Glaucoma is a potentially blinding ocular disease that commonly affects elderly persons. In this review, we discuss the range of clinical findings, appropriate diagnostic tests, and available medical, laser, and surgical treatment options. New developments in the evaluation of the optic nerve and in visual field testing may facilitate the early detection of glaucoma, and new therapeutic agents hold promise for the future.
Glaucoma remains a challenging and puzzling disorder. Many of the questions raised about this condition a century ago are still being pondered today. Although great strides have been made in its understanding and treatment, the underlying cause of the most prevalent kinds of glaucoma remains a mystery. Glaucoma affects more than 2 million Americans; 3% of people older than 65 years of age are affected. It is the leading cause of blindness in the United States.
Glaucoma is actually a group of diseases of the eye, having the common feature of progressive damage to the optic nerve usually caused by elevated intraocular pressure. As optic nerve damage occurs, characteristic blind spots and patterns develop, which lead to total blindness if the disease remains uncontrolled.
The word “glaucoma” may have been derived from a Greek prefix meaning bright, shining, sparkling, or chromatic (glauco) or from the Greek word for owl (glaux).
2The word must have originally been used to distinguish persons who were blind with clear pupils (Latin, guttata serena) from those who were blind from cataracts (Latin, guttata obscura). During the 1600s, it evolved to mean blindness associated with elevated intraocular pressure.
Two types of glaucoma were recognized by the 1860s, acute congestive and simple noncongestive. Not until 1938 was the importance of narrow, open, or closed drainage angles realized.
3Thus, acute congestive glaucoma is now termed acute angle-closure glaucoma, and simple noncongestive glaucoma is now called open-angle glaucoma. In addition, open-angle glaucoma is divided into a variety of subtypes, and as our knowledge increases the list of subclassifications of glaucoma will undoubtedly grow.
A German ophthalmologist, von Graefe, developed an operation for angle-closure glaucoma more than 100 years ago (in 1857). Interestingly, the reason the operation was successful was not discovered until more than 50 years later. The concept of pupillary block—the buildup of aqueous humor behind the iris that causes the iris to balloon forward like a sail in the wind—became recognized in the 1920s and is a key factor in angle-closure glaucoma.
The normal flow of aqueous is from the posterior chamber to the anterior chamber through the pupil. Aqueous must squeeze between the lens and the iris to enter the pupil and hence the anterior chamber (Fig. 1, Fig. 2). In pupillary block, aqueous is unable to enter the pupil because of an abnormally tight contact between the lens and the iris. In severe cases, the iris balloons into the trabecular meshwork (the drainage system), and the “angle” formed by the iris, trabecular meshwork, and cornea becomes closed. Because the production of aqueous humor is autonomous,
4the intraocular pressure increases until blood flow into the eye is jeopardized. Von Graefe's operation, peripheral iridectomy, allows aqueous to bypass the pupil and enter the anterior chamber by a short circuit, a surgically made hole in the iris. The iris drops backward, and the angle opens. This procedure remains outstandingly successful; the patient is “cured” by permanent elimination of pupillary block.
An eye that has had an attack of angle-closure glaucoma is at grave risk of further attacks unless an iridectomy is performed. Pilocarpine and other miotics offer temporary protection from angle-closure attacks but are not a long-term solution. When an eye is affected with angle-closure glaucoma, the contralateral eye is also at high risk of developing angle closure. In one study, a 50% incidence of acute angle-closure glaucoma was observed in fellow eyes within 5 years after an attack in the initial eye.
5In most cases, prophylactic iridectomy or iridotomy should be done in the fellow eye.
As discussed later in this article, laser devices now permit an opening to be made in the iris without incising the eye. Laser iridotomy is an office procedure that eliminates many of the risks associated with conventional surgical treatment. The patient can resume normal activities the same day.
Because of the intense pain, redness, and loss of vision produced by acute angle-closure glaucoma, that condition was easily recognized and was considered the most prevalent and serious form of glaucoma. In contrast, the insidious nature of open-angle glaucoma, with its gradual and painless loss of vision in a normal-appearing eye, made it much more difficult to detect. Its course is usually measured in years, not in days as in angle-closure glaucoma. Indeed, open-angle glaucoma was not recognized as a separate entity until 1862.
The elevated intraocular pressure of open-angle glaucoma leads to optic nerve damage and irreversible loss of axons. This damage is manifested by the development of blind spots above and below the area of central vision. As the disease progresses, these blind spots enlarge, coalesce, and create arcuate patterns that reflect the pattern of distribution of the retinal axons. Central vision usually remains normal until late in the course of the disease, although sensitive psychophysical tests can detect loss of vision earlier.
