Phacoemulsification could play key role in glaucoma treatment paradigm

The number of cataract and glaucoma cases is estimated to increase as the population ages, so physicians may need to take a closer look at the IOP-lowering effect of cataract extraction. Phacoemulsification may prove to be a viable option in treating or even preventing glaucoma.

In the next 6 years, cataract surgery is estimated to rise in the United States from 3 million to 4 million cases per year. U.S. surgeons are already making key treatment decisions for patients with co-existing cataract and glaucoma in an estimated 300,000 to 400,000 cases a year.

“Let’s face it: Cataracts and glaucoma are ubiquitous. Every general ophthalmologist, cataract surgeon and glaucoma surgeon has to deal with it,” Bradford J. Shingleton, MD, said.

Brooks J. Poley, MD, and colleagues conducted a study and found that eyes with the highest presurgical pressure had the best IOP reductions. Image: Mak K

While some experts advocate phaco as a treatment option for glaucoma, others caution that more study is warranted.

The glaucoma subsets that have shown the best pressure-lowering effects after phaco are ocular hypertension, pseudoexfoliation syndrome, primary open-angle glaucoma and primary angle-closure glaucoma. Additional research is needed to determine why phaco lowers IOP in these subsets and whether that effect is sustained over time. In addition, the impact of a postoperative pressure spike should be investigated.

Furthermore, glaucoma patients should have phaco performed with a clear corneal incision to keep the conjunctiva intact for possible future filtration or laser surgery, according to some experts.

Dennis S.C. Lam

Although modern phaco has a high level of safety, it is a surgical procedure, with all the inherent complications posed when performing any surgery, Dennis S.C. Lam, MD, FRCOphth, said.

“Lens extraction is not without risk. Vision-threatening complications may occur,” Prof. Lam said. “The treatment option for glaucoma patients should be individualized with consideration of the patient’s preference, age, stage of disease and other risk factors for progression.”

Dr. Shingleton said phaco offers surgeons another option in individualizing glaucoma treatment.

“If you do have a glaucoma patient that co-exists [with cataract], and that is extremely common because of our aging population, they both go together,” he said. “Depending on the status of the optic nerve, without question in my hands, I’m doing many more cataract operations alone without an adjunctive glaucoma procedure.”

Early research on IOP impact

Research has shown the impact that phaco has on lowering IOP in ocular hypertensive and glaucoma patients. In 1996, Tennen and Masket conducted a retrospective study of 135 eyes randomly selected to receive scleral tunnel or clear corneal cataract surgery. A year later, the clear corneal group had statistically significantly lower mean IOP, dropping from 15.57 mm Hg to 13.65 mm Hg. IOP was also decreased in the scleral tunnel group, but the difference was not statistically significant.

In 1997, Suzuki and colleagues looked at 10-year results in a prospective study of 498 eyes that underwent phaco, finding that eyes with the highest presurgical IOP had the greatest postoperative pressure reductions. A study by Issa and colleagues in 2005 found that pressure reduction was highest after cataract surgery in patients with a higher preoperative IOP and narrower angle.

In 2006, Dr. Shingleton and colleagues conducted a retrospective study of 3-year and 5-year follow-up of normal eyes, glaucoma suspect eyes and open-angle glaucoma eyes. The study found a mean decrease in IOP of nearly 2 mm Hg after uncomplicated phaco and IOL implantation.

“In the glaucoma population, it is important to note that although the pressure was still reduced, there was still, by 5 years, a gradual increase in the need for glaucoma medications back to a similar level pre-cataract surgery – that was the only change. But still, [there was] a small but substantial decrease in IOP,” Dr. Shingleton said.

Bradford J. Shingleton

Recent research on IOP impact

In 2008, Brooks J. Poley, MD, presented at the American Society of Cataract and Refractive Surgery meeting a retrospective study that he and colleagues conducted on the long-term effect of phaco in normotensive and ocular hypertensive eyes. The study looked at 588 eyes that were divided into five groups based on various factors, including IOP measurements before surgery and 10 years after surgery.

Dr. Poley and colleagues found that eyes with the highest presurgical pressure had the best IOP reductions. The group with the highest preoperative pressure, ranging from 23 mm Hg to 31 mm Hg, had a mean reduction of 6.5 mm Hg.

