- Email: [email protected]
Diagnosis and Management of Lens-induced Glaucoma
Diagnosis and Management of
Lens-induced Glaucoma DAVID L. EPSTEIN, MD
Abstract: Lens-induced glaucoma may occur as either secondary angle-closure or open-angle glaucoma. Dislocation or swelling of the lens can cause pupillary block and subsequent angle-closure glau90ma. Leakage of soluble lens proteins from a relatively intact cataractous lens can result in a severe secondary open-angle glaucoma (phacolytic glaucoma). Heavy molecular weight protein, believed to be of lens origin, has now been identified in 12 of 12 anterior chamber specimens from such patients. This liberated lens protein can directly obstruct the trabecular outflow pathways. After extracapsular cataract surgery or after lens trauma, liberated fragments of lens material may mechanically impair the drainage of aqueous humor through the outflow channels (lens particle glaucoma). The diagnosis and management of these different lens-induced glaucomas are reviewed. With proper recognition, these glaucomas are promptly cured by the surgical removal of the lens (material). [Key words: cataract, heavy molecular weight lens protein, lensinduced glaucoma, phacolytic glaucoma, pupillary block, secondary glaucoma.] Ophthalmology 89:227 -230, 1982
Abnormalities in the crystalline lens can cause secondarily either angle-closure or open-angle glaucoma. The former is invariably a result of pupillary block,l whereas the latter has been ascribed to the leakage of lens proteins and particles from the lens or to the cellular reaction to this. 2.3
ANGLE-CLOSURE GLAUCOMA; LENS DISLOCATION
LENS~INDUCED
Dislocation of the crystalline lens may cause pupillary block by the filling of the pupil with the lens, vitreous, or both} This form of glaucoma can be cured by peripheral iridotomy or iridectomy. Laser iridotomy is the treatment of first choice sirice it avoids From the Glaucoma Clinical Research Center and Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
surgical entry of the anterior chamber and the attendant problems of vitreous loss, etc. Although laser iridotomies are not always successful, they may close after several weeks (and require retreatment),4 and, rarely, they may be blocked by movement ofthe dislocated lens or vitreous, the procedure can be remarkably effective for the mechanism of the glaucoma is usually simple pupillary block. (Anterior movement of the dislocated lens behind the iris may mechanically force the iris directly into the angle iri a portion of the circumference, but the opposite half of the angle remains open unless vitreous occludes the pupil). If a visual need exists, the dislocated lens (and invariably vitreous) may be removed by a variety of techniques employing microvitrectomy instrumentation. Before such techniques, the visual prognosis was poor due to complications of the invariable vitreous loss.5 Even with such instrumentation, iridotomy should be considered first because of its simplicity and safety.
Supported in part by grants P50 EY 02518, R01 EY 01894, and R01 EY 00002 from the National Eye Institute, Bethesda, Maryland.
LENS SWELLING
Reprint requests to David L. Epstein, MD,243 Charles Street Boston, MA 02114.
Swelling of a cataractous lens may occur and cause secondary angle-closure glaucoma because of pupil-
0161-6420/82/03001227/$00.70
© American Academy
of Ophthalmology
227
OPHTHALMOLOGY • MARCH 1982 • VOLUME 89 • NUMBER 3
lary block. Cataract surgery is definitive in restoring vision and curing the glaucoma, unless permanent peripheral anterior synechiae have formed. In eyes with no visual potential, iridotomy or iridectomy may be employed. Such swollen lenses, however, should be followed for subsequent signs of leakage of lens proteins and secondary open-angle glaucoma.
