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Reproducibility of Photogramnnetric Optic Disc Cup Measurements Takenori Takamoro and Bernard Schwartz To detect early glaucoma-associated changes in the optic disc cup, the authors analyzed reproducibility of optic disc cup measurements by photogrammetry of three age-matched groups: 10 normal, 10 ocular hypertensive, and 10 glaucomatous subjects. For each eye, three simultaneous stereophotographs were taken on the same day and one measurement was made for each stereophotograph. In order to reduce the effects of refractive error of the eye and photographic magnification, the authors computed cup parameters as relative measurements, ie, a ratio to the optic disc area. The median coefficients of variation for glaucomatous eyes were 4.5% for cup volume/disc area, 6.1% for cup depth/disc area, and 4.7% for cup area/disc area. Coefficients of variation of normal and ocular hypertensive subjects were slightly larger than those of glaucomatous subjects. Coefficients of variation generally were larger for quadrants than for total disc area. These findings suggest that the photogrammetric technique is highly reproducible and sensitive and could be a valuable quantitative technique for the clinical study of glaucoma. Invest Ophthalmol Vis Sci 26:814-817, 1985 A three-dimensional depression below the retinal surface of the optic nerve is referred to as cupping of the optic disc. It appears to correlate with the development of glaucomatous visual field defects,1 and an increase in its volume may precede a glaucomatous visual field defect.2 Reproducible measurement of optic disc cupping may be effective to detect an early stage of glaucoma. As an objective and quantitative method to evaluate the cupping of the optic disc, photogrammetric techniques using simultaneous stereophotographs have been applied for measurement of topographic cup parameters3"9 and for detection of relative changes in the dimensions of the optic disc cup. 10 In this investigation, we determined the reproducibility of our methods of photogrammetric measurements of the optic disc cup parameters by measuring normal, ocular hypertensive, and open-angle glaucomatous subjects. England Medical Center as follows: 10 normal subjects [intraocular pressure (IOP) of <21 mmHg in both eyes on two or more independent examinations, normal visual fields]; 10 untreated ocular hypertensive subjects (IOP of >21 mmHg in at least one eye on at least two independent examinations, normal visual fields); and 10 subjects with open-angle glaucoma (IOP of >21 mmHg in at least one eye on at least two independent examinations, with visual field and optic disc changes characteristic of glaucoma). Informed human consent was obtained prior to undertaking the study. Both eyes of all subjects had simultaneous stereophotographs taken three times on each visit. We used the Donaldson stereoscopic fundus camera" with 3X photographic magnification, 4-mm camera aperture size, and Kodak Ektachrome 200 color film, all of which contributed to optimum reproducibility.7 In order to minimize image distortions, which were larger at the periphery than at the center of the film frame,12 the image of the optic disc was centered on the film frame. We adjusted for camera alignment, focusing, and centering of optic disc image at each exposure. We selected one eye from each subject (five left eyes and five right eyes from each group). With the stereoplotter Kern PG2 (Kern Co., Ltd.; Aarau, Switzerland) and a pair of stereophotographs, we digitized each optic disc in three dimensions, including margins, with well-distributed points (about 300). Each of three stereopairs of each eye was digitized separately. The digitized data were then stored in the disc memory of a Digital Equipment Corporation (Maynard, MA) VAX 11/780 computer and were Materials and Methods Thirty age-matched subjects were randomly selected from the ophthalmology clinic of the Tufts-New From the Department of Ophthalmology, New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts. Supported in part by grants EY-00936 and EY-03661 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland. Submitted for publication: April 5, 1984. Reprint requests: Takenori Takamoto, PhD, Department of Ophthalmology, New England Medical Center, 171 Harrison Avenue, Boston, MA 02111. 