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Clinicopathologic Correlation of a Macular Hole Treated by Cortical Vitreous Peeling and Gas Tamponade
Clinicopathologic Correlation of a Macular Hole Treated by Cortical Vitreous Peeling and Gas Tamponade Steven A. Madreperla, MD, PhD, I Greer L. Geiger, MD, 2 Midori Funata, MD, I Zenaida de la Cruz, BS, I W. Richard Green, MDI Purpose: To study the histopathology of a stage '" macular hole that had been treated by vitrectomy with cortical vitreous and epicortical vitreous membrane peeling and gas tamponade. Methods: The light and electron microscopic features of a treated macular hole were studied. Results: A 16-JLm-wide break was present in the external limiting membrane. This was sealed by MO"er cell processes. Photoreceptors adjacent to the healed defect appeared normal. No cystoid macular edema was present. Conclusion: Cortical vitreous peeling and gas tamponade can allow the macular hole to settle and the edges to re-approximate. The residual defect can be sealed by MO"er cells. Ophthalmology 1994;101:682-686
Idiopathic macular hole formation was recognized as a clinical entity as early as 1900. I However, the mechanism by which this occurs has remained controversia1. 2- 1O Numerous lines of evidence support a primary role for the vitreous in macular hole formation . A typical fully developed macular hole is approximately 0.33 disc diameter and is surrounded by a cuff of detached retina and an adjacent area with cystoid macular edema (CME).IO-I 2 Spontaneous closure of macular holes has been reported and can result in improved vision, presumably due to improved photoreceptor function in the area of previous detachment and CME. 13 •I4 These observations lead to the application ofvitreoretinal surgical techniques Originally received: August 19, 1993. Revision accepted: November 8, 1993. I Eye Pathology Laboratory, Wilmer Ophthalmological Institute and Department of Pathology, Johns Hopkins Medical Institutions, Baltimore. 2 Brookwood Eye Institute, Brookwood Medical Center, Birmingham. Supported in part by The Macula Foundation, Inc, New York, New York, and core grant EYO 176517 from the National Eye Institute, Bethesda, Maryland. Reprint requests to W. Richard Green, MD, Eye Pathology Laboratory, Johns Hopkins Hospital, 600 N. Wolfe St, Baltimore, MD 21287-9248.
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to achieve closure of macular holes. Two uncontrolled studies have demonstrated the efficacy of vitreous surgery in causing closure of macular holes and improving vision. I5 - I7 Although the precise indications for performing such operations await further study,I8 it seems clear that the procedure is efficacious in some patients. The procedure for macular hole repair involves removal of residual premacular cortical vitreous and intraocular gas tamponade. Theories regarding the mechanisms by which macular hole closure occurs include release of vitreous traction and formation of a glial scar. In the only published clinicopathologic study to date, one of a pair of bilateral, treated, macular holes was sealed by fibrous astrocytes, whereas the other showed no gliosis. 19 We report a clinicopathologic study of a successfully treated macular hole which was sealed by Muller cells.
Case Report A 72-year-old white woman presented in December 1992 with decreased vision in her left eye of 4 months' duration. Ocular history included extracapsular cataract extraction and posterior chamber intraocular lens (PC IOL) in 1983. Results of examination showed visual acuity of 20/40-1 in the right eye and
Madreperla et al . Histopathology of a Treated Macular Hole 20/80-2 in the left. Results of slit-lamp examination showed 2+ nuclear sclerosis in the right eye, a well-centered PC IOL in the left eye, and a 3-mm posterior capsulotomy. A partial posterior vitreous detachment was present without vitreofoveal separation, and a positive Watzke sign was observed in the left eye. A stage III macular hole and an epicortical vitreous membrane was present in the left eye (Fig 1). Fluorescein angiography showed a window defect corresponding to the macular hole. A pars plana vitrectomy with removal ofthe cortical vitreous was performed on January 2, 1992. Sulfurhexafluoride (20%) was used for gas tamponade. The patient maintained a facedown position for 2 weeks. On follow-up examination on January 10, 1993, the hole was closed (Fig 2). By June 24, 1992, visual acuity had improved to 20/40-1. The patient died 7 months after surgery, and the left eye was obtained for histopathologic study.
