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Diabetic Retinopathy as Detected Using Ophthalmoscopy, a Nonmyciriatic Camera and a Standard Fundus Camera
Diabetic Retinopathy as Detected Using Ophthalmoscopy, a Nonmydriatic Camera and a S·tandard Fundus Camera RONALD KLEIN, MD, MPH, BARBARA E. K. KLEIN, MD, MPH, MICHAEL W. NEIDER, BA, LARRY D. HUBBARD, MA, STACY ,M. MEUER, BS, ROSEMARY J. BROTHERS, BS Abstract: The study was performed to evaluate whether the severity of diabetic retinopathy as assessed by three alternative methods was concordant with the severity of retinopathy as determined from 30° stereoscopic photographs. The three methods were direct ophthalmoscopy through an undilated pupil, nonstereoscopic 45° retinal photography through a pharmacologically undilated pupil and non stereoscopic 45° photography through a dilated pupil. A single 45° photograph centered between the disc and fovea was taken and direct ophthalmoscopy was performed on 99 persons prior to pharmacological dilation of the pupil. After dilation, another 45° photograph was taken of the same field, as well as 30 0 stereoscopic color photographs of DRS fields 1, 2 and 4 (modified). Corresponding photographic fields were graded by masked, trained graders for the severity of retinopathy and for the presence of specified diabetic lesions using the Modified Airlie House Classification scheme. For three levels of severity of retinopathy (none, nonproliferative or proliferative) exact agreement between direct ophthalmoscopy and grading of retinopathy from stereoscopic photographs taken with the standard 30 0 camera was 54.3% (n = 94). For four levels of severity of retinopathy (none, microaneurysms only, all other nonproliferative retinopathy and proliferative retinopathy), exact agreement between gradings of retinopathy of the 45° photographs taken through undilated pupils and 30 0 photographs taken through dilated pupils was 82.5% (n = 63); and for 45 0 photographs and 30 0 photographs taken through dilated pupils it was 86.5% (n = 74). These data suggest that 45° non stereoscopic fundus photographs, when graded according to a standard classification scheme, provide reasonably reliable photographic representation of the severity of retinopathy when broad overall categories are used. [Key words: diabetic retinopathy, direct ophth~l moscopy, fundus camera, fundus photography, methodology.] Ophthalmology
92:485-491, 1985
From the Department of Ophthalmology, University of Wisconsin Medical School, Madison. Supported by U.S. Public Health Service Grant EY 03083 (Dr. R. Klein) from the National Eye Institute. Reprint requests to Ronald Klein, MD, Department of Ophthalmology, Clinical Science Center, 600 Highland Avenue, Madison, WI 53792.
Diabetic retinopathy is a major cause of visual impairment in the United States. l Ophthalmoscopy and fundus photography l)ave been routinely used to document the presence and the progression of retinopathy in diabetic patients. 2 Optimally, these procedures are performed through a pharmacologically dilated pupil. situations where mydriatic agents cannot be used, a
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Fig 2. Forty-five degrees fundus photograph taken with the "non mydriatic" camera through pharrnacologically undilated pupil demonstrating standard field taken for study.
Fig I. Nonmydriatic camera and television screen used for field definition and focusing the retinal image.
new "non mydriatic" camera has been introduced as an alternative means of documenting diabetic and other retinal pathology. The purpose of this report is to compare the severity of diabetic retinopathy as determined: (1) by direct ophthalmoscopy through an undilated pupil; (2) by grading of nonstereoscopic 45 0 retinal photographs taken with the new camera through a pharmacologically undilated pupil; (3) and by grading of nonstereoscopic 45 0 retinal photographs taken with the new camera through a dilated pupil, versus grading of stereoscopic retinal photographs taken with a standard 30° camera. In addition, this new camera was compared to a standard 30 0 stereoscopic camera with respect to: (1) ease of use; (2) acceptance by patients and photographers; and (3) quality of the resulting photographs.
MATERIALS AND METHODS Ninety-nine persons participated in the study. Only one eye of each patient was used. All participants were examined in a similar fashion. Their birthdates and history of previous fundus photography or diabetes were 486
ascertained. Prior to instillation of dilating drops, the subject was seated in a darkened room, and the pupil size was estimated by comparing it to progressively increasing circles (from 1-9 mm in diameter). The iris color was determined by direct observation and was recorded as blue, hazel-green or brown. The nonmydriatic camera (Topcon TRC NW-2) which uses infrared light to televise a view of the fundus (Fig 1) was used to photograph the retina of the phaimacologically undilated eye of each subject. Field alignment and focusing of the retinal image was adjusted using a cathode ray tube screen. One photograph was taken of a field centered slightly above a horizontal line between the center of the disc and the fovea. The 45° image produced included an area above and below the temporal arcades, as well as areas just nasal to the disc and temporal to the macula (Fig 2). This image is minified 0.64X (at zero diopters) compared to that taken with a standard 30 0 camera (Zeiss FF3)-(Fig 3). Each of the three photographers next recorded the time it took to take the photograph (from the time the subject sat down to the time of the camera flash). The subject was asked to evaluate the flash of the nonmydriatic camera as to whether it was comfortable or uncomfortable, and to judge the ease of following the fixation target as "easy" or "difficult." The photographer was asked to rate the process of focusing, the subject's ability to follow the fixation target and the controls and maneuverability of the camera as "easy," "acceptable" or "difficult." Direct ophthalmoscopy was performed through the undilated pupil and diabetic retinopathy was described as being absent, non proliferative, proliferative or not determinable. The ophthalmoscopist, an experienced ophthalmic technician, was asked to examine an area of the retina similar to that which was photographed. The ophthalmoscopist was also asked to evaluate any media opacities.
