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Differentiating Macular Holes from Macular Pseudoholes
Differentiating Macular Holes From Macular Fseudoholes Jose Martinez, M.D., W i l l i a m E. S m i d d y , M.D., Judy Kim, M.D., and J. D o n a l d M. Gass, M . D .
Surgical treatments of macular holes have become increasingly effective in inducing res olution of the cuff of surrounding subretinal fluid, resulting in increased vision in many patients. However, for many conditions that mimic a macular hole, either surgery is not indicated or different surgical manipulations are necessary. Differentiating macular holes from some forms of macular pseudoholes can be difficult or impossible based solely on clin ical examination. Adjunctive tests that may enhance the accuracy of diagnosis are either not feasible or not available to most clinical practices. We evaluated three clinic-based tests for their value in allowing the differenti ation between macular holes and macular pseudoholes: Amsler grid testing, WatzkeAllen sign, and laser aiming beam test. These tests were evaluated in three groups of clini cally defined patients: those with full-thick ness macular holes, those with macular pseudoholes, and those who had previously undergone successful macular hole treatment. Although the Amsler grid testing was sensi tive in correlating with clinically defined macular holes, it was not specific. The WatzkeAllen sign and, to a greater extent, the laser aiming beam test were extremely sensitive and specific in correlating clinically defined full-thickness macular holes and pseudoholes. These tests improve the accuracy of diagnosis of full-thickness macular holes. usually cause de crease in visual acuity to the range of 20/100. 1 8
The stages of macular hole formation have been characterized by Gass. 9 The causes of decreased vision include loss of neurosensory tissue and the effect of a cuff of subretinal fluid surround ing the macular hole. Spontaneous resolution of the subretinal fluid cuff is rare,7,10,11 but surgi cal intervention has been shown to be effective in inducing resolution of the cuff of subretinal fluid in 58% to 100% of cases. 1214 When ana tomic resolution occurs, vision increases in 72% to 9 1 % of cases. 1214 Many conditions mimic a macular hole for which either no treatment or different surgical maneuvers are necessary, including epiretinal membrane with pseudohole, age-related macu lar degeneration, impending macular hole, and others. 1520 Thus, proper diagnosis is essential to avoid needless or incorrect surgical interven tion. One of us (J.D.M.G.) has used the 50-μπι argon laser aiming beam in selected cases as an aid to differentiate pseudohole lesions from full-thickness macular holes. We applied the Amsler grid,21 Watzke-Allen sign,22 and laser aiming beam tests in a series of patients with clinically defined macular holes or lesions sim ulating macular holes (pseudoholes) to deter mine their value in diagnostically differentiat ing macular holes from pseudoholes.
Patients and Methods
IDIOPATHIC MACULAR HOLES
Accepted for publication Jan. 24, 1994. From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida. This study was supported in part by Public Health Service Research Grant 5V01 EY02549, Department of Health and Human Services, National Institutes of Health, National Eye Institute, Bethesda, Maryland. Reprint requests to William E. Smiddy, P.O. Box 016880, Miami, FL 33101.
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Patients referred to one of us (W.E.S.) were included in this study if they had the diagnosis of macular hole or pseudohole. The diagnosis was made based on clinical features and was correlated with test results. This series repre sents an approximately consecutive series, and all patients were tested between May 15 and July 1, 1993. A complete ocular examination was performed in each case. Age, gender, and best-corrected distance visual acuity were not ed for each patient. Amsler grid testing of the involved eye was performed using near correction with the fel-
©AMERICAN JOURNAL OF OPHTHALMOLOGY 117:762-767, JUNE, 1994
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Macular Holes vs Macular Pseudoholes
low eye patched. The patient outlined the area of visual aberration and categorized the lines as either wavy (metamorphopsia) or darkened (relative scotoma). A Watzke-Allen test22 was performed using a macular contact lens; a 100-μπι diameter slit beam oriented perpendicularly was centered on the macular lesion. The width of the slit beam was calibrated to the 100-μπι laser aiming beam spot. The patient was shown three images and asked to describe what was seen by correlating it with one of three drawings (Figure). If none of the illustrations characterized their view, they were asked to draw what they saw. The laser aiming beam test was performed using a slit-lamp delivery laser system and a small (100 μηι), vertical slit beam of light to illuminate the posterior pole. The aiming beam was set at the second lowest of four intensity settings. Initially, a spot size of 50 μπ\ was moved from normal-appearing retina toward the center until it was imaged at the center of the macular lesion while asking the patient whether this colored, focal light disappeared. The test was repeated until the patient's re sponse was consistent and reproducible. This same procedure was repeated with 100-, 200-, and 500-μπι aiming beam, using both the argon green and the krypton red lasers. In one case, the 500-μπι spot size was not seen in normal retina, so the aiming beam intensity was in creased to the fourth setting, and the patient was rechecked. The results of these tests were correlated within the three diagnostic groups. The diagno sis and assignment to each group were based on clinical examination and historical features. Group 1 included patients with full-thickness macular holes; group 2 included all patients with pseudoholes; and group 3 consisted of patients with surgically closed holes. Most
cases of pseudoholes (group 2) were in patients referred with the diagnosis of macular hole, but in three cases they were selected because their appearance mimicked a macular hole.