11Most patients are unaware of the loss of vision until late in the disease, when a substantial number of nerve fibers have been irreparably damaged. In extreme cases, only a small central and peripheral island of vision remains (“tunnel vision”). Thus, a patient may be legally blind because of loss of peripheral vision despite having a “normal” visual acuity of 20/20. Early detection is imperative because treatment can usually halt or slow the progression of the disease, but it cannot restore the vision that has been lost.
Primary Open-Angle Glaucoma
For almost a century, faulty drainage of aqueous humor has been known to produce the elevated intraocular pressure in primary open-angle glaucoma.
6Although the aqueous outflow channels—the trabecular meshwork and the canal of Schlemm—have been examined in considerable detail, the exact site and mechanism of the blockage remain unknown. Early researchers found “sclerosis,” thickening, and fusion of the trabecular meshwork.
12Most of the eyes examined, however, were in the last stages of the condition and had severe scarring and secondary changes from elevated intraocular pressure. Examination of eyes with earlier stages of glaucoma has failed to reveal specific changes; many of the eyes have shown only an exaggeration of the normal aging processes.
Today, electron microscopy can demonstrate some relatively specific changes, such as an excess of collagen and fibrillar extracellular material in the extracellular pathways of the trabecular meshwork.
15These changes may represent redundant peritendinous sheaths
16but also can be seen in aged normal eyes. These changes do not account for all the resistance to aqueous drainage found in glaucoma.
Recent studies have focused on physiologic functions of the trabecular meshwork. Trabecular cells are known to secrete an extracellular ground substance, and changes in the quality or quantity of this material may contribute to glaucoma.
18In addition, investigators have recently shown that trabecular cells decline in number with aging and decrease even further in glaucomatous eyes.
19Trabecular cells probably maintain the extracellular ground substance and keep the meshwork clear of debris. Inadequate numbers or decreased activity of these cells could lead to secondary changes that block aqueous outflow.
Secondary Open-Angle Glaucoma
In several recognized ocular syndromes, glaucoma seems to occur in response to specific factors. These syndromes are of special interest because of the insight they provide into our understanding of the aqueous system and the potential avenues that lead to glaucoma.
Exfoliation syndrome (sometimes called “pseudoexfoliation”) is a diffuse ocular condition with a high incidence of glaucoma. In this condition, whitish flakes and sheets are seen on the surface of the lens and ciliary processes. This material, which has a filamentous, banded structure, can be found microscopically in blood vessel walls and in the trabecular meshwork. The material is probably an abnormal basement membrane that is secreted in excessive amounts.
20It probably leaves its site of origin, flows in the aqueous, and becomes deposited throughout the anterior portion of the eye. It may occlude the trabecular meshwork. The exfoliation syndrome can occur in one or both eyes and is associated with glaucoma in up to 90% of cases that have been under surveillance for 10 years.
21Some eyes escape the adverse effects of the exfoliative material and do not develop glaucoma.
Pigment dispersion syndrome is another condition in which glaucoma seems to result from occlusion of the trabeculum by particles. Patients with this condition have an abnormally deep anterior chamber.
22Friction occurs between the posterior surface of the iris and the zonular fibers that suspend the lens as the pupil dilates and constricts. As a result, the zonular fibers erode the delicate pigment cells of the posterior surface of the iris.
23Pigment granules are released from these spokelike areas of damage and flow along with the aqueous humor. The trabeculum becomes so heavily covered with pigment that it appears as a black line. Why glaucoma develops in some patients with this syndrome but not in others is unknown.
Optic Nerve Damage
Damage to the optic nerve, with resultant loss of vision, is the common sequela of all types of glaucoma. The sequence of damage usually results in loss of visual fields in characteristic patterns. The loss can be both diffuse and localized.
24The optic cup enlarges and often becomes vertically elongated. As more axons are lost, the cup enlarges further and the lamina cribrosa becomes more prominent. The lamina begins to bow posteriorly, and the cup becomes deeper. At some sites around the perimeter of the optic disk, the cup may reach the rim of the scleral opening. The superior and inferior poles of the optic disk are most susceptible to these changes. This anatomic weakness is the basis for the characteristic visual field defects that occur in the middle stages of glaucoma. Further damage results in total loss of all optic disk tissue, leaving only a large, deep cup with prominent laminar markings.