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One drop of 21f2Cl'o phenylephrine and one drop of 1% tropicamide were then instilled in the cul-de-sac of one eye to obtain dilation. About liz hr. to 1 hr. later, pupil size was estimated and recorded. One photograph of the same retinal field was taken with the nonmydriatic camera. The time to take this photograph, as well as the participant's subjective response to the flash and ease of following the fixation target, were again recorded. Shortly thereafter, stereoscopic retinal photographs were taken with a standard 30° fundus camera. An attempt was made to get retinal fields comparable to the one 45° field obtained with the "nonmydriatic" camera. To do this, stereoscopic photographs of Diabetic Retinopathy Study (DRS) standard fields I, 2 and a modified field 4 were taken. 3 The latter was centered infero-nasal to the normal standard DRS field 4. The time required to take these photographs was recorded. The participant was again asked to evaluate his/her subjective response to the flashes and the ease of following the fixation target. The photographer rated the process of focusing, the subject's ability to follow the fixation target and the controls and maneuverability of the standard 30° camera as "easy," "acceptable," or "difficult." The subject was asked if being dilated was "unacceptable," "acceptable only if necessary," "acceptable," or "no bother." All photographs for a given patient were taken either with color Kodachrome 25 or Ektachrome 64 slide film and were processed and returned as 2 X 2 inch color slides. The slides were mounted in clear plastic mounting sheets and graded at the University of Wisconsin Fundus Photography Reading Center in Madison. Prior to the grading, all photographs were examined and comparable areas of retina among the photograph sets were outlined on the plastic sheets with an indelible pen. All photographs taken with the nonmydriatic camera were removed from the set and all such photographs (taken through a dilated or undilated pupil) were mixed in a random fashion prior to being sent to the grader. The grader was masked with respect to any information about the subject. The grader was asked to judge field definition, focus of the photographs (using ETDRS standard 14) and the appearance of artifacts prior to determining the retinopathy level. 4 The severity of retinopathy was determined using a subset of the Modified Airlie House Classification scheme. This method has been described in detail elsewhere. 4 For purposes of this report one of four levels of severity of diabetic retinopathy was assigned to each eye: no; very early nonproliferative (retinal microaneurysms alone); moderate to severe nonproliferative (retinal microaneurysms plus other retinal abnormalities such as hemorrhages, hard exudates, cotton-wool spots, venous beading, or intraretinal microvascular abnormalities); or proliferative (fibrous proliferans, retinal new vessels or preretinal or vitreous hemorrhage). Two weeks after grading the photographs taken with the nonmydriatic camera, the same grader received the standard 30° stereoscopic fundus photographs taken of the same participants, and repeated the process.
~
Fig 3. Thirty degrees fundus photograph taken of Diabetic Retinopathy Study Field I. Note relative magnification of image compared to the 45° photograph.
To examine interobserver variation, a second experienced grader graded 27 sets of 45° photographs from the original set using the same grading procedure. To examine intraobserver variation, the original grader regraded the same 27 sets of 45° photographs three months later. Wisconsin Storage and Retrieval, a data processing software system, was used for processing all subject files. 5
RESULTS There were 55 male and 44 female participants. They ranged in age from 15 to 84 years; the median age was 54. Seventy-one had a history of diabetes mellitus and 76 had been previously photographed. A high proportion of subjects stated that the flash of all cameras was "comfortable" (Table 1). The largest proportion of subjects rated the flash of the non mydriatic camera (used prior to dilation) as most comfortable. Persons with blue eyes were more likely to manifest discomfort with the flash than brown eyed persons, especially after pharmacological dilation. No association was found between dilated pupil size and subjective discomfort with the flash. As indicated in Table 1, most subjects reported that the fixation target of both cameras was easy to follow. The photographers rated the standard 30° fundus camera as easier to focus than the nonmydriatic camera (Table I). Ease of focusing was found to be positively associated with pupil size in the darkened room. In the nonpharmacologically dilated eyes "easy focusing" varied from 21.4% for pupils less than 5 mm in diameter to 88.9% for pupils 6 mm or greater. The presence of media problems also increased the difficulty reported by the photographers in focusing the non mydriatic camera through pharmacologically undilated pupils. They reported such problems more often for the nonmydriatic camera (38.6%) than for the standard 30° camera 487
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Table 1. Photographer and Participant Evaluation of Features of Two Cameras
Responses by Participants & Photographers Participants who found camera flash comfortable by iris color Blue Medium Brown Total Participants who reported ease of following camera fixation target Photographers' evaluation Easy focusing Easy to use fixation target Easy use of controls Easy maneuverability
Pharmacologically Undilated Nonmydriatic 45° Camera (%)
Nonmydriatic 45° Camera (%)
38/44 22/24 28/31
(86.4) (91.7) (90.3)
29/43 21/24 28/31
(67.4) (87.5) (90.3)
36/44 19/24 27/31
(81.8) (79.2) (87.1)
88/99
(88.9)
78/98
(79.6)
82/99
(82.8)
84/99
(84.8)
85/98
(86.7)
91/99
(91.9)
69/99
(69.7)
93/99
(93.9)
85/99 97/99 98/99
(859) (98.0) (99.0)
93/99 99/99 99/99
(93.9) (100) (100)