Results Baseline information—Of 33 patients, 37 eyes were studied. The ages of the 22 women and 11 men ranged from 53 to 85 years (mean, 66.4 years). The age and gender ratios were similar in each of three defined groups (Table 1). Group 1 consisted of 16 eyes with full-thickness macu lar holes, including three with stage 2 (hole < 400 μιη with posterior hyaloid attached near hole), 12 with stage 3 (hole > 400 μπι with posterior hyaloid layer attached around hole), and one with stage 4 (complete posterior vitre ous separation). Group 2 included 14 eyes with pseudoholes, including epiretinal membranes (nine eyes), impending macular holes (two eyes), vitreomacular traction syndrome (one eye), cystoid macular edema (one eye), and lamellar macular hole (one eye). Group 3 in cluded seven eyes in which successful macular hole surgery had been performed three to 18 months previously (mean, 12 months). Visual acuity measurements of patients in whom macular holes were diagnosed (group 1) ranged from 20/50 to 20/400 with a median of 20/125 (Table 1). Visual acuity measurements of patients in whom pseudoholes were diag nosed (group 2) ranged from 20/20 to 20/200 with a median of 20/50. Visual acuity measure ments of patients who had undergone success-
TABLE 1 BASELINE CHARACTERISTICS OF STUDY GROUPS GROUP 1
Figure (Martinez and associates). Diagram that was given to the patient to determine results of WatzkeAllen sign testing. Choices for response were break (left), thinning (middle), no break (right), or other (patient asked to draw).
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No. of eyes Age (yrs) Range Median Visual acuity Range Median Gender Male Female
MACULAR
GROUP 2 PSEUDO-
GROUP 3 CLOSED
HOLES
HOLES
HOLES
16
14
7
53-57 67
64-77 71
58-85 68
20/50-20/400 20/200
20/20-20/200 20/40
20/40-20/200 20/50
4 12
6 8
3 4
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TABLE 2 RESULTS OF AMSLER GRID TESTING
TABLE 3 RESULTS OF WATZKE-ALLEN TESTING
RESPONSE TO AMSLER GRID
WATZKE-ALLEN TEST
TEST
GROUP 1
GROUP 2
GROUP 3
Scotoma Metamorphopsia Both Normal Not done Total
4 5 6 0 1 16
1 10 2 1 0 14
1 4 0 2 0 7
ful macular hole surgery (group 3) ranged from 20/40 to 20/200 with a median of 20/50. Amsler grid testing—All 15 tested patients with macular holes (group 1) noted some Ams ler grid aberration, including metamorphopsia in five (33%), relative scotomas in four (27%), and both metamorphopsia and scotomas in six (40%)(Table 2). One patient was not tested, and no patients described a normal pattern. Aberrations were noted in 13 of 14 patients (93%) with pseudoholes (group 2) including metamorphopsia in ten (71%), scotomas in one (7%), and both metamorphopsia and scotomas in two (14%). One patient described a normal Amsler grid. Thus, the sensitivity of Amsler testing corre lating with a clinically defined macular pseudohole was 100% (15 of 15), but the specificity of the test for excluding macular holes was only 8% (one of 13). If the definition of a positive Amsler test is narrowed to the finding of a scotoma, the sensitivity falls to 67% (ten of 15) while the specificity increases to 79% (11 of 14). Thus, the Amsler test had limited utility in differentially correlating with macular holes and pseudoholes. Aberrations were described in five of seven patients who had undergone macular hole sur gery (group 3) including metamorphopsia in four and a scotoma in one. A normal Amsler grid result was described in two patients. All patients who had undergone macular hole sur gery indicated that their Amsler grid aberration was subjectively decreased compared to what they remembered preoperatively. Watzke-AUen sign testing—All 16 patients with clinically defined full-thickness macular holes (group 1) noted abnormalities, including a complete break in 12 (75%) and narrowing of the slit beam in four (25%) (Table 3). In con trast, among the 14 patients with pseudoholes
Break Thinning Other Normal Total
GROUP 1
GROUP 2
GROUP 3
12 4 0 0 16
0 2 4 8 14
2 0 0 5 7
(group 2), none described a complete break in the slit beam, two (14%) noted thinning of the slit beam centrally, four (28%) described blur ring changes of the slit beam centrally, and eight (57%) saw no abnormality of the slit beam. In seven patients who had undergone successful macular hole surgery (group 3), five reported a normal slit beam and two described a complete break in the slit beam. If a positive Watzke response is defined as observing a complete break, the sensitivity of the test to correlate with a clinically defined macular hole was 75% (12 of 16) and the speci ficity was 100% (14 of 14) (P = .00002). The consideration of a positive test as observing a break or thinning increases sensitivity to 100% (16 of 16) but decreases specificity to 86% (12 of 14) (P < .00001). Thus, the finding of a com plete break correlated well with the clinical diagnosis of macular hole, but a negative re sponse did not rule out this diagnosis. Laser aiming beam testing—In the 16 patients with clinically defined full-thickness macular holes, none could see the 50-μπι laser aiming beam spot, two (13%) could see the 100-μπ\ spot, five (31%) could see the 200-μπι spot, 13 (81%) could see the 500-μπι spot, and three (19%) could not see any of the laser aiming beams when imaged directly within the lesion (Table 4). In contrast, 13 of 14 patients (93%) with clinically defined pseudoholes (group 2) could see the 50-μπι spot size laser aiming beam, and all 14 could see the 100-, 200-, and 500-μπι spots. The patient who did not see the 50-μπι spot had a diagnosis of an impending macular hole. In the group of patients who had undergone macular hole surgery (group 3), six of seven could see the 50-μπι spot, and all could see the 100-, 200-, and 500-μιη spots. No differences were noted in the responses between the red and green spots in any group. If the inability to see a 50-μπ\ laser aiming
Macular Holes vs Macular Pseudoholes
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TABLE 4 RESULTS OF LASER AIMING BEAM (NUMBER OF PATIENTS UNABLE TO SEE SPOT) SPOT SIZE, μΜ
50 100 200 500 Total
GROUP 1
GROUP 2
16 15 11 3 16
1 0 0 0 14
beam spot is defined as a positive test result, the sensitivity of the test to correlate with a clinical diagnosis of macular hole was 100% (16 of 16), and the specificity (negative responses in pa tients with pseudoholes) was 93% (13 of 14) (P < .00001). If a positive test result is defined as an inability to see the 100-μπι spot, the sensi tivity dropped to 94% (15 of 16), but the speci ficity was 100% (14 of 14) (P < .00001). Within the macular hole group (group 1), the three patients who could not see any of the aiming beams had visual acuity of 20/200. The eight patients who could see the 500-μπι spot had visual acuity measurements that ranged from 20/50 to 20/400. The three patients who could see the 200- and 500-μπι spot had visual acuity measurement of 20/60, 20/200, and 20/300, respectively. The only patient with a macular hole who could see the 100-μπι spot had visual acuity of 20/80. Thus, the ability to perceive a smaller laser aiming beam was not strictly correlated to visual acuity. Combining information from both Watzke and laser aiming beam testing did not allow for both 100% sensitivity and 100% specificity. The patient with macular hole who could see the 100-μπι spot (but not the 50-μπι one) described thin ning by Watzke testing. The one patient with pseudohole (which was actually diagnosed as a stage 1 hole) who could not see the 50-μιη spot also described thinning by Watzke testing.