LENS-INDUCED OPEN-ANGLE GLAUCOMA; PHACOL YTIC Secondary open-angle glaucoma is perhaps the most interesting form of lens-induced glaucoma. The classic type is that of phacolytic glaucoma, in which a mature or hypermature (rarely immature) cataract begins to leak its soluble contents into the anterior chamber, resulting in a severe, acute open-angle glaucoma that must be differentiated from acute angle-closure glaucoma or neovascular glaucoma. 2,3,6,7 Patients present with acutely injected eyes and corneal edema, but open angles on gonioscopy (after clearing the cornea with topical glycerin). The anterior chamber contains a heavy flare, but a variable cell content that is often small. Many of these anterior chamber cells are macrophages that are larger and clearer than white blood cells. Small chunks of white particles, presumably derived from the lens, are often also seen circulating in the aqueous. The cataractous lens typically contains white capsular patches. In eyes with a dense white cataract, light projection is often faulty. In phacolytic glaucoma cataract surgery is curative. 6- 8 Patients should be hospitalized as emergency admissions since the intraocular pressure may continue to rise precipitously despite antiglaucomatous therapy. Urgent cataract surgery may be required. Before operation osmotics, carbonic anhydrase inhibitors, and timolol are effective in temporarily lowering the intraocular pressure. 8 Miotics seem without effect, and, although steroids may quiet the eye and occasionally seem to temporarily lower the pressure, this is most often without sustained effect. 2,3 Sector iridectomy and use of alpha chymotrypsin are preferred because of the dire consequences, including possible phacoanaphylaxis, that follow breakage of the capsule and spilling of the "bag of lens proteins" back into the eye. 2,3 Curiously, alpha-chymotrypsin-associated postoperative glaucoma is rare, and visual results, if the condition has been promptly treated, are good despite the usually poor preoperative vision. Originally, the pathogenesis of phacolytic glaucoma was believed to involve obstruction of the outflow channels for aqueous humor by a combination of lens debris and swollen macrophages. 6,7 In ensuing years somehow only the latter has been emphasized. Recent work in our laboratory has indicated that direct blockage of the trabecular meshwork by the leaking lens proteins may, in fact, be the most important mechanism. 9,10 Initially we identified heavy molecular weight (HMW) protein, believed to be of lens origin, in the 228
aqueous humor of six patients with clinical phacolytic glaucoma, but not in aqueous humor from patients with nonphacolytic cataracts or those with other forms of glaucoma. 10 Experimental anterior chamber perfusion studies with like amounts of HMW lens protein caused a severe secondary open-angle glaucoma. 9 We have now identified such HMW protein in 12 of 12 phacolytic aqueous humor specimens. In several of these 12 cases, no macrophages were identified upon morphologic examination of the anterior chamber fluid. Yet all patients responded to cataract surgery with complete alleviation of their glaucoma. Ordinarily if the diagnosis is suspected but uncertain, paracentesis and examination of the anterior chamber fluid by either phase contrast microscopy or Millipore filter technique 7 for the presence of macrophages is performed. We are aware of cases in which no macrophages were seen, and, therefore, cataract surgery was inappropriately delayed because the glaucoma was mistakingly felt not to be of lens origin. These findings indicate that the presence of HMW protein in the aqueous humor specimen may be more specific than the identification of macro phages (which perhaps may be suppressed by the use of preoperative topical steroids).2,3 Thus, examination of anterior chamber fluid for the presence of HMW protein is an important diagnostic aid in suspected cases of phacolytic glaucoma. However, until this assay method is more widely available, the clinician should also rely on the clinical signs of phacolysis if the characteristic bloated macrophages 6,7 are not seen on microscopic examination. The most characteristic of these signs is the presence of white patches on the anterior lens capsule (which are macrophages attempting to seal capsular leaks) and the peculiar small white chunks of presumed lens origin that are seen circulating in the anterior chamber on slit-lamp examination. Often there is a very heavy flare, but small cellular reaction in the anterior chamber and the large size of these macrophagic cells are helpful in suspecting phacolysis. When in doubt, if the glaucoma is not too severe, a diagnostic trial of topical steroids with careful follow-up may be indicated to differentiate uveitis from phacolysis. In phacolysis the glaucoma invariably returns to uncontrollable levels. Analysis of anterior chamber fluid for the presence of HMW protein probably is most useful in atypical cases of phacolytic glaucoma. Phacolytic glaucoma may uncommonly occur with an immature cataract, and we have recently observed cases in which a hypermature cataract seemed to leak lens proteins into the aqueous humor only intermittently. These studies have led us to suspect that there may be other unusual "protein-obstructive" glaucomas as well as phacolytic glaucoma. Serum proteins that leak into the aqueous humor in various forms of uveitis can cause moderate obstruction of aqueous outflow, 11,12 and this may be a mechanism for open-angle glaucoma in some patients with uveitis. Ordinarily, classic