(19.2%). Iris color was not associated with ease of focusing. The photographers rated the standard 30° camera fixation target slightly ea~ier to use than that of the nonmydriatic camera (Table 1). The control and maneuverability of the cameras were judged to be comparable and both were easy to handle. . The mean time to photograph the fundus varied from 1.6 minutes using the nonmydriatic camera through a pharmacologically dilated pupil to 2.4 minutes using the same camera through a pharmacologically undilated pupil. It took a longer tim~(~3 minutes) to take photographs with the nonmydriatic camera through an undilated pupil in older persons (~60 years vs. <60 years), with darker iris color or media opacities. Pupillary dilation with phenylephrine and tropicamide drops was stated to be unacceptable by 6%, and acceptable only if necessary by 5% of the subjects. There was no consistent relationship between participant acceptance of pharmacologic dilation arid either current age or history of diabetes. Ophthalmoscopy was performed in 98 persons. Retinopathy was classified as being absent in 26, nonproliferative in 39, and proliferative in 17. The severity of retinopathy could not be determined in 16 subjects. It was not possible to determine the severity of retinopathy by ophthalmoscopy 23% of the time when media opacities were present as compared to 7% of the time if opacities were absent. Neither pupil size nor iris color was associated with decreased ability to detect severity of retinopathy. Of the 198 photographs taken with the nonmydriatic 488
Pharmacologically Dilated Standard 30° Camera (%)
camera, 61 (36 through a pharmacologically undilated pupil, 25 through the dilated pupil) were "lost" due to a malfunction of flash synchronization. The problem was present in both available 35 mm camera bodies, and caused partial or total image loss. There were no camera malfunctions using the standard 30° camera. Because of these instances of camera failure, the comparison of gradings of photographs taken with the standard 30° fundus camera (dilated pupil), to those taken with the nonmydriatic camera (undilated pupil) is limited to 63 pairs; and to the nonmydriatic camera (dilated pupil) is limited to 74 pairs. The comparisons of severity of retinopathy was determined by grading photographs taken with the non mydriatic camera to those taken with the standard 30° camera are presented (Table 2). Exact agreement between severity of retinopathy based on grading of photographs taken with these two different cameras was 82.5% (52/ 63). Gradings of 45° photographs and 30° stereoscopic photographs taken through pharmacologically dilated pupils were in agreement 86.5% (64/74) of the time. There was a greater likelihood to "undercall" than to "overcall" the severity of retinopathy when grading 45° photographs compared to grading 30° stereoscopic photographs. Of the photographs taken through an undilated pupil, 12.7% (8/63) could not be graded. Of the 45° photographs taken through the pharmacologically dilated pupil, 6.8% (5/74) could not be graded, while only 2.0% (2/99) of those taken with the standard camera could not be graded. The retinopathy status based on the ophthalmoscopy (undilated pupil) agreed with that based on grading 30°
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Table 2. Comparison of Severity of Retinopathy (4 levels) Grading Photographs Taken with Both a Nonmydriatic Camera and a Standard 30° Camera Standard 30° Camera (dilated pupil)
Nonmydriatic 45° Camera Pharmacologically undilated pupil No retinopathy Microaneurysms alone Microaneurysms & more severe NPDR ProlifEirative retinopathy Cannot grade Total Pharmacologically dilated pupil No retinopathy Microaneurysms alone Microaneurysms & more severe NPDR Proliferative retinopathy Cannot grade Total NPDR
=
No Retinopathy
Microaneurysms Alone
Microaneurysms & More Severe NPDR
10 1
0 7
0 2
0 0 1
0 0 0
12
Proliferative Retinopathy
Cannot Grade
Total
0 0
0 0
10 10
20 1 5
1 13 0
0 0 2
21 14 8
7
28
14
2
63
14 0
0 4
1 4
0 0
0 0
15 8
0 0 1
1 0 0
30 0 1
1 14 1
0 0 2
32 14 5
15
5
36
16
2
74
non proliferative diabetic retinopathy
stereoscopic photographs in 54.3% (51/94) of cases (Table 3). In 14 eyes the ophthalmoscopist was unable to determine the severity of retinopathy, even though the 30° retinal photographs were gradable. In 9 eyes where retinopathy was judged to be present on 30° fundus photographs, these abnormalities were not detected by the ophthalmoscopist. Agreement between graders on severity of retinopathy was 85.1% for 45° photographs (undilated), 85.1% for 45° photographs (dilated), and slightly better at 90.0% for the 30° stereoscopic photographs. The corresponding intraobserver agreements were 81.4%, 81.4%, and 86.0%.
Significant focus problems were present more commonly in 45° photographs through an undilated pupil (21.0%) than in photographs through a dilated pupil (8.7%) or in 30° stereoscopic photographs (5.9%). Media opacities accentuated the problem for undilated 45° photographs (31.8% with opacities to 13.8% without opacities), as did a smaller pupil (11.1 % if the pupil was 7 mm or greater mm vs 28.1 % if the pupil was less than 5 mm in diameter). Focusing problems were not related to media opacities or pupil size in photographs taken through pharmacologically dilated pupils. Artifacts were more prevalent (48.1%) in the photographs taken through
Table 3. Comparison of Severity of Retinopathy (3 levels) by Direct Ophthalmoscopy and a Standard 30° Camera Standard 30° Camera Ophthalmoscopy
No Retinopathy
Nonproliferative Retinopathy
Proliferative Retinopathy
Cannot Grade
No retinopathy Nonproliferative retinopathy Proliferative retinopathy Cannot determine
15 5 0 4
8 24 6 9
1 8 10 1
1 0 2
0
24 38 16 16
24
47
20
3
94
Total
Total
For one participant no ophthalmoscopy was performed; 4 participants' photographs were not available for grading.
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the phannacologically undilated pupil. Only 13.7% of the photographs taken, with the standard 30° camera had artifacts.