Discussion Because surgical intervention is considered increasingly for patients with macular hole, accuracy of diagnosis takes on more than aca demic importance. Many conditions that mimic macular holes have a favorable natural course, require different surgical maneuvers, or are not amenable to surgical intervention.
765
A full-thickness macular hole is most accu rately diagnosed clinically using a fundus con tact lens and slit-lamp biomicroscopy. Supple mental tests that may assist in or allow for more accurate diagnosis include Amsler grid test ing,21 testing for the Watzke-Allen sign,22 and fluorescein angiography. 3 Accurate diagnosis in some cases is challenging or impossible. The most common conditions mimicking macular holes include epimacular membranes with pseudoholes and impending macular holes, 1520 but the results of even these supplemental tests may be misleading in some cases. An objective means of differentiating macular holes from pseudoholes would be extremely valuable. Other ancillary tests such as focal electroretinograms, 23 scanning laser ophthalmoscope, 242δ and confocal laser tomographic analysis sys tems 26 have been applied to the study of macu lar holes with some success, but these modali ties are not available or feasible for many clinical practices. We demonstrated the utility of easily per formed, clinic-based tests for differentiating macular holes from pseudoholes. Amsler grid testing was sensitive in that all patients with clinically defined macular holes complained of some abnormality, but it was not specific in differentiating macular holes from pseudoholes. Of 15 patients with macular holes, ten (67%) tested described a relative scotoma; in contrast, only three of 14 patients with pseudoholes (21%) noted a scotoma on the Amsler grid. A previous study reported a scotoma by Amsler testing in only 3 1 % of eyes with macu lar holes. 27 The subjective nature of the test response may account for this discrepancy. In deed, the validity and interpretation of Amsler grid reports have been questioned. 28 Thus, Amsler grid testing was sensitive in detecting any form of macular abnormality, but it was not specific enough to be useful in estab lishing a diagnosis of macular hole. A scotoma was noted by Amsler grid testing in only one of the patients with a postoperative macular hole, and all patients indicated retrospectively a sub jective improvement compared to their preoperative perception. This suggests functional im provement in such patients, but preoperative testing had not been standardized. Scanning laser ophthalmoscopic studies have established this functional improvement. 24 The application of the slit-beam test in the diagnosis of macular holes was originally re ported by Watzke and Allen.22 Our results clear ly document the utility of this test, since all
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patients with clinically defined macular holes noted a break or thinning of the slit beam. We found that showing the patient a schematic illustration of what they might see before test ing was helpful to standardize and clarify re sponses. Thinning of the slit beam was seen in both macular hole and pseudohole cases, so thinning was not as specific as a total break in the slit beam. Remarkably, most patients with postoperative macular hole (71%) saw a normal vertical slit beam, indicating a measure of func tional improvement in this group of patients. Recently, the scanning laser ophthalmoscope has been applied to the study of macular holes.24,25 The laser aiming beam test may yield similar diagnostic information, allowing the clinician to test focal areas of the retina for a scotoma. We demonstrated that a 50-μπι spot laser aiming beam could be hidden in the macu lar lesion of all patients with a clinically de fined full-thickness macular hole. This con trasts with the finding that 93% of pseudohole eyes could detect the 50-μπι spot. Conversely, the inability to detect a 200- or 500-μπι spot size was noted only by patients with macular holes. Thus, the absolute scotoma detected by the laser aiming beam test is sensitive and specific (100% and 93%, respectively, for the 50-μιη spot) for full-thickness macular holes. The specificity and sensitivity of hiding the laser aiming beam within a macular hole gives the clinician a powerful and practical test that may aid in the accuracy of diagnosing macular holes. Interestingly, 86% of the patients with post operative macular hole closure could see the 50-μπι spot as well. This suggests functional postoperative macular improvement, although these patients were not tested preoperatively. Furthermore, this observation is consistent with the hypothesis that centripetal contraction of a fibrocellular patch pulls the edges of the macular hole centrally, decreasing its size. This hypothesis is supported by and inferred from the findings of a postmortem histopathologic study of a patient who had undergone success ful macular hole surgery. 29 At 300 mW, the 50-μπι laser aiming spot at the second-lowest energy yields about 2 W/cm 2 irradiance. If we assume a ten-second exposure (and the aiming beam is rarely stationary for this long), then this represents 20 J/cm 2 , well under the 200 J/cm 2 threshold of damage found experimentally. 30 Thus, the laser aiming beam test poses little threat to healthy patient retina when used in this manner.
