Aqueous misdirection, or malignant glaucoma, is a rare type of secondary angle-closure glaucoma most commonly encountered after filtering surgery. The syndrome (also known as ciliary block glaucoma) also can occur spontaneously or following any type of intraocular surgery.
The diagnosis rests on three criteria: axial shallowing of the anterior chamber, a patent peripheral iridectomy and the absence of choroidal fluid.
All other possible causes of shallow anterior chamber must be ruled out, as aqueous misdirection is a rare phenomenon and one that is established by a diagnosis of exclusion.
Axial shallowing means that both the peripheral and central anterior chamber should be shallowed, with anterior displacement of the lens or lens implant. Postoperative overfiltration with or without a conjunctival wound leak must be ruled out by close inspection of the bleb and assessment of hypotony. IOP in aqueous misdirection is most often elevated, but it may be within the normal range (but not low) after filtration surgery.
Primary angle closure by pupillary block is ruled out by the presence of a patent and functional iridectomy. One must ensure that the iridectomy is not blocked by lens material or vitreous. Pupillary block usually does not result in extreme shallowing of the central anterior chamber. Secondary causes of pupillary block—such as posterior synechiae causing iris bombé or iridovitreal block in aphakia—also may occur, but they are unlikely to cause axial anterior chamber shallowing.
Finally, the presence of choroidal elevation must be sought out by direct exam or, preferably, ultrasound imaging. This can take the form of serous choroidal detachments, choroidal hemorrhage or annular choroidal detachments. The latter may be occult, anteriorly located and difficult to recognize except by careful B-scan or high-frequency ultrasound imaging.
Mydriatic-cycloplegic therapy was originally intended to treat phakic patients with intact zonular attachments. It was thought to tighten the lens-zonular diaphragm to resist posterior pressure of the vitreous;1 however, this does not explain its ability to successfully treat some cases of aphakic or pseudophakic patients with disrupted or absent capsules. An alternate explanation is that cycloplegia may move the ciliary body ring outward and away from the hyaloid face, in some way improving its permeability to aqueous. Mydriasis also may increase the effective surface area of anterior hyaloid available for fluid exchange by dilating the pupil.
If aqueous misdirection is suspected, a rational sequence of interventions includes medical therapy with cycloplegics and hyperosmotic agents that may resolve the problem over several hours to days.
Laser iridotomy with anterior hyaloidotomy and posterior capsulotomy (if pseudophakic) may restore the normal dynamics of aqueous humor flow. The goal of YAG laser hyaloidotomy is to disrupt the anterior hyaloid.2 This can be performed through surgical or laser iridectomies, often in multiple areas. It also can be accomplished centrally, posterior to the lens capsule or combined with capsulotomy in pseudophakic patients. The photo-disruption of vitreous may reestablish the anterior flow of aqueous by creating channels through a previously intact and impermeable anterior hyaloid.
However, the effect may be transient and still require surgical vitrectomy,2 or the procedure may be impossible to perform because of corneal edema or opacification.
Argon laser shrinking of the ciliary processes can be performed through a surgical iridectomy if two to four processes are accessible. Slight deepening of the anterior chamber may occur after treatment, but the full effect is delayed for several days. Herschler postulated that the shrinking of the ciliary processes normalized anterior aqueous flow by disrupting ciliolenticular block.3 Yet other mechanisms may be responsible, such as thermal rupture of the anterior hyaloid membrane or alteration of the vitreous. A major limitation of this procedure is dependence upon a clear cornea and a large peripheral iridectomy, permitting the treatment of several ciliary processes.
We developed a needle revision procedure that was successful in a small case series of pseudophakic patients, all of whom had developed aqueous misdirection following trabeculectomy and had failed medical and laser treatment.4 This procedure is performed at the slit lamp under topical anesthesia and may obviate or delay the need for surgical intervention. Using this procedure, one is able to disrupt the anterior hyaloid through the surgical iridectomy and reform the anterior chamber through the same corneal paracentesis incision.
If less-invasive treatments fail, surgical vitrectomy, with or without lensectomy, may be required. Mechanical vitrectomy surgery with suction and cutting instruments is now preferred to manual techniques.5 The goal is to disrupt the anterior hyaloid face and release any pockets of aqueous that are sequestered within the vitreous.
Reestablishing communication between anterior and posterior chambers is critical, as aqueous misdirection may persist even after pars plana vitrectomy.6 These reported cases of recurrence all had a posterior vitrectomy that did not include disruption of the anterior vitreous. An intact anterior hyaloid face may subsequently become impermeable to fluid exchange and contribute to the postoperative development of aqueous misdirection glaucoma.
1 Chandler, P. A. et al. Am J Ophthalmol 1968;66:495–502.
2 Epstein, D. L. et al. Am J Ophthalmol 1984; 98:137–143.
3 Ophthalmology 1980;87:1155–1157.
4 Francis, B. A. et al. J Glaucoma 2002;11: 183–188.
5 Harbour, J. W. et al. Arch Ophthalmol 1996;114:1073–1079.
6 Massicotte, E. C. and J. S. Schuman. Ophthalmology 1999;106:1375–1379.
The precise causes of posterior diversion of aqueous flow are unknown. Precipitating events may include ocular decompression and a subsequent shift in the normal pressure gradients between anterior and posterior chambers. It has long been speculated that poorly understood changes in anterior vitreous permeability may contribute to the risk of developing aqueous misdirection.
Experiments performed by Epstein in enucleated human eyes1 indicate the following:
- If the physiologic flow of aqueous is diverted completely into the vitreous cavity, aqueous misdirection does not occur. Rather, the resistance to forward flow of fluid by the vitreous and anterior hyaloid is negligible. However, when the perfusion pressure is increased to 60 mmHg, the resistance to flow increases significantly. This effect is greatly diminished when hyaluronidase is administered concurrently.
- When the surface area of the hyaloid available for fluid transfer is reduced, flow resistance increases and posterior diversion of fluid results in pressurization of the vitreous and axial shallowing of the anterior chamber.
If the anterior chamber is decompressed and then reformed, this phenomenon is exaggerated.
These experimental results combined with clinical observations suggest a hypothesis for the pathogenesis of aqueous misdirection.
The initiating event appears to be decompression of the eye, which increases relative vitreous pressure and pushes the vitreous, lens, ciliary body and iris forward, causing shallowing or flattening of the anterior chamber. Aqueous is then diverted posteriorly behind or into the vitreous body.
Under normal circumstances, fluid would flow freely from the vitreous to the anterior chamber, equalizing pressure across the lens iris diaphragm. An abnormal impermeability of the anterior hyaloid face may prevent posterior to anterior chamber flow, triggering a vicious cycle fueled by continued aqueous production. Other factors, including organization of the anterior hyaloid and decrease in the surface area available for fluid exchange also may contribute to the problem.
Progressive axial shallowing of the anterior chamber associated with forward movement of the lens iris diaphragm eventually results in complete angle closure.
Successful treatment must break this cycle and reestablish free exchange of fluid between the vitreous cavity and anterior segment.
1 Am J Ophthalmol 1979;88:1078–1086.
Dr. Francis is assistant professor of ophthalmology at the University of Southern California’s Doheny Eye Institute.