DISCUSSION Our experience demonstrated strengths and weaknesses of both the non mydriatic 45° camera and the standard 30° camera. The advantages of the 45 ° in contrast to the 30° camera were that: (1) it was less expensive to purchase; (2) it took a shorter time to learn to use; (3) it required only one photograph to view the posterior pole of the retina while the standard camera required three stereoscopic pairs; and (4) it was not necessary to dilate the pupil pharmacologically before taking photographs. The relative disadvantages of the nonmydriatic camera were that: (1) the resultant photograph was of lower magnification (1.6X vs 2.5X at zero diopters); (2) it was not possible to obtain stereoscopic photographs; and (3) its use resulted in a higher frequency of ungradable photographs (especially, in the presence of small pharmacologically undilated pupils and/or media opacities). Use of the cameras was similar in three ways: (1) patient acceptance, (2) photographer ease of use, and (3) time required to photograph the posterior retina (two minutes). Photographs from both cameras provide an objective recording of retinal pathology (or its absence) which may be useful in examination for screening, routine care, or epidemiologic studies. These data suggest that the 45° nonstereoscopic fundus photographs when graded according to a four level classification scheme by experienced graders provides a reasonably reliable measure of the severity of diabetic retinopathy. The agreement between graded severity of retinopathy from fundus photographs taken with the nonmydriatic camera through a phannacologically undilated or dilated pupil and from fundus photographs taken with the standard 30° camera through dilated pupils was found to be 82.5% and 86.5%, respectively. The disagreements in gradings were due, in a large part, to the presence of 45° photographs which could not be graded. In addition disagreements usually resulted in a tendency to "undercall" the severity of retinopathy when grading photographs taken with the nonmydriatic camera. The less magnified nonstereoscopic field found in the single nonmydriatic photograph might have contributed to the grader missing retinal abnonnalities, such as microaneurysms, which might have been detected more easily in the stereoscopic photographs taken with the standard 30° camera. Grader variability might also account for the disagreements in grading severity of diabetic retinopathy. Photographs taken with a nonmydriatic camera may be of value in routine screening of diabetic patients in areas where ophthalmologic care or physician availability is limited. The need for such detection has been suggested because proliferative retinopathy may be present before affecting vision and it is possible in some cases to 490
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prevent severe visual impairment with laser photocoagulation. 2,6 In addition, because non ophthalmologists have only a 50% chance of correctly diagnosing the presence of proliferative retinopathy,? ophthalmologic examinations have been suggested for insulin-dependent patients who have had diabetes for at least five years and for newly diagnosed non-insulin-dependent patients. s However, there are diabetic patients for whom such ophthalmologic care is not readily available. 2 In such cases trained ophthalmic technician-photographers could test visual acuity, measure intraocular pressure and photograph the retina using the non mydriatic camera. Photographs could then be sent for evaluation to an experienced grader working with ophthalmologists at a central location and referral procedures developed for patients at risk of visual loss due to retinopathy. However, the finding that 27% of cases of proliferative diabetic retinopathy occur outside of the area covered by the photographic field used in the current investigation (Klein R, unpublished data) indicates a relative limitation of this method of screening. The appropriateness of use of nonmydriatic cameras in epidemiologic studies depends on the objectives of the specific study. If the objectives are to document the severity of retinopathy as described in this report without pharmacologically dilating the pupil (to increased participant compliance) photographs taken with the nonmydriatic camera graded by experienced graders may be an acceptable alternative. If on the other hand. the objective is to use retinopathy as an outcome variable for a controlled clinical trial, or to reliably document the appearance of specific lesions, grading of stereoscopic 30° photographs taken with a standard camera would be the method of choice. The inability to obtain stereoscopic photographs with the non mydriatic camera would preclude its use in detecting retinal edema, and may lead to errors in differentiating retinal hard exudates from drusen, or intraretinal microvascular abnonnalities from flat retinal new vessels. In addition, it has been estimated that between 8-15% of diabetic retinopathy may be missed since it may fall outside the one 45° field taken with the non mydriatic camera (Klein R, unpublished data). Direct ophthalmoscopy through an undilated pupil was found to be both insensitive and nonspecific as a means of detecting and classifying diabetic retinopathy. This is consistent with previous studies in which high error rates in classifying retinopathy by ophthalmoscopy have been reported. 7,9 Training of examiners and dilation of pupils have been reported to increase the agreement between ophthalmoscopy and grading of photographs to 86%.10 The data reported herein suggest that if the pupil is not to be dilated, then the nonmydriatic camera may offer a more sensitive and objective method of detecting retinopathy than direct ophthalmoscopy.
ACKNOWLEDGMENTS The authors are grateful to Matthew D. Davis, MD, David L. DeMets, PhD, Scot E. Moss, MA for consultation and
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criticism; to Bob Harrison and Gene Knutson for examining and photographing patients; to Larry Thomas of Wisconsin Optical Services for providing the Topcon fundus camera; to Anik Ganguly, BE for programming and data management advice; to Mae Wildt and Bernadette Bull for providing secretarial assistance.
REFERENCES 1. National Society to Prevent Blindness. Vision Problems in the US; Data Analysis: Definitions, Data Sources, Detailed Data Tables, Analysis, Interpretation. New York: National Society to Prevent Blindness, 1980. 2. Herman WH, Teutsch SM, Sepe SJ, et al. An approach to the prevention of blindness in diabetes. Diabetes Care 1983; 6:608-
13. 3. Diabetic Retinopathy Study Research Group. Report 7. A modification of the Airlie House classification of diabetic retinopathy. Invest Ophthalmol Vis Sci 1981; 21:210-26.