Morgan and Schatz 6 reported a close correla tion between macular hole diameter and visual acuity. The size of a hideable laser aiming beam appeared to correlate to hole size and visual acuity. We did not find any correlation between the laser aiming beam test result and visual acuity of the patients with macular hole. It might be interesting to correlate prospectively the preoperative laser aiming beam test results with postoperative visual outcome. The Watzke-Allen test and to a greater degree the laser aiming beam test further improve the accuracy of diagnosis of full-thickness macular holes. The major advantage of these tests is that they are simple to perform, can be done in the office, and are easily accessible.
ACKNOWLEDGMENTS
William Feurer, M.S., performed the statisti cal analyses in this study, and David Buzawa, Iris Medical Instruments, Inc., assisted in photoxicity calculations.
References 1. Yaoeda, H.: Clinical observation on macular hole. Nippon Ganka Gakkai Zasshi 71:1723, 1967. 2. Margherio, R. R., and Schepens, C. L.: Macular breaks. I. Diagnosis, etiology, and observations. Am. J. Ophthalmol. 74:219, 1972. 3. Aaberg, T. M., Blair, C. J., and Gass, J. D.: Macular holes. Am. J. Ophthalmol. 69:555, 1970. 4. James, M., and Feman, S. S.: Macular holes. Graefes Arch. Klin. Ophthalmol. 215:59, 1980. 5. McDonnell, P. J., Fine, S. L., and Hillis, H. I.: Clinical features of idiopathic macular cysts and holes. Am. J. Ophthalmol. 93:777, 1982. 6. Morgan, C. M., and Schatz, H.: Idiopathic macu lar holes. Am. J. Ophthalmol. 99:437, 1985. 7. Bidwell, A. E., Jampol, L. M., and Goldberg, M. F.: Macular holes and excellent visual acuity. Case report. Arch. Ophthalmol. 106:1350, 1988. 8. Johnson, R. N., and Gass, J. D.: Idiopathic macular holes. Observations, stages of formation, and implications for surgical intervention. Ophthal mology 95:917, 1988. 9. Gass, J. D.: Idiopathic senile macular hole. Its early stages and pathogenesis. Arch. Ophthalmol. 106:629, 1988. 10. Lewis, H., Cowan, G. M., and Straatsma, B. R.: Apparent disappearance of a macular hole associated with development of an epiretinal membrane. Am. J. Ophthalmol. 102:172, 1986. 11. Guyer, D. R., de Bustros, S., Diener-West, M., and Fine, S. L.: Observations on patients with idio-
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Macular Holes vs Macular Pseudoholes
pathic macular holes and cysts. Arch. Ophthalmol. 110:1264, 1992. 12. Kelly, N. E., and Wendel, R. T.: Vitreous sur gery for idiopathic macular holes. Results of a pilot study. Arch. Ophthalmol. 109:654, 1991. 13. Glaser, B. M., Michels, R. G., Kuppermann, B. D., Sjaarda, R. N., and Pena, R. A.: Transforming growth factor-ß2 for the treatment of full-thickness macular holes. A prospective randomized study. Ophthalmology 77:1162, 1992. 14. Lansing, M., Glaser, B. M., Thompson, J. T., Sjaarda, R. N., and Hanham, A.: The effect of pars plana vitrectomy and transforming growth factor-ß2 without epiretinal membrane peeling on full-thick ness macular holes. Ophthalmology 100:868, 1993. 15. Fish, R. H., Anand, R., and Izbrand, D. ].: Macular pseudoholes, clinical features and accuracy of diagnosis. Ophthalmology 99:1665, 1992. 16. Smiddy, W. E., Michels, R. G., and Green, W. R.: Morphology, pathology, and surgery of idio pathic vitreoretinal macular disorders. Retina 10:288, 1990. 17. Gass, J. D., and Joondeph, B. C : Observations concerning patients with suspected impending mac ular holes. Am. J. Ophthalmol. 109:638, 1990. 18. Gass, J. D.: Lamellar macular hole. A complica tion of cystoid macular edema after cataract extrac tion. Arch. Ophthalmol. 94:793, 1976. 19. Allen, A. W., Jr., and Gass, J. D.: Contraction of a perifoveal epiretinal membrane simulating a macu lar hole. Am. J. Ophthalmol. 82:684, 1976. 20. Smiddy, W. E., and Gass, J. D. M.: Masquerades of macular holes. Ophthalmic Surg. In press. 21. Amsler, M.: Quantitative and qualitative vi sion. Trans. Ophthalmol. Soc. U.K. 69:397, 1949.
