Glaucoma - Part 1: Is The Treatment Worse Than The Disease?

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Glaucoma -- Part 1: Is The Treatment Worse Than The Disease?

Introduction

Conventional medical treatment of glaucoma has been called equivocal. A holistic non-pharmacological approach to this blinding ocular disorder that includes dietary measures, exercise, life-style changes and nutritional supplements may come closer to resolving this mysterious eye disease than standard medical therapy which is fraught with the risk of serious side effects.

Thousands of research reports have been written on glaucoma since the turn of the century and researchers claim they are no closer to identifying the cause of this disease which primarily afflicts adults over age 40.

Glaucoma is called a mysterious disease, the "sneak thief of sight," because it is characterized by silent (non-painful, non-apparent) insidious loss of peripheral vision. Even physicians have a difficult time detecting this disease. One study shows that 47% of the patients with newly detected common (open-angle) glaucoma had been examined by an ophthalmologist or optometrist in the preceding 12 months.( 1) George L. Spaeth, a noted glaucoma researcher, indicates 70% of the visual loss in glaucoma occurs prior to the time the patient is first seen by a physician.( 2)

Fixation on Pressure

Most physicians diagnose glaucoma solely upon eye fluid pressure readings. So-called normal eye fluid pressure displaces 15-18mm of mercury (Hg) in a glass tube. When the intraocular pressure begins to rise above the normal range (>21 mm Hg) then physicians diagnose a condition called ocular hypertension. Most adults with ocular hypertension will not show any visual field deficits for years. It is only when visual field loss occurs and the optic disc begins to show changes that glaucoma is diagnosed.

W. Leydhecker indicates a significant portion of the adult population, 20%, exhibits intraocular fluid pressure exceeding 21 mm Hg in mass eye screenings. However, only 3% of the eyes below 23 mm Hg will develop narrowed visual fields. And only 8.4% of the patients with fluid pressure above 23 mm Hg develop visual field loss.

Sohan S. Hayreh writes that "the tragedy surrounding glaucoma has been attempts to blame the development of this disease on a single factor, such as raised intraocular pressure."( 3)

The Failure of Medical Therapy

Frank S. Ashburn, speaking at the 1994 American Academy of Ophthalmology meeting, said: "After a century of common practice, there is only equivocal evidence to suggest the validity of hypotensive therapy for glaucomatous optic atrophy."( 4)

A report released from the Center for Health Care Policy Research concludes there is no solid evidence that medical therapy for open-angle glaucoma or ocular hypertension reduces the risk or progression of visual field defects and that medical therapy subjects patients to unnecessary risks and is a waste of money. A review of some small studies seems to indicate reversal of cupping of the optic disc only after glaucoma surgery, not with medication.( 5) Another study conducted by Jay and Murray showed that 53% of eyes treated medically over a 4-year period eventually required surgery because topical medications failed to control the disease.( 6)

Pharmaceutical companies would like to expand the use of beta-blocker eye drops to the millions of adults who have ocular hypertension. Again, this is a condition that may precede glaucomatous visual field loss, but most of the time it doesn't affect vision. The likelihood that ocular hypertension will result in glaucoma ranges from zero to 30%. Frequently eye physicians are eager to start their patients on beta blockers upon the measurement of elevated eye fluid pressure alone, even though they have no other signs of glaucoma. Thus they expose the eye to the side effects of the glaucoma drops which not only can cause systemic problems but may well excite chronic inflammation that leads to glaucoma itself. In one Italian study, patients with ocular hypertension were divided into two groups. One group received the beta blocker eye drops and the other underwent no treatment. After 24 months there was no difference in the visual field between these two groups?

It is estimated that adults with ocular hypertension lose 0.5-1.0% of their peripheral vision per year. Such a slowly progressive disease makes it difficult to measure the effects of treatment. An authoritative 5-year study of ocular hypertensive patients showed that beta-blocking eye drops tend to reduce eye fluid pressure and retard visual field loss compared to ocular hypertensive patients who were withheld from treatment.( 8) Another study shows that early medical treatment of ocular hypertension (intraocular pressure between 22-28 mm Hg) appears to significantly reduce the number of patients who develop visual field loss compared to those who receive no treatment.( 9) Yet another recent six-year prospective study shows that only those ocular hypertensive patients who had coexisting cupping of the optic disc at the time of diagnosis were susceptible to visual field loss.( 10)