In the 10-year duration of the study, 74% of eyes were converted from ocular hypertensive status to normotensive status with phaco and IOL implantation.

Dr. Poley compared results of this study with those of the landmark Ocular Hypertensive Treatment Study (OHTS), a prospective trial examining the use of eye drops in 1,636 patients. The trial followed the progression of ocular hypertensive patients to glaucoma over 5 years. In the OHTS, 817 patients were treated with glaucoma drops and 819 were not. Of those treated with medication, 4.4% converted to glaucoma; of those not treated with drops, 9.5% converted to glaucoma.

In Dr. Poley’s study, the rate of glaucoma conversion after phaco alone was 1.1%. Only one patient needed medication, although that patient did not technically convert to glaucoma.

“Here’s the thing that I want to emphasize, that nobody’s paying attention to,” Dr. Poley said. “Drops don’t solve the problem; they just slow the progression. On the other hand, what we’ve done — the patients that had ocular hypertension, their pressures went down after surgery for the 10 years of our study. … We returned them to a normal status. How many patients treated with drops did that? None. That’s mind boggling.”

After moderating the ASCRS session in which Dr. Poley presented his results, Reay H. Brown, MD, was inspired to conduct his own study to see how phaco reduces IOP in narrow angles and chronic angle-closure glaucoma. Dr. Brown and colleagues examined 83 patients with angle-closure glaucoma or narrow angles who had phaco and IOL implantation.

They found an average reduction in pressure of 3.8 mm Hg. In the groups with pressure greater than 20 mm Hg, there was an average reduction in IOP of 5.2 mm Hg.

Overall, 90% of the patients showed an improvement in pressure.

Dr. Brown presented the unpublished data at the American Glaucoma Society meeting in March.

“At the AGS, I said if you were testing cataract surgery as a treatment for angle-closure glaucoma, and you did a multicenter study and found what we had found in our highest pressure group, the [U.S. Food and Drug Administration] would approve cataract surgery as a treatment for angle-closure glaucoma,” Dr. Brown said. “In other words, if cataract surgery came in a bottle, the label could say that cataract surgery has been found to be effective in the treatment of angle-closure glaucoma.”

Additional research

Recently, Dr. Poley has been conducting another retrospective study, this one looking at the IOP-lowering effects of phaco in 124 eyes with open-angle and narrow-angle glaucoma and pseudoexfoliation syndrome. The cases were stratified into five groups, from highest pressures to lowest pressures.

The mean IOP reduction in the highest pressure group after phaco alone was 8 mm Hg, Dr. Poley said. The final IOP in the 29 mm Hg to 23 mm Hg group at 10 years was 16.3 mm Hg. The lowest pressure group, at 14 mm Hg to 5 mm Hg, had a pressure elevation of about 2 mm Hg but remained normal.

The study, which has not yet been presented or published, found that 10 years after phaco surgery, 77% of glaucomatous eyes had pressures of 19 mm Hg or less.

Dr. Poley said the study shows higher pressure reductions than previously reported because it stratified results based on groupings of pressures instead of averaging pressures overall. That stratification could be the key to explaining differences in subset IOP reduction.

“There’s an association between chronic narrow angle with high presurgical pressures and high pressure reductions, compared with open-angle eyes that have lower presurgical means, say 7 mm Hg, and a 1.5 mm Hg reduction,” Dr. Poley said. “It appears that it’s the presurgical pressure that determines the probability of pressure reduction after surgery. This is very interesting and, of course, contrary to what most people think.”

Possible mechanism of disease

Dr. Poley has examined the mechanism of glaucoma and postulated that the cause of the disease is the aging crystalline lens. The lens originates from the ectodermal surface of the embryo, composed of cells that reproduce forever, despite the fact that the anterior segment does not grow any larger after the age of 24 years, he said.

The enlarging lens compresses the trabecular meshwork and collapses Schlemm’s canal as it presses forward, Dr. Poley said. As this compression occurs, the outflow channel slowly begins to fail.

“That’s what causes elevated IOP. When we do phaco IOL, we remove the enlarged lens that has done the compression, and we replace it with a thin artificial lens. The anterior surface of the old large lens, which is compressing the iris and ciliary body, [is gone and] this opens up the trabecular meshwork, allowing it to regain the function that it had at its earlier age,” he said.

Dr. Poley said the growth of the crystalline lens appears to be the most logical explanation for the development of glaucomatous damage.