Histopathologic Examination The eye was fixed in buffered formalin for 72 hours. Results of gross examination showed a healed limbal scar from the 10:30 to 1:30 positions. A C-Ioop PC IOL was present with haptics in the ciliary sulcus. Defects in the anterior and posterior capsules were present centrally. Small defects in the pigment of the pars plana were present
Figure 1. Macular hole, preoperatively. A, left eye with macular hole (approximately 0.33 disc diameter). There are numerous drusen. B, flu· orescein angiographic image shows an area of faint hyperfluorescence at the site of the macular hole. C, higher magnification image of macular hole and surrounding cuff of subretinal fluid. Retinal striae are present from a presumed epicortical vitreous membrane.
Figure 2. Appearance of macular hole 4 weeks after surgery. A small dark area is still present centrally. No retinal striae are seen.
at 2, 5, and 9 o'clock, corresponding to sclerotomy sites. A portion of the eye wall, including the macula and optic nerve head, was embedded in plastic and stepped sectioned at 0.1 mm from temporal to nasal for light microscopy until the area of stripped internal limiting membrane was reached. Additional stepped sections were prepared and examined until the margin of the foveal pit and finally at 0.05 mm until the center of the foveola and defect in the external limiting membrane was evident. Ultrathin sections at two levels within the area of defect were prepared for electron microscopy. A total of 33 levels were used. Results of microscopic examination showed imprints of the haptics eroded into the ciliary body at the ciliary sulcus and a small amount of residual lens cortex. Defects were present in the anterior and posterior capsules centrally. Scars of perforation in the pars plana without fibrous tissue ingrowth were present in available sections corresponding to the 2- and 5-0'clock sclerotomy sites. Light and electron microscopic evaluation of the macula showed a 16-~m defect in the external limiting membrane corresponding to the healed macular hole (Fig 3). At this level, the defect was filled by cell processes and nuclei. A single pigmented macrophage (Fig 3C) was present in the outer aspect of the defect, but there were no other signs of inflammation. Electron microscopic analysis of the cells within the defect showed numerous cytoplasmic processes with prominent smooth endoplasmic reticulum, a few 10-nm filaments and numerous junctional complexes (Fig 4). These features are characteristic of Miiller cells. 20 The internal limiting membrane was absent over a 4-mm area centered on the temporal parafoveal area (Fig 5). The retinal pigment epithelium (RPE) in the macular area appeared normal and was associated with a 12-~m-thick layer of basal laminar deposit (Fig 6). A 5-~m-thick zone of granular and vesicular material (basal linear deposit) was located external to the RPE basement membrane (Fig 6). Occasional accumulation of basal linear material had a mound-shaped configuration that measured up to 16 ~m in thickness (soft drusen).
683
Ophthalmology
Volume 101, Number 4, April 1994 prevalence of complete posterior vitreous detachment in eyes with macular holes as compared with fellow eyes without macular holes. 4 ,6 Also, eyes with early stages of macular hole formation are less likely to have such a detachment than eyes in later stages of hole formation. 9 The early stages of macular hole formation can be reversed by spontaneous vitreofoveal separationY Similarly, preliminary studies suggest that the incidence of macular hole can be lessened for eyes in the early stages of hole formation by vitrectomy.22.23 These data lead to the hypothesis that closure of a macular hole could be facilitated by release of vitreous traction on the retina. Thus, surgical repair of macular holes has involved peeling of residual cortical vitreous and/or epicortical vitreous membranes to relieve traction. Gas tamponade is used to temporarily seal the hole and flatten the retina. The use of a growth factor (e.g., transforming growth factor-beta) has been advocated to induce a cellular seal and has been shown to be advantageous in an uncontrolled pilot study. 16 Our histopathologic study showed that Muller cells can form a seal leading to successful closure of a macular hole.