814 Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933352/ on 06/14/2017 No. 6 815 REPRODUCIDILITY OF OPTIC DISC PHOTOGRAAAMETRY / ToKomoro ond Schworrz Table 1. Reproducibility of photogrammetric measurements of the optic disc cup" Ocular hypertensives (n = 10) Normals (n = 10) Cup volume/disc area Superior Inferior Nasal Temporal Total Cup depth/disc area Superior Inferior Nasal Temporal Total Cup area/disc area Superior Inferior Nasal Temporal Total Glaucomas (n = 10) Median SD CV (%) Median SD CV (%) Median SD CV (%) 0.151 0.151 0.080 0.189 0.151 0.012 0.012 0.015 0.024 0.010 7.2 7.2 12.5 11.9 7.7 0.214 0.178 0.138 0.194 0.173 0.019 0.014 0.025 0.026 0.018 6.5 8.8 17.5 12.1 7.9 0.386 0.389 0.326 0.329 0.352 0.037 0.016 0.026 0.033 0.018 11.9 5.7 9.3 0.178 0.146 0.162 0.154 0.165 0.010 0.014 0.021 0.017 0.009 6.5 7.2 10.9 9.8 4.6 0.182 0.188 0.189 0.187 0.200 0.018 0.016 0.019 0.016 0.012 11.9 9.5 9.7 9.5 6.7 0.240 0.206 0.248 0.229 0.238 0.016 0.019 0.026 0.019 0.015 8.7 10.0 13.8 10.1 6.1 0.491 0.479 0.328 0.600 0.470 0.029 0.042 0.042 0.074 0.026 5.9 9.1 12.8 12.0 5.2 0.620 0.429 0.379 0.568 0.486 0.037 0.048 0.054 0.050 0.037 6.0 9.8 19.2 8.8 7.6 0.713 0.758 0.693 0.690 0.717 0.031 0.032 0.027 0.041 0.027 4.9 8.9 4.5 3.9 4.4 5.0 4.7 * The medians, standard deviations (SD), and the coefficients of variation (CV) of the cup parameters were medians (50th percentile) for the three groups: 10 normal, 10 ocular hypertensive, and 10 open-angle glaucomatous subjects. used to compute cup parameters across the entire disc and for each disc quadrant by the radial section method.6 This method is used to: (1) define the optic disc plane as a reference plane of horizontal-vertical coordinates; (2) define the depth axis at the gravity center of the disc area; and (3) compute the size of an averaged radial section on each quadrant. Cup edge is a change of slope from the cup wall to the neural rim. The cup edge was digitized as a series of discrete points. The disc edge was similarly digitized. The cup area was computed as an area delineated by cup edge, and the disc area was computed as an area delineated by disc edge. Cup depth was computed as the distance from the bottom of the cup to the plane defined by the disc edge. The cup volume was computed as the depressed area of the optic disc surface relative to the plane defined by the disc edge. Photographic magnification and refractive error of the eye affect the measurement of the area and depth (and therefore the volume) of the optic disc cup. 13 In order to reduce these effects, we computed cup parameters as relative to the optic disc area; that is, cup volume/disc area, cup depth/disc area, and cup area/disc area. The mean of each cup parameter and its standard deviation and coefficient of variation, that is, the standard deviation divided by the mean and expressed as a percentage, were computed from three measurements (one measurement of each of three photographs of the same eye) for quadrants and the total disc. Medians of these means, standard deviations, and coefficients of variation were computed for the group of normal, ocular hypertensive, and open-angle glaucomatous subjects. Results The median for the cup parameters, the standard deviations, and coefficients of variation for each group are listed in Table 1. Generally the coefficients of variation were slightly larger in normal and ocular hypertensive subjects than in glaucomatous subjects except for cup depth/disc area. Comparing the coefficients of variation among quadrants for each cup parameter, the largest was usually found in nasal quadrants. In the total disc area, the cup volume/disc area in glaucomatous eyes was more than twice as large as in the normal and ocular hypertensive eyes. The median cup depth/disc area in open-angle glaucoma was about 20% larger than in ocular hypertensive eyes and more than 40% larger than in normal eyes. The median cup area/disc area of glaucomatous eyes was about 50% larger than in normal and ocular hypertensive eyes. In the nasal quadrant, the median cup volume/ disc area of glaucoma was more than four times as large as in the normal eyes and more than twice as large as in the ocular hypertensive eyes. The median value for the ocular hypertensive eyes was about 70% larger than for the normal eyes. Spearman correlations between mean and coeffi- Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933352/ on 06/14/2017 816 INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / June 1985 Vol. 26 Table 2. Comparison of reported reproducibility of optic cup measurements Coefficient of variation Author Method 14 No. of eyes Volume Depth Area 3.1 (median) 6.1 (median) Holm and Krakau (1970) Optical sectioning (photograph with projected section lines) 1N 1G 7.3, 5.6 8.8 Krakau and Torlegard15 (1972) Optical sectioning (photograph with projected section lines) 1N 2.2 Rosenthal et al3 (1977) Digital photogrammetry (simultaneous stereophotographs) 3* 7.8 (median) Takamoto et al6 (1979) Stereophotogrammetry (simultaneous stereophotographs) 3N Takamoto and Schwartz7 (1979) Stereophotogrammetry (simultaneous stereophotographs) 5N 9.6 (average) 4.2 (average) 8.4 (average cup/disc) Krohn et al5 (1979) Stereophotogram metry (simultaneous stereophotographs) 3 N, 5 G 8.0 (median) 7.0 (median) 8.0 (median) Takamoto and Schwartz (1984) Stereophotogrammetry (simultaneous stereophotographs) 10 N 10 OH 10G 7.7f 7.9f 4.5f 4.6* 6.7* 6.1* 5.2§ 7.6§ 4.7§ N: normal eye: G: glaucomatous eye; OH: ocular hypertensive eye. * Diagnoses were not available for these eyes. t Median cup volume/disc area. cient of variation of cup parameters of total disc area were calculated. No significant correlations at a P level of <0.05 were found for cup depth/disc area in any of the three groups (normal, ocular hypertensive, or open-angle glaucomatous subjects) or in the total population. Borderline negative correlations (the larger the mean, the smaller the coefficient of variation) were found for cup area/disc area (r = -0.3157, P = 0.089) for the total population (n = 30) and for cup volume/disc area (r = -0.6000, P = 0.074) for normal subjects (n = 10). Discussion The object of our study was to estimate the reproducibility of the cup parameters of the optic disc by photogrammetry with the use of simultaneous stereophotographs taken under routine clinical conditions. Therefore, none of 90 pairs of stereophotographs (30 eyes X three stereophotographs) were rejected because of poor image quality or poor centration of the image of the optic disc on the film format. The reproducibility of cup parameter measurements as determined by the coefficients of variation for the quadrants usually were greater than those for the whole disc; medians of the coefficient of variation for the total disc for all cup parameters ranged from 4.5% to 7.9%, while medians of the coefficient of 3.0 (average) ^ Median cup depth/disc area. § Median cup area/disc area. variation for the quadrants ranged from 3.9% to 19.2%. Two major factors may have contributed to this. First, the number of measured points used to compute the quadrant area was about one-fourth of that of total disc area. This cannot be changed since we use the same amount of digitized data for cup parameters of quadrants and total disc area. Second, the consistency of the process of quadrant subdivision depends on the vertical (superior-inferior) axis of the optic disc relative to that of the camera. This error can be reduced by careful positioning of the subject's head but appears to be difficult to avoid completely. No significant correlation was found between mean and coefficient of variation of cup parameters of total disc area or of any quadrant; that is, reproducibility was the same for large and small optic discs. Reproducibility of cup parameters was significantly better3 or similar5 with simultaneous stereophotographs than with sequential stereophotographs, which may be affected by movements of the camera or of the patient's eye between exposures. Therefore, we did not include sequential stereophotographs in this investigation of reproducibility. A comparison of the results of the present study and those of several other investigations of reproducibility of optic disc cup measurements is presented in Table 2. Holm and Krakau14 and Krakau and Tor- Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933352/ on 06/14/2017 No. 6 REPRODUCIBILITY OF OPTIC DISC PHOTOGRAMMETRY / Tokomoro ond Schworrz legard15 projected slit beams of light onto optic discs and used a fundus camera to photograph the discs. Results of optical sectioning in studies based on one or two eyes had coefficients of variation that ranged from 2.2% to 8.8%. Using digital photogrammetry, which is a computer image analysis of stereophotographs of the optic disc, Rosenthal and colleagues3 achieved results similar to ours, but from a smaller sample size. In our study with Marzan6 (Table 2), cup depth was computed as the distance between two points, a point on the cup rim and a point on the cup bottom. In the present study, cup depth was computed as the distance between two planes, with one plane representing the top of the retinal surface and the other representing the bottom of the cup. The point-topoint method yielded better reproducibility of cup depth measurement than the current investigation but selected a smaller sample of points for depth measurement. In another study,7 we compensated for differences in magnification between photographs obtained at different times by using several anatomic reference points on the disc; this study demonstrated reproducibility generally poorer than that found in the present study. Krohn, Keltner, and Johnson, 5 using a