Pneumatic Trabeculoplasty (PNT) Has Not Been
Proven Safe and Effective for Treating Glaucoma

Stephen Barrett, M.D.

Glaucoma is a group of disorders in which pressure within the eyeball [intraocular pressure (IOP)] exceeds the person's tolerance and, over a period of years, can damage the eye and impair vision. The damage can range from slight impairment to complete blindness. The pressure results from an imbalance between production and drainage of the intraocular fluid (aqueous humor). The pressure is usually high, but damage can occur at relatively low levels in people whose tolerance to pressure is apparently low. Most cases of glaucoma can be controlled with eyedrops [1]. Oral medication and/or surgery may be used when control cannot be achieved with the drops.

This article concerns pneumatic trabeculoplasty (PNT), a surgical procedure claimed to lower IOP and reduce or eliminate the need for medication. After studying the evidence with help from several experts, I have concluded that PNT does not work and poses serious danger to patients.

Background History

In 1997, the Arizona Glaucoma Institute (AGI), of Scottsdale, Arizona, began offering a "new treatment" for open-angle and pigmentary glaucoma using a patented vacuum-ring device. Devices of this type are FDA-approved for stabilizing the eye during refractive surgery, but they are not approved in the United States for treating glaucoma. The institute's parent company, Coronado Industries, marketed the device through another subsidiary called Ophthalmic International. The device was invented by company chairman Richard G. Smith and ophthalmologist John T. LiVecchi, M.D. and patented by Coronado in 1994 [2]. Company documents have described LiVecchi as medical director and a major shareholder of Coronado Industries.

The patent document states:

The open angle glaucoma treatment apparatus is a vacuum source and a vacuum applicator coupled by a hose. The vacuum applicator is an eye ring or an eye cup that is placed on the frontal surface of an eye. Suction (negative pressure) in the range of 10 to 30 mm. Hg. is applied by the vacuum source, which will fixture the ring or cup to the eye, or alternatively pressure is applied for 15 to 120 seconds. A second treatment is recommended later. It could be within twelve hours, on the following day, or within the next couple of days [2].

An AGI brochure stated that a 2-minute treatment with the device lowers IOP in most cases. [3] Another AGI document stated that during the previous four years, "a good number" of patients had been taken off of their medication completely and that "a number of patients" remained on medication but required reduced dosage [4]. PNT cost about $200 per treatment. In September 1997, the institute offered free glaucoma screenings in connection with its "grand opening." [5]

Early in 1998, an Arizona investment firm seeking investors for Coronado Industries issued a private offering summary which noted that the AGI's medical director, ophthalmologist Leo D. Bores, M.D., had originated the radial keratotomy procedure [6]. The solicitation, intended "for broker-dealer internal use only," projected after-tax earnings of $12 million in 1998, $46 million in 1999, and $99 million in the year 2000. The solicitation also stated that the proceeds would be used to open additional Glaucoma Treatment Centers and that Coronado Industries believed that "insurance companies will . . . quickly approve payment for the new device and procedure since it is projected to reduce the cost of long-term care costs associated with alternative treatments." [6] However, the company's Form SB-2 Registration Statement filed with the Securities and Exchange Commission on 8/24/98, noted receipts of only $179,767 and an overall loss of $648,702 for the first half of 1998 [7].

Coronado's hopes for financial success have not materialized. The AGI clinic closed in 1999 after the Arizona Medical Board took action (described below) against Dr. Bores, and lack of FDA approval has blocked sale of the device within the United States. The device received CERMET certification in 2004, which means it can be marketed in about 25 other countries. So far, however, Coronado has steadily lost money since its inception.

No Evidence of Effectiveness

The fluid within the eyeball normally drains through the trabecular meshwork, a thin net-like band that lies between between the cornea (the clear window of the eye) and the sclera (the white portion of the eye). Glaucoma usually occurs because the mesh becomes clogged or is unable to allow sufficient drainage. When this happens, since fluid production continues, IOP builds up. Proponents postulate that PNT reduces IOP by stretching the trabecular meshwork so that more fluid flows out of the eye. However, this has not been anatomically demonstrated.

