- Email: [email protected]
The natural history of macular pseudoholes
The Natural History of Macular CRAIG M. GREVEN, MD, M. MADISON AND CRAIG N. CZYZ PURPOSE: To report the natural history of macular pseudoholes with regard to ophthalmoscopic appearance and visual acuity. l METHODS: Thirty-six eyes of 34 patients with macular pseudoholes who were followed up for 1 year or longer were retrospectively evaluated to compare the initial ophthalmoscopic appearance and visual acuity with the most recent follow-up appearance and visual acuity. l RESULTS: Mean visual acuity at initial examination was 20/32 (median, 20/30); mean follow-up visual acuity was 20/32 (median, 20/30). Fourteen eyes (39%) had identical initial and final visual acuities, and 30 eyes (83%) had final visual acuity within 2 lines on the visual acuity chart from their initial examination. Four eyes had improved visual acuity of more than 2 lines, and two eyes lost more than 2 lines of visual acuity. Thirty-one eyes had adequate initial and follow-up photographs allowing comparison of macular appearance. Twentyethree (74%) of the 3 1 eyes showed a definitive change in macular appearance. l CONCLUSIONS: Visual acuity in patients with macular pseudoholes tended to remain stable. However, the macular appearance changed in 74% of eyes. (Am J Ophthalmol 1998;125:360-366. 0 1998 by El sevier Science Inc. All rights reserved.) l
M
ACULAR
HOLES
ARE
FULL-THICKNESS
DE-
fects or dehiscences in the neurosensory retina involving the fovea1 region. Several conditions may simulate macular holes.‘,*
Accepted for publication July 1, 1997. From the Wake Forest University Eye Center, Bowman Gray School of Medicine, Winston-Salem, North Carolina. Reprint requests to Craig M. Greven, MD, Wake Forest University Eye Center, Medical Center Blvd, Winston-Salem, NC 27157-1033; fax: (910) 716-7994; e-mail: cgrevenObgsm.edu
360
0
1~8
BY ELSEWER SCIENCE
Pseudoholes
SLUSHER, MD,
Although clinical features, diagnostic accuracy, fundus appearance, and fluorescein angiographic characteristics have been described,3y4 little information is available on the natural history of macular pseudohole. We report a retrospective analysis of visual acuity and fundus appearance in patients with macular pseudoholes who were followed up for more than 1 year.
PATIENTS AND METHODS WE
RETROSPECTIVELY
REVIEWED
THE
CHARTS
OF ALL
patients coded as having epiretinal membranes, epiretinal membranes with macular pseudoholes, and macular holes seen at the Wake Forest University Eye Center from 1988 through 1993. For the purpose of this study, macular pseudohole was defined as a round to oval defect in a fibrocellular epiretinal membrane overlying the fovea1 region. Other lesions that may simulate macular holes were not included in this study. Forty-nine eyes of 47 patients wet-e identified as having epiretinal membranes with macular pseudoholes. None of these 49 eyes was documented as having vitreoretinal surgery performed for epiretinal membrane with macular pseudohole. Thirty-six eyes of thirty-four patients had 12 months or longer follow-up and were included in this study. At the time of diagnosis, patients ranged in age from 25 to 84 years (mean + SD, 65 + 6 years; median, 66 years). Of the 34 patients, 23 (68%) were women and 11 (32%) were men. In each patient a complete history and ophthalmic evaluation was performed. Best-corrected visual acuity was measured at 20 feet using a standard Snellen visual acuity chart with best-refracted correction. Each eye had initial and follow-up color fundus photographs available for evaluation. Photographs INC. ALL
RIGHTS
RESERVED.
0002-9394/98/$19.00
were evaluated by two of us (C.M.G., M.M.S.) and classified as having no change or a definitive change. If a definitive change was present, the changes were subclassified as minor change, moderate change, or major change in fundus appearance. A minor change was defined as a slight change in retinal striae or a slight change in axis of the macular pseudohole. A moderate change required more substantial alteration in retinal striae or size and shape of the macular pseudohole, or both. A major change was defined as an extensive alteration in the epiretinal membrane, pseudohole, and macular angioarchitecture. The association between changes in visual acuity and macular appearance was described by a Pearson correlation coefficient. The statistical significance of this relationship was evaluated using a z test for correlation coefficients.
RESULI-S THIRTYSIX
EYES OF THIRTY-FOUR
PATIENTS
WITH
MACU-
lar pseudohole met the criteria for our study. Twentyone (58%) of the affected eyes were the patient’s right eye, and 15 (42%) were the left eye. The range of follow-up in our 34 patients was 12 months to 157 months (mean, 53 months). Twentynine eyes (8 1%) were followed up for longer than 24 months, 19 eyes (53%) had a greater than 36-month follow-up, and 13 eyes (36%) had greater than 48 months of follow-up. The mean initial visual acuity was 20/32 (median, 20/30). Initial visual acuity ranged from 20/20 to 20/400. Only two eyes had initial visual acuity of worse than 20/50 (Table). Visual acuity at the most recent followup visit ranged from 20/20 to 20/200 (mean, 20/32; median, 20/30). Four eyes (11%) had visual acuity worse than 2Of50. Fourteen eyes (39%) had identical initial and final visual acuities, and 11 additional eyes (3 1%) had final visual acuities within 1 line on the Snellen visual acuity chart from their initial examination. Five additional patients’ eyes (14%) had initial and final visual acuity within 2 lines of each other. Four eyes (11%) improved by more than 2 lines on VOL.