4. Early Treatment Diabetic Retinopathy Study. Manual of Operations. Baltimore: ETDRS Coordinating Center, Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, 1980; Chapter 18. 5. Harberg J, Holladay D, Entine S, et al. W1SAR; Wisconsin Storage and Retrieval System. Madison, WI: University of Wisconsin Clinical Cancer Center, 1979. 6. Klein R, Klein BEK, Moss SE. Visual impairment in diabetes. Ophthalmology 1984; 91:1-8. 7. Sussman EJ, Tsiaras WG, Soper KA. Diagnosis of diabetic eye disease. JAMA 1982; 247:3231-4. 8. National Diabetes Advisory Board. The Prevention and Treatment of Five Complications of Diabetes; A Guide for Primary Care Practitiqners. Bethesda, Maryland, 1983. 9. Palmberg P, Smith M, Waltman S, et al. The natural history of retinopathy in insulin-dependent juvenile-onset diabetes. Ophthalmology 1981; 88:613-8. 10. Moss SE, Klein R, Kessler SO, Richie KA. Comparison between ophthalmoscopy and fundus photography in determining severity of diabetic retinopathy. Ophthalmology 1985; 92:62-7.
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From the Department of Ophthalmology, University of Wisconsin Medical School, Madison. Supported by U.S. Public Health Service Grant EY 03083 (Dr. R. Klein) from the National Eye Institute. Reprint requests to Ronald Klein, MD, Department of Ophthalmology, Clinical Science Center, 600 Highland Avenue, Madison, WI 53792.
Diabetic retinopathy is a major cause of visual impairment in the United States. l Ophthalmoscopy and fundus photography l)ave been routinely used to document the presence and the progression of retinopathy in diabetic patients. 2 Optimally, these procedures are performed through a pharmacologically dilated pupil. situations where mydriatic agents cannot be used, a
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Fig 2. Forty-five degrees fundus photograph taken with the "non mydriatic" camera through pharrnacologically undilated pupil demonstrating standard field taken for study.
Fig I. Nonmydriatic camera and television screen used for field definition and focusing the retinal image.
new "non mydriatic" camera has been introduced as an alternative means of documenting diabetic and other retinal pathology. The purpose of this report is to compare the severity of diabetic retinopathy as determined: (1) by direct ophthalmoscopy through an undilated pupil; (2) by grading of nonstereoscopic 45 0 retinal photographs taken with the new camera through a pharmacologically undilated pupil; (3) and by grading of nonstereoscopic 45 0 retinal photographs taken with the new camera through a dilated pupil, versus grading of stereoscopic retinal photographs taken with a standard 30° camera. In addition, this new camera was compared to a standard 30 0 stereoscopic camera with respect to: (1) ease of use; (2) acceptance by patients and photographers; and (3) quality of the resulting photographs.
MATERIALS AND METHODS Ninety-nine persons participated in the study. Only one eye of each patient was used. All participants were examined in a similar fashion. Their birthdates and history of previous fundus photography or diabetes were 486
ascertained. Prior to instillation of dilating drops, the subject was seated in a darkened room, and the pupil size was estimated by comparing it to progressively increasing circles (from 1-9 mm in diameter). The iris color was determined by direct observation and was recorded as blue, hazel-green or brown. The nonmydriatic camera (Topcon TRC NW-2) which uses infrared light to televise a view of the fundus (Fig 1) was used to photograph the retina of the phaimacologically undilated eye of each subject. Field alignment and focusing of the retinal image was adjusted using a cathode ray tube screen. One photograph was taken of a field centered slightly above a horizontal line between the center of the disc and the fovea. The 45° image produced included an area above and below the temporal arcades, as well as areas just nasal to the disc and temporal to the macula (Fig 2). This image is minified 0.64X (at zero diopters) compared to that taken with a standard 30 0 camera (Zeiss FF3)-(Fig 3). Each of the three photographers next recorded the time it took to take the photograph (from the time the subject sat down to the time of the camera flash). The subject was asked to evaluate the flash of the nonmydriatic camera as to whether it was comfortable or uncomfortable, and to judge the ease of following the fixation target as "easy" or "difficult." The photographer was asked to rate the process of focusing, the subject's ability to follow the fixation target and the controls and maneuverability of the camera as "easy," "acceptable" or "difficult." Direct ophthalmoscopy was performed through the undilated pupil and diabetic retinopathy was described as being absent, non proliferative, proliferative or not determinable. The ophthalmoscopist, an experienced ophthalmic technician, was asked to examine an area of the retina similar to that which was photographed. The ophthalmoscopist was also asked to evaluate any media opacities.