The pattern and extent of visual field loss can be predicted on the basis of the location and the degree of cupping. Because the retinal image is inverted, loss of inferior disk tissue results in a visual field loss above fixation. By examination of the disk alone, an experienced observer can diagnose glaucoma in 85% of patients who have a visual field loss and can correctly distinguish normal eyes with normal visual fields from those with defects in about 90% of cases.
Clinically, a damaged optic disk is susceptible to further damage at relatively normal intraocular pressures.
27This susceptibility, as well as the mechanism for the initial disk damage, invokes controversy among experts. We favor the hypothesis that increased intraocular pressure deforms the lamina, compresses bundles of axons, and interrupts axonal transport. In some cases, increased intraocular pressure may reduce blood flow in critical capillaries,
28especially in progressive low-tension glaucoma. Low-tension glaucoma is a syndrome that mimics primary open-angle glaucoma but lacks evidence of elevated intraocular pressure.
Recently, investigators have confirmed the pathologic changes of early optic nerve damage in glaucoma.
31Quigley and associates
24have shown that an optic nerve can lose 40% of its axons before the damage—either an enlarged cup or a visual field defect—is clinically evident. Through careful microdissection techniques, they have shown that the superior and inferior areas have less mechanical support than do other regions of the lamina cribrosa,
29a finding that may explain the preferential loss of axons in these areas. Furthermore, they have demonstrated that as the multilayered lamina cribrosa bows backward, the canals of the axons become displaced. This malalignment creates shearing forces on the axons, which compress the axons and block axonal transport.
Drance and associates
32have pointed out that the occurrence of a splinter-shaped hemorrhage on the disk margin portends a worsening of the visual field in 3 to 5 years. These hemorrhages may also result from the shearing forces produced by early cupping. When stretched too far, the capillaries break, and a local flame-shaped hemorrhage is created.
When the classic triad of elevated intraocular pressure, damage to the optic disk, and visual field loss is present, glaucoma is easy to diagnose. In patients with only one or two of these findings, the diagnosis is more difficult to make with confidence. Because optic nerve damage is irreversible, every attempt should be made to diagnose glaucoma before extensive damage has occurred. No single test, however, can accurately predict which patients will have optic nerve damage and which will not. For purposes of classification, patients with moderately elevated intraocular pressure but normal optic disks and visual fields are termed “glaucoma suspects” or “ocular hypertensives.” Visual field defects will develop in approximately 1% of these patients annually with moderately elevated intraocular pressures (23 to 30 mm Hg; normal range, 10 to 22 mm Hg).
33The decision to treat or not to treat must be made on the basis of several risk factors that collectively are of prognostic importance.
The greatest single risk factor that is predictive of future damage is a large cup-to-disk ratio. This measurement is made ophthalmoscopically by estimating the vertical diameter of the central pale area of the optic disk in comparison with the vertical diameter of the entire disk. The average cup occupies 30% of the optic disk surface; 99% of normal persons have optic cups that occupy between 0 and 70% of the optic disk.
35A cup larger than 70% of the optic disk should suggest the presence of glaucoma, even if intraocular pressures are normal. A discrepancy in cup size between fellow eyes should also arouse suspicion. A difference in cup-to-disk ratios of greater than 20% between the two eyes should alert the clinician to the possibility of glaucoma. Thus, although a 60% cup in one eye could be considered normal, the appearance of only a 10% cup in the contralateral eye should strongly suggest disk damage and unilateral glaucoma in the widely cupped eye.
Age is known to play a substantial role in the appearance of glaucoma. Primary open-angle glaucoma rarely occurs in patients younger than 40 years of age, but the incidence increases markedly thereafter. By age 80 years, 14% of all persons have glaucoma.
32In patients with diabetes mellitus, another risk factor for glaucoma, glaucoma is 3 times more likely to develop than in normal persons,
36perhaps because of the associated microvascular disease. A family history of glaucoma also increases the likelihood of glaucoma in a patient; about 20% of patients with glaucoma have a family history of it.
38Myopia is likewise a risk factor for the development of glaucomatous damage,
39perhaps because myopic eyes tend to be larger, have a thinner sclera, and thus have a weaker lamina cribrosa. Interestingly, once the intraocular pressure has been controlled, patients with myopia are no longer at a disadvantage; visual field losses occur at the same rate in these patients as in nonmyopic patients.
40Race is a factor in the development of glaucoma and of blindness from glaucoma; blacks have a significantly higher incidence than do whites.