125,
No.
3
NATURAL
HISTORY
the visual acuity chart in our study. Two eyes (6%) lost more than 2 lines of visual acuity. Thirty-one of the 36 eyes in our study had initial and most recent fundus photographs available that were of adequate quality to determine whether a change had occurred in the appearance of the macula. In five patients, the fundus photographs were not of sufficient quality to allow adequate evaluation. Eight (26%) of the 31 eyes available showed no discernible change in macular appearance. The degree of change in macular appearance in our patients was quite variable. Eyes with minor changes in macular appearance often had a slight shift in the epicenter of the membrane and a slight change in the direction of the associated retinal striae (Figure 1). The moderate changes in macular appearance were present less frequently and were depicted as having a change in axis of the macular pseudohole or a substantial change in retinal striae patterns (complete absence of striae in some areas where they had previously been present), or both (Figure 2). Major changes in macular appearance were noted in two cases in which the epiretinal membrane showed a marked decrease in macular distortion with almost total disappearance of the membrane and the macular pseudohole (Figure 3). Of the 31 eyes in whom fundus photographs could be compared, 14 (45%) showed a minor change in macular appearance, seven (23%) showed a moderate change, and two (6%) showed a major change in macular appearance. Overall, neither the occurrence nor the severity of changes in macular appearance were correlated with changes in visual acuity (P > .7). Four eyes improved by more than 2 lines of visual acuity during the follow-up period. One of these patients underwent cataract surgery between the initial evaluation and the final evaluation, and his visual acuity improved from 20/400 to 20/60. It was believed that his visual acuity improvement was related to cataract extraction and not to macular changes. Two patients improved from 20/50 to 20/2O and had minor changes in fundus appearance. One patient improved from 20/50 to 20/25 and was graded as having moderate change in macular appearance. Of the two patients who lost more than 2 lines of visual acuity during follow-up, one had a moderate change in macular appearance. The other patient’s
OF MACULAR
PSEUDOHOLES
361
Best-corrected
Eye Patient
2,62,
No., Age (yrs), Sex
F &ga: ," r , F
!$/ 6, 65, F
16, 74, F l~~~~~!~ ,
F
23, 67, M 241 *iw 25, 68, M
32, 63, M 34, 68, F
Initial Visual
Acuity
2 8 4 a 6 7 8 B 10 1-l 12 'I3 14
12,66,F
22,63,
NO.
15 16 I7 18 19 20 21 22 23 24 2s 26 27 28 2s 30 31 32 3% 34 35 36
Acuity Final Visual
Acuity
20120
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20130
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20130 2at25 20125 20/26 20/30 2q20 20150 20/100 20125 aq20 20/20 20140
ma 20140 mm 20130
AMERICAN
@BQ 20120
&flQ 20120 aif 20140 a@0
photographs were not of sufficient quality to allow interpretation. However, clinical examination suggested that the macular appearance had worsened. The eye with the macular pseudohole was symptomatic in 26 (72%) of the cases, and 10 eyes with macular pseudoholes (28%) were asymptomatic. Of the patients with 26 symptomatic eyes, 24 complained of a nonspecific blur at initial evaluation, and two complained of distortion. Thirty-two of the 36 eyes were phakic at the initial
362
Visual
JOURNAL
Follow-up
25 59 48 95 62 sa 36 2‘l 29 25 12 32 145 6Q 36 146 15 72 24 28 24 24 44 29 30 27 133 22 36 73 63 42 30 157 27
(mos)
Change in Fundus Appearance
:_,
None
Minor
None
MW Minor Ik%lkw None f+imie
Minor
Moderate
Moderate
evaluation, and the other four patients had posterior chamber intraocular lenses. At the final evaluation, 30 eyes were phakic and two additional eyes had undergone cataract extraction with intraocular lens implantation. Two patients included in our study had bilateral macular pseudoholes. Of the remaining 32 patients, nine had macular disease in the fellow eye. Five patients had a full-thickness macular hole at initial evaluation or at follow-up, two patients had epiretinal
OF OPHTHALMOLOGY
MARCH
1998
FIGURE 1. Patient 5. Left eye. Initial (left) and final (right) fundus photographs showing mild change in macular appearance. Visual acuity was 20/40 for both. Note the change in the shape of the macular pseudohole and more striae temporally at right (arrow).
membranes, one patient had a macular branch vein occlusion, and one patient had a macular pseudohole but was followed up for less than 1 year.