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One drop of 21f2Cl'o phenylephrine and one drop of 1% tropicamide were then instilled in the cul-de-sac of one eye to obtain dilation. About liz hr. to 1 hr. later, pupil size was estimated and recorded. One photograph of the same retinal field was taken with the nonmydriatic camera. The time to take this photograph, as well as the participant's subjective response to the flash and ease of following the fixation target, were again recorded. Shortly thereafter, stereoscopic retinal photographs were taken with a standard 30° fundus camera. An attempt was made to get retinal fields comparable to the one 45° field obtained with the "nonmydriatic" camera. To do this, stereoscopic photographs of Diabetic Retinopathy Study (DRS) standard fields I, 2 and a modified field 4 were taken. 3 The latter was centered infero-nasal to the normal standard DRS field 4. The time required to take these photographs was recorded. The participant was again asked to evaluate his/her subjective response to the flashes and the ease of following the fixation target. The photographer rated the process of focusing, the subject's ability to follow the fixation target and the controls and maneuverability of the standard 30° camera as "easy," "acceptable," or "difficult." The subject was asked if being dilated was "unacceptable," "acceptable only if necessary," "acceptable," or "no bother." All photographs for a given patient were taken either with color Kodachrome 25 or Ektachrome 64 slide film and were processed and returned as 2 X 2 inch color slides. The slides were mounted in clear plastic mounting sheets and graded at the University of Wisconsin Fundus Photography Reading Center in Madison. Prior to the grading, all photographs were examined and comparable areas of retina among the photograph sets were outlined on the plastic sheets with an indelible pen. All photographs taken with the nonmydriatic camera were removed from the set and all such photographs (taken through a dilated or undilated pupil) were mixed in a random fashion prior to being sent to the grader. The grader was masked with respect to any information about the subject. The grader was asked to judge field definition, focus of the photographs (using ETDRS standard 14) and the appearance of artifacts prior to determining the retinopathy level. 4 The severity of retinopathy was determined using a subset of the Modified Airlie House Classification scheme. This method has been described in detail elsewhere. 4 For purposes of this report one of four levels of severity of diabetic retinopathy was assigned to each eye: no; very early nonproliferative (retinal microaneurysms alone); moderate to severe nonproliferative (retinal microaneurysms plus other retinal abnormalities such as hemorrhages, hard exudates, cotton-wool spots, venous beading, or intraretinal microvascular abnormalities); or proliferative (fibrous proliferans, retinal new vessels or preretinal or vitreous hemorrhage). Two weeks after grading the photographs taken with the nonmydriatic camera, the same grader received the standard 30° stereoscopic fundus photographs taken of the same participants, and repeated the process.
~
Fig 3. Thirty degrees fundus photograph taken of Diabetic Retinopathy Study Field I. Note relative magnification of image compared to the 45° photograph.
To examine interobserver variation, a second experienced grader graded 27 sets of 45° photographs from the original set using the same grading procedure. To examine intraobserver variation, the original grader regraded the same 27 sets of 45° photographs three months later. Wisconsin Storage and Retrieval, a data processing software system, was used for processing all subject files. 5
RESULTS There were 55 male and 44 female participants. They ranged in age from 15 to 84 years; the median age was 54. Seventy-one had a history of diabetes mellitus and 76 had been previously photographed. A high proportion of subjects stated that the flash of all cameras was "comfortable" (Table 1). The largest proportion of subjects rated the flash of the non mydriatic camera (used prior to dilation) as most comfortable. Persons with blue eyes were more likely to manifest discomfort with the flash than brown eyed persons, especially after pharmacological dilation. No association was found between dilated pupil size and subjective discomfort with the flash. As indicated in Table 1, most subjects reported that the fixation target of both cameras was easy to follow. The photographers rated the standard 30° fundus camera as easier to focus than the nonmydriatic camera (Table I). Ease of focusing was found to be positively associated with pupil size in the darkened room. In the nonpharmacologically dilated eyes "easy focusing" varied from 21.4% for pupils less than 5 mm in diameter to 88.9% for pupils 6 mm or greater. The presence of media problems also increased the difficulty reported by the photographers in focusing the non mydriatic camera through pharmacologically undilated pupils. They reported such problems more often for the nonmydriatic camera (38.6%) than for the standard 30° camera 487
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Table 1. Photographer and Participant Evaluation of Features of Two Cameras
Responses by Participants & Photographers Participants who found camera flash comfortable by iris color Blue Medium Brown Total Participants who reported ease of following camera fixation target Photographers' evaluation Easy focusing Easy to use fixation target Easy use of controls Easy maneuverability
Pharmacologically Undilated Nonmydriatic 45° Camera (%)
Nonmydriatic 45° Camera (%)
38/44 22/24 28/31
(86.4) (91.7) (90.3)
29/43 21/24 28/31
(67.4) (87.5) (90.3)
36/44 19/24 27/31
(81.8) (79.2) (87.1)
88/99
(88.9)
78/98
(79.6)
82/99
(82.8)
84/99
(84.8)
85/98
(86.7)
91/99
(91.9)
69/99
(69.7)
93/99
(93.9)
85/99 97/99 98/99
(859) (98.0) (99.0)
93/99 99/99 99/99
(93.9) (100) (100)
