Ian Conner, MD, PhD; Joel S. Schuman, MD, FACS; and David L. Epstein, MD, MMM
We use the term lens-induced glaucoma for the secondary open-angle glaucomas associated with leakage of lens proteins into the eye, from lens particles directly affecting the function of the trabecular meshwork (TM), or from phacoantigenic inflammation. Prior laboratory investigations have given insight into underlying mechanisms and offer a framework for understanding and classification.
PHACOLYTIC GLAUCOMA
History
The term phacolytic glaucoma was first proposed by Flocks and colleagues1 as a type of secondary open-angle glaucoma of rapid onset associated with a leaking hypermature cataract. Subsequently, others have occasionally misused the term phacolytic as though it applied to all lens-induced glaucomas. Flocks and colleagues1 believed that phacolytic glaucoma was attributable to obstruction of the intertrabecular spaces by macrophages distended with engulfed lens material and Morgagnian fluid that had escaped from the intact crystalline lens capsule. Goldberg2 popularized Millipore filtration for diagnostic identification of the macrophages in this condition but also suspected that the glaucoma was caused by blockage of the angle by both proteinaceous debris and macrophages. In recent years, the supposed role of macrophages in producing the glaucoma has been emphasized, and the possible direct obstruction of the TM by liberated lens material has fallen out of favor.
Mechanisms for the Glaucoma
Our laboratory investigations indicate that soluble lens proteins leaked from hypermature cataracts cause severe obstruction of aqueous outflow and that this is likely important in the pathogenesis of phacolytic glaucoma.3
In these experiments, heavy-molecular-weight lens protein, infused into the anterior chamber of enucleated human eyes in amounts similar to those found clinically in the aqueous humor of patients with phacolytic glaucoma, produced a severe obstruction of fluid outflow that increased with the length of the perfusion time. This obstruction was not relieved by simple irrigation of the anterior chamber, suggesting that dynamic mechanisms, perhaps involving macrophages, may be required in vivo to relieve such an obstruction.
Other experiments indicated that the aqueous outflow channels were also easily obstructed by particulate lens material. It was not determined what proportion of the lens particle obstruction was attributable to insoluble lens protein and what proportion to cell membrane fragments. This lens-particle glaucoma seems likely to be the predominant mechanism in early postoperative glaucoma due to retained lens material and to be less often involved in spontaneous phacolytic glaucoma. In some cases of phacolytic glaucoma, however, a hypermature lens may rupture either spontaneously or during surgery, and in such cases, glaucoma of acute onset may be due to a combination of both obstructing lens particles and soluble lens proteins.
Analogous to interference with outflow by lens proteins, we found that obstruction of outflow by serum proteins may be an important factor in open-angle glaucoma associated with uveitis.4 In related experiments, infusion of human serum into enucleated human eyes produced a significant decrease in outflow facility that likewise was not relieved by simple irrigation of the anterior chamber. Diluted serum caused greater obstruction upon perfusion than would be expected on the basis of viscosity alone. Lens depression, induced experimentally to mechanically simulate longitudinal ciliary muscle contraction, improved the facility of outflow but did not alleviate the partial obstruction induced by serum. It is possible that normal serum components may become entrapped in the outflow channels and produce glaucoma. Such serum obstruction may be a factor in glaucoma refractory to corticosteroid therapy in eyes with chronic uveitis (see Chapter 43), especially when there is little cellular reaction but persistent flare.
Figure 48-1. Leaking hypermature cataract with pseudohypopyon layering in the anterior chamber angle. (Reprinted with permission from Amina Malik, MD.)
In phacolytic glaucoma, the role of macrophages is unclear, but they may be present simply as scavengers of lens material in the anterior chamber, clearing lens protein from the outflow pathways. In children, macrophages have been observed in the anterior chamber in the presence of lens material without causing elevation of intraocular pressure (IOP). Yanoff and Scheie5 in particular described typical engorged macrophages, although perhaps fewer than in phacolytic glaucoma, in the anterior chamber fluid of children at the time of surgery for secondary cataracts, without evidence of glaucoma. Interestingly, D. K. Dueker (personal communication, 1977) has placed large numbers of rabbit macrophages, which have engulfed oil in the peritoneum, into the anterior chamber of rabbits and failed to observe any significant elevation of IOP.
Clinical Findings
In phacolytic glaucoma, there is typically rapid onset of pain and redness in the eye. IOP may become extremely high, even greater than 80 mm Hg in some cases. Corneal epithelial edema is usually present. The angle remains open and without visible abnormality. The lens usually shows hypermature or mature cataract, or rarely an immature cataract in which there is liquefaction of the posterior cortex. When seen with immature cataract, the glaucoma tends to be less acute in onset and not associated with such high IOP at presentation. Patches of white material, thought to be clusters of macrophages, may be seen on the anterior surface of the crystalline lens. In rare cases, the cataractous lens is dislocated into the vitreous cavity, either spontaneously or as a result of trauma.
Inflammatory precipitates, such as scattered cells or conglomerate keratic precipitates (KPs), may or may not be present on the corneal endothelium. Rarely in this condition have we seen what looked like KPs in the anterior chamber angle. Cellular reaction in the anterior chamber can vary from mild to the appearance of a noninfectious hypopyon (Figure 48-1).6 Usually, one sees circulating white particles that are significantly larger than white blood cells and that have been variously interpreted as very large cells7,8 (presumably swollen macrophages), cellular aggregates, or small particles of lens material (likely aggregated insoluble lens protein).
Treatment
The eye in phacolytic glaucoma is typically recalcitrant to medical antiglaucoma and anti-inflammatory therapy. The IOP may be reduced considerably, but only temporarily, with beta-blockers, brimonidine, carbonic anhydrase inhibitors, and osmotic agents; usually the IOP rebounds and remains too high for adequate medical management. As a rule, patients with presumed phacolytic glaucoma will require cataract surgery for definitive treatment. This may be indicated emergently if the IOP does not respond from a dangerously high level in response to the initial medical treatment. The IOP usually returns to normal within a few days after cataract surgery.
Possible Laboratory Studies
Microscopic examination of anterior chamber fluid usually reveals engorged macrophages.7,8 They are not often numerous, and their number does not correlate with the severity of the glaucoma. Occasionally, there are no macrophages in the aspirated fluid, but in almost all cases, there is fine amorphous material in the anterior chamber fluid. Biochemical studies have identified heavy-molecular-weight lens protein in aqueous humor from all cases of phacolytic glaucoma so far examined for this material.9
The heavy-molecular-weight lens protein is not present in the aqueous humor of nonglaucomatous patients with ordinary cataracts or in patients with cataract and primary open-angle glaucoma. Biochemical analysis of anterior chamber fluid is potentially useful in the clinical diagnosis of phacolytic glaucoma. It is considered accepted practice in suspected cases to aspirate the aqueous humor and to obtain washings of the anterior chamber for microscopic search for macrophages and lens proteins (polymerase chain reaction analysis for viral agents, eg, herpes simplex virus, varicella zoster virus, and cytomegalovirus, is usually also performed if aqueous is aspirated). However, one can usually arrive at the correct diagnosis on purely clinical grounds.
UNDERSTANDING LENS-INDUCED GLAUCOMAS
Ian Conner, MD, PhD and David L. Epstein, MD, MMM
A simple way to view these lens-induced glaucomas is to conceptualize that, with the exception of phacoantigenic glaucoma (previously termed phacoanaphylaxis), these entities exist as mechanical glaucomas that are due to the direct obstructive properties1 of lens proteins in the case of a leaking but essentially intact crystalline lens or lens particles in the case of a grossly disrupted lens (free lens cortical material)—hence, the terms lens protein glaucoma (phacolytic) and lens particle glaucoma. In the former, it is the viscous heavy-molecular-weight lens proteins2 present in advanced cataracts that leak into the anterior chamber that obstruct the TM, and in the latter the fragments of gross crystalline lens material.1 The inflammatory macrophage-type cellular response is not itself viewed as impairing trabecular outflow and may actually help in clearing the liberated lens material from the outflow pathway. In fact, the presence of macrophages likely represents part of the spectrum of presentation of phacolytic glaucoma and is not truly necessary for the occurrence or diagnosis of this entity.3
With this construct, the treatment is fairly straightforward and consists of removing at least the continuing source of the lens material. In lens particle glaucoma, the free lens material is removed from the anterior chamber, and in lens protein glaucoma, where there is a relatively intact cataractous lens, treatment consists of cataract surgery. Common presentations of lens particle glaucoma include postoperative, where fragments of lens material are unintentionally left in the eye, and post-traumatic, when the lens capsule is violated. In the past, intracapsular cataract surgery was preferred for phacolytic (lens protein) glaucoma because there was usually a friable lens capsule (through which the lens proteins were leaking), commonly weak zonules, and typically a large, floppy capsular bag. This presented the potential for phacoanaphylaxis or other forms of severe inflammation should lens material containing these aggregated lens proteins be mixed with vitreous due to unexpected vitreous loss. (These heavy-molecular-weight lens proteins are normally concentrated in the crystalline lens nucleus and may be responsible for phacoanaphylaxis and severe complications that ensue when a nucleus is lost into the vitreous and al lowed to remain.) However, this practice transitioned to extracapsular cataract surgery after several reports4,5 with good results in patients with phacolytic glaucoma. In planned extracapsular cataract surgery, an adequately wide incision should be employed, with attention to potentially loose zonules and a friable capsule, with an adequate cortical clean-up. With advances in viscoelastic stabilization of the eye intraoperatively and improvements in phacoemulsification technique and efficiency, it is now usually possible to even avoid the extracapsular technique, although the surgeon should be prepared to convert to deliver the nucleus if phacoemulsification should prove inadequate. Attention should be placed especially on avoiding capsular tears and thus the mixing of the offending lens contents with the vitreous.
REFERENCES
1. Epstein DL, Jedziniak JA, Grant WM. Obstruction of aqueous outflow by lens particles and by heavy-molecular-weight soluble lens proteins. Invest Ophthalmol Vis Sci. 1978;17:272-277.
2. Epstein DL, Jedziniak JA, Grant WM. Identification of heavy-molecular-weight soluble lens protein in aqueous humor in human phacolytic glaucoma. Invest Ophthalmol Vis Sci. 1978;17:398-402.
3. Mavrakanas N, Axmann S, Issum CV, Schutz JS, Shaarawy T. Phacolytic glaucoma: are there 2 forms? J Glaucoma. 2012;21(4):248-249.
4. Lane SS, Kopietz LA, Lindquist TD, et al. Treatment of phacolytic glaucoma with extracapsular cataract extraction. Ophthalmology. 1988;95:749-753.
5. Singh G, Kaur J, Mall S. Phacolytic glaucoma—its treatment by planned extracapsular cataract extraction with posterior chamber intraocular lens implantation. Ind J Ophthalmol. 1994;42:145-147.
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