DISCUSSION MACULAR
PSEUDOHOLES
ARE
LESIONS
SIMULATING
A
macular hole, in which a round or oval defect in a fibrocellular membrane is present in the fovea1 region. The diagnostic accuracy in patients with epiretinal membranes and macular pseudoholes is 10w.~ Fish and associate? reported a 43% accuracy in correctly diagnosing macular pseudoholes. Most macular pseudoholes were misdiagnosed as macular holes, impending macular holes, or lamellar macular holes. Visual acuity is a key element in allowing the accurate differentiation between macular holes and macular pseudoholes. Mean visual acuity in patients with macular holes is 20/200, whereas the mean visual acuity in our series of macular pseudoholes was 20/32. Both full-thickness macular holes and macular pseudoholes often have an associated epiretinal membrane. However, clinical features that facilitate the differentiation of these lesions include the presence of a cuff of detachment around the margins of a
VOL.
125,
No. 3
NATURAL
HISTORY
full-thickness macular hole and fine yellow deposits at the base of a full-thickness macular hole. Macular pseudoholes do not have these features. In confirming the diagnostic accuracy in our series, we used the visual acuity and ophthalmoscopic features discussed above in differentiating macular pseudoholes from simulating lesions. Additionally, clinical tests such as Amsler grid testing, WatzkeAllen test, and the laser aiming beam test were used.5 On Amsler grid testing, 16 (55%) of 29 eyes were normal, and 13 eyes (45%) had distortion. Results of the Watzke-Allen test were normal in 18 (72%) of 25 eyes tested and abnormal in seven (28%). Of note, all 28 eyes tested with the laser aiming beam test were able to see the 50qm spot when the area of the pseudohole was illuminated. One variable that we believe confirmed our diagnostic accuracy in determining these to be macular pseudoholes was the ability to follow up these 36 eyes over an extended period. Fish and associate& have stated that macular pseudoholes are round to oval, with a mean horizontal diameter of 384 nm and a vertical diameter of 410 nm. The fluorescein angiographic characteristics of macular pseudoholes have been well described. Most cases have early fluorescence on intravenous fluores-
OF MACULAR
PSEUDOHOLES
363
FIGURE 2. Patient 14. Symptomatic right eye. Initial (left) and final (right) fundus photographs showing moderate change in macular appearance. Initial visual acuity was 20/50, and final visual acuity was 20/25. Note the release of part of the membrane just temporal to the fovea (arrow) and the change in the shape of the pseudohole and relaxation of striae superonasal to fovea (arrowhead).
cein angiography at the base of the macular pseudohole.4 Fluorescein angiography was not routinely performed because nearly one third of the eyes were asymptomatic, and two thirds had initial and final visual acuities of 20/40 or better. The natural history and long-term prognosis of macular pseudoholes has not been well defined. Allen and Gas8 described four patients with epiretinal membranes and macular pseudoholes, three of whom had a final visual acuity within 2 lines of their initial visual acuity. Of the five patients with 1 year or longer of follow-up described by Fish and associates,’ four had a final visual acuity within 2 lines of their initial visual acuity.j Thirty of the 36 eyes in our series had final visual acuities within 2 lines of their initial visual acuity. To determine the natural history of a disease process adequately, it is necessary to know the time of onset of rhe condition. One limitation in our study was determining the time of onset of the macular pseudohole. Because many patients were either asymptomatic at the time of diagnosis or had nonspecific symptoms of visual blur, we considered the time of diagnosis to be the time of onset of the condition. 364
AMERICAN
JOURNAL
Confounding variables occur in any study that examines the natural history of a disease process. Coexisting conditions such as cataracts may directly influence the initial and final visual acuities. One patient in our study had a visually significant cataract when initially evaluated for his epiretinal membrane and macular pseudohole. He is one of four patients whose visual acuity improved over time, but the appearance of his macula was not deemed changed, and his visual improvement was thought ro be secondary to cataract extraction. Another patient developed a cataract during 6 years of follow-up and underwent cataract extraction with lens implantation, subsequently improving to within 1 line of initial visual acuity. The remaining 30 phakic eyes were believed to have stable lenticular changes that did not significantly alter final visual acuity. Posterior vitreous detachment with spontaneous improvement in macular appearance in patients with epiretinal membranes is a well-recognized entity.7Jj Although we realize the importance of the posterior hyaloid in traction maculopathies, because of the retrospective nature of this study and the lack of precise criteria for diagnosing a posterior vitreous OF OPHTHALMOLOGY
MARCH
19%
FIGURE 3. Patient 8. Asymptomatic right eye. Initial (left) and final (right) fundus photographs showing major change in retinal appearance. Initial visual acuity was 20/25, and final visual acuity was 2O/20. Note the disappearance of the pseudohole and the epiretinal membrane.