EPSTEIN • LENS-INDUCED GLAUCOMA
phacolytic glaucoma does not occur in children or young adults, 13 and it is noteworthy that HMW protein is not present in the lenses of patients in this age group.14-18 On the other hand, it is possible that leakage of lower molecular weight proteins from lower age cataracts, similar to leakage of serum proteins in uveitis, could be responsible for certain milder forms of secondary open-angle glaucoma. There is evidence that immature cataracts may commonly be leaking very small amounts of lens proteins into the aqueous humor .19 The most important aspect of our study may, in fact, be the recognition of this mechanism of protein obstruction of outflow. Although our studies suggest to us that HMW protein obstruction may be the most important factor in phacolytic glaucoma, we do not rule out entirely that the cellular reaction to this protein leakage may also contribute to the glaucoma, although there is some evidence against this.2,3 When phacolysis occurs with a lens dislocated into the vitreous, in which case the glaucoma and other clinical signs are more subtle and subacute, cellular reaction may be an important factor since HMW protein must diffuse through the vitreous and may enter the anterior chamber in only small amounts.
LENS-PARTICLE GLAUCOMA In contrast to phacolytic glaucoma in which soluble lens proteins leak from the lens through a relatively intact lens capsule, there is another form of lensinduced secondary open-angle glaucoma that is associated with a grossly disrupted lens capsule and the presence of obvious fragments of lens material circulating in the aqueous humor. 2,3 This condition may occur after extracapsular cataract surgery or trauma to the lens, or an advanced cataract may rarely rupture spontaneously. These fragments of the lens leave the eye via the trabecular outflow pathways, and experimental studies have indicated that such lens particles can directly cause a severe obstruction of aqueous humor outflow. 9 The cellular reaction to these lens particles possibly may also contribute to the glaucoma, but it seems clear that these lens particles, themselves, can mechanically impair trabecular drainage of fluid. This is most important to the clinician because lens particle glaucoma responds very well to simple surgical irrigation and removal of the lens material from the eye. 8 If there is only a moderate glaucoma and a small amount of liberated lens material present, a trial of medical anti-glaucomatous therapy such as timolol and carbonic anhydrase inhibitors may be attempted to allow the normal cellular processes in the trabecular meshwork to "clear" the offending lens material. Miotics should be avoided. Since some inflammation invariably accompanies the lens injury or surgery, mild to moderate topical steroid therapy should be initiated to prevent synechiae, pupillary membranes, etc, but intensive steroid therapy probably should be avoided
since this might, in fact, delay "absorption" of free lens material. If the glaucoma is severe and/or there is a large amount of lens material in the anterior chamber that will continue to flow into the trabecular meshwork, surgical removal of this lens material should be undertaken. 8 If one keeps in mind that the glaucoma is commonly related to the "dose" of free lens material that flows into the trabecular meshwork, the diagnosis usually can be made on slit-lamp examination. Diagnostic paracentesis will merely confirm the presence of lens material seen on slit-lamp examination. Since the glaucoma is due to particulate lens material rather than leakage of soluble lens proteins, HMW protein need not be present in the anterior chamber specimen. An unusual form of lens-particle glaucoma can occur many years after extracapsular surgery when lens material somehow is spontaneously freed into the anterior chamber. Occasionally there may be a spontaneous dislocation of a Soemmering's ring into the anterior chamber. 3 When the liberated lens particles have been "absorbed" via cellular processes in the trabecular meshwork, intraocular pressure returns to normal unless complications such as peripheral anterior synechiae have formed. However, we have wondered whether "absorption" of excessive quantities of lens material by the trabecular meshwork could result in premature "wearing out" of this tissue and subsequent open-angle glaucoma many years later, as has been described after congenital cataract surgery. 20
ACKNOWLEDGMENT The author wishes to express his long-standing gratitude to W. Morton Grant, MD, and Paul Chandler, MD, for their advice and encouragement in these studies and to Judith Jedziniak-MacGregor, PhD, and Levon Karageuzian for their biochemical analyses.