Irving M. Leopold writes: "The rate of visual loss among ocular hypertensive patients appears to be so low that it is highly probable that many will never succumb in their lifetime. The second important point that we consider is that all prophylactic therapy causes, rather than relieves, symptoms. What we are doing, therefore, is trying to balance the risk of permanent damage to vision through withholding active treatment against the disadvantages of taking asymptomatic patients, probably happy until we saw them, and giving them iatrogenic symptoms that may make them miserable, or at least reduce the quality of their lives."( 11)

Two noted researchers, Brian J. Caputo and L. Jay Katz, have offered a candid assessment of glaucoma treatment. In their words "It is sometimes difficult to determine whether these treatments are more detrimental than the disease itself." Here are pertinent facts offered by Caputo and Katz concerning conventional glaucoma therapy:( 12)

At least 2 million Americans have glaucoma. Some studies estimate that as many as 15 million Americans have glaucoma and 1.6 million have visual field loss. Glaucoma accounts for more than 7 million physicians' office visits annually. The out-of-pocket cost of glaucoma medications ranges from $79 to $204 a year.
In one study 80% of glaucoma patients who were not taking beta-blocker eye drops expressed that they were depressed compared with only 26% of patients with other serious ocular disorders.
Patient surveys confirm that 30% of patients experienced side effects from the medication used to control eye fluid pressure. These include bradycardia, congestive heart failure, arrhythmia, syncope, and pulmonary effects (wheezing and dyspnea). Author's notation: It is estimated that a few hundred glaucoma patients taking beta blockers die annually from medication-related respiratory problems.
Beta-blocker eye drops reduce high-density lipoprotein (HDL "good" cholesterol) and increase high-density lipoprotein (LDL). Carteolol (Ocupress) decreases HDL by 3.3% and timolol (Timoptic) by 8%. This translates into a 17% increased risk of myocardial infarction taking timolol and 6.6% taking carteolol.
A three times greater incidence of hip fracture has been documented among beta-blocker users (10.5%) compared to nonusers (3.3%). This is attributed to the syncope and dizziness that oftentimes occurs as a side effect when taking anti-glaucoma medication. This is no small problem since prevention of hip fracture has been identified by the AARP's Healthy Adults 2000 project as the major health threat to elderly females.( 12) Repair of a hip fracture costs about $25,000. About one out of three elderly hip fracture patients are dead one year following their fall.
Adverse side effects are not confined to beta-blocker eye drops. Carbonic anhydrase inhibitors are known to cause fatigue, lethargy, anorexia, weight loss, depression, dementia, diminished libido, and rarely, aplastic anemia.
Some studies reveal that glaucoma surgery, which involves the surgical removal of part of the fluid drain within the eye, is more effective at retarding visual field loss and in reducing costs of care.
Even if medical therapy can be proven to be efficacious, somewhere between 22-62% of glaucoma patients are noncompliant.( 14) A study of glaucoma patients whose vision progressed to legal blindness reveals that 39-46% of these patients were considered to be uncooperative.( 15) The mean number of days that patients forget to take their medications in a year is 112.( 16) In a controlled clinical study, 13% of experienced glaucoma patients are unable to instill eye drops into one or both eyes following repeated attempts and 80% fail to maintain the sterility of the bottle tip during administration.( 17)

Some patients have been documented to intentionally overdose in the false belief they were further alleviating their glaucoma. Some elderly patients are confused over proper dosage. Patients who overdose are at the greatest risk to develop bradycardia, depression, shortness of breath, hypotension and dizziness.( 18)

Diagnostic Tests are Unreliable

Eye physicians are trained to evaluate how much of the optic disc, observed at the back of the eye through an ophthalmoscope, is "cupped" or pushed out by the elevated fluid pressure. The evaluation of cup-to-disc ratio, which is helpful in estimating the progression of the disease, varies from one physician to another. One study showed that optometrists could only agree on their cup-to-disc estimate 56% of the time while this improved to 78% among ophthalmologists.( 19) But given the large number of patients who have glaucoma, this measurement appears to be crude and outdated.

The hallmark vision test for glaucoma is the visual fields test. This is often a very confusing test for elderly patients to take. It calls for the patient to push a button when they see flashing lights. A recent study reveals that twice-repeated visual field tests inaccurately indicate progression of the glaucoma 57% of the time.( 20) Eye physicians then make decisions to increase medication dosage, perform laser treatment or schedule surgery based upon this sometimes faulty data.