detachment, we are unable to report accurately the percentage of patients with a posterior vitreous separation. However, we did not think that posterior vitreous detachment was the mechanism for changes in macular appearance. Rather, we believed that the changes we observed in our study were related to a tangential shift of the epiretinal membrane secondary to contraction and relaxation in various areas of the membrane. Two patients in our study had bilateral macular pseudoholes that were followed up for longer than 1 year. One of these patients had pseudoholes in both maculae at initial examination, whereas the other demonstrated bilateral pseudoholes on a subsequent follow-up visit. Nine (28%) of the remaining 32 patients had macular disease in the fellow eye. In one patient, a macular branch vein occlusion developed in the fellow eye, and another patient had a macular pseudohole that received less than 1 year of follow-up. Two patients had macular epiretinal membranes with macular distortion. In our study, five fellow eyes ( 14%) had a fullthickness macular hole at the initial evaluation or during follow-up. The prevalence of full-thickness macular holes has been estimated at 3.3 per 1,000 VOL. I 25, No. 3
people aged 55 years or older.’ The mechanism of macular hole formation in most cases of macular hole is thought to be secondary to tangential traction of the posterior cortical vitreous on the fovea1 retina.‘@“’ Our observations that epiretinal membranes with macular pseudoholes changed the fundus appearance suggest that tangential traction forces are at work in macular pseudoholes as well. The higher than expected percentage of fellow eyes with macular holes leads one to consider whether, in certain circumstances, macular pseudoholes may be an early aborted attempt at macular hole formation. We speculate that the vitreous cortex adhesion to the retina is less “firm” in the area of the epiretinal membrane adjacent to the pseudohole. Therefore, the degree of tangential traction on the retina is diminished, and true hole formation becomes less likely. Epiretinal membranes may occur in patients with no posterior vitreous detachment, partial posterior vitreous detachment, or complete posterior vitreous detachment.l’ Epitetinal membranes occut because of a proliferation of multiple cell types on the retinal surface.13,1j Despite these well-documented and histopathologically proven observations, the mechanism of pseudohole formation remains poorly understood. It is speculative whether a true defect in the epiretinal
NATURAL HISTORY OF MACULAR PSEUDOHOLES
345
membrane is present or whether the membrane is relatively thin and hypoplastic in this region and therefore less visible. If a true defect is present, whether it occurred at the time of membrane formation or resulted from a dehiscence in the membrane because of tractional forces present is uncertain. We believe that a true defect in the epiretinal membrane is present. A speculative mechanism for pseudohole formation is that many epiretinal membranes with macular pseudoholes develop before posterior vitreous separation occurs. Because of the firm vitreoretinal adhesion at the foveola, proliferating cells have less “access” to this area, creating the defect (pseudohole) in the epiretinal membrane (J.D.M. Gass, MD, oral communication, October 1996.) In the two patients in this series in whom pseudoholes developed after the initial evaluation demonstrated a normal macular region, it appeared as though the pseudohole occurred simultaneously with membrane formation and not because of dehiscence in the membrane. In conclusion, visual acuity in eyes with macular pseudoholes followed up for 1 year or longer tended to remain stable, with 30 eyes (83%) having similar initial and final visual acuities. However, macular appearance did change in 23 (74%) of the eyes in this study.
REFERENCES 1. Smiddy WE, Gass JDM. Masquerades of macular holes. Ophthalmic Surg 1995;26:16-24.
2. Gass JDM, Joondeph BC. Observations concerning patients with suspected impending macular holes. Am J Ophthalmol 1990;109:638-646. 3. Fish RH, Anand R, Izbrand DJ. Macular pseudoholes: clinical features and accuracy of diagnosis. Ophthalmology 1992;99:1665-1670. 4. Klein BR, Hiner CJ, Glaser BM, et al. Fundus photographic and Auorescein angiographic characteristics of pseudoholes of the macula in eyes with epiretinal membranes. Ophthalmology 1995;102:768-774. 5. Martinez J, Smiddy WC, Kim J, Gass JDM. Differentiating macular holes from macular pseudoholes. Am J OphthaImol 1994;117:762-767. 6. Allen AW, Gass JDM. Contraction of a perifoveal epiretinal membrane simulating a macular hole. Am J Ophthalmol 1976;82:684-691. 7. Greven CM, Slusher MM, Weaver RG. Epimtinal membrane release and posterior vitreous detachment. Ophthalmology 1988;95:902-905. 8. Gass JDM. Stereoscopic atlas of macular diseases: diagnosis and treatment, 3rd ed. Volume 2. St Louis: CV Mosby, 1987~694-704. 9. Kim JW, Freeman WR, El-Ha& W, et al. Baseline characteristics, natural history, and risk factors to progression in eyes with stage 2 macular holes. Ophthalmology 1995;102:18181829. 10. Gass JDM. Idiopathic senile macular hole: in early stages and pathogenesis. Arch Ophthalmol 1988;106:629-639. 11. Gass JDM. Reappraisal of biomicroscopic classification of stages of development of a macular hole. Am J Ophthalmol 1995;119:752-759. 12. Hirokawa H, Jalkh AE, Takahashi M, et al. Role of the vitreous in idiopathic preretinal macular fibrosis. Am J Ophthalmol 1986;101:166-169. 13. Roth AM, Foos RY. Surface wrinkling retinopathy in eyes enucleated at autopsy. Tmns Am Acad Ophthalmol 1971;75: 1047-1058. 14. Clarkson JG, Green WR, Massof D. A histopathologic review of 168 cases of preretinal membrane. Am J Ophthalmol 1977;84:1-17. 15. Kampik AM, Kenyon KP, Michels RG, Green WR, et al. Epiretinal and vitreous membranes: comparative study of 56 cases. Arch Ophthalmol 1981;99:1445-1454.
