Pseudoexfoliation Glaucoma

Chat Highlights
June 6, 2007

On Wednesday, June 6, 2007, Dr. Richard Lee, a glaucoma specialist, and the glaucoma chat group discussed "Pseudoexfoliation Glaucoma."

Moderator:  Our topic is pseudoexfoliation glaucoma.  We are pleased to have with us again tonight Dr. Richard K. Lee, M.D., Ph.D., Bascom Palmer Eye Institute, Miami, Florida.

Dr. Rick Wilson:  I just wanted everyone to know that we have a treat for you tonight.  Dr. Lee is one of the foremost researchers in glaucoma and an excellent clinician.

Moderator:  Thank you, Dr. Lee, for being here.

Dr. Rick Wilson:  Dr. Lee's expertise is the molecular basis of pseudoexfoliation, as well as chronic open-angle glaucoma and neuroprotection.

Dr. Richard Lee:  Thank you for asking me to join you.

Dr. Rick Wilson:  As before, Dr. Lee, a copy of the original transcript and the highlights of this chat will be sent to you for review before being posted online.  I'll leave you to your audience - - a much larger one than just the attendees tonight.  Thanks again.

Dr. Richard Lee:  Thank you for the kind introduction, Dr. Wilson.  I’m ready to start.

P:  Dr. Lee, what is pseudoexfoliation?

Dr. Richard Lee:  Pseudoexfoliation (I will shorten to PXF as an abbreviation) is a protein complex that forms in the front part of the eye (anterior chamber).  This material is believed to cause glaucoma by plugging the trabecular meshwork (the outflow track) and causing increased eye pressures that lead to glaucoma.

Moderator:  What causes PXF?

Dr. Richard Lee:  The identity of the PXF proteins is not known, and is an area of active research in my lab and several other labs throughout the world. Interestingly, the material is formed and present throughout the body, as first shown by Dr. Barbara Streeten.  The eye, however, is the only place this PXF material is known to cause a disease process - - namely, glaucoma.

P:  Why is it called "pseudo" exfoliation?

Dr. Richard Lee:  True exfoliation was first seen in arc welders and glass blowers.  The intense lights literally fried off the top layer of the lens capsule, much like flaking skin off.  The PXF material looks like this dandruff, flaking-off material, but is not truly lens capsular material; therefore, “pseudo”.

P:  What symptoms distinguish PXF from other forms of glaucoma?

Dr. Richard Lee:  PXF glaucoma is known as one of the secondary glaucomas; that is, a cause is known.  The presence of the PXF material is seen in the eye. The PXF proteins leave a characteristic bull's-eye pattern on the lens capsule.  That’s because of the pattern in which the PXF material is deposited on the surface of the lens capsule.

P:  How do you diagnose PXF?

Dr. Richard Lee:  PXF glaucoma currently is diagnosed solely by slit-lamp examination in the doctor’s office.

P:  Is there a blood test for the PXF protein?

Dr. Richard Lee:  There is not yet a genetic or blood test that identifies the PXF material.  We are certainly working toward this by identifying the constituent proteins in the PXF material.

Moderator:  Is there anything else that distinguishes PXF from other types of glaucoma?

Dr. Richard Lee:  PXF glaucoma is differentiated from the many other types of secondary glaucomas by its classic appearance at the slit-lamp. In some cases, the clinician can identify early, suggestive signs of PXF by the mottling of the peripupillary border (the edge of pupil) and early deposits seen in the angle (drainage area of the eye), in addition to the dandruff-like PXF material.  That material can sometimes be seen floating in the anterior chamber, resting on the cornea and, classically, on the lens capsule.

P:  Should most ophthalmologists and optometrists be able to recognize the PXF pattern?

Dr. Richard Lee:  All eye doctors are trained to recognize the PXF material, because it is a leading cause of glaucoma and is a classic disease entity in the eye.  However, the key thing is a careful slit-lamp examination, with varying intensities of light, angles of light, and good dilation to look carefully for the material on the lens capsule.  An undilated, careful look at the pupillary border for signs of PXF damage suggestive of PXF is also important.

Moderator:  Does PXF usually occur in both eyes?

Dr. Richard Lee:  PXF is a systemic disorder.  As I mentioned earlier, the material is present all over the body.  One eye can have clinically evident PXF, and the other eye can look completely normal.  Given enough time, however, both eyes will eventually have clinically evident PXF material (based on some long-term, longitudinal Scandinavian studies).

P:  Is this pattern on the lens difficult for an ophthalmologist to see?  Can it be easily missed, or not noted until considerable damage is done?