Studying whether a treatment is effective against glaucoma is complicated because (a) IOP can vary from day to day, (b) sensitivity to increased pressure can vary considerably from person to person, (c) blindness from glaucoma typically takes 12 to 15 years to develop, so long-term monitoring is necessary, and (d) the tests that measure IOP involve interpretations that could be influenced by observer bias. To be valid, a test protocol should include the following:

PNT proponents claim that three published studies demonstrate effectiveness. Two of these studies were described by Drs. Bores and LiVecchi and a Mexican ophthalmologist (Guillermo Avalos Urzúa, M.D.) in a paper that was published in 2005 in the Annals of Ophthalmology [8]. The first study involved 177 patients of Avelos and LiVecchi who underwent PNT twice one week apart and then about every 3 months for from 2 to 8 years between 1994 and 2001. The report stated that many of these patients were able to reduce or eliminate their glaucoma medication and that there was a 6.3 mm Hg drop in average IOP. The second study involved 317 eyes from 172 patients that Bores treated at the Arizona Glaucoma Institute for up to 18 months beginning in 1997. The report stated that many of these patients were able to reduce or eliminate the the amount of medication they took. However, these studies were so poorly designed that they should be regarded as meaningless.

The third allegedly positive study was published in 2005 in the European Journal of Ophthalmology [9]. This study involved 37 patients who were observed during 2001 and 2002 in two Italian clinics. The protocol called for treating one eye in each patient while the other served as a control for 30 days. The second eye was then treated, and the first eye was treated again two months later. The first eye treated was the one with the higher IOP. The authors claim that PNT lowered the average IOP by about 2 mg Hg. However, the study had many flaws, and proper statistical analysis actually shows no benefit.

The best designed study of PNT was reported in 1998 by researchers at Duke University. This study involved 8 glaucoma patients with who had one eye treated while the other served as a control. Measurements at 1 hour, 2 hours, 1 day, 1 week, 1 month, and 3 months later found no reduction of IOP or improvement in the drainage of fluid from within the eye [10].

The European Journal of Ophthalmology paper mentions but does not identify another study that involved 49 patients with glaucoma who took multiple medications and/or had prior multiple surgeries, and "did not respond well to PNT."

Significant Safety Risk

Normal IOPs range from 8 to 20 millimeters of mercury (mm Hg). In high-pressure glaucoma, the levels range from 21 to 40. In rare cases, new patients present with higher levels. The higher the IOP, the more likely that optic nerve damage will occur.

PNT temporarily squeezes the front of the eyeball and raises the IOP to 65 and perhaps even higher. In someone with an already damaged optic nerve, this could be serious. The accepted treatment for glaucoma is to lower the IOP with medication or surgery. Experiments in monkeys have demonstrated that sudden pressure elevations can compromise the blood supply to the optic nerve and accelerate nerve cell death in already weakened cells [11,12], and human experiments have found that acute pressure increases can increase cupping of the optic nerve [13,14]. Two cases have been reported of patients who lost part of their vision following refractive surgery during which a suction ring was applied to their eyeball [15,16]. Although no such complications have been reported with PNT, it still should be viewed with caution. Damage from high IOP may not be immediately apparent because visual impairment from glaucoma typically takes many years to develop. Proof of safety and effectiveness would require long-term studies showing not only that IOP is lowered, but also that the patients' visual fields have not been adversely affected.

Minor complications from PNT appear to be common. The Italian researchers stated that 34 of their 37 patients had adverse effects such as redness of the eye (26 patients) or conjunctival bleeding (14 patients), but these effects were temporary and not serious.