Psychophysical testing of the visual fields has undergone revolutionary advances in recent years. The continued refinement of these tests has allowed earlier detection of visual field defects. The presence of optic nerve damage can be substantiated long before the patient is aware of the loss. A visual field loss can encompass either loss of all vision in an anatomic area of the field or loss of sensitivity for functions such as color vision or light perception. In general, the laborious task of plotting visual fields manually has now been supplanted by computerized, semiautomated devices. Many elderly and frail patients, however, can be tested only by a skilled perimetrist who has cultivated the art through experience.
New methods of measuring visual function are emerging. Small-field electroretinograms, visually evoked electroencephalograms, color discrimination tests, color perimetry, and peripheral field acuity perimetry are being investigated.
Management of glaucoma depends as much on careful observation and consistent follow-up as it does on treatment by medical, laser, or surgical techniques. The patient shares the responsibility for a satisfactory long-term program. Usually, three or four examinations a year are necessary. A routine examination should include measurement of intraocular pressure, comparison of the optic disk with previous photographs, and review of the patient's medications. Periodic visual field tests should be performed to detect advancement of the disease. Because intraocular pressure can follow a diurnal pattern, measurements should be made at different times of the day.
Although the normal range of intraocular pressure is from 10 to 22 mm Hg, an optic disk damaged by glaucoma seems more susceptible to further damage than a nondamaged disk. Therefore, as the cup enlarges, the pressure must be brought progressively lower to avoid this further damage. An eye with a glaucomatous cup and a “normal” intraocular pressure of 21 mm Hg may actually develop more damage, as this pressure may be too high for that degree of cupping. In each patient, the intraocular pressure must be viewed in light of the degree of damage to the optic disk. There is no arbitrary pressure level below which all patients can be considered safe.
Glaucoma has been treated medically for more than 100 years, and this approach continues to be the mainstay of therapy. When medication fails, laser treatment or surgical intervention must be used. Three classes of drugs are currently in use.
Pilocarpine, a derivative of the plant genus Pilocarpus, has been used for more than a century. Its efficacy and safety are unsurpassed, and it remains the cornerstone of glaucoma therapy. As a parasympathetic agent related to acetylcholine, it causes ciliary muscle contraction and improves aqueous drainage. The ciliary muscle is usually considered in its role of focusing the lens, but it also has tendinous connections to the trabecular meshwork.
16When the muscle contracts, it opens the drainage pathways. The most evident sign of pilocarpine therapy, the small pupil, has no beneficial effect on intraocular pressure and is actually an unwanted side effect.
Although pilocarpine is an excellent agent, it has several characteristics or side effects that can limit its use. It has a short duration of action (4 to 6 hours) and thus must be used four times a day. Miosis decreases the amount of light that enters the eye and thus dims the sense of vision and prolongs dark adaptation. This problem is worse if a cataract is present. In young patients with active accommodation, the contraction of the ciliary muscle by pilocarpine induces artificial nearsightedness and may also cause an uncomfortable spasm of the muscle. Longacting and slow-release preparations are being developed to reduce the peak responses and the frequency of administration.
Cholinesterase inhibitors, by binding and inactivating the enzyme acetylcholinesterase, prolong the action of endogenously released acetylcholine. The net effect is almost identical to that of pilocarpine. These compounds, however, are long acting and necessitate only once-a-day administration. Because they can cause intense spasm of the ciliary muscle in young patients and can produce cataracts with long-term administration, they are used mainly in elderly patients with aphakia. Systemic absorption may occur and decrease the level of circulating cholinesterases. Consequently, these agents can prolong the effect of succinylcholine, used in general anesthesia.
Epinephrine has been used in ophthalmology since the turn of the century and continues to be used frequently in therapy for glaucoma. The mechanism by which this α- and β-agonist lowers intraocular pressure is still not fully clear. Epinephrine seems to have both an immediate and a long-term effect on the eye. In early studies, epinephrine was thought to decrease the amount of aqueous humor formed.
42Recent studies, however, have shown that epinephrine actually increases the amount of aqueous humor formed during short-term use.
43Its effect on aqueous formation with long-term use is under investigation. Epinephrine also improves aqueous drainage with long-term use,
44perhaps by decreasing the amount of extracellular glycosaminoglycans in the trabecular meshwork.
Timolol, a β-adrenergic blocking agent, has been used in the United States since 1978. Because it is an effective, well-tolerated, easy-to-use medication, both patients and physicians are enthusiastic about this drug. Timolol lowers intraocular pressure by decreasing aqueous formation about 40%.