Diagnosis May Make the Patient Worse

Considerable anxiety and stress is involved once the diagnosis of glaucoma has been made. In one study 79% of glaucoma patients indicated that worry about blindness had seriously affected their health and quality of life. While glaucoma surgery has certain advantages over everyday medication (avoidance of side effects of medication, reduced out-of-pocket expense and freedom from daily use of drops), 15% of patients indicate the quality of their life was worse following surgery and 40% indicate there was no perceived improvement following surgery.( 21)

The Growing Cost of Care

An estimated $1.9 billion is spent on glaucoma care annually ($903 million on exams, $516 million on laser or surgical treatment, $351 million on medications, and $164 million on nursing home care and rehabilitation services). With lost wages and other associated costs the total cost of treatment for the common type of glaucoma exceeds $2.5 billion annually.( 22)

Paul Lee of the Doheny Eye Institute at the University of Southern California, predicts a four-times increase in the costs of glaucoma care by the year 2000 compared to 1988, which is largely attributed to the growth of senior adults in the U.S. population. Even if the cost of glaucoma medications could be reduced by 20%, and physicians' fees by 5%, this would not significantly reduce the costs of glaucoma care. Dr. Lee then asks how health care costs will be constrained given a growing population of glaucoma patients and the fact that 50% of glaucoma cases are undiagnosed. Dr. Lee calls for new approaches to glaucoma care that are more effective at a lower cost, but falls short of suggesting any specifics.( 23)

To further complicate the problem, the greater use of primary care specialists as "gatekeepers" in the health care system should dramatically increase the number of undetected cases of glaucoma. Family practice physicians, internal medicine specialists and OB-GYN physicians, who perform most of the primary care in the U.S., have not received proper training in the diagnosis of glaucoma and do not have the equipment to properly detect this disease. A recent study revealed that 78.4% of primary care physicians erroneously indicated elevated eye fluid pressure as the sole diagnostic indicator of the disease and only 38% were aware that beta blocker eye drops used to reduce intraocular pressure are contraindicated in cases of respiratory disease.( 24)

Is Modern Medicine Curing or Causing Glaucoma?

There is substantial evidence that the use of topical steroidal anti-inflammatory eye drops, or the instillation of any eye drops that contain preservatives, may actually exacerbate glaucoma itself.

An Italian study reveals that the use of corticosteroid eye drops dramatically increase the risk of developing ocular hypertension or glaucoma by seven times!( 25) Steroidal preparations are frequently used to reduce eye inflammation for a variety of eye conditions, especially following the more than 2 million eye operations performed in the U.S. annually. Patients are not usually warned of the potential risk of developing glaucoma before they are placed on these medications.

While anti-glaucoma drops decrease the production of fluid within the eye, they also reduce the flow of moisturizing tears on the surface of the eyes. In between blinks, dry spots can be observed to occur sooner on the surface of the eyes in patients who use glaucoma drops that contain the preservative benzalkonium chloride.( 26) When preservative-free anti-glaucoma drops are used there is a 60% reduction in symptoms of dry eyes.( 27)

Benzalkonium chloride, the preservative used in anti-glaucoma eye drops, helps to enhance the absorption of the medication by making the cornea more permeable. The cornea cannot heal itself as long as its surface layer is leaky (permeable). Artificial tears, without the preservative benzalkonium chloride, will reduce the permeability of the corneal surface by 44%, but eye drops with this preservative actually increase the leakiness of the corneal surface by 8%.( 28) Once the surface layer of the cornea is disrupted, more of the preservative accumulates, producing toxic effects.

After evaluating four different eye drop preservatives, researchers at the Medical College of Wisconsin said: "There is potential for severe damage with habitual use by a patient with corneal epithelial damage. Patients with severe dry eye who use artificial tears frequently should avoid tear preparations containing benzalkonium chloride; non-preserved preparations are preferable."( 29)

Even though benzalkonium chloride is used in only tiny amounts in anti-glaucoma eye drops and artificial tears, 4/100ths of 1% to 1/10th of 1%, these concentrations have been shown to be toxic to the cornea. One glaucoma patient is documented to have had to undergo a corneal transplant operation as a result of toxic effects of this preservative.( 30) How many other corneal transplants have been required because of this unrecognized toxic hazard?