FDA Objections

Documents obtained with a Freedom of Information Act request indicate that in February 1998, the FDA issued a warning letter to Ophthalmic International president G. Richard Smith. The letter stated:

During an inspection of your firm conducted between November 25 and December 11, 1997, our investigators determined that your firm distributed two vacuum fixation devices with suction rings to the Arizona Glaucoma Institute. . . for use in treating patients with glaucoma using a pneumatic trabeculoplasty (PNT) procedure. These products are devices as defined by . . . the Federal Food, Drug, and Cosmetic Act.

Your vacuum fixation devices are adulterated . . . in that they are Class III devices. . . and do not have approved applications for investigational device exemption (IDE). . . . Your . . . devices are also misbranded . . . in that a notice or other information respecting the devices was not provided to the FDA as required [17].

The letter indicated that because the device is not approved for the treatment of glaucoma, the FDA regards it as a new device for which FDA approval is required and that:

The sponsors of investigations, investigators, or any persons acting for or on behalf of a sponsor or an investigator may not promote or test market an investigational device or represent that it is safe or effective for the purpose for which it is being investigated.

Smith replied that (a) the vacuum fixation device did have an IDE and should not be considered a Class III device, (b) an Institutional Review Board (IRB) had determined that the device did not pose an unreasonable risk to patients, and (c)his company plans to submit an application to broaden the way the device is used [18]. However, an FDA official responded that (a) the device had not been formally classified, (b) new devices are automatically placed in Class III, and (c) the agency disagreed with the IRB's conclusion [19]. In August 1998, the company submitted an IDE application, which the FDA rejected.

Disciplinary Action

In March 1999, Dr. Bores announced that he had retired from clinical practice but would continue to direct research at anther clinic with which AGI had merged [20]. In December 1999, after additional communication with the FDA, Ophthalmic International was given permission to conduct a small "feasibility study." [23] Federal regulations state that during clinical studies, no investigator or sponsor can commercially distribute an unapproved device, charge subjects more than the amount needed to cover costs, or represent that the device is safe or effective for its intended purpose. The Arizona Medical Board concluded that Bores did all of these things, lacked FDA approval to conduct any PNT studies, and improperly collected Medicare payments for patients treated between December 1997 and February 1999. In April 2003, the board reprimanded Bores and placed him on two years' probation under which he was barred from conducting studies that did not meet FDA criteria. He was also required to reimburse Medicare for $15,539.81 that he had been paid for the 1997-1999 treatments [21].

The Current Situation

Press releases from Coronado Industries indicate that the company has received approval to market its PNT equipment in several countries and has begun to do that. However, it appears to be a long way off from getting FDA clearance to sell within the United States. Its third-quarter 2005 report to the U.S. Securities and Exchange Commission states:

The Company has not made an operating profit since its reorganization in 1996. Further, the Company has a working capital deficit of $891,435 and a negative net worth of $878,266.

At this time the greatest impediment to the Company’s profitability is the FDA approval of the sale of its products in the United States. The Company has been attempting to negotiate the protocol for a clinical study in the United States which would be relatively short in duration and inexpensive to complete. The previous finding of a “significant patient risk” by the FDA has thus far been a problem to negotiating a favorable clinical study protocol. The Company is hopeful that the results of a recent animal study and a new presentation of older patient records will permit a favorable clinical study protocol to be granted by the FDA within the next year.

If a favorable clinical study protocol were granted by the FDA the Company anticipates it will be about two years after the clinical study commences before the Company’s products could be sold in the U.S. The estimated cost of the clinical study is several million dollars. The Company is hopeful a major medical equipment distributor will pay the majority of the clinical study expenses as consideration for receiving the U.S. or worldwide marketing rights to the products. If the Company is unable to obtain third party funding of the clinical study, the Company will seek equity or debt financing for the clinical study. There is no assurance that the Company will be able to adequately fund any clinical study permitted by the FDA.

Until the Company receives its FDA approval the Company will be dependent on loans from its management and improved international sales. During 2004 the Company received its Type 2a product classification and began shipping its products overseas pursuant to four distribution contracts. The Company recorded product revenue of approximately $88,330 during the first three quarters of 2005. The Company anticipates slightly increased product revenues in 2006 from these European distribution agreements [22].