Figure 3. Healed macular hole. A, entire thickness of retina at the level of defect in external limiting membrane (between arrows). B, higher power view of 16-l'm-thick defect in external limiting membrane (between arrows), filled by cells (asterisks). C, another level with glial cells (asterisk) and a macrophage (arrowhead) in the area of the defect (paraphylenediamine: A, original magnification, x218; Band C, original magnification, XS44).
Discussion Several lines of evidence implicate vitreoretinal traction in the cause of idiopathic macular holes. Trempe et al 7 found that macular holes developed in 8 of28 fellow eyes without a posterior vitreous detachment, whereas no macular holes developed in 21 eyes with such a detachment. These findings suggest that once a posterior vitreous detachment is present, macular hole formation does not occur. Several studies have found a significantly greater
684
Figure 4. Ultrastructural appearance of healed macular hole. A, defect in external limiting membrane measures 16 I'm (between arrowheads). The defect is filled by cell processes (between arrows) (original magnification, X3000). B, higher magnification of cell processes shows abundant smooth endoplasmic reticulum (asterisk) and numerous junctional complexes (arrows) (original magnification, X30,OOO).
Madreperla et al . Histopathology of a Treated Macular Hole by RPE or glial cell proliferation. 12 In all three cases, a relatively large gap remained between the edges of the hole. As mentioned above, the surgical technique may promote re-approximation of the edges of the hole in ways that do not occur in these spontaneously sealed holes. We do not know how representative the two previously reported eyes l9 and the eye in this study are of all treated macular holes. Several features are common to all three of the studied eyes. These include (1) a relatively small break in the external limiting membrane with re-approximation of the edges of the hole with some cellular proliferation filling the small gap; (2) an abrupt transition to a normal-appearing photoreceptor layer outside of the defect; (3) the internal limiting membrane was removed along with the cortical vitreous in a relatively large area surrounding the hole; (4) the underlying RPE appears normal; (5) no inflammatory response is present in the treated macular holes; and (6) there was no cystoid edema, whereas this was seen in 68% of untreated macular holes. 12 Based on the eye reported here and the two previously reported eyes, we postulate that relief of tangential traction by cortical vitreous peeling allows settling of the retina with re-approximation of the edges of the hole. Gas tamponade may further enhance re-approximation and provide a temporary seal. The residual small defect may be sealed permanently by resident fibrous astrocytes or
Figure 5. Inner retina adjacent to macular hole. A, the internal limiting membrane is absent. B, area shows the margin of the internal limiting membrane (arrow) (paraphylenediamine, phase contrast; original magnification, X544).
Interestingly, there appeared to be a typical O.S-mm diameter hole before surgery but only a 0.016-mm break in the external limiting membrane was seen histologically. It could be argued that this actually was a stage II hole with only a small retinal dehiscence. Arguments against this are (1) there was a positive Watzke sign, or a break, in the slit-lamp beam preoperatively; (2) the fluorescein angiogram showed a window defect corresponding to the 0.33-DD appearing hole; and (3) the full-sized hole was confirmed intraoperatively. Also, in a clinicopathologic study of two other treated, stage III macular holes, similarsized, small defects in the external limiting membrane were noted. 19 It may be that relief of tangential traction allows re-approximation of the edges of the hole. In addition, flattening of the edematous edges of the hole (as they appear in histopathologic studies) 11 may further accentuate re-approximation. As noted in another report, the· histologic appearance of the treated macular holes is different than that of the spontaneously healed holes that have been studied. 19 In one report, three such holes were spontaneously sealed
Figure 6. Retinal pigment epithelium (RPE) with accumulation of lipofuscin and melanolipofuscin. A 12-JLm-thick layer of basal laminar deposit (between arrows) (main figure and inset) is present between the RPE and its basement membrane (arrowhead). A 5-JLm-thick layer of basal linear material (asterisks) is present external to the RPE basement membrane (original magnification, x4200; inset: phase contrast, paraphylenediamine; original magnification, X544).
