus the diagnosis and follow up of acute macular neuroretinopathy could be facilitated by this non-invasive imaging technique.