46With use of timolol (as with any eyedrops), systemic absorption occurs; consequently, this agent can aggravate preexisting asthma or cardiac problems, such as atrioventricular conduction block.
Carbonic Anhydrase Inhibitors
Acetazolamide (Diamox) and methazolamide (Neptazane) both lower intraocular pressure by decreasing aqueous formation.
47Carbonic anhydrase is found in the eye and in many other body tissues. Generation of carbonic acid from carbon dioxide is needed in some way for aqueous secretion. The effects of carbonic anhydrase inhibitors and timolol are partly additive. During waking hours, aqueous secretion with use of a combination of timolol and acetazolamide treatment is decreased by 45 to 50%.
47During sleep, aqueous secretion is endogenously reduced to 50% of the normal daytime rate and is not reduced further by either drug.
All carbonic anhydrase inhibitors produce several side effects and are generally not well tolerated; up to 50% of patients are unable to tolerate long-term use.
49Major problems include a malaise syndrome (fatigue, depression, anorexia, and weight loss) that seems to be related to systemic acidosis and a gastrointestinal syndrome (cramping, nausea, and diarrhea). With use of these agents (as with any sulfonamide), aplastic anemia can occur as a very rare idiosyncratic reaction. Because carbonic anhydrase inhibitors can reduce renal excretion of citrate, they can be associated with the formation of renal calculi.
One of the most exciting developments in the management of glaucoma during the past decade has been the application of laser technology to treatment of glaucoma. Three separate and distinct developments have altered the usual management strategies of open-angle glaucoma, angle-closure glaucoma, and neovascular glaucoma.
The currently accepted management of neovascular glaucoma, a dreaded complication of diabetes mellitus and central vein occlusion, evolved as a spinoff of the technique of photocoagulation of the retina for diabetic retinopathy. Panretinal photocoagulation has been shown to be an effective means of reducing the possibility of proliferative retinopathy.
50This treatment reduces the chance of neovascularization of the iris and the trabeculum, a process that usually leads to intractable glaucoma and blindness. The best available treatment of neovascular glaucoma is panretinal photocoagulation, performed according to the diabetic retinopathy protocol. After the neovascularization of the iris has regressed, a standard filtration procedure can be done if necessary. Many eyes can be salvaged by this therapeutic approach, whereas most eyes involved with neovascular glaucoma were lost before photocoagulation was introduced.
In 1970, Zweng and associates
51attempted to introduce laser iridotomy as a substitute for surgical iridectomy in the management of angle-closure glaucoma. The technique was not established as a reasonable alternative until a report by Abraham and Miller
52was published in 1975. Abraham and others
55have shown that laser iridotomy is a simple, safe, and effective means of creating an opening in the iris, relieving pupillary block, and preventing angle-closure glaucoma. The argon laser has been the most commonly used instrument for performing this procedure. Several different types of lasers, such as the neodymium-yttrium-aluminum-garnet laser, may make this procedure even simpler and more reliable.
Laser technology has also been applied to the treatment of open-angle glaucoma. A widely accepted procedure today, laser trabeculoplasty has its roots in scientific investigations of laser effects on the trabeculum during the past decade. The results of this early work were encouraging and stimulated James Wise to conduct a study that led directly to the currently accepted technique.
56On the basis of theoretical considerations, Wise attempted a procedure that he reasoned would cause shrinkage of the collagenous tissue of the trabecular meshwork and thereby open the tortuous drainage channels. Numerous studies have shown that his technique effectively decreases intraocular pressure, although the mechanism by which this effect is achieved has been questioned.
60This technique is widely performed on patients who have uncontrollable open-angle glaucoma and might otherwise require a more extensive surgical procedure. As technologic improvements in lasers and ophthalmic delivery systems are made and as the biologic effects of intense light on the physical and physiologic properties of the trabecular meshwork are more thoroughly understood, this office procedure is likely to undergo modification and improvement. Laser trabeculoplasty is not a substitute for medical management, nor is it a substitute for surgical management, but it serves as a convenient and safe transition from one to the other in several kinds of glaucoma.
Conventional Surgical Procedures
The creation of a surgical fistula to bypass the trabecular meshwork and to create another route of aqueous drainage has been performed with use of numerous techniques for many years. The new route of drainage into the subconjunctival space allows the aqueous humor to be absorbed by capillaries or to filter through the conjunctiva into the tears. These procedures are known collectively as filtration procedures. Often these procedures create a “bleb,” an elevated mound of aqueous-laden conjunctiva, at the surgical site.