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Volume 101, Number 4, April 1994
Muller cell proliferation. Resultant attachment of retina and resolution of CME in the region adjacent to the defect probably provides the improvement in vision that is noted clinically. It is likely that some central photoreceptor cell degeneration occurs at the time of hole formation because vision does not return to a normal level.
References 1. Kuhnt H. Ueber eine eigenthiimliche Veriinderung der Netzhaut ad maculam (retinitis atrophicans sive rareficans centralis). Z Augenh 1900;3:105-13. 2. Komzweig AL, Feldstein M. Studies of the eye in old age. II. Hole in the macula: a clinico-pathologic study. Am J Ophthalmol 1950;33:243-7. 3. Aaberg TM, Blair CJ, Gass JDM. Macular holes. Am J Ophthalmol 1970;69:555-62. 4. McDonnell PJ, Fine SL, Hillis AI. Clinical features of idiopathic macular cysts and holes. Am J OphthalmoI1982;93: 777-86. 5. Avila MP, Jalkh AE, Murakami K, et al. Biomicroscopic study of the vitreous in macular breaks. Ophthalmology 1983;90: 1277-83. 6. Morgan CM, Schatz H. Idiopathic macular holes. Am J Ophthalmol 1985;99:437-44. 7. Trempe CL, Weiter JJ, Furukawa H. Fellow eyes in cases of macular hole. Biomicroscopic study of the vitreous. Arch Ophthalmol 1986; 104:93-5. 8. Gass JDM. Idiopathic senile macular hole. Its early stages and pathogenesis. Arch Ophthalmol 1988;106:629-39. 9. Johnson RN, Gass JDM. Idiopathic macular holes. Observations, stages of formation, and implications for surgical intervention. Ophthalmology 1988;95:917-24. 10. Guyer DR, Green WR. Idiopathic macular holes and precursor lesions. In: Franklin RM, ed. Retina and Vitreous: Proceedings ofthe Symposium on Retina and Vitreous. New Orleans Academy of Ophthalmology, 1992. Amsterdam: Kugler 1993;399-428.
686
II. Frangieh GT, Green WR, Engel HM. A histopathologic study of macular cysts and holes. Retina 1981;1:311-36. 12. Guyer DR, Green WR, de Bustros S, Fine SL. Histopathologic features of idiopathic macular holes and cysts. Ophthalmology 1990;97: 1045-51. 13. Lewis H, Cowan GM, Straatsma BR. Apparent disappearance of a macular hole associated with development of an epiretinal membrane. Am J Ophthalmol 1986; 102: 172-5. 14. Bidwell AE, Jampol LM, Goldberg MF. Macular holes and excellent visual acuity [letter]. Arch OphthalmoI1988;106: 1350-1. 15. Kelly NE, Wendel RT. Vitreous surgery for idiopathic macular holes. Results of a pilot study. Arch Ophthalmol 1991;109:654-9. 16. Glaser BM, Michels RG, Kuppermann BD, et al. Transforming growth factor-/12 for the treatment of full-thickness macular holes. A prospective randomized study. Ophthalmology 1992;99: 1162-73. 17. Poliner LS, Tomambe PE. Retinal pigment epitheliopathy after macular hole surgery. Ophthalmology 1992;99:16717. 18. Fine SL. Vitreous surgery for macular hole in perspective. Is there an indication [editorial]? Arch Ophthalmol 1991; 109:635-6. 19. Funata M, Wendel RT, de la Cruz Z, Green WR. Clinicopathologic study of bilateral macular holes treated with pars plana vitrectomy and gas tamponade. Retina 1992; 12: 289-98. 20. Hogan MJ, Alvarado JA, Weddell JE. Histology of the Human Eye: An Atlas and Textbook. Philadelphia: WB Saunders, 1971 ;21-3. 21. Wiznia RA. Reversibility of the early stages of idiopathic macular holes. Am J Ophthalmol 1989;107:241-5. 22. Jost BF, Hutton WL, Fuller DG, et al. Vitrectomy in eyes at risk for macular hole formation. Ophthalmology 1990;97: 843-7. 23. Smiddy WE, Michels RG, Glaser BM, de Bustros S. Vitrectomy for impending idiopathic macular holes. Am J OphthalmoI1988;105:371-6.