REFERENCES 1. Chandler PA, Grant WM. Glaucoma, 2nd ed. Philadelphia: Lea & Febiger, 1979; 205-8, 213-5. 2. Chandler PA, Grant WM. Glaucoma, 2nd ed. Philadelphia: Lea & Febiger, 1979; 216-23. 3. Epstein DL. Lens-induced glaucoma. In: Ritch R, Shields MB, eds. The Secondary Glaucomas. St Louis: CV Mosby, in press. 4. Pollack IP. Use of argon laser energy to produce iridotomies. Trans Am Ophthalmol Soc 1979; 77:674-706. 5. Jensen AD, Cross HE. Surgical treatment of dislocated lenses in the Marfan syndrome and homocystinuria. Trans Am Acad Ophthalmol Otolaryngol 1972; 761491-9. 6. Flocks M, Littwin CS, Zimmerman LE. Phacolytic glaucoma. A clinicopathologic study of one hundred thirty-eight cases of glaucoma associated with hypermature cataract. Arch Ophthalmol 1955; 5437-45. 7. Goldberg MF. Cytological diagnosis of phacolytic glaucoma utilizing Millipore filtration of the aqueous. Br J Ophthalmol 1967; 51847-53.
229
OPHTHALMOLOGY • MARCH 1982 • VOLUME 89 • NUMBER 3
8. Epstein DL. Phacolytic glaucoma. In: Fraunfelder FT, Roy FH , eds. Current Ocular Therapy. Philadelphia: WB Saunders,
1980; 463 - 5. 9. Epstein OL, Jedziniak JA, Grant WM. Obstruction of aqueous outflow by lens particles and by heavy-molecular-weight soluble lens proteins. Invest Ophthalmol Vis Sci 1978; 17:272- 7.
10. Epstein DL, Jedziniak JA, Grant WM. Identification of heavymolecular-weight soluble protein in aqueous humor in human phacolytic glaucoma . Invest Ophthalmol Vis Sci 1978;
17:398-402. 11. Uribe Y Troncoso M. Recherches experimentales sur la filtration de liquides salins et albumineux a travers la chambre anterieure, et son role dans la genese du glaucome. Ann Oculist 1905; 133:5-31. 12. Epstein OL, Hashimoto JM, Grant WM. Serum obstruction of aqueous outflow in enucleated eyes. Am J Ophthalmol 1978;
86101-5. 13. VOlcker HE, Naumann G. Zur Klinik des phakolytischen Glaukoms. Klin Monatsbl Augenheilkd 1975; 166:613-8 14. Jedziniak JA, Kinoshita JH , Yates EM, Benedek GB. The concentration and localization of heavy molecular weight aggre-
230
gates in aging normal and cataractous human lenses. Exp Eye Res 1975; 20:367 - 9. 15. Jedziniak JA, Kinoshita JH, Yates EM, et aL On the presence and mechanism of formation of heavy molecular weight aggregates in human normal and cataractous lenses. Exp Eye Res
1973; 15:185-92. 16. Jedziniak JA, Nicoli OF, Baram H, Benedek GB. Quantitative verification of the existence of high molecular weight protein aggregates in the intact normal human lens by light-scattering spectroscopy. Invest Ophthalmol Vis Sci 1978; 17:51-7 . 17. Spector A, Li S, Sigel man J. Age-dependent changes in the molecular size of human lens proteins and their relationship to light scatter. Invest Ophthalmol 1974; 13:795-8. 18. Spector A, Stauffer J, Sigel man J. Preliminary observations upon the proteins of the human lens. In: Ciba Foundation symposium 19: The Human Lens-in Relation to Cataract Amsterdam, Associated Scientific Publishers , 1973; 185-202. 19. Sandberg HO. The alpha -crystallin content of aqueous humour in cortical, nuclear, and complicated cataracts. Exp Eye Res
1976; 22:75-84. 20. Phelps CD, Arafat NL Open-angle glaucoma following surgery for congenital cataracts . Arch Ophthalmol 1977;95:1985 - 7.
Lens-induced Glaucoma DAVID L. EPSTEIN, MD
Abstract: Lens-induced glaucoma may occur as either secondary angle-closure or open-angle glaucoma. Dislocation or swelling of the lens can cause pupillary block and subsequent angle-closure glau90ma. Leakage of soluble lens proteins from a relatively intact cataractous lens can result in a severe secondary open-angle glaucoma (phacolytic glaucoma). Heavy molecular weight protein, believed to be of lens origin, has now been identified in 12 of 12 anterior chamber specimens from such patients. This liberated lens protein can directly obstruct the trabecular outflow pathways. After extracapsular cataract surgery or after lens trauma, liberated fragments of lens material may mechanically impair the drainage of aqueous humor through the outflow channels (lens particle glaucoma). The diagnosis and management of these different lens-induced glaucomas are reviewed. With proper recognition, these glaucomas are promptly cured by the surgical removal of the lens (material). [Key words: cataract, heavy molecular weight lens protein, lensinduced glaucoma, phacolytic glaucoma, pupillary block, secondary glaucoma.] Ophthalmology 89:227 -230, 1982
Abnormalities in the crystalline lens can cause secondarily either angle-closure or open-angle glaucoma. The former is invariably a result of pupillary block,l whereas the latter has been ascribed to the leakage of lens proteins and particles from the lens or to the cellular reaction to this. 2.3
ANGLE-CLOSURE GLAUCOMA; LENS DISLOCATION
LENS~INDUCED
Dislocation of the crystalline lens may cause pupillary block by the filling of the pupil with the lens, vitreous, or both} This form of glaucoma can be cured by peripheral iridotomy or iridectomy. Laser iridotomy is the treatment of first choice sirice it avoids From the Glaucoma Clinical Research Center and Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
surgical entry of the anterior chamber and the attendant problems of vitreous loss, etc. Although laser iridotomies are not always successful, they may close after several weeks (and require retreatment),4 and, rarely, they may be blocked by movement ofthe dislocated lens or vitreous, the procedure can be remarkably effective for the mechanism of the glaucoma is usually simple pupillary block. (Anterior movement of the dislocated lens behind the iris may mechanically force the iris directly into the angle iri a portion of the circumference, but the opposite half of the angle remains open unless vitreous occludes the pupil). If a visual need exists, the dislocated lens (and invariably vitreous) may be removed by a variety of techniques employing microvitrectomy instrumentation. Before such techniques, the visual prognosis was poor due to complications of the invariable vitreous loss.5 Even with such instrumentation, iridotomy should be considered first because of its simplicity and safety.
Supported in part by grants P50 EY 02518, R01 EY 01894, and R01 EY 00002 from the National Eye Institute, Bethesda, Maryland.
LENS SWELLING
Reprint requests to David L. Epstein, MD,243 Charles Street Boston, MA 02114.
Swelling of a cataractous lens may occur and cause secondary angle-closure glaucoma because of pupil-
0161-6420/82/03001227/$00.70
© American Academy
of Ophthalmology
227
OPHTHALMOLOGY • MARCH 1982 • VOLUME 89 • NUMBER 3
lary block. Cataract surgery is definitive in restoring vision and curing the glaucoma, unless permanent peripheral anterior synechiae have formed. In eyes with no visual potential, iridotomy or iridectomy may be employed. Such swollen lenses, however, should be followed for subsequent signs of leakage of lens proteins and secondary open-angle glaucoma.
LENS-INDUCED OPEN-ANGLE GLAUCOMA; PHACOL YTIC Secondary open-angle glaucoma is perhaps the most interesting form of lens-induced glaucoma. The classic type is that of phacolytic glaucoma, in which a mature or hypermature (rarely immature) cataract begins to leak its soluble contents into the anterior chamber, resulting in a severe, acute open-angle glaucoma that must be differentiated from acute angle-closure glaucoma or neovascular glaucoma. 2,3,6,7 Patients present with acutely injected eyes and corneal edema, but open angles on gonioscopy (after clearing the cornea with topical glycerin). The anterior chamber contains a heavy flare, but a variable cell content that is often small. Many of these anterior chamber cells are macrophages that are larger and clearer than white blood cells. Small chunks of white particles, presumably derived from the lens, are often also seen circulating in the aqueous. The cataractous lens typically contains white capsular patches. In eyes with a dense white cataract, light projection is often faulty. In phacolytic glaucoma cataract surgery is curative. 6- 8 Patients should be hospitalized as emergency admissions since the intraocular pressure may continue to rise precipitously despite antiglaucomatous therapy. Urgent cataract surgery may be required. Before operation osmotics, carbonic anhydrase inhibitors, and timolol are effective in temporarily lowering the intraocular pressure. 8 Miotics seem without effect, and, although steroids may quiet the eye and occasionally seem to temporarily lower the pressure, this is most often without sustained effect. 2,3 Sector iridectomy and use of alpha chymotrypsin are preferred because of the dire consequences, including possible phacoanaphylaxis, that follow breakage of the capsule and spilling of the "bag of lens proteins" back into the eye. 2,3 Curiously, alpha-chymotrypsin-associated postoperative glaucoma is rare, and visual results, if the condition has been promptly treated, are good despite the usually poor preoperative vision. Originally, the pathogenesis of phacolytic glaucoma was believed to involve obstruction of the outflow channels for aqueous humor by a combination of lens debris and swollen macrophages. 6,7 In ensuing years somehow only the latter has been emphasized. Recent work in our laboratory has indicated that direct blockage of the trabecular meshwork by the leaking lens proteins may, in fact, be the most important mechanism. 9,10 Initially we identified heavy molecular weight (HMW) protein, believed to be of lens origin, in the 228
aqueous humor of six patients with clinical phacolytic glaucoma, but not in aqueous humor from patients with nonphacolytic cataracts or those with other forms of glaucoma. 10 Experimental anterior chamber perfusion studies with like amounts of HMW lens protein caused a severe secondary open-angle glaucoma. 9 We have now identified such HMW protein in 12 of 12 phacolytic aqueous humor specimens. In several of these 12 cases, no macrophages were identified upon morphologic examination of the anterior chamber fluid. Yet all patients responded to cataract surgery with complete alleviation of their glaucoma. Ordinarily if the diagnosis is suspected but uncertain, paracentesis and examination of the anterior chamber fluid by either phase contrast microscopy or Millipore filter technique 7 for the presence of macrophages is performed. We are aware of cases in which no macrophages were seen, and, therefore, cataract surgery was inappropriately delayed because the glaucoma was mistakingly felt not to be of lens origin. These findings indicate that the presence of HMW protein in the aqueous humor specimen may be more specific than the identification of macro phages (which perhaps may be suppressed by the use of preoperative topical steroids).2,3 Thus, examination of anterior chamber fluid for the presence of HMW protein is an important diagnostic aid in suspected cases of phacolytic glaucoma. However, until this assay method is more widely available, the clinician should also rely on the clinical signs of phacolysis if the characteristic bloated macrophages 6,7 are not seen on microscopic examination. The most characteristic of these signs is the presence of white patches on the anterior lens capsule (which are macrophages attempting to seal capsular leaks) and the peculiar small white chunks of presumed lens origin that are seen circulating in the anterior chamber on slit-lamp examination. Often there is a very heavy flare, but small cellular reaction in the anterior chamber and the large size of these macrophagic cells are helpful in suspecting phacolysis. When in doubt, if the glaucoma is not too severe, a diagnostic trial of topical steroids with careful follow-up may be indicated to differentiate uveitis from phacolysis. In phacolysis the glaucoma invariably returns to uncontrollable levels. Analysis of anterior chamber fluid for the presence of HMW protein probably is most useful in atypical cases of phacolytic glaucoma. Phacolytic glaucoma may uncommonly occur with an immature cataract, and we have recently observed cases in which a hypermature cataract seemed to leak lens proteins into the aqueous humor only intermittently. These studies have led us to suspect that there may be other unusual "protein-obstructive" glaucomas as well as phacolytic glaucoma. Serum proteins that leak into the aqueous humor in various forms of uveitis can cause moderate obstruction of aqueous outflow, 11,12 and this may be a mechanism for open-angle glaucoma in some patients with uveitis. Ordinarily, classic
EPSTEIN • LENS-INDUCED GLAUCOMA
phacolytic glaucoma does not occur in children or young adults, 13 and it is noteworthy that HMW protein is not present in the lenses of patients in this age group.14-18 On the other hand, it is possible that leakage of lower molecular weight proteins from lower age cataracts, similar to leakage of serum proteins in uveitis, could be responsible for certain milder forms of secondary open-angle glaucoma. There is evidence that immature cataracts may commonly be leaking very small amounts of lens proteins into the aqueous humor .19 The most important aspect of our study may, in fact, be the recognition of this mechanism of protein obstruction of outflow. Although our studies suggest to us that HMW protein obstruction may be the most important factor in phacolytic glaucoma, we do not rule out entirely that the cellular reaction to this protein leakage may also contribute to the glaucoma, although there is some evidence against this.2,3 When phacolysis occurs with a lens dislocated into the vitreous, in which case the glaucoma and other clinical signs are more subtle and subacute, cellular reaction may be an important factor since HMW protein must diffuse through the vitreous and may enter the anterior chamber in only small amounts.
LENS-PARTICLE GLAUCOMA In contrast to phacolytic glaucoma in which soluble lens proteins leak from the lens through a relatively intact lens capsule, there is another form of lensinduced secondary open-angle glaucoma that is associated with a grossly disrupted lens capsule and the presence of obvious fragments of lens material circulating in the aqueous humor. 2,3 This condition may occur after extracapsular cataract surgery or trauma to the lens, or an advanced cataract may rarely rupture spontaneously. These fragments of the lens leave the eye via the trabecular outflow pathways, and experimental studies have indicated that such lens particles can directly cause a severe obstruction of aqueous humor outflow. 9 The cellular reaction to these lens particles possibly may also contribute to the glaucoma, but it seems clear that these lens particles, themselves, can mechanically impair trabecular drainage of fluid. This is most important to the clinician because lens particle glaucoma responds very well to simple surgical irrigation and removal of the lens material from the eye. 8 If there is only a moderate glaucoma and a small amount of liberated lens material present, a trial of medical anti-glaucomatous therapy such as timolol and carbonic anhydrase inhibitors may be attempted to allow the normal cellular processes in the trabecular meshwork to "clear" the offending lens material. Miotics should be avoided. Since some inflammation invariably accompanies the lens injury or surgery, mild to moderate topical steroid therapy should be initiated to prevent synechiae, pupillary membranes, etc, but intensive steroid therapy probably should be avoided
since this might, in fact, delay "absorption" of free lens material. If the glaucoma is severe and/or there is a large amount of lens material in the anterior chamber that will continue to flow into the trabecular meshwork, surgical removal of this lens material should be undertaken. 8 If one keeps in mind that the glaucoma is commonly related to the "dose" of free lens material that flows into the trabecular meshwork, the diagnosis usually can be made on slit-lamp examination. Diagnostic paracentesis will merely confirm the presence of lens material seen on slit-lamp examination. Since the glaucoma is due to particulate lens material rather than leakage of soluble lens proteins, HMW protein need not be present in the anterior chamber specimen. An unusual form of lens-particle glaucoma can occur many years after extracapsular surgery when lens material somehow is spontaneously freed into the anterior chamber. Occasionally there may be a spontaneous dislocation of a Soemmering's ring into the anterior chamber. 3 When the liberated lens particles have been "absorbed" via cellular processes in the trabecular meshwork, intraocular pressure returns to normal unless complications such as peripheral anterior synechiae have formed. However, we have wondered whether "absorption" of excessive quantities of lens material by the trabecular meshwork could result in premature "wearing out" of this tissue and subsequent open-angle glaucoma many years later, as has been described after congenital cataract surgery. 20
ACKNOWLEDGMENT The author wishes to express his long-standing gratitude to W. Morton Grant, MD, and Paul Chandler, MD, for their advice and encouragement in these studies and to Judith Jedziniak-MacGregor, PhD, and Levon Karageuzian for their biochemical analyses.
REFERENCES 1. Chandler PA, Grant WM. Glaucoma, 2nd ed. Philadelphia: Lea & Febiger, 1979; 205-8, 213-5. 2. Chandler PA, Grant WM. Glaucoma, 2nd ed. Philadelphia: Lea & Febiger, 1979; 216-23. 3. Epstein DL. Lens-induced glaucoma. In: Ritch R, Shields MB, eds. The Secondary Glaucomas. St Louis: CV Mosby, in press. 4. Pollack IP. Use of argon laser energy to produce iridotomies. Trans Am Ophthalmol Soc 1979; 77:674-706. 5. Jensen AD, Cross HE. Surgical treatment of dislocated lenses in the Marfan syndrome and homocystinuria. Trans Am Acad Ophthalmol Otolaryngol 1972; 761491-9. 6. Flocks M, Littwin CS, Zimmerman LE. Phacolytic glaucoma. A clinicopathologic study of one hundred thirty-eight cases of glaucoma associated with hypermature cataract. Arch Ophthalmol 1955; 5437-45. 7. Goldberg MF. Cytological diagnosis of phacolytic glaucoma utilizing Millipore filtration of the aqueous. Br J Ophthalmol 1967; 51847-53.
229
OPHTHALMOLOGY • MARCH 1982 • VOLUME 89 • NUMBER 3
8. Epstein DL. Phacolytic glaucoma. In: Fraunfelder FT, Roy FH , eds. Current Ocular Therapy. Philadelphia: WB Saunders,
1980; 463 - 5. 9. Epstein OL, Jedziniak JA, Grant WM. Obstruction of aqueous outflow by lens particles and by heavy-molecular-weight soluble lens proteins. Invest Ophthalmol Vis Sci 1978; 17:272- 7.
10. Epstein DL, Jedziniak JA, Grant WM. Identification of heavymolecular-weight soluble protein in aqueous humor in human phacolytic glaucoma . Invest Ophthalmol Vis Sci 1978;
17:398-402. 11. Uribe Y Troncoso M. Recherches experimentales sur la filtration de liquides salins et albumineux a travers la chambre anterieure, et son role dans la genese du glaucome. Ann Oculist 1905; 133:5-31. 12. Epstein OL, Hashimoto JM, Grant WM. Serum obstruction of aqueous outflow in enucleated eyes. Am J Ophthalmol 1978;
86101-5. 13. VOlcker HE, Naumann G. Zur Klinik des phakolytischen Glaukoms. Klin Monatsbl Augenheilkd 1975; 166:613-8 14. Jedziniak JA, Kinoshita JH , Yates EM, Benedek GB. The concentration and localization of heavy molecular weight aggre-
230
gates in aging normal and cataractous human lenses. Exp Eye Res 1975; 20:367 - 9. 15. Jedziniak JA, Kinoshita JH, Yates EM, et aL On the presence and mechanism of formation of heavy molecular weight aggregates in human normal and cataractous lenses. Exp Eye Res
1973; 15:185-92. 16. Jedziniak JA, Nicoli OF, Baram H, Benedek GB. Quantitative verification of the existence of high molecular weight protein aggregates in the intact normal human lens by light-scattering spectroscopy. Invest Ophthalmol Vis Sci 1978; 17:51-7 . 17. Spector A, Li S, Sigel man J. Age-dependent changes in the molecular size of human lens proteins and their relationship to light scatter. Invest Ophthalmol 1974; 13:795-8. 18. Spector A, Stauffer J, Sigel man J. Preliminary observations upon the proteins of the human lens. In: Ciba Foundation symposium 19: The Human Lens-in Relation to Cataract Amsterdam, Associated Scientific Publishers , 1973; 185-202. 19. Sandberg HO. The alpha -crystallin content of aqueous humour in cortical, nuclear, and complicated cataracts. Exp Eye Res
1976; 22:75-84. 20. Phelps CD, Arafat NL Open-angle glaucoma following surgery for congenital cataracts . Arch Ophthalmol 1977;95:1985 - 7.