Filtration procedures are successful in 80 to 90% of cases of open-angle glaucoma.
61They are less effective (60% successful) in patients with aphakia.
62If the operation fails, the cause of failure usually is conjunctival scarring, which prevents aqueous drainage. Complications include excessive aqueous drainage (creating a soft, shrunken eye), choroidal effusions, choroidal hemorrhage, and cataracts. Also, in patients who have undergone a filtration procedure, endophthalmitis can develop from external bacterial conjunctivitis.
The creation of an internal drainage route to bypass the trabecular meshwork is the basis for a procedure called cyclodialysis. Separation of the attachment of the ciliary muscle to the scleral spur creates such a path for aqueous to drain into the supraciliary space. Unfortunately, the procedure is successful in only 40% of cases
63and is associated with a high risk of bleeding.
Cyclodestructive procedures reduce intraocular pressure by decreasing the amount of aqueous humor produced. They are especially helpful when a filtration procedure fails and other options are limited. The idea of destroying a portion of the ciliary body to decrease aqueous production was conceived in the 1930s. Originally, heat was used (cyclodiathermy). Because of the high complication rate with diathermy, freezing of the ciliary body (cyclocryotherapy) was frequently used in the 1960s and is the commonest cyclodestructive procedure used today. Results of both methods are somewhat unpredictable, and unintentional overtreatment that leads to hypotonia occurs in 10% of cases.
64Other problems include development of macular edema, a chronic change in the composition of the aqueous humor (increased protein content), and pain and inflammation early postoperatively. Cyclodestruction can also be performed by use of laser beams
Many ingenious devices have been invented to maintain patency of the surgical fistula after filtration procedures. Various materials have been used, including horsehair, silk, gold, platinum, polyethylene, glass, silicone, and iris (iridencleisis). The use of these devices has not met with greater success than simpler procedures. Currently, the most frequently used setons are a pressure-sensitive one-way valve, the Krupin-Denver valve,
68and the Molteno implant.
Advances in pharmacology, cell biology, and molecular biology are quickly being assimilated into glaucoma research. As basic physiologic functions become understood in the normal eye, the abnormalities in glaucoma can be recognized and rational approaches to therapy can be developed. A wide variety of new drugs are being studied, including carbonic anhydrase inhibitors, cholinergics, adrenergics, dopaminergics, chelators, calcium channel blockers, natriuretic factors, ei-cosanoids, and stimulators of adenylate cyclase. Several β-blockers are being tested, including betaxolol, a β1-specific antagonist that has little effect on bronchial smooth muscle and may be preferred in asthmatics, and levobunolol. Long-acting cholinergics related to pilocarpine are being used in clinical trials. Topical carbonic anhydrase inhibitors are also under study. Forskolin, a naturally occurring diterpin derivative, increases the synthesis of cyclic adenosine monophosphate and has been shown to lower intraocular pressure.
71Forskolin holds promise as the prototype of a new class of pressure-lowering drugs.
Early detection of optic nerve damage is critical to the successful treatment of glaucoma. Computerized mapping and photogrammetric techniques are being evaluated to provide earlier detection of subtle changes in the contour of the optic cup.
72Another technique, observation and photography of the nerve fiber layer of the retina, has been shown to be a sensitive method of detecting early changes.
Improvements in clinical testing of visual function are also being developed at a rapid pace. Computerized perimetry allows early detection of subtle field changes and opens the door to standardization. Other methods and findings under study include reduced sensitivity to blue colors,
77reduced ability to distinguish the flickering of a light,
78subtle changes in visual acuity involving a series of light and dark stripes,
79and abnormal visualevoked responses.
Measurement or prediction of disk susceptibility by quantitative means would allow the distinction of glaucomatous eyes from normal eyes before damage occurs and might facilitate the development of drugs that reduce disk susceptibility.
An Ultimate Cure
Basic physiologic and pathophysiologic questions must be answered before glaucoma can be cured. Biologic, anatomic, and biochemical investigations of the trabecular meshwork are necessary to determine the mechanism of aqueous outflow in the normal eye and the site and cause of increased resistance to outflow in the glaucomatous eye. The role of trabecular cells may be vital to the entire process, and a better understanding of their functions and life cycle is needed. Once the basic outflow problems are understood, solutions should be possible. Trabecular meshwork cells can be grown in