“What’s amazing here is, the phaco/IOL operation is actually rolling back the years of compression to a time at the age of 24,” he said.

Magnetic resonance images of the lens in a 25-year-old patient, a 49-year-old patient and a 74-year-old patient, published by Strenk and colleagues, have shown how the growth of the lens compresses the trabecular meshwork and Schlemm’s canal, Dr. Poley said. However, without preop and postop tomographic testing and preop and postop measurement of aqueous outflow, the exact mechanism has yet to be proven.

According to Dr. Poley, glaucoma could be a preventable disease if indicated cases of ocular hypertension were treated with phaco and IOL implantation. However, cataract surgery as glaucoma prevention and treatment should be used only in appropriate cases. Those with extensive glaucomatous damage are not indicated for phaco treatment alone, he said.

Dr. Poley and colleagues have suggested a “decision tree” for preventing and treating glaucoma. They said that phaco is the ideal treatment for patients who have IOP of 24 mm Hg or higher and any risk factors, including family history of glaucoma, early cataract, shallow anterior chamber and poor adherence to medication.

More mechanism research

Others have also investigated the mechanism of glaucoma. Murray A. Johnstone, MD, said Ellingsen and Grant were among the first clinicians to make a connection between lens position and IOP. They showed that outflow resistance increases in correlation with IOP increases, especially in glaucomatous eyes.

“They concluded that movement of the lens backward caused traction on the scleral spur, preventing closure of Schlemm’s, and postulated that the lens movement backward opened the canal, improving aqueous outflow,” Dr. Johnstone said. “About a year later, I was able to show that increases in intraocular pressure actually do cause the walls of Schlemm’s canal to come together, fitting in with their thesis.”

The further work of Van Buskirk and Grant showed that backward movement of the lens opens Schlemm’s canal and markedly improves aqueous outflow.

More recent evidence from MRI studies demonstrates that the lens in humans grows only anteriorly with age, Dr. Johnstone said. The lens capsule and zonules move forward, causing the ciliary body to shift more anteriorly. The forward shift of the ciliary body in turn causes vector forces that favor narrowing and closure of Schlemm’s canal. The combined laboratory and clinical evidence is consistent with the idea that lens growth with age may be a causal factor in the closure of Schlemm’s canal and the increase in IOP in glaucoma.

Dr. Johnstone said growth of the lens may be one part of the complex equation of the mechanism of glaucoma. Removal of the lens may in turn be one mechanism for resolution of the glaucoma problem.

In his own practice, many glaucoma surgery case referrals are pseudophakic.

“That suggests to me that cataract surgery alone is not beneficial in many patients with advanced glaucoma,” Dr. Johnstone said. On the other hand, patients may have experienced possible “permanent immobilization of the meshwork” from chronic Schlemm’s canal wall apposition or phaco that was performed too late to be effective, he said.

“I’m left with the impression that there may be a subset of patients who will benefit, but that many may not. I think it will take time to sort out what percentage of patients will benefit and especially what subset might be most benefitted,” Dr. Johnstone said. Ivan Goldberg, FRANZCO, FRACS, said the mechanism of IOP elevation could explain the difference in IOP reductions among subsets of the disease. Eyes with angle-closure glaucoma could have the best results from phaco because removal of the lens changes the anterior segment configuration, thus reducing IOP.

Ivan Goldberg

Dr. Goldberg said that for patients who have clear lenses and open drainage angles, removing the lens would not be the most effective way to lower IOP.

“In open-angle eyes with elevated IOP, the response to lens removal is highly variable and unpredictable,” he said.

Impact on current treatment paradigm

Cataract surgery has already had an impact on the glaucoma treatment paradigm, Jonathan S. Myers, MD, said. There has been an increased use of phaco alone, instead of trabeculectomy or phaco combined with trabeculectomy, in acute angle-closure glaucoma cases, he said. Also, in cases with co-existing cataracts and early to moderate glaucoma, there has been a decrease in the use of combined procedures.

“Phaco alone is often a safer alternative, allowing quicker visual recovery for patients than combined procedures,” Dr. Myers said.

Dr. Myers has been sent cases suffering from severe IOP spikes after phaco, often in advanced glaucoma cases on maximal medications. Those spikes can result in more field loss and glaucoma surgery, he said.