(19.2%). Iris color was not associated with ease of focusing. The photographers rated the standard 30° camera fixation target slightly ea~ier to use than that of the nonmydriatic camera (Table 1). The control and maneuverability of the cameras were judged to be comparable and both were easy to handle. . The mean time to photograph the fundus varied from 1.6 minutes using the nonmydriatic camera through a pharmacologically dilated pupil to 2.4 minutes using the same camera through a pharmacologically undilated pupil. It took a longer tim~(~3 minutes) to take photographs with the nonmydriatic camera through an undilated pupil in older persons (~60 years vs. <60 years), with darker iris color or media opacities. Pupillary dilation with phenylephrine and tropicamide drops was stated to be unacceptable by 6%, and acceptable only if necessary by 5% of the subjects. There was no consistent relationship between participant acceptance of pharmacologic dilation arid either current age or history of diabetes. Ophthalmoscopy was performed in 98 persons. Retinopathy was classified as being absent in 26, nonproliferative in 39, and proliferative in 17. The severity of retinopathy could not be determined in 16 subjects. It was not possible to determine the severity of retinopathy by ophthalmoscopy 23% of the time when media opacities were present as compared to 7% of the time if opacities were absent. Neither pupil size nor iris color was associated with decreased ability to detect severity of retinopathy. Of the 198 photographs taken with the nonmydriatic 488
Pharmacologically Dilated Standard 30° Camera (%)
camera, 61 (36 through a pharmacologically undilated pupil, 25 through the dilated pupil) were "lost" due to a malfunction of flash synchronization. The problem was present in both available 35 mm camera bodies, and caused partial or total image loss. There were no camera malfunctions using the standard 30° camera. Because of these instances of camera failure, the comparison of gradings of photographs taken with the standard 30° fundus camera (dilated pupil), to those taken with the nonmydriatic camera (undilated pupil) is limited to 63 pairs; and to the nonmydriatic camera (dilated pupil) is limited to 74 pairs. The comparisons of severity of retinopathy was determined by grading photographs taken with the non mydriatic camera to those taken with the standard 30° camera are presented (Table 2). Exact agreement between severity of retinopathy based on grading of photographs taken with these two different cameras was 82.5% (52/ 63). Gradings of 45° photographs and 30° stereoscopic photographs taken through pharmacologically dilated pupils were in agreement 86.5% (64/74) of the time. There was a greater likelihood to "undercall" than to "overcall" the severity of retinopathy when grading 45° photographs compared to grading 30° stereoscopic photographs. Of the photographs taken through an undilated pupil, 12.7% (8/63) could not be graded. Of the 45° photographs taken through the pharmacologically dilated pupil, 6.8% (5/74) could not be graded, while only 2.0% (2/99) of those taken with the standard camera could not be graded. The retinopathy status based on the ophthalmoscopy (undilated pupil) agreed with that based on grading 30°
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Table 2. Comparison of Severity of Retinopathy (4 levels) Grading Photographs Taken with Both a Nonmydriatic Camera and a Standard 30° Camera Standard 30° Camera (dilated pupil)
Nonmydriatic 45° Camera Pharmacologically undilated pupil No retinopathy Microaneurysms alone Microaneurysms & more severe NPDR ProlifEirative retinopathy Cannot grade Total Pharmacologically dilated pupil No retinopathy Microaneurysms alone Microaneurysms & more severe NPDR Proliferative retinopathy Cannot grade Total NPDR
=
No Retinopathy
Microaneurysms Alone
Microaneurysms & More Severe NPDR
10 1
0 7
0 2
0 0 1
0 0 0
12
Proliferative Retinopathy
Cannot Grade
Total
0 0
0 0
10 10
20 1 5
1 13 0
0 0 2
21 14 8
7
28
14
2
63
14 0
0 4
1 4
0 0
0 0
15 8
0 0 1
1 0 0
30 0 1
1 14 1
0 0 2
32 14 5
15
5
36
16
2
74
non proliferative diabetic retinopathy
stereoscopic photographs in 54.3% (51/94) of cases (Table 3). In 14 eyes the ophthalmoscopist was unable to determine the severity of retinopathy, even though the 30° retinal photographs were gradable. In 9 eyes where retinopathy was judged to be present on 30° fundus photographs, these abnormalities were not detected by the ophthalmoscopist. Agreement between graders on severity of retinopathy was 85.1% for 45° photographs (undilated), 85.1% for 45° photographs (dilated), and slightly better at 90.0% for the 30° stereoscopic photographs. The corresponding intraobserver agreements were 81.4%, 81.4%, and 86.0%.
Significant focus problems were present more commonly in 45° photographs through an undilated pupil (21.0%) than in photographs through a dilated pupil (8.7%) or in 30° stereoscopic photographs (5.9%). Media opacities accentuated the problem for undilated 45° photographs (31.8% with opacities to 13.8% without opacities), as did a smaller pupil (11.1 % if the pupil was 7 mm or greater mm vs 28.1 % if the pupil was less than 5 mm in diameter). Focusing problems were not related to media opacities or pupil size in photographs taken through pharmacologically dilated pupils. Artifacts were more prevalent (48.1%) in the photographs taken through
Table 3. Comparison of Severity of Retinopathy (3 levels) by Direct Ophthalmoscopy and a Standard 30° Camera Standard 30° Camera Ophthalmoscopy
No Retinopathy
Nonproliferative Retinopathy
Proliferative Retinopathy
Cannot Grade
No retinopathy Nonproliferative retinopathy Proliferative retinopathy Cannot determine
15 5 0 4
8 24 6 9
1 8 10 1
1 0 2
0
24 38 16 16
24
47
20
3
94
Total
Total
For one participant no ophthalmoscopy was performed; 4 participants' photographs were not available for grading.
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the phannacologically undilated pupil. Only 13.7% of the photographs taken, with the standard 30° camera had artifacts.