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366
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH 1998
M
ACULAR
HOLES
ARE
FULL-THICKNESS
DE-
fects or dehiscences in the neurosensory retina involving the fovea1 region. Several conditions may simulate macular holes.‘,*
Accepted for publication July 1, 1997. From the Wake Forest University Eye Center, Bowman Gray School of Medicine, Winston-Salem, North Carolina. Reprint requests to Craig M. Greven, MD, Wake Forest University Eye Center, Medical Center Blvd, Winston-Salem, NC 27157-1033; fax: (910) 716-7994; e-mail: cgrevenObgsm.edu
360
0
1~8
BY ELSEWER SCIENCE
Pseudoholes
SLUSHER, MD,
Although clinical features, diagnostic accuracy, fundus appearance, and fluorescein angiographic characteristics have been described,3y4 little information is available on the natural history of macular pseudohole. We report a retrospective analysis of visual acuity and fundus appearance in patients with macular pseudoholes who were followed up for more than 1 year.
PATIENTS AND METHODS WE
RETROSPECTIVELY
REVIEWED
THE
CHARTS
OF ALL
patients coded as having epiretinal membranes, epiretinal membranes with macular pseudoholes, and macular holes seen at the Wake Forest University Eye Center from 1988 through 1993. For the purpose of this study, macular pseudohole was defined as a round to oval defect in a fibrocellular epiretinal membrane overlying the fovea1 region. Other lesions that may simulate macular holes were not included in this study. Forty-nine eyes of 47 patients wet-e identified as having epiretinal membranes with macular pseudoholes. None of these 49 eyes was documented as having vitreoretinal surgery performed for epiretinal membrane with macular pseudohole. Thirty-six eyes of thirty-four patients had 12 months or longer follow-up and were included in this study. At the time of diagnosis, patients ranged in age from 25 to 84 years (mean + SD, 65 + 6 years; median, 66 years). Of the 34 patients, 23 (68%) were women and 11 (32%) were men. In each patient a complete history and ophthalmic evaluation was performed. Best-corrected visual acuity was measured at 20 feet using a standard Snellen visual acuity chart with best-refracted correction. Each eye had initial and follow-up color fundus photographs available for evaluation. Photographs INC. ALL
RIGHTS
RESERVED.
0002-9394/98/$19.00
were evaluated by two of us (C.M.G., M.M.S.) and classified as having no change or a definitive change. If a definitive change was present, the changes were subclassified as minor change, moderate change, or major change in fundus appearance. A minor change was defined as a slight change in retinal striae or a slight change in axis of the macular pseudohole. A moderate change required more substantial alteration in retinal striae or size and shape of the macular pseudohole, or both. A major change was defined as an extensive alteration in the epiretinal membrane, pseudohole, and macular angioarchitecture. The association between changes in visual acuity and macular appearance was described by a Pearson correlation coefficient. The statistical significance of this relationship was evaluated using a z test for correlation coefficients.
RESULI-S THIRTYSIX
EYES OF THIRTY-FOUR
PATIENTS
WITH
MACU-
lar pseudohole met the criteria for our study. Twentyone (58%) of the affected eyes were the patient’s right eye, and 15 (42%) were the left eye. The range of follow-up in our 34 patients was 12 months to 157 months (mean, 53 months). Twentynine eyes (8 1%) were followed up for longer than 24 months, 19 eyes (53%) had a greater than 36-month follow-up, and 13 eyes (36%) had greater than 48 months of follow-up. The mean initial visual acuity was 20/32 (median, 20/30). Initial visual acuity ranged from 20/20 to 20/400. Only two eyes had initial visual acuity of worse than 20/50 (Table). Visual acuity at the most recent followup visit ranged from 20/20 to 20/200 (mean, 20/32; median, 20/30). Four eyes (11%) had visual acuity worse than 2Of50. Fourteen eyes (39%) had identical initial and final visual acuities, and 11 additional eyes (3 1%) had final visual acuities within 1 line on the Snellen visual acuity chart from their initial examination. Five additional patients’ eyes (14%) had initial and final visual acuity within 2 lines of each other. Four eyes (11%) improved by more than 2 lines on VOL.