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22. Watzke, R. C , and Allen, L.: Subjective slitbeam sign for macular disease. Am. J. Ophthalmol. 68:449, 1969. 23. Birch, D. G., Jost, B. F., and Fish, G. E.: The focal electroretinogram in fellow eyes of patients with idiopathic macular holes. Arch. Ophthalmol. 106:1558, 1988. 24. Sjaarda, R. N., Frank, D. A., Glaser, B. M., Thompson, J. T., and Murphy, R. P.: Resolution of an absolute scotoma and improvement of relative scotoma after successful macular hole surgery. Am. J. Ophthalmol. 116:129, 1993. 25. Acosta, F., Lashkari, K., Reynaud, X., Jalkh, A. E., Van de Velde, F., and Chedid, N.: Characteriza tion of functional changes in macular holes and cysts. Ophthalmology 98:1820, 1991. 26. Bartsch, D. U., Intaglietta, M., Bille, J. F., Dreher, A. W., Gharib, M., and Freeman, W. R.: Confocal laser tomographic analysis of the retina in eyes with macular hole formation and other focal macular diseases. Am. J. Ophthalmol. 108:277, 1989. 27. Smith, R. G., Hardman-Lea, S. J., and Gallo way, N. R.: Visual performance in idiopathic macular holes. Eye 4:190, 1990. 28. Schuchard, R. A.: Validity and interpretation of Amsler grid reports. Arch. Ophthalmol. 111:776, 1993. 29. Funata, M., Wendel, R. T., de la Cruz, Z., and Green, W. R.: Clinicopathologic study of bilateral macular holes treated with pars plana vitrectomy and gas tamponade. Retina 12:289, 1992. 30. Kremers, J. J., and van Norren, D.: Retinal damage in macaque after white light exposures last ing ten minutes to twelve hours. Invest. Ophthalmol. Vis. Sei. 30:1032, 1989.
OPHTHALMIC MINIATURE
"There, you s e e , " said the pharmacist, " a scrofulous infection." And despite the fact that he knew the poor devil, he p r e t e n d e d to be seeing him for the first time, murmuring the terms, " c o r n e a , " " o p a q u e cornea," "sclerotic," "faciès," and then asking him in a paternal tone: "Have you had this dreadful infirmity a long time, my friend? Instead of getting drunk in the tavern, you'd be better off on a special d i e t . " He advised him to take good wine, good beer, good roasts. The blind m a n continued to sing. In fact, he seemed to be almost an idiot. Finally Homais opened his purse. Gustave Flaubert, Madame Bovary New York, New American Library, 1979, p . 280
Surgical treatments of macular holes have become increasingly effective in inducing res olution of the cuff of surrounding subretinal fluid, resulting in increased vision in many patients. However, for many conditions that mimic a macular hole, either surgery is not indicated or different surgical manipulations are necessary. Differentiating macular holes from some forms of macular pseudoholes can be difficult or impossible based solely on clin ical examination. Adjunctive tests that may enhance the accuracy of diagnosis are either not feasible or not available to most clinical practices. We evaluated three clinic-based tests for their value in allowing the differenti ation between macular holes and macular pseudoholes: Amsler grid testing, WatzkeAllen sign, and laser aiming beam test. These tests were evaluated in three groups of clini cally defined patients: those with full-thick ness macular holes, those with macular pseudoholes, and those who had previously undergone successful macular hole treatment. Although the Amsler grid testing was sensi tive in correlating with clinically defined macular holes, it was not specific. The WatzkeAllen sign and, to a greater extent, the laser aiming beam test were extremely sensitive and specific in correlating clinically defined full-thickness macular holes and pseudoholes. These tests improve the accuracy of diagnosis of full-thickness macular holes. usually cause de crease in visual acuity to the range of 20/100. 1 8
The stages of macular hole formation have been characterized by Gass. 9 The causes of decreased vision include loss of neurosensory tissue and the effect of a cuff of subretinal fluid surround ing the macular hole. Spontaneous resolution of the subretinal fluid cuff is rare,7,10,11 but surgi cal intervention has been shown to be effective in inducing resolution of the cuff of subretinal fluid in 58% to 100% of cases. 1214 When ana tomic resolution occurs, vision increases in 72% to 9 1 % of cases. 1214 Many conditions mimic a macular hole for which either no treatment or different surgical maneuvers are necessary, including epiretinal membrane with pseudohole, age-related macu lar degeneration, impending macular hole, and others. 1520 Thus, proper diagnosis is essential to avoid needless or incorrect surgical interven tion. One of us (J.D.M.G.) has used the 50-μπι argon laser aiming beam in selected cases as an aid to differentiate pseudohole lesions from full-thickness macular holes. We applied the Amsler grid,21 Watzke-Allen sign,22 and laser aiming beam tests in a series of patients with clinically defined macular holes or lesions sim ulating macular holes (pseudoholes) to deter mine their value in diagnostically differentiat ing macular holes from pseudoholes.
Patients and Methods
IDIOPATHIC MACULAR HOLES
Accepted for publication Jan. 24, 1994. From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida. This study was supported in part by Public Health Service Research Grant 5V01 EY02549, Department of Health and Human Services, National Institutes of Health, National Eye Institute, Bethesda, Maryland. Reprint requests to William E. Smiddy, P.O. Box 016880, Miami, FL 33101.