Patients on maximum medications are more likely to spike in the event of a complicated phaco procedure, Dr. Myers added.

Postop IOP spikes are also an issue in pseudoexfoliation syndrome eyes, Dr. Shingleton said. He and colleagues conducted a study of 1,000 pseudoexfoliation eyes and found that 17% to 18% of those eyes had a pressure of 30 mm Hg or more on the first day postop.

Dr. Brown said physicians should use care when using phaco to treat glaucoma because it will not work effectively with every patient.

There are patients in whom cataract surgery is not going to be enough,” he said. “We can’t count on a reduction of 5 mm Hg or more in every case we do cataract surgery on. So we have to go into the borderline cases at least prepared for glaucoma surgery later on if the cataract surgery doesn’t lower the pressure enough.”

Dr. Brown credited work by Prof. Lam in helping change surgeons’ mindset about phaco. Prof. Lam had examined the aftermath of angle-closure and angle-closure attack and found cataract surgery an effective treatment compared with laser iridectomy.

“Patients have fewer spikes, and they’re less likely to have high pressures. I think this has really changed our view of cataract surgery,” Dr. Brown said. “Ophthalmologists in general are more aware of cataract surgery as being a beneficial step in patients with angle closure, at least.”

Role of combined procedures

Although performed less frequently in recent years, combined procedures are still an important option for many glaucoma patients. Dr. Shingleton said he has found that combined procedures are most indicated in patients with significant glaucomatous optic nerve cupping and optic field loss.

“There’s still a role for all the aspects of adjunctive therapy with cataract surgery,” he said. “What’s important to understand is that the cataract surgery itself can have a significant impact that’s positive for glaucoma treatment, which wasn’t quite as well appreciated in the past.”

Canaloplasty, the Glaukos iStent, endocyclophotocoagulation and shunts to the suprachoroidal space are providing surgeons with options other than filtration surgery to significantly reduce high pressures, Dr. Shingleton said.

For those with permanent angle-closure, cataract surgery with goniosynechialysis is an effective way of lowering high pressure, sometimes achieving a normal pressure with limited to no medications, according to Dr. Brown.

Prof. Lam said combined procedures will most likely continue into the future because removing the lens alone is not always enough to achieve target pressure.

“Glaucoma surgery is one of the most effective means to lowering the IOP,” he said.

Future of phaco as glaucoma treatment

In the future, a better understanding of the precise role that cataract surgery plays in elevating pressure in all subsets of glaucoma could enhance its place in the glaucoma treatment paradigm. It could also increase its use as treatment, especially as presbyopia IOL lens exchange technology improves, according to Dr. Myers.

“If multifocal and accommodative IOL technology reaches the point at which large numbers of patients are choosing clear lens extraction to deal with presbyopia at younger ages, then the IOP-lowering aspect of the procedure may be more widely exploited as more patients with early glaucoma and ocular hypertension have an additional reason to consider lens extraction,” he said.

Dr. Poley predicted that one day, patients with potentially progressive ocular hypertension will be treated with preventive lens extraction and IOL implantation. He compared the glaucoma treatment scenario to the historical treatment of polio and appendicitis. Both medical conditions were treated based on their symptoms because medical professionals did not know the causes. As soon as causes were discovered for both conditions, they were prevented or treated more effectively, he said.

“The best treatment for any disease is to discover the cause. Once we understand the cause, the treatment will follow,” Dr. Poley said.

However, Dr. Johnstone said it is too early to predict where phaco will be in the glaucoma treatment paradigm in the next 10 years.

“As with so many new findings, early promise does not always turn out to represent the full picture,” he said. – by Erin L. Boyle

In light of research showing adequate IOP-lowering effects of cataract surgery alone, do you think combined procedures are still viable? If so, why?

References:

• Ellingsen BA, Grant WM. Trabeculotomy and sinusotomy in enucleated human eyes. Invest Ophthalmol. 1972;11(1):21-28.
• Issa SA, Pacheco J, Mahmood U, Nolan J, Beatty S. A novel index for predicting intraocular pressure reduction following cataract surgery. Br J Ophthalmol. 2005; 89(5):543-546.
• Johnstone MA. The aqueous outflow system as a mechanical pump: evidence from examination of tissue and aqueous movement in human and non-human primates. J Glaucoma. 2004;13(5):421-438.
• Johnstone MA. A new model describes an aqueous outflow pump and explores causes of pump failure in glaucoma. In: Grehn H, Stamper R, eds. Essentials in Ophthalmology: Glaucoma II. Vol. 2. Heidelberg: Springer; 2006.
• Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713.
• Pohjalainen T, Vesti E, Uusitalo RJ, Laatikainen L. Phacoemulsification and intraocular lens implantation in eyes with open-angle glaucoma. Acta Ophthalmol Scand. 2001;79(3):313-316.
• Poley BJ, Lindstrom RL, Samuelson TW. Long-term effects of phacoemulsification with intraocular lens implantation in normotensive and ocular hypertensive eyes. J Cataract Refract Surg. 2008;34:735-742.
• Shingleton BJ, Gamell LS, O’Donoghue MW, Baylus SL, King R. Long-term changes in intraocular pressure after clear corneal phacoemulsification: normal patients versus glaucoma suspect and glaucoma patients. J Cataract Refract Surg. 1999;25(7):885-890.
• Shingleton BJ, Pasternack JJ, Hung JW, O’Donoghue MW. Three and five year changes in intraocular pressures after clear corneal phacoemulsification in open angle glaucoma patients, glaucoma suspects, and normal patients. J Glaucoma. 2006;15(6):494-498.
• Strenk SA, Strenk LM, Guo S. Magnetic resonance imaging of aging, accommodating, phakic, and pseudophakic ciliary muscle diameters. J Cataract Refract Surg. 2006;32(11):1792-1798.
• Suzuki R, Kuroki S, Fujiwara N. Ten-year follow-up of intraocular pressure after phacoemulsification and aspiration with intraocular lens implantation performed by the same surgeon. Ophthalmologica. 1997;211(2):79-83.
• Tennen DG, Masket S. Short-and long-term effect of clear corneal incisions on intraocular pressure. J Cataract Refract Surg. 1996;22(5):568-570.
• Tham CC, Kwong YY, Leung DY, et al. Phacoemulsification versus combined phaco-trabeculectomy in medically controlled chronic angle-closure glaucoma with cataract. Ophthalmology. 2008;115(12):2167-2173.
• Van Buskirk EM. Anatomic correlates of changing aqueous outflow facility in excised human eyes. Invest Ophthalmol Vis Sci. 1982;22(5):625-632.
• Van Buskirk EM. Changes in the facility of aqueous outflow induced by lens depression and intraocular pressure in excised human eyes. Am J Ophthalmol. 1976;82(5):736-740.
• Van Buskirk EM, Grant WM. Lens depression and aqueous outflow in enucleated primate eyes. Am J Ophthalmol. 1973;76(5):632-640.

• Reay H. Brown, MD, can be reached at 993-D Johnson Ferry Road NE, Suite 250, Atlanta, GA 30342; 404-252-1194; fax: 404-252-1196; e-mail: reaymary@comcast.net.
• Ivan Goldberg, FRANZCO, FRACS, can be reached at 187 Macquarie St. Park House, Floor 4, Suite 2, Sydney NSW 2000, Australia; 61-2-9247-9972; fax: 61-2-9232-3086; e-mail: eyegoldberg@gmail.com.
• Murray A. Johnstone, MD, can be reached at Glaucoma Consultants Northwest, 1221 Madison St. Suite 1124, Seattle, WA 98104-3536; 206-682-3447; fax: 206-682-8219; e-mail: glaucomadocs@hotmail.com.
• Dennis S.C. Lam, MD, FRCOphth, can be reached at Hong Kong Eye Hospital, The Chinese University of Hong Kong, 3/F, 147K Argyle St., Kowloon, Hong Kong SAR, China; 852-2762-3157; fax: 852-2715-9490; e-mail: dennislam8@cuhk.edu.hk.
• Jonathan S. Myers, MD, can be reached at Wills Eye Institute, 840 Walnut St., Philadelphia, PA 19107; 215-928-3197; fax: 215-928-0166; e-mail: myers@willsglaucoma.org.
• Brooks J. Poley, MD, can be reached at scbrooks@hargray.com.
• Bradford J. Shingleton, MD, can be reached at Ophthalmic Consultants of Boston, 50 Staniford St., Suite 600, Boston, MA 02114; 617-367-4800; fax: 617-589-0552; e-mail: bjshingleton@eyeboston.com.