125,
No.
3
NATURAL
HISTORY
the visual acuity chart in our study. Two eyes (6%) lost more than 2 lines of visual acuity. Thirty-one of the 36 eyes in our study had initial and most recent fundus photographs available that were of adequate quality to determine whether a change had occurred in the appearance of the macula. In five patients, the fundus photographs were not of sufficient quality to allow adequate evaluation. Eight (26%) of the 31 eyes available showed no discernible change in macular appearance. The degree of change in macular appearance in our patients was quite variable. Eyes with minor changes in macular appearance often had a slight shift in the epicenter of the membrane and a slight change in the direction of the associated retinal striae (Figure 1). The moderate changes in macular appearance were present less frequently and were depicted as having a change in axis of the macular pseudohole or a substantial change in retinal striae patterns (complete absence of striae in some areas where they had previously been present), or both (Figure 2). Major changes in macular appearance were noted in two cases in which the epiretinal membrane showed a marked decrease in macular distortion with almost total disappearance of the membrane and the macular pseudohole (Figure 3). Of the 31 eyes in whom fundus photographs could be compared, 14 (45%) showed a minor change in macular appearance, seven (23%) showed a moderate change, and two (6%) showed a major change in macular appearance. Overall, neither the occurrence nor the severity of changes in macular appearance were correlated with changes in visual acuity (P > .7). Four eyes improved by more than 2 lines of visual acuity during the follow-up period. One of these patients underwent cataract surgery between the initial evaluation and the final evaluation, and his visual acuity improved from 20/400 to 20/60. It was believed that his visual acuity improvement was related to cataract extraction and not to macular changes. Two patients improved from 20/50 to 20/2O and had minor changes in fundus appearance. One patient improved from 20/50 to 20/25 and was graded as having moderate change in macular appearance. Of the two patients who lost more than 2 lines of visual acuity during follow-up, one had a moderate change in macular appearance. The other patient’s
OF MACULAR
PSEUDOHOLES
361
Best-corrected
Eye Patient
2,62,
No., Age (yrs), Sex
F &ga: ," r , F
!$/ 6, 65, F
16, 74, F l~~~~~!~ ,
F
23, 67, M 241 *iw 25, 68, M
32, 63, M 34, 68, F
Initial Visual
Acuity
2 8 4 a 6 7 8 B 10 1-l 12 'I3 14
12,66,F
22,63,
NO.
15 16 I7 18 19 20 21 22 23 24 2s 26 27 28 2s 30 31 32 3% 34 35 36
Acuity Final Visual
Acuity
20120
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20130
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AMERICAN
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photographs were not of sufficient quality to allow interpretation. However, clinical examination suggested that the macular appearance had worsened. The eye with the macular pseudohole was symptomatic in 26 (72%) of the cases, and 10 eyes with macular pseudoholes (28%) were asymptomatic. Of the patients with 26 symptomatic eyes, 24 complained of a nonspecific blur at initial evaluation, and two complained of distortion. Thirty-two of the 36 eyes were phakic at the initial
362
Visual
JOURNAL
Follow-up
25 59 48 95 62 sa 36 2‘l 29 25 12 32 145 6Q 36 146 15 72 24 28 24 24 44 29 30 27 133 22 36 73 63 42 30 157 27
(mos)
Change in Fundus Appearance
:_,
None
Minor
None
MW Minor Ik%lkw None f+imie
Minor
Moderate
Moderate
evaluation, and the other four patients had posterior chamber intraocular lenses. At the final evaluation, 30 eyes were phakic and two additional eyes had undergone cataract extraction with intraocular lens implantation. Two patients included in our study had bilateral macular pseudoholes. Of the remaining 32 patients, nine had macular disease in the fellow eye. Five patients had a full-thickness macular hole at initial evaluation or at follow-up, two patients had epiretinal
OF OPHTHALMOLOGY
MARCH
1998
FIGURE 1. Patient 5. Left eye. Initial (left) and final (right) fundus photographs showing mild change in macular appearance. Visual acuity was 20/40 for both. Note the change in the shape of the macular pseudohole and more striae temporally at right (arrow).
membranes, one patient had a macular branch vein occlusion, and one patient had a macular pseudohole but was followed up for less than 1 year.
DISCUSSION MACULAR
PSEUDOHOLES
ARE
LESIONS
SIMULATING
A
macular hole, in which a round or oval defect in a fibrocellular membrane is present in the fovea1 region. The diagnostic accuracy in patients with epiretinal membranes and macular pseudoholes is 10w.~ Fish and associate? reported a 43% accuracy in correctly diagnosing macular pseudoholes. Most macular pseudoholes were misdiagnosed as macular holes, impending macular holes, or lamellar macular holes. Visual acuity is a key element in allowing the accurate differentiation between macular holes and macular pseudoholes. Mean visual acuity in patients with macular holes is 20/200, whereas the mean visual acuity in our series of macular pseudoholes was 20/32. Both full-thickness macular holes and macular pseudoholes often have an associated epiretinal membrane. However, clinical features that facilitate the differentiation of these lesions include the presence of a cuff of detachment around the margins of a
VOL.