Idiopathic macular hole formation was recognized as a clinical entity as early as 1900. I However, the mechanism by which this occurs has remained controversia1. 2- 1O Numerous lines of evidence support a primary role for the vitreous in macular hole formation . A typical fully developed macular hole is approximately 0.33 disc diameter and is surrounded by a cuff of detached retina and an adjacent area with cystoid macular edema (CME).IO-I 2 Spontaneous closure of macular holes has been reported and can result in improved vision, presumably due to improved photoreceptor function in the area of previous detachment and CME. 13 •I4 These observations lead to the application ofvitreoretinal surgical techniques Originally received: August 19, 1993. Revision accepted: November 8, 1993. I Eye Pathology Laboratory, Wilmer Ophthalmological Institute and Department of Pathology, Johns Hopkins Medical Institutions, Baltimore. 2 Brookwood Eye Institute, Brookwood Medical Center, Birmingham. Supported in part by The Macula Foundation, Inc, New York, New York, and core grant EYO 176517 from the National Eye Institute, Bethesda, Maryland. Reprint requests to W. Richard Green, MD, Eye Pathology Laboratory, Johns Hopkins Hospital, 600 N. Wolfe St, Baltimore, MD 21287-9248.
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to achieve closure of macular holes. Two uncontrolled studies have demonstrated the efficacy of vitreous surgery in causing closure of macular holes and improving vision. I5 - I7 Although the precise indications for performing such operations await further study,I8 it seems clear that the procedure is efficacious in some patients. The procedure for macular hole repair involves removal of residual premacular cortical vitreous and intraocular gas tamponade. Theories regarding the mechanisms by which macular hole closure occurs include release of vitreous traction and formation of a glial scar. In the only published clinicopathologic study to date, one of a pair of bilateral, treated, macular holes was sealed by fibrous astrocytes, whereas the other showed no gliosis. 19 We report a clinicopathologic study of a successfully treated macular hole which was sealed by Muller cells.
Case Report A 72-year-old white woman presented in December 1992 with decreased vision in her left eye of 4 months' duration. Ocular history included extracapsular cataract extraction and posterior chamber intraocular lens (PC IOL) in 1983. Results of examination showed visual acuity of 20/40-1 in the right eye and
Madreperla et al . Histopathology of a Treated Macular Hole 20/80-2 in the left. Results of slit-lamp examination showed 2+ nuclear sclerosis in the right eye, a well-centered PC IOL in the left eye, and a 3-mm posterior capsulotomy. A partial posterior vitreous detachment was present without vitreofoveal separation, and a positive Watzke sign was observed in the left eye. A stage III macular hole and an epicortical vitreous membrane was present in the left eye (Fig 1). Fluorescein angiography showed a window defect corresponding to the macular hole. A pars plana vitrectomy with removal ofthe cortical vitreous was performed on January 2, 1992. Sulfurhexafluoride (20%) was used for gas tamponade. The patient maintained a facedown position for 2 weeks. On follow-up examination on January 10, 1993, the hole was closed (Fig 2). By June 24, 1992, visual acuity had improved to 20/40-1. The patient died 7 months after surgery, and the left eye was obtained for histopathologic study.