762
Patients referred to one of us (W.E.S.) were included in this study if they had the diagnosis of macular hole or pseudohole. The diagnosis was made based on clinical features and was correlated with test results. This series repre sents an approximately consecutive series, and all patients were tested between May 15 and July 1, 1993. A complete ocular examination was performed in each case. Age, gender, and best-corrected distance visual acuity were not ed for each patient. Amsler grid testing of the involved eye was performed using near correction with the fel-
©AMERICAN JOURNAL OF OPHTHALMOLOGY 117:762-767, JUNE, 1994
Vol. 117, No. 6
Macular Holes vs Macular Pseudoholes
low eye patched. The patient outlined the area of visual aberration and categorized the lines as either wavy (metamorphopsia) or darkened (relative scotoma). A Watzke-Allen test22 was performed using a macular contact lens; a 100-μπι diameter slit beam oriented perpendicularly was centered on the macular lesion. The width of the slit beam was calibrated to the 100-μπι laser aiming beam spot. The patient was shown three images and asked to describe what was seen by correlating it with one of three drawings (Figure). If none of the illustrations characterized their view, they were asked to draw what they saw. The laser aiming beam test was performed using a slit-lamp delivery laser system and a small (100 μηι), vertical slit beam of light to illuminate the posterior pole. The aiming beam was set at the second lowest of four intensity settings. Initially, a spot size of 50 μπ\ was moved from normal-appearing retina toward the center until it was imaged at the center of the macular lesion while asking the patient whether this colored, focal light disappeared. The test was repeated until the patient's re sponse was consistent and reproducible. This same procedure was repeated with 100-, 200-, and 500-μπι aiming beam, using both the argon green and the krypton red lasers. In one case, the 500-μπι spot size was not seen in normal retina, so the aiming beam intensity was in creased to the fourth setting, and the patient was rechecked. The results of these tests were correlated within the three diagnostic groups. The diagno sis and assignment to each group were based on clinical examination and historical features. Group 1 included patients with full-thickness macular holes; group 2 included all patients with pseudoholes; and group 3 consisted of patients with surgically closed holes. Most
cases of pseudoholes (group 2) were in patients referred with the diagnosis of macular hole, but in three cases they were selected because their appearance mimicked a macular hole.
Results Baseline information—Of 33 patients, 37 eyes were studied. The ages of the 22 women and 11 men ranged from 53 to 85 years (mean, 66.4 years). The age and gender ratios were similar in each of three defined groups (Table 1). Group 1 consisted of 16 eyes with full-thickness macu lar holes, including three with stage 2 (hole < 400 μιη with posterior hyaloid attached near hole), 12 with stage 3 (hole > 400 μπι with posterior hyaloid layer attached around hole), and one with stage 4 (complete posterior vitre ous separation). Group 2 included 14 eyes with pseudoholes, including epiretinal membranes (nine eyes), impending macular holes (two eyes), vitreomacular traction syndrome (one eye), cystoid macular edema (one eye), and lamellar macular hole (one eye). Group 3 in cluded seven eyes in which successful macular hole surgery had been performed three to 18 months previously (mean, 12 months). Visual acuity measurements of patients in whom macular holes were diagnosed (group 1) ranged from 20/50 to 20/400 with a median of 20/125 (Table 1). Visual acuity measurements of patients in whom pseudoholes were diag nosed (group 2) ranged from 20/20 to 20/200 with a median of 20/50. Visual acuity measure ments of patients who had undergone success-
TABLE 1 BASELINE CHARACTERISTICS OF STUDY GROUPS GROUP 1
Figure (Martinez and associates). Diagram that was given to the patient to determine results of WatzkeAllen sign testing. Choices for response were break (left), thinning (middle), no break (right), or other (patient asked to draw).
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No. of eyes Age (yrs) Range Median Visual acuity Range Median Gender Male Female
MACULAR
GROUP 2 PSEUDO-
GROUP 3 CLOSED
HOLES
HOLES
HOLES
16
14
7
53-57 67
64-77 71
58-85 68
20/50-20/400 20/200
20/20-20/200 20/40
20/40-20/200 20/50
4 12
6 8
3 4
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TABLE 2 RESULTS OF AMSLER GRID TESTING
TABLE 3 RESULTS OF WATZKE-ALLEN TESTING
RESPONSE TO AMSLER GRID
WATZKE-ALLEN TEST
TEST
GROUP 1
GROUP 2
GROUP 3
Scotoma Metamorphopsia Both Normal Not done Total
4 5 6 0 1 16
1 10 2 1 0 14
1 4 0 2 0 7
ful macular hole surgery (group 3) ranged from 20/40 to 20/200 with a median of 20/50. Amsler grid testing—All 15 tested patients with macular holes (group 1) noted some Ams ler grid aberration, including metamorphopsia in five (33%), relative scotomas in four (27%), and both metamorphopsia and scotomas in six (40%)(Table 2). One patient was not tested, and no patients described a normal pattern. Aberrations were noted in 13 of 14 patients (93%) with pseudoholes (group 2) including metamorphopsia in ten (71%), scotomas in one (7%), and both metamorphopsia and scotomas in two (14%). One patient described a normal Amsler grid. Thus, the sensitivity of Amsler testing corre lating with a clinically defined macular pseudohole was 100% (15 of 15), but the specificity of the test for excluding macular holes was only 8% (one of 13). If the definition of a positive Amsler test is narrowed to the finding of a scotoma, the sensitivity falls to 67% (ten of 15) while the specificity increases to 79% (11 of 14). Thus, the Amsler test had limited utility in differentially correlating with macular holes and pseudoholes. Aberrations were described in five of seven patients who had undergone macular hole sur gery (group 3) including metamorphopsia in four and a scotoma in one. A normal Amsler grid result was described in two patients. All patients who had undergone macular hole sur gery indicated that their Amsler grid aberration was subjectively decreased compared to what they remembered preoperatively. Watzke-AUen sign testing—All 16 patients with clinically defined full-thickness macular holes (group 1) noted abnormalities, including a complete break in 12 (75%) and narrowing of the slit beam in four (25%) (Table 3). In con trast, among the 14 patients with pseudoholes