Thus Benzalkonium chloride, the preservative used in beta-blocker eye drops (Brand names: Timoptic, Betagan, Betoptic, Optipranolol, Ocupress), promotes chronic inflammation and allergy that predisposes the eyes to perpetual inflammation. Chronic inflammation in the eye may, over time, promote the gradual onset of glaucoma. Inflammatory proteins can clog up the drainage canals of the inner eye and increase fluid pressure. It is likely that any artificial tear drop with benzalkonium chloride, or other toxic preservatives, actually increases the risk of developing glaucoma over time. While it would take years to prove this theory, it is a plausible conclusion based upon currently available medical data.

In the Physicians Desk Reference some manufacturers of beta-blocker eye drops indicate side effects such as dry eye and inflammation are "rare." But the makers of one beta-blocker eye drop more accurately indicate that "transient eye irritation, burning, tearing, eye redness and swelling occur in about one in every four patients." ( 31)Ocular symptoms include blurred and cloudy vision, photophobia, decreased night vision, droopy eyelids, puffy eyelids and conjunctivitis.

When medications for glaucoma fail to keep the eye fluid pressure under control, glaucoma surgery is considered. This operation involves the creation of a "pressure relief valve" (called a filtering bleb) inside the eye. The surgically created canal has a tendency to become scarred, inflamed, and closes up, and the pressure in the eye rises once again. When researchers went looking for the cause of these surgical failures they found that benzalkonium chloride, the preservative in glaucoma drops, was the cause of allergic and inflammatory reactions in half of the patients who underwent surgery.( 32) Another study also confirms that benzalkonium chloride preservative is responsible for exciting the production of fibroblasts (inflammatory cells) that cause the failure of glaucoma operations.( 33)

Additional problem: Contact lens cleaning solutions also contain preservatives, such as benzalkonium chloride and thimerosal. Benzalkonium chloride accumulates within soft contact lenses to a concentration beyond safety levels.( 34)

Medicine, Laser or Surgery?

Numerous studies indicate glaucoma surgery appears to reduce intraocular pressure better than medicines or laser treatment. Over a five-year period average intraocular pressure was 14.1 mm Hg for surgery patients compared to 18.5 mm Hg for glaucoma patients treated with laser or topical medications. Success rates for laser, medicine and surgery were 68%, 83% and 98% respectively, over the same time period. And in the measurement of peripheral vision, which is what really counts in glaucoma treatment, patients treated with laser and medicines experienced 3-6 times more deterioration of their side vision compared to surgically treated patients.( 35) The drawback of glaucoma surgery is the eventual onset of a cataract, which could be averted by postoperative nutritional therapy (outlined previously by this author in the June, 1995 Townsend Letter for Doctors).( 36) It is no wonder that surgery appears to work better than medications, given the deleterious side effects of the medications themselves.

Summary

In short, the state of glaucoma care is in a mess, in need of an overhaul, and no one has even hinted at details of how to provide timely, quality glaucoma care at less cost. For the above reasons, alternative approaches to glaucoma care need to be fully explored. A review of the current medical literature (to be presented in part III of this paper) provides sufficient reason to believe that glaucoma can be prevented, arrested or even eradicated through non-pharmacological treatment at considerable less cost and increased safety over conventional care.

The current approach to eradicating glaucoma is so fraught with side effects that it is difficult to separate the treatment from the disease. Antiglaucoma therapy should follow the dictum to "first do no harm."

References
(1.) Wright M, Testing, coverage must improve to make progress in glaucoma, Ophthalmology Times 1993; p. 18, June 15.

(2.) Leydhecker W, Krieglstein GK, Glaucoma Update II, Springer-Verlag, Berlin, 1983, pp. 95-102.

(3.) Hayreh SS, Progress in understanding the vascular etiology of glaucoma, Current Opinion in Ophthalmology 1994; 5: 26-35.

(4.) Sabbagh L, Glaucoma care is reappraised, Ophthalmology Times 1995; 20: 1 & 22.

(5.) Weighing the evidence for glaucoma treatment, Ocular Surgery News, July 15, 1988, pp. 33-37.

(6.) Jay FL, Murray SB, Ealy trabeculectomy versus conventional management in primary open-angle glaucoma, British Journal Ophthalmology 1988; 72: 881-89.

(7.) Ravalico G, et al, Ocular hypertension: a follow-up study in treated and untreated patients, New Trends in Ophthalmology 1994; 2: 97-101.

(8.) Kass MA, Timolol treatment prevents or delays glaucomatous visual field loss in individuals with ocular hypertension: a five-year randomized double-masked, clinical trial, Transactions American Ophthalmic Society 1989; 87: 598-618.

(9.) Epstein DL, et al, A long-term clinical trial of timolol therapy versus no treatment in the management of glaucoma suspects, Ophthalmology 1989; 96: 1460-67.