Histopathologic Examination The eye was fixed in buffered formalin for 72 hours. Results of gross examination showed a healed limbal scar from the 10:30 to 1:30 positions. A C-Ioop PC IOL was present with haptics in the ciliary sulcus. Defects in the anterior and posterior capsules were present centrally. Small defects in the pigment of the pars plana were present
Figure 1. Macular hole, preoperatively. A, left eye with macular hole (approximately 0.33 disc diameter). There are numerous drusen. B, flu· orescein angiographic image shows an area of faint hyperfluorescence at the site of the macular hole. C, higher magnification image of macular hole and surrounding cuff of subretinal fluid. Retinal striae are present from a presumed epicortical vitreous membrane.
Figure 2. Appearance of macular hole 4 weeks after surgery. A small dark area is still present centrally. No retinal striae are seen.
at 2, 5, and 9 o'clock, corresponding to sclerotomy sites. A portion of the eye wall, including the macula and optic nerve head, was embedded in plastic and stepped sectioned at 0.1 mm from temporal to nasal for light microscopy until the area of stripped internal limiting membrane was reached. Additional stepped sections were prepared and examined until the margin of the foveal pit and finally at 0.05 mm until the center of the foveola and defect in the external limiting membrane was evident. Ultrathin sections at two levels within the area of defect were prepared for electron microscopy. A total of 33 levels were used. Results of microscopic examination showed imprints of the haptics eroded into the ciliary body at the ciliary sulcus and a small amount of residual lens cortex. Defects were present in the anterior and posterior capsules centrally. Scars of perforation in the pars plana without fibrous tissue ingrowth were present in available sections corresponding to the 2- and 5-0'clock sclerotomy sites. Light and electron microscopic evaluation of the macula showed a 16-~m defect in the external limiting membrane corresponding to the healed macular hole (Fig 3). At this level, the defect was filled by cell processes and nuclei. A single pigmented macrophage (Fig 3C) was present in the outer aspect of the defect, but there were no other signs of inflammation. Electron microscopic analysis of the cells within the defect showed numerous cytoplasmic processes with prominent smooth endoplasmic reticulum, a few 10-nm filaments and numerous junctional complexes (Fig 4). These features are characteristic of Miiller cells. 20 The internal limiting membrane was absent over a 4-mm area centered on the temporal parafoveal area (Fig 5). The retinal pigment epithelium (RPE) in the macular area appeared normal and was associated with a 12-~m-thick layer of basal laminar deposit (Fig 6). A 5-~m-thick zone of granular and vesicular material (basal linear deposit) was located external to the RPE basement membrane (Fig 6). Occasional accumulation of basal linear material had a mound-shaped configuration that measured up to 16 ~m in thickness (soft drusen).
683
Ophthalmology
Volume 101, Number 4, April 1994 prevalence of complete posterior vitreous detachment in eyes with macular holes as compared with fellow eyes without macular holes. 4 ,6 Also, eyes with early stages of macular hole formation are less likely to have such a detachment than eyes in later stages of hole formation. 9 The early stages of macular hole formation can be reversed by spontaneous vitreofoveal separationY Similarly, preliminary studies suggest that the incidence of macular hole can be lessened for eyes in the early stages of hole formation by vitrectomy.22.23 These data lead to the hypothesis that closure of a macular hole could be facilitated by release of vitreous traction on the retina. Thus, surgical repair of macular holes has involved peeling of residual cortical vitreous and/or epicortical vitreous membranes to relieve traction. Gas tamponade is used to temporarily seal the hole and flatten the retina. The use of a growth factor (e.g., transforming growth factor-beta) has been advocated to induce a cellular seal and has been shown to be advantageous in an uncontrolled pilot study. 16 Our histopathologic study showed that Muller cells can form a seal leading to successful closure of a macular hole.
Figure 3. Healed macular hole. A, entire thickness of retina at the level of defect in external limiting membrane (between arrows). B, higher power view of 16-l'm-thick defect in external limiting membrane (between arrows), filled by cells (asterisks). C, another level with glial cells (asterisk) and a macrophage (arrowhead) in the area of the defect (paraphylenediamine: A, original magnification, x218; Band C, original magnification, XS44).