125,
No. 3
NATURAL
HISTORY
full-thickness macular hole and fine yellow deposits at the base of a full-thickness macular hole. Macular pseudoholes do not have these features. In confirming the diagnostic accuracy in our series, we used the visual acuity and ophthalmoscopic features discussed above in differentiating macular pseudoholes from simulating lesions. Additionally, clinical tests such as Amsler grid testing, WatzkeAllen test, and the laser aiming beam test were used.5 On Amsler grid testing, 16 (55%) of 29 eyes were normal, and 13 eyes (45%) had distortion. Results of the Watzke-Allen test were normal in 18 (72%) of 25 eyes tested and abnormal in seven (28%). Of note, all 28 eyes tested with the laser aiming beam test were able to see the 50qm spot when the area of the pseudohole was illuminated. One variable that we believe confirmed our diagnostic accuracy in determining these to be macular pseudoholes was the ability to follow up these 36 eyes over an extended period. Fish and associate& have stated that macular pseudoholes are round to oval, with a mean horizontal diameter of 384 nm and a vertical diameter of 410 nm. The fluorescein angiographic characteristics of macular pseudoholes have been well described. Most cases have early fluorescence on intravenous fluores-
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FIGURE 2. Patient 14. Symptomatic right eye. Initial (left) and final (right) fundus photographs showing moderate change in macular appearance. Initial visual acuity was 20/50, and final visual acuity was 20/25. Note the release of part of the membrane just temporal to the fovea (arrow) and the change in the shape of the pseudohole and relaxation of striae superonasal to fovea (arrowhead).
cein angiography at the base of the macular pseudohole.4 Fluorescein angiography was not routinely performed because nearly one third of the eyes were asymptomatic, and two thirds had initial and final visual acuities of 20/40 or better. The natural history and long-term prognosis of macular pseudoholes has not been well defined. Allen and Gas8 described four patients with epiretinal membranes and macular pseudoholes, three of whom had a final visual acuity within 2 lines of their initial visual acuity. Of the five patients with 1 year or longer of follow-up described by Fish and associates,’ four had a final visual acuity within 2 lines of their initial visual acuity.j Thirty of the 36 eyes in our series had final visual acuities within 2 lines of their initial visual acuity. To determine the natural history of a disease process adequately, it is necessary to know the time of onset of rhe condition. One limitation in our study was determining the time of onset of the macular pseudohole. Because many patients were either asymptomatic at the time of diagnosis or had nonspecific symptoms of visual blur, we considered the time of diagnosis to be the time of onset of the condition. 364
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Confounding variables occur in any study that examines the natural history of a disease process. Coexisting conditions such as cataracts may directly influence the initial and final visual acuities. One patient in our study had a visually significant cataract when initially evaluated for his epiretinal membrane and macular pseudohole. He is one of four patients whose visual acuity improved over time, but the appearance of his macula was not deemed changed, and his visual improvement was thought ro be secondary to cataract extraction. Another patient developed a cataract during 6 years of follow-up and underwent cataract extraction with lens implantation, subsequently improving to within 1 line of initial visual acuity. The remaining 30 phakic eyes were believed to have stable lenticular changes that did not significantly alter final visual acuity. Posterior vitreous detachment with spontaneous improvement in macular appearance in patients with epiretinal membranes is a well-recognized entity.7Jj Although we realize the importance of the posterior hyaloid in traction maculopathies, because of the retrospective nature of this study and the lack of precise criteria for diagnosing a posterior vitreous OF OPHTHALMOLOGY
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FIGURE 3. Patient 8. Asymptomatic right eye. Initial (left) and final (right) fundus photographs showing major change in retinal appearance. Initial visual acuity was 20/25, and final visual acuity was 2O/20. Note the disappearance of the pseudohole and the epiretinal membrane.