Donaldson stereofundus camera and stereophotogram metric methods to measure normal and glaucomatous eyes that had been masked for diagnosis, also achieved poorer reproducibility than our present study (Table 2). The advantages of our methods and results are apparent in Table 2. Compared to other investigators, we used a larger series in three groups and achieved smaller coefficients of variation. Using model eyes, Rosenthal, Falconer, and Pieper16 reported on the sensitivity of photogrammetric measurements with digital image processing. They compared actual cup depths of a model eye with photogrammetric measurements, and the differences were less than 260 iim for the cup depth of up to 3.18 mm. In our similar study,12 calibrated cup depths of a model eye were compared with measurements obtained by photogram metric methods; the differences were less than 200 jum when the image of the fundus of the model eye was located in the central part of the film frame. Our results suggest that the photogram metric technique is highly reproducible and sensitive in detecting cup changes and could be beneficial in a clinical setting. The clinician applying this technique could send stereophotographs to a photogrammetry center for optic disc cup measurement, which presently takes only about 10 min for one optic disc and is followed by computations and plottings of cup parameters by computer programs. The further development of computerized image analysis for photo- 817 grammetric measurements will allow for even more efficiency and cost-effectiveness. Key words: optic disc cup volume, glaucoma, ocular hypertension, stereophotograph, photogrammetry Acknowledgments The authors thank Judith Barton, MS, for statistical analysis; Susan Glick, MS, for editing the manuscript; Eileen Walsh, for secretarial help; and Benedicto Arevalo, for assistance in preparation of the manuscript. References 1. Sommer A, Pollack I, and Maumenee AE: Optic disc parameters and onset of glaucomatous field loss. I. Methods and progressive changes in disc morphology. Arch Ophthalmol 97:1444, 1979. 2. Pederson JE and Anderson DR: The mode of progressive disc cupping in ocular hypertension and glaucoma. Arch Ophthalmol 98:490, 1980. 3. Rosenthal AR, Kottler MS, Donaldson DD, and Falconer DG: Comparative reproducibility of the digital photogrammetric procedure"utilizing three methods of stereophotography. Invest Ophthalmol Vis Sci 16:54, 1977. 4. Johnson CA, Keltner JL, Krohn MA, and Portney GL: Photogrammetry of the optic disc in glaucoma and ocular hypertension with simultaneous stereo photography. Invest Ophthalmol Vis Sci 18:1252, 1979. 5. Krohn MA, Keltner JL, and Johnson CA: Comparison of photographic techniques and films used in stereophotogrammetry of the optic disc. Am J Ophthalmol 88:859, 1979. 6. Takamoto T, Schwartz B, and Marzan GT: Stereo measurements of the optic disc. Photogrammetric Engineering and Remote Sensing 45:79, 1979. 7. Takamoto T and Schwartz B: Topographic parameters of the optic disc by the radial section method. In Proceedings of the American Society of Photogrammetry, Falls Church, VA, The Society, 1979, pp. 238-251. 8. Betz P, Camps F, Collignon-Brach J, and Weekers R: Photographie stereoscopique et photogrammetrie de 1'excavation physiologique de la papille. J Fr Ophtalmol 4:193, 1981. 9. Betz P, Camps F, Collignon-Brach J, Lavergne G, and Weekers R: Biometric study of the disc cup in open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol 218:70, 1982. 10. Takamoto T and Schwartz B: Photogrammetric measurements of the optic disc in glaucoma. International Archives of Photogrammetry 23(B5):732, 1980. 11. Donaldson D, Prescott R, and Kennedy S: Simultaneous stereoscopic fundus camera utilizing a single optical axis. Invest Ophthalmol Vis Sci 19:289, 1980. 12. Takamoto T, Kennedy S, and Schwartz B: Image distortions of Donaldson stereoscopic fundus camera. In Proceedings of The American Society of Photogrammetry, Falls Church, VA, The Society, 1981, pp. 325-334. 13. Takamoto T and Schwartz B: Stereo measurements of the optic disc cup shape: volume profile method. In Proceedings of the American Society of Photogrammetry, Falls Church, VA, The Society, 1984, pp. 352-358. 14. Holm O and Krakau CET: A photographic method for measuring the volume of papillary excavation. Ann Ophthalmol 1: 327, 1970. 15. Krakau CET and Torlegard K: Comparison between stereo and slit like image photogrammetric measurements of the optic disc. Acta Ophthalmol 50:863, 1972. 16. Rosenthal AR, Falconer DG, and Pieper I: Photogrammetry experiments with a model eye. Br J Ophthalmol 64:881, 1980. Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933352/ on 06/14/2017