DISCUSSION Our experience demonstrated strengths and weaknesses of both the non mydriatic 45° camera and the standard 30° camera. The advantages of the 45 ° in contrast to the 30° camera were that: (1) it was less expensive to purchase; (2) it took a shorter time to learn to use; (3) it required only one photograph to view the posterior pole of the retina while the standard camera required three stereoscopic pairs; and (4) it was not necessary to dilate the pupil pharmacologically before taking photographs. The relative disadvantages of the nonmydriatic camera were that: (1) the resultant photograph was of lower magnification (1.6X vs 2.5X at zero diopters); (2) it was not possible to obtain stereoscopic photographs; and (3) its use resulted in a higher frequency of ungradable photographs (especially, in the presence of small pharmacologically undilated pupils and/or media opacities). Use of the cameras was similar in three ways: (1) patient acceptance, (2) photographer ease of use, and (3) time required to photograph the posterior retina (two minutes). Photographs from both cameras provide an objective recording of retinal pathology (or its absence) which may be useful in examination for screening, routine care, or epidemiologic studies. These data suggest that the 45° nonstereoscopic fundus photographs when graded according to a four level classification scheme by experienced graders provides a reasonably reliable measure of the severity of diabetic retinopathy. The agreement between graded severity of retinopathy from fundus photographs taken with the nonmydriatic camera through a phannacologically undilated or dilated pupil and from fundus photographs taken with the standard 30° camera through dilated pupils was found to be 82.5% and 86.5%, respectively. The disagreements in gradings were due, in a large part, to the presence of 45° photographs which could not be graded. In addition disagreements usually resulted in a tendency to "undercall" the severity of retinopathy when grading photographs taken with the nonmydriatic camera. The less magnified nonstereoscopic field found in the single nonmydriatic photograph might have contributed to the grader missing retinal abnonnalities, such as microaneurysms, which might have been detected more easily in the stereoscopic photographs taken with the standard 30° camera. Grader variability might also account for the disagreements in grading severity of diabetic retinopathy. Photographs taken with a nonmydriatic camera may be of value in routine screening of diabetic patients in areas where ophthalmologic care or physician availability is limited. The need for such detection has been suggested because proliferative retinopathy may be present before affecting vision and it is possible in some cases to 490
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prevent severe visual impairment with laser photocoagulation. 2,6 In addition, because non ophthalmologists have only a 50% chance of correctly diagnosing the presence of proliferative retinopathy,? ophthalmologic examinations have been suggested for insulin-dependent patients who have had diabetes for at least five years and for newly diagnosed non-insulin-dependent patients. s However, there are diabetic patients for whom such ophthalmologic care is not readily available. 2 In such cases trained ophthalmic technician-photographers could test visual acuity, measure intraocular pressure and photograph the retina using the non mydriatic camera. Photographs could then be sent for evaluation to an experienced grader working with ophthalmologists at a central location and referral procedures developed for patients at risk of visual loss due to retinopathy. However, the finding that 27% of cases of proliferative diabetic retinopathy occur outside of the area covered by the photographic field used in the current investigation (Klein R, unpublished data) indicates a relative limitation of this method of screening. The appropriateness of use of nonmydriatic cameras in epidemiologic studies depends on the objectives of the specific study. If the objectives are to document the severity of retinopathy as described in this report without pharmacologically dilating the pupil (to increased participant compliance) photographs taken with the nonmydriatic camera graded by experienced graders may be an acceptable alternative. If on the other hand. the objective is to use retinopathy as an outcome variable for a controlled clinical trial, or to reliably document the appearance of specific lesions, grading of stereoscopic 30° photographs taken with a standard camera would be the method of choice. The inability to obtain stereoscopic photographs with the non mydriatic camera would preclude its use in detecting retinal edema, and may lead to errors in differentiating retinal hard exudates from drusen, or intraretinal microvascular abnonnalities from flat retinal new vessels. In addition, it has been estimated that between 8-15% of diabetic retinopathy may be missed since it may fall outside the one 45° field taken with the non mydriatic camera (Klein R, unpublished data). Direct ophthalmoscopy through an undilated pupil was found to be both insensitive and nonspecific as a means of detecting and classifying diabetic retinopathy. This is consistent with previous studies in which high error rates in classifying retinopathy by ophthalmoscopy have been reported. 7,9 Training of examiners and dilation of pupils have been reported to increase the agreement between ophthalmoscopy and grading of photographs to 86%.10 The data reported herein suggest that if the pupil is not to be dilated, then the nonmydriatic camera may offer a more sensitive and objective method of detecting retinopathy than direct ophthalmoscopy.
ACKNOWLEDGMENTS The authors are grateful to Matthew D. Davis, MD, David L. DeMets, PhD, Scot E. Moss, MA for consultation and
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criticism; to Bob Harrison and Gene Knutson for examining and photographing patients; to Larry Thomas of Wisconsin Optical Services for providing the Topcon fundus camera; to Anik Ganguly, BE for programming and data management advice; to Mae Wildt and Bernadette Bull for providing secretarial assistance.
REFERENCES 1. National Society to Prevent Blindness. Vision Problems in the US; Data Analysis: Definitions, Data Sources, Detailed Data Tables, Analysis, Interpretation. New York: National Society to Prevent Blindness, 1980. 2. Herman WH, Teutsch SM, Sepe SJ, et al. An approach to the prevention of blindness in diabetes. Diabetes Care 1983; 6:608-
13. 3. Diabetic Retinopathy Study Research Group. Report 7. A modification of the Airlie House classification of diabetic retinopathy. Invest Ophthalmol Vis Sci 1981; 21:210-26.
4. Early Treatment Diabetic Retinopathy Study. Manual of Operations. Baltimore: ETDRS Coordinating Center, Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, 1980; Chapter 18. 5. Harberg J, Holladay D, Entine S, et al. W1SAR; Wisconsin Storage and Retrieval System. Madison, WI: University of Wisconsin Clinical Cancer Center, 1979. 6. Klein R, Klein BEK, Moss SE. Visual impairment in diabetes. Ophthalmology 1984; 91:1-8. 7. Sussman EJ, Tsiaras WG, Soper KA. Diagnosis of diabetic eye disease. JAMA 1982; 247:3231-4. 8. National Diabetes Advisory Board. The Prevention and Treatment of Five Complications of Diabetes; A Guide for Primary Care Practitiqners. Bethesda, Maryland, 1983. 9. Palmberg P, Smith M, Waltman S, et al. The natural history of retinopathy in insulin-dependent juvenile-onset diabetes. Ophthalmology 1981; 88:613-8. 10. Moss SE, Klein R, Kessler SO, Richie KA. Comparison between ophthalmoscopy and fundus photography in determining severity of diabetic retinopathy. Ophthalmology 1985; 92:62-7.
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