(10.) Schulzer M, Drance SM, Douglas GR, A comparison of treated and untreated glaucoma suspects, Ophthalmology 1991; 98: 301-07.

(11.) Leopold IH, Perspectives in drug therapy of glaucoma, Glaucoma: Applied Pharmacology in Medical Treatment, Grune & Stratton, 1984, p. 3.

(12.) Caputo BJ, Katz LJ, The quality of life of the glaucoma patient in the light of treatment modalities, Current Opinion in Ophthalmology 1994; 5, II: 10-14

(13.) Developing fall prevention programs for older adults, American Association of Retired Persons 1993.

(14.) Wright M, What are the reasons for patient noncompliance?, Ophthalmology Times 1990, June 1, p. 20.

(15.) Grant M, Burke JF Jr., Why do some people go blind from glaucoma?, Ophthalmology 1982; 89: 991-98.

(16.) Gurwitz JH, et al, Treatment for glaucoma: adherence by the elderly, American Journal of Public Health 1993; 83: 711-16.

(17.) Brown MM, Brown GC, Spaeth GL, Improper topical self-administration of ocular medication among patients with glaucoma, Canadian Journal Ophthalmology 1984; 19: 2-4.

(18.) Hayes LP, et al, Timolol side effects and inadvertent overdosing, Journal American Geriatric Society 1989; 37: 261-62.

(19.) Abrams LS, et al, Agreement among optometrists, ophthalmologists and residents in evaluating the optic disc for glaucoma, Ophthalmology 1994; 101: 1662-67.

(20.) Schulzer M, Errors in the diagnosis of visual field progression in normal-tension glaucoma, Ophthalmology 1994; 101: 1589-95.

(21.) Spaeth GL, Birbilis EP, The effect of glaucoma and treatment of glaucoma on the quality of life, Glaucoma Update IV, Springer-Verlag, Berlin, 1991, pp. 206-07.

(22.) Guzman G, et al, Glaucoma in the United States population: the economic burden of illness, Investigative Ophthalmology 1992; 33: Arvo Abstracts 327.

(23.) Lee P, Economic concerns in glaucoma management in the 21st Century, Journal of Glaucoma 1993; 2: 148-51.

(24.) Cowan CL, Levy T, Physician knowledge and attitudes on glaucoma, Investigative Ophthalmology 1994; 35 Arvo Abstracts.

(25.) Ponte F, et al, Risk factors of ocular hypertension and glaucoma, Documenta Ophthalmologica 1994; 85: 203-10.

(26.) Marquardt R, Schubert T, Effect of preservative-free beta-blocking eye drops on break-up time, Klin. Mbl, Augenheilk 1991: 199; 75-78.

(27.) Jong de C, et al, Topical timolol with and without benzalkonium chloride, Graefe's Archives of Clinical Ophthalmology 1994; 232: 221-24.

(28.) Gobbels M, Spitznas M, Effects of artificial tears on corneal epithelial permeability in dry eyes, Graefe's Archives of Ophthalmology 1991; 229: 345-49.

(29.) Bernal LL, Ubels JL, Quantitative evaluation of the corneal epithelial barrier: effect of artificial tears and preservatives, Current Eye Research 1991; 10: 645-56.

(30.) Lemp MA, Zimmerman LE, Toxic endothelial degeneration in ocular surface disease treated with topical medications containing benzalkonium chloride, American Journal of Ophthalmology 1988; 105: 670-73.

(31.) Physicians Desk Reference 1993, p. 305

(32.) Baudouin C, et al, Expression of inflammatory membrane markers by conjunctival cells in chronically treated patients with glaucoma, Ophthalmology 1994; 101: 454-60.

(33.) Williams DE, et al, Effects of timolol, betaxolol, and levobunolol on human tenon's fibroblasts in tissue culture, Investigative Ophthalmology and Visual Sciences 1992; 33: 2233-41, 1992.

(34.) Chapman JM, Cheeks L, Green K, Interactions of benzalkonium chloride with soft and hard contact lenses, Archives of Ophthalmology 1990; 108: 244-46.

(35.) Migdal C, Gregory W, Hitchings R, Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma, Ophthalmology 1994; 101: 1651-57.

(36.) Sardi, B, Eradicating cataracts, Townsend Letter for Doctors and Patients, 1995; 143:50-59.

Townsend Letter for Doctors & Patients.

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By Bill Sardi

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