Discussion Several lines of evidence implicate vitreoretinal traction in the cause of idiopathic macular holes. Trempe et al 7 found that macular holes developed in 8 of28 fellow eyes without a posterior vitreous detachment, whereas no macular holes developed in 21 eyes with such a detachment. These findings suggest that once a posterior vitreous detachment is present, macular hole formation does not occur. Several studies have found a significantly greater
684
Figure 4. Ultrastructural appearance of healed macular hole. A, defect in external limiting membrane measures 16 I'm (between arrowheads). The defect is filled by cell processes (between arrows) (original magnification, X3000). B, higher magnification of cell processes shows abundant smooth endoplasmic reticulum (asterisk) and numerous junctional complexes (arrows) (original magnification, X30,OOO).
Madreperla et al . Histopathology of a Treated Macular Hole by RPE or glial cell proliferation. 12 In all three cases, a relatively large gap remained between the edges of the hole. As mentioned above, the surgical technique may promote re-approximation of the edges of the hole in ways that do not occur in these spontaneously sealed holes. We do not know how representative the two previously reported eyes l9 and the eye in this study are of all treated macular holes. Several features are common to all three of the studied eyes. These include (1) a relatively small break in the external limiting membrane with re-approximation of the edges of the hole with some cellular proliferation filling the small gap; (2) an abrupt transition to a normal-appearing photoreceptor layer outside of the defect; (3) the internal limiting membrane was removed along with the cortical vitreous in a relatively large area surrounding the hole; (4) the underlying RPE appears normal; (5) no inflammatory response is present in the treated macular holes; and (6) there was no cystoid edema, whereas this was seen in 68% of untreated macular holes. 12 Based on the eye reported here and the two previously reported eyes, we postulate that relief of tangential traction by cortical vitreous peeling allows settling of the retina with re-approximation of the edges of the hole. Gas tamponade may further enhance re-approximation and provide a temporary seal. The residual small defect may be sealed permanently by resident fibrous astrocytes or
Figure 5. Inner retina adjacent to macular hole. A, the internal limiting membrane is absent. B, area shows the margin of the internal limiting membrane (arrow) (paraphylenediamine, phase contrast; original magnification, X544).
Interestingly, there appeared to be a typical O.S-mm diameter hole before surgery but only a 0.016-mm break in the external limiting membrane was seen histologically. It could be argued that this actually was a stage II hole with only a small retinal dehiscence. Arguments against this are (1) there was a positive Watzke sign, or a break, in the slit-lamp beam preoperatively; (2) the fluorescein angiogram showed a window defect corresponding to the 0.33-DD appearing hole; and (3) the full-sized hole was confirmed intraoperatively. Also, in a clinicopathologic study of two other treated, stage III macular holes, similarsized, small defects in the external limiting membrane were noted. 19 It may be that relief of tangential traction allows re-approximation of the edges of the hole. In addition, flattening of the edematous edges of the hole (as they appear in histopathologic studies) 11 may further accentuate re-approximation. As noted in another report, the· histologic appearance of the treated macular holes is different than that of the spontaneously healed holes that have been studied. 19 In one report, three such holes were spontaneously sealed
Figure 6. Retinal pigment epithelium (RPE) with accumulation of lipofuscin and melanolipofuscin. A 12-JLm-thick layer of basal laminar deposit (between arrows) (main figure and inset) is present between the RPE and its basement membrane (arrowhead). A 5-JLm-thick layer of basal linear material (asterisks) is present external to the RPE basement membrane (original magnification, x4200; inset: phase contrast, paraphylenediamine; original magnification, X544).
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Ophthalmology
Volume 101, Number 4, April 1994
Muller cell proliferation. Resultant attachment of retina and resolution of CME in the region adjacent to the defect probably provides the improvement in vision that is noted clinically. It is likely that some central photoreceptor cell degeneration occurs at the time of hole formation because vision does not return to a normal level.
References 1. Kuhnt H. Ueber eine eigenthiimliche Veriinderung der Netzhaut ad maculam (retinitis atrophicans sive rareficans centralis). Z Augenh 1900;3:105-13. 2. Komzweig AL, Feldstein M. Studies of the eye in old age. II. Hole in the macula: a clinico-pathologic study. Am J Ophthalmol 1950;33:243-7. 3. Aaberg TM, Blair CJ, Gass JDM. Macular holes. Am J Ophthalmol 1970;69:555-62. 4. McDonnell PJ, Fine SL, Hillis AI. Clinical features of idiopathic macular cysts and holes. Am J OphthalmoI1982;93: 777-86. 5. Avila MP, Jalkh AE, Murakami K, et al. Biomicroscopic study of the vitreous in macular breaks. Ophthalmology 1983;90: 1277-83. 6. Morgan CM, Schatz H. Idiopathic macular holes. Am J Ophthalmol 1985;99:437-44. 7. Trempe CL, Weiter JJ, Furukawa H. Fellow eyes in cases of macular hole. Biomicroscopic study of the vitreous. Arch Ophthalmol 1986; 104:93-5. 8. Gass JDM. Idiopathic senile macular hole. Its early stages and pathogenesis. Arch Ophthalmol 1988;106:629-39. 9. Johnson RN, Gass JDM. Idiopathic macular holes. Observations, stages of formation, and implications for surgical intervention. Ophthalmology 1988;95:917-24. 10. Guyer DR, Green WR. Idiopathic macular holes and precursor lesions. In: Franklin RM, ed. Retina and Vitreous: Proceedings ofthe Symposium on Retina and Vitreous. New Orleans Academy of Ophthalmology, 1992. Amsterdam: Kugler 1993;399-428.
686
II. Frangieh GT, Green WR, Engel HM. A histopathologic study of macular cysts and holes. Retina 1981;1:311-36. 12. Guyer DR, Green WR, de Bustros S, Fine SL. Histopathologic features of idiopathic macular holes and cysts. Ophthalmology 1990;97: 1045-51. 13. Lewis H, Cowan GM, Straatsma BR. Apparent disappearance of a macular hole associated with development of an epiretinal membrane. Am J Ophthalmol 1986; 102: 172-5. 14. Bidwell AE, Jampol LM, Goldberg MF. Macular holes and excellent visual acuity [letter]. Arch OphthalmoI1988;106: 1350-1. 15. Kelly NE, Wendel RT. Vitreous surgery for idiopathic macular holes. Results of a pilot study. Arch Ophthalmol 1991;109:654-9. 16. Glaser BM, Michels RG, Kuppermann BD, et al. Transforming growth factor-/12 for the treatment of full-thickness macular holes. A prospective randomized study. Ophthalmology 1992;99: 1162-73. 17. Poliner LS, Tomambe PE. Retinal pigment epitheliopathy after macular hole surgery. Ophthalmology 1992;99:16717. 18. Fine SL. Vitreous surgery for macular hole in perspective. Is there an indication [editorial]? Arch Ophthalmol 1991; 109:635-6. 19. Funata M, Wendel RT, de la Cruz Z, Green WR. Clinicopathologic study of bilateral macular holes treated with pars plana vitrectomy and gas tamponade. Retina 1992; 12: 289-98. 20. Hogan MJ, Alvarado JA, Weddell JE. Histology of the Human Eye: An Atlas and Textbook. Philadelphia: WB Saunders, 1971 ;21-3. 21. Wiznia RA. Reversibility of the early stages of idiopathic macular holes. Am J Ophthalmol 1989;107:241-5. 22. Jost BF, Hutton WL, Fuller DG, et al. Vitrectomy in eyes at risk for macular hole formation. Ophthalmology 1990;97: 843-7. 23. Smiddy WE, Michels RG, Glaser BM, de Bustros S. Vitrectomy for impending idiopathic macular holes. Am J OphthalmoI1988;105:371-6.