Break Thinning Other Normal Total
GROUP 1
GROUP 2
GROUP 3
12 4 0 0 16
0 2 4 8 14
2 0 0 5 7
(group 2), none described a complete break in the slit beam, two (14%) noted thinning of the slit beam centrally, four (28%) described blur ring changes of the slit beam centrally, and eight (57%) saw no abnormality of the slit beam. In seven patients who had undergone successful macular hole surgery (group 3), five reported a normal slit beam and two described a complete break in the slit beam. If a positive Watzke response is defined as observing a complete break, the sensitivity of the test to correlate with a clinically defined macular hole was 75% (12 of 16) and the speci ficity was 100% (14 of 14) (P = .00002). The consideration of a positive test as observing a break or thinning increases sensitivity to 100% (16 of 16) but decreases specificity to 86% (12 of 14) (P < .00001). Thus, the finding of a com plete break correlated well with the clinical diagnosis of macular hole, but a negative re sponse did not rule out this diagnosis. Laser aiming beam testing—In the 16 patients with clinically defined full-thickness macular holes, none could see the 50-μπι laser aiming beam spot, two (13%) could see the 100-μπ\ spot, five (31%) could see the 200-μπι spot, 13 (81%) could see the 500-μπι spot, and three (19%) could not see any of the laser aiming beams when imaged directly within the lesion (Table 4). In contrast, 13 of 14 patients (93%) with clinically defined pseudoholes (group 2) could see the 50-μπι spot size laser aiming beam, and all 14 could see the 100-, 200-, and 500-μπι spots. The patient who did not see the 50-μπι spot had a diagnosis of an impending macular hole. In the group of patients who had undergone macular hole surgery (group 3), six of seven could see the 50-μπι spot, and all could see the 100-, 200-, and 500-μιη spots. No differences were noted in the responses between the red and green spots in any group. If the inability to see a 50-μπ\ laser aiming
Macular Holes vs Macular Pseudoholes
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TABLE 4 RESULTS OF LASER AIMING BEAM (NUMBER OF PATIENTS UNABLE TO SEE SPOT) SPOT SIZE, μΜ
50 100 200 500 Total
GROUP 1
GROUP 2
16 15 11 3 16
1 0 0 0 14
beam spot is defined as a positive test result, the sensitivity of the test to correlate with a clinical diagnosis of macular hole was 100% (16 of 16), and the specificity (negative responses in pa tients with pseudoholes) was 93% (13 of 14) (P < .00001). If a positive test result is defined as an inability to see the 100-μπι spot, the sensi tivity dropped to 94% (15 of 16), but the speci ficity was 100% (14 of 14) (P < .00001). Within the macular hole group (group 1), the three patients who could not see any of the aiming beams had visual acuity of 20/200. The eight patients who could see the 500-μπι spot had visual acuity measurements that ranged from 20/50 to 20/400. The three patients who could see the 200- and 500-μπι spot had visual acuity measurement of 20/60, 20/200, and 20/300, respectively. The only patient with a macular hole who could see the 100-μπι spot had visual acuity of 20/80. Thus, the ability to perceive a smaller laser aiming beam was not strictly correlated to visual acuity. Combining information from both Watzke and laser aiming beam testing did not allow for both 100% sensitivity and 100% specificity. The patient with macular hole who could see the 100-μπι spot (but not the 50-μπι one) described thin ning by Watzke testing. The one patient with pseudohole (which was actually diagnosed as a stage 1 hole) who could not see the 50-μιη spot also described thinning by Watzke testing.
Discussion Because surgical intervention is considered increasingly for patients with macular hole, accuracy of diagnosis takes on more than aca demic importance. Many conditions that mimic macular holes have a favorable natural course, require different surgical maneuvers, or are not amenable to surgical intervention.
765
A full-thickness macular hole is most accu rately diagnosed clinically using a fundus con tact lens and slit-lamp biomicroscopy. Supple mental tests that may assist in or allow for more accurate diagnosis include Amsler grid test ing,21 testing for the Watzke-Allen sign,22 and fluorescein angiography. 3 Accurate diagnosis in some cases is challenging or impossible. The most common conditions mimicking macular holes include epimacular membranes with pseudoholes and impending macular holes, 1520 but the results of even these supplemental tests may be misleading in some cases. An objective means of differentiating macular holes from pseudoholes would be extremely valuable. Other ancillary tests such as focal electroretinograms, 23 scanning laser ophthalmoscope, 242δ and confocal laser tomographic analysis sys tems 26 have been applied to the study of macu lar holes with some success, but these modali ties are not available or feasible for many clinical practices. We demonstrated the utility of easily per formed, clinic-based tests for differentiating macular holes from pseudoholes. Amsler grid testing was sensitive in that all patients with clinically defined macular holes complained of some abnormality, but it was not specific in differentiating macular holes from pseudoholes. Of 15 patients with macular holes, ten (67%) tested described a relative scotoma; in contrast, only three of 14 patients with pseudoholes (21%) noted a scotoma on the Amsler grid. A previous study reported a scotoma by Amsler testing in only 3 1 % of eyes with macu lar holes. 27 The subjective nature of the test response may account for this discrepancy. In deed, the validity and interpretation of Amsler grid reports have been questioned. 28 Thus, Amsler grid testing was sensitive in detecting any form of macular abnormality, but it was not specific enough to be useful in estab lishing a diagnosis of macular hole. A scotoma was noted by Amsler grid testing in only one of the patients with a postoperative macular hole, and all patients indicated retrospectively a sub jective improvement compared to their preoperative perception. This suggests functional im provement in such patients, but preoperative testing had not been standardized. Scanning laser ophthalmoscopic studies have established this functional improvement. 24 The application of the slit-beam test in the diagnosis of macular holes was originally re ported by Watzke and Allen.22 Our results clear ly document the utility of this test, since all