detachment, we are unable to report accurately the percentage of patients with a posterior vitreous separation. However, we did not think that posterior vitreous detachment was the mechanism for changes in macular appearance. Rather, we believed that the changes we observed in our study were related to a tangential shift of the epiretinal membrane secondary to contraction and relaxation in various areas of the membrane. Two patients in our study had bilateral macular pseudoholes that were followed up for longer than 1 year. One of these patients had pseudoholes in both maculae at initial examination, whereas the other demonstrated bilateral pseudoholes on a subsequent follow-up visit. Nine (28%) of the remaining 32 patients had macular disease in the fellow eye. In one patient, a macular branch vein occlusion developed in the fellow eye, and another patient had a macular pseudohole that received less than 1 year of follow-up. Two patients had macular epiretinal membranes with macular distortion. In our study, five fellow eyes ( 14%) had a fullthickness macular hole at the initial evaluation or during follow-up. The prevalence of full-thickness macular holes has been estimated at 3.3 per 1,000 VOL. I 25, No. 3
people aged 55 years or older.’ The mechanism of macular hole formation in most cases of macular hole is thought to be secondary to tangential traction of the posterior cortical vitreous on the fovea1 retina.‘@“’ Our observations that epiretinal membranes with macular pseudoholes changed the fundus appearance suggest that tangential traction forces are at work in macular pseudoholes as well. The higher than expected percentage of fellow eyes with macular holes leads one to consider whether, in certain circumstances, macular pseudoholes may be an early aborted attempt at macular hole formation. We speculate that the vitreous cortex adhesion to the retina is less “firm” in the area of the epiretinal membrane adjacent to the pseudohole. Therefore, the degree of tangential traction on the retina is diminished, and true hole formation becomes less likely. Epiretinal membranes may occur in patients with no posterior vitreous detachment, partial posterior vitreous detachment, or complete posterior vitreous detachment.l’ Epitetinal membranes occut because of a proliferation of multiple cell types on the retinal surface.13,1j Despite these well-documented and histopathologically proven observations, the mechanism of pseudohole formation remains poorly understood. It is speculative whether a true defect in the epiretinal
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membrane is present or whether the membrane is relatively thin and hypoplastic in this region and therefore less visible. If a true defect is present, whether it occurred at the time of membrane formation or resulted from a dehiscence in the membrane because of tractional forces present is uncertain. We believe that a true defect in the epiretinal membrane is present. A speculative mechanism for pseudohole formation is that many epiretinal membranes with macular pseudoholes develop before posterior vitreous separation occurs. Because of the firm vitreoretinal adhesion at the foveola, proliferating cells have less “access” to this area, creating the defect (pseudohole) in the epiretinal membrane (J.D.M. Gass, MD, oral communication, October 1996.) In the two patients in this series in whom pseudoholes developed after the initial evaluation demonstrated a normal macular region, it appeared as though the pseudohole occurred simultaneously with membrane formation and not because of dehiscence in the membrane. In conclusion, visual acuity in eyes with macular pseudoholes followed up for 1 year or longer tended to remain stable, with 30 eyes (83%) having similar initial and final visual acuities. However, macular appearance did change in 23 (74%) of the eyes in this study.
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2. Gass JDM, Joondeph BC. Observations concerning patients with suspected impending macular holes. Am J Ophthalmol 1990;109:638-646. 3. Fish RH, Anand R, Izbrand DJ. Macular pseudoholes: clinical features and accuracy of diagnosis. Ophthalmology 1992;99:1665-1670. 4. Klein BR, Hiner CJ, Glaser BM, et al. Fundus photographic and Auorescein angiographic characteristics of pseudoholes of the macula in eyes with epiretinal membranes. Ophthalmology 1995;102:768-774. 5. Martinez J, Smiddy WC, Kim J, Gass JDM. Differentiating macular holes from macular pseudoholes. Am J OphthaImol 1994;117:762-767. 6. Allen AW, Gass JDM. Contraction of a perifoveal epiretinal membrane simulating a macular hole. Am J Ophthalmol 1976;82:684-691. 7. Greven CM, Slusher MM, Weaver RG. Epimtinal membrane release and posterior vitreous detachment. Ophthalmology 1988;95:902-905. 8. Gass JDM. Stereoscopic atlas of macular diseases: diagnosis and treatment, 3rd ed. Volume 2. St Louis: CV Mosby, 1987~694-704. 9. Kim JW, Freeman WR, El-Ha& W, et al. Baseline characteristics, natural history, and risk factors to progression in eyes with stage 2 macular holes. Ophthalmology 1995;102:18181829. 10. Gass JDM. Idiopathic senile macular hole: in early stages and pathogenesis. Arch Ophthalmol 1988;106:629-639. 11. Gass JDM. Reappraisal of biomicroscopic classification of stages of development of a macular hole. Am J Ophthalmol 1995;119:752-759. 12. Hirokawa H, Jalkh AE, Takahashi M, et al. Role of the vitreous in idiopathic preretinal macular fibrosis. Am J Ophthalmol 1986;101:166-169. 13. Roth AM, Foos RY. Surface wrinkling retinopathy in eyes enucleated at autopsy. Tmns Am Acad Ophthalmol 1971;75: 1047-1058. 14. Clarkson JG, Green WR, Massof D. A histopathologic review of 168 cases of preretinal membrane. Am J Ophthalmol 1977;84:1-17. 15. Kampik AM, Kenyon KP, Michels RG, Green WR, et al. Epiretinal and vitreous membranes: comparative study of 56 cases. Arch Ophthalmol 1981;99:1445-1454.
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