Dr. Richard Lee:  The pattern of PXF on the lens capsule can be very subtle. In the early stages, the PXF material is a very light dusting of material on the lens capsule.  At times, it is really only under good light conditions, with certain angles of the slit-lamp, that this material can be appreciated.  In addition, good dilation of the pupil is important to seeing the material. Since PXF eyes tend to dilate poorly, the material can be overlooked.

P:  Does PXF always affect both eyes?

Dr. Richard Lee:  Although the disease is systemic and the material can be in one eye or both eyes, the presence of glaucoma can be asymmetric.  The presence of PXF material does not guarantee glaucoma:  It is a significant risk factor for the development of glaucoma (i.e., optic nerve damage).

P:  Why is the true incidence of PXF difficult to determine?

Dr. Richard Lee:  The true incidence depends on the patient’s background (i.e., family history) and where the patient is from.  Some have argued for an environmental role in the manifestation of the disease, but there is no real evidence for this.

P:  My understanding is that PXF is seen more often in individuals of Scandinavian descent.  How prevalent is it in that group?

Dr. Richard Lee:  The incidence of PXF varies considerably and depends upon geography and genetics.  PXF used to be thought of as a Scandinavian disease because of its high incidence in Sweden. That thinking, however, was due to a heightened sensitivity to PXF and its high prevalence, especially within certain villages.  The incidence of PXF can be as high as 90% of the open-angle glaucomas in some villages and as low as 10%. On average, Scandinavians have a higher incidence of PXF glaucoma.  However, there are now known to be certain cohorts in South Americans, Australians, and others that have very high incidences. One only finds what one looks for.

P:  Are PXF and pigmentary glaucoma two different types?

Dr. Richard Lee:  PXF and pigmentary are two very different secondary glaucomas. Pigmentary involves a characteristic pattern of pigment loss from the iris that is also observed on the slit-lamp.  PXF and pigmentary glaucoma (among others) are in a class of glaucomas I call the “slit-lamp glaucomas” because the diagnosis is based almost strictly on a good slit-lamp exam.

P:  What kinds of increases in IOP occur with PXF?

Dr. Richard Lee:  PXF is very difficult to treat and is responsible, at times, for very high pressure fluctuations.  It can be thought of in plumbing terms.  The material forms, plugs the drain, the pressure rises, the plug passes, and the pressure returns to normal.  Pressures from PXF can be as high as 40 to 50 mm Hg, but that is often temporary.  I am always suspicious of occult PXF when I see a patient with wide pressure fluctuations.  Over time, PXF patients have a much higher baseline IOP.  Thus, some patients with PXF will have normal IOPs on many clinic visits.  However, their glaucoma is progressing, presumably because their pressures at home between office visits may be sky high, then return to normal.  I am much more aggressive about treating PXF glaucoma than other types of open-angle glaucoma.

P:  Does cataract surgery pose higher risks for PXF patients?

Dr. Richard Lee:  Yes, PXF leads to a number of other issues, such as zonular weakness, which increases the risk of problems during cataract surgery.  To prepare for this increased risk, I look for PXF in all patients before cataract surgery.

P:  Are ALT (argon laser trabeculoplasty) and SLT (Selective Laser Trabeculoplasty) used to treat PXF? If so, which is preferable?

Dr. Richard Lee:  I have found that PXF responds very well to laser treatment, although it is not known why.  I do not think anyone (myself included) has compared, systematically and carefully, the difference between SLT and ALT.  My opinion is that they both work equally well.

P:  Is there some way to remove the protein deposits?

Dr. Richard Lee:  No, there is no way to safely remove the material, aside from the material probably being constantly formed and slowly passed out of the eye.  I have noted an occasional, significant decrease in eye pressure after cataract surgery with PXF patients, which may be due to the “vacuum cleaner” effect.  That, however, is usually temporary (on the order of months). In generally, cataract surgery can lower the eye pressure by a few millimeters of mercury for many patients, independent of PXF.

P:  I have had PXF syndrome for over six years.  My IOPs rose to the mid-20’s, were controlled by glaucoma medications for a short time, then rose, and I was switched to a different medication.  Apparently, my optic nerve has not changed or suffered any damage, and my visual fields show no change.  My first question is: Would that be considered PXF glaucoma or PXF without glaucoma?

Dr. Richard Lee:  No damage with your eye pressures is pseudoexfoliation without glaucoma, which is frequently the case early on.  The PXF material increases the risk of development of glaucoma, but does not guarantee it.  I have patients with thick scrolled-over PXF material without glaucoma, and they are being watched closely.

P:  My second question is:  At age 65, how long can my vision be preserved?

Dr. Richard Lee:  The course over time cannot be predicted.  The eye may be compensating for these pressures using the functional reserve of nerve tissue.  Then, too, with people living longer and longer, 66-years-old is fairly young, in my opinion.  You should be watched closely.  Once damage is detected (either at the optic nerve or visual field level), treatment should be aggressive.  Patients with PXF glaucoma tend to have a more aggressive course of the disease if not treated.

Moderator:  Is PXF less common than POAG?

Dr. Richard Lee:  PXF is much less common than POAG, but is the most commonly identifiable form of glaucoma with a known etiology (that of the PXF material) for open-angle glaucoma.

P:  Is PXF treated with the same eyedrops that are used for open-angle glaucoma?

Dr. Richard Lee:  PXF is treated like any other open-angle glaucoma, often with drops, with or without laser, and surgery.  Adding to the complexity of the pathophysiology of this disease, PXF patients can develop narrow angles as their zonules become weaker and their cataracts become fatter.  Therefore, PXF can lead to intermittent angle closure in late stages.

P:  If PXF scrapes and traumatizes the back of the iris and there's a low level of inflammation, should the use of prostaglandins like Lumigan and Xalatan be avoided by PXF patients?

Dr. Richard Lee:  PXF does not scrape the back of the iris.  The bull's-eye pattern of PXF material on the lens capsule is from areas where the iris edge rubs the PXF material off of the lens capsule surface due to the normal excursion of the iris as it gets smaller and larger.  Prostaglandins work well in treating PXF.

On a separate note, I personally believe that most glaucomas have an associated, underlying, low-level of inflammation.  Some of my research in animal models of glaucoma shows elevation in the expression of pro-inflammatory genes in glaucoma.

P:  If a patient has additional surgery for PXF to lower the IOP, will the base cause of the problem continue to get worse and still cause the problems?

Dr. Richard Lee:  The glaucomatous damage to the optic nerve is due to the elevated eye pressure, caused by the PXF material.  Therefore, lowering the eye pressure either by meds, laser, or surgery is usually sufficient to slow down or stop the glaucoma from progressing.

P:  Is it known whether a patient is born with PXF or if it develops years later?

Dr. Richard Lee:  The answer is not known because we usually only identify PXF in older people.  As I mentioned, genetics probably plays a role and some environmental factor may play a modifying role in the disease course.  However, whatever these modifiers are, age is clearly the most important one for the PXF material to manifest itself.  To understand the natural course of this complex disease, a test needs to be developed to follow PXF patients.

P:  Does vision loss from PXF have a unique or characteristic pattern?  For example, do you see patchy loss on visual fields, or scotomas of a particular elevation and shape?

Dr. Richard Lee:  The pattern of visual field loss and optic nerve damage is similar to that seen for POAG and most other types of glaucoma.  The exception is normal-tension glaucoma, which has more paracentral visual field defects. PXF glaucoma looks like POAG, except for the presence of the PXF material seen on examination, and the high IOP fluctuations that can sometimes be seen in PXF glaucoma.

P:  Which type of surgery is performed?  Would laser be attempted first if glaucoma drops are not keeping the pressure under control?  Do some glaucoma eyedrops work better than others for PXF?

Dr. Richard Lee:  Every doctor should customize his or her treatment to the patient, especially with regard to allergies and systemic-disease problems that may affect the activity of a drug on the body.

In general, I start with either prostaglandins or beta-blockers.  Prostaglandins are preferred because they have longer IOP lowering power. I think that helps to blunt the IOP spikes better in PXF.  As to surgery, trabeculectomies and tubes both work well. I would tailor the surgery to the patient and to which surgery the doctor prefers.

P:  Are you doing any research with stem cells?

Dr. Richard Lee:  My lab is not currently working on stem cells, but other labs in my department are, in animal models.  There has been a lot of hype about stem cells for human transplantation, including a recent article.  This important work is in its infancy.  Much like the talk about the bionic eye and eye chips, stem-cell technology will need lots of time to develop and understand.

P:  Do you feel the eye chip holds promise for blind eyes?

Dr. Richard Lee:  Currently, the eye chip is able to restore some small sense of motion to blind eyes.  The field is nowhere close to being able to help the visually handicapped in the way that low-vision aids can help to increase vision, especially with the current risks involved.  Part of the problem is the technology and need for nanotechnology that is biocompatible.  The larger problem, however, is understanding the pathophysiology of retinal ganglion cell death and its downstream effects.  In the advanced blind eye, is there still enough of a garden environment to allow something to flower if planted there, or is the soil forever ruined?

Moderator:  Dr Lee, it is now past 9:30 p.m.  Sorry for running a little late.  Thank you from all of us for your clear and complete answers to our questions.  Hope to see you here again.

Dr. Richard Lee:  You’re welcome.  I enjoyed it.

On June 20, Dr. Michael James Pro discussed "Examining the Optic Nerve, Man vs. Machine" in the Chat room. Click here for highlights of that meeting.

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