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patients with clinically defined macular holes noted a break or thinning of the slit beam. We found that showing the patient a schematic illustration of what they might see before test ing was helpful to standardize and clarify re sponses. Thinning of the slit beam was seen in both macular hole and pseudohole cases, so thinning was not as specific as a total break in the slit beam. Remarkably, most patients with postoperative macular hole (71%) saw a normal vertical slit beam, indicating a measure of func tional improvement in this group of patients. Recently, the scanning laser ophthalmoscope has been applied to the study of macular holes.24,25 The laser aiming beam test may yield similar diagnostic information, allowing the clinician to test focal areas of the retina for a scotoma. We demonstrated that a 50-μπι spot laser aiming beam could be hidden in the macu lar lesion of all patients with a clinically de fined full-thickness macular hole. This con trasts with the finding that 93% of pseudohole eyes could detect the 50-μπι spot. Conversely, the inability to detect a 200- or 500-μπι spot size was noted only by patients with macular holes. Thus, the absolute scotoma detected by the laser aiming beam test is sensitive and specific (100% and 93%, respectively, for the 50-μιη spot) for full-thickness macular holes. The specificity and sensitivity of hiding the laser aiming beam within a macular hole gives the clinician a powerful and practical test that may aid in the accuracy of diagnosing macular holes. Interestingly, 86% of the patients with post operative macular hole closure could see the 50-μπι spot as well. This suggests functional postoperative macular improvement, although these patients were not tested preoperatively. Furthermore, this observation is consistent with the hypothesis that centripetal contraction of a fibrocellular patch pulls the edges of the macular hole centrally, decreasing its size. This hypothesis is supported by and inferred from the findings of a postmortem histopathologic study of a patient who had undergone success ful macular hole surgery. 29 At 300 mW, the 50-μπι laser aiming spot at the second-lowest energy yields about 2 W/cm 2 irradiance. If we assume a ten-second exposure (and the aiming beam is rarely stationary for this long), then this represents 20 J/cm 2 , well under the 200 J/cm 2 threshold of damage found experimentally. 30 Thus, the laser aiming beam test poses little threat to healthy patient retina when used in this manner.
Morgan and Schatz 6 reported a close correla tion between macular hole diameter and visual acuity. The size of a hideable laser aiming beam appeared to correlate to hole size and visual acuity. We did not find any correlation between the laser aiming beam test result and visual acuity of the patients with macular hole. It might be interesting to correlate prospectively the preoperative laser aiming beam test results with postoperative visual outcome. The Watzke-Allen test and to a greater degree the laser aiming beam test further improve the accuracy of diagnosis of full-thickness macular holes. The major advantage of these tests is that they are simple to perform, can be done in the office, and are easily accessible.
ACKNOWLEDGMENTS
William Feurer, M.S., performed the statisti cal analyses in this study, and David Buzawa, Iris Medical Instruments, Inc., assisted in photoxicity calculations.
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22. Watzke, R. C , and Allen, L.: Subjective slitbeam sign for macular disease. Am. J. Ophthalmol. 68:449, 1969. 23. Birch, D. G., Jost, B. F., and Fish, G. E.: The focal electroretinogram in fellow eyes of patients with idiopathic macular holes. Arch. Ophthalmol. 106:1558, 1988. 24. Sjaarda, R. N., Frank, D. A., Glaser, B. M., Thompson, J. T., and Murphy, R. P.: Resolution of an absolute scotoma and improvement of relative scotoma after successful macular hole surgery. Am. J. Ophthalmol. 116:129, 1993. 25. Acosta, F., Lashkari, K., Reynaud, X., Jalkh, A. E., Van de Velde, F., and Chedid, N.: Characteriza tion of functional changes in macular holes and cysts. Ophthalmology 98:1820, 1991. 26. Bartsch, D. U., Intaglietta, M., Bille, J. F., Dreher, A. W., Gharib, M., and Freeman, W. R.: Confocal laser tomographic analysis of the retina in eyes with macular hole formation and other focal macular diseases. Am. J. Ophthalmol. 108:277, 1989. 27. Smith, R. G., Hardman-Lea, S. J., and Gallo way, N. R.: Visual performance in idiopathic macular holes. Eye 4:190, 1990. 28. Schuchard, R. A.: Validity and interpretation of Amsler grid reports. Arch. Ophthalmol. 111:776, 1993. 29. Funata, M., Wendel, R. T., de la Cruz, Z., and Green, W. R.: Clinicopathologic study of bilateral macular holes treated with pars plana vitrectomy and gas tamponade. Retina 12:289, 1992. 30. Kremers, J. J., and van Norren, D.: Retinal damage in macaque after white light exposures last ing ten minutes to twelve hours. Invest. Ophthalmol. Vis. Sei. 30:1032, 1989.
OPHTHALMIC MINIATURE
"There, you s e e , " said the pharmacist, " a scrofulous infection." And despite the fact that he knew the poor devil, he p r e t e n d e d to be seeing him for the first time, murmuring the terms, " c o r n e a , " " o p a q u e cornea," "sclerotic," "faciès," and then asking him in a paternal tone: "Have you had this dreadful infirmity a long time, my friend? Instead of getting drunk in the tavern, you'd be better off on a special d i e t . " He advised him to take good wine, good beer, good roasts. The blind m a n continued to sing. In fact, he seemed to be almost an idiot. Finally Homais opened his purse. Gustave Flaubert, Madame Bovary New York, New American Library, 1979, p . 280