The Bottom Line

Pneumatic trabeculoplasty has not been proven safe or effective for treating glaucoma; and Coronado Industries' vacuum fixation device lacks FDA approval for such use. It remains to be seen whether additional research will demonstrate benefit. I do not believe that it will.

For Additional Information about Glaucoma

Acknowledgement

Two ophthalmologist served as consultants for this article:

References

  1. Glaucoma. In Beers MH, Berko R, editors. The Merck Manual of Diagnosis and Therapy, Seventeenth Edition. Whitehouse Station, NJ: Merck Research Laboratories, 1999, pp 733-738.
  2. Open angle treatment apparatus and method. Patent No. 5,601,548, Feb 11, 1997.
  3. Announcing a new treatment for glaucoma. Flyer from the Arizona Glaucoma Institute, Scottsdale, Arizona, 1997.
  4. "Dear Glaucoma Patient." Letter from Arizona Glaucoma Institute. Undated, acquired in 1997.
  5. Coronado Industries, Inc., announces grand opening of exclusive glaucoma treatment center. Press release, Sept 5, 1997.
  6. Private offering summary. $5,600,000. Coronado Industries, Inc. (NASDAQ Symbol CDIK) 12% 5-year Convertible Notes. Fox & Company Investments, Phoenix, Arizona, January 29, 1998.
  7. Coronado Industries. Form SB-2 Registration Statement filed 8/24/98 with the Securities and Exchange Commission.
  8. Urzua GA, Bores LD, LiVecchi JT. A new method to treat primary open-angle glaucoma and reduce the number of concomitant medications. Annals of Ophthalmology 37:37-46, 2005.
  9. Bucci MG and others. Pilot study to evaluate the efficacy and safety of pneumatic trabeculoplasty in glaucoma and ocular hypertension. European Journal of Ophthalmology 15:347-352, 2005.
  10. Harris JW and others. Determination of the efficacy and mechanism of action for pneumatic trabeculoplasty in the treatment of open-angle glaucoma. Abstract. Investigative Ophthalmology & Visual Science 39(4), 1998.
  11. Shirakashi M. The effects of intraocular pressure elevation on optic nerve axonal transport in the monkey. Acta Ophthalmologica 68:37-43, 1990.
  12. Coleman AL and others. Displacement of the optic nerve head by acute changes in intraocular pressure in monkey eyes. Ophthalmology 98:35-40, 1991.
  13. Parrow KA and others. Intraocular pressure-dependent dynamic changes of optic disc cupping in adult glaucoma patients. Ophthalmology 99:36-40, 1992.
  14. Azuara-Blanco A and others. Effects of short term increase of intraocular pressure on optic disc cupping. British Journal of Ophthalmology 82:880-883, 1998.
  15. Bushley DM and others. Visual field defect associated with laser in situ keratomileusis. American Journal of Ophthalmology 129:668-671, 2000.
  16. Weiss HS and others. LASIK-associated visual field loss in a glaucoma suspect. Archives of Ophthalmology 119:173-174, 2001.
  17. Messa EC. Warning letter to Gary Smith, President, Ophthalmic International. FDA Los Angeles District Office, February 12, 1998.
  18. Smith GR. Letter to FDA Compliance Officer Dannie E. Rowland, March 30, 1998.
  19. Messa EC. Letter to G. Richard Smith, May 4, 1998.
  20. Bores LD. A notice from the Arizona Glaucoma Institute, February 26, 1999.
  21. Consent agreement and order for letter of reprimand and probation. In the matter of Leo Bores, M.D. Arizona Medical Board Case # MD-97-0948, April 4, 2003.
  22. Coronado Industries. Quarterly report under section 13 or 15(d) of the Securities Exchange Act of 1934. For the quarterly period ended September 30, 2005.

This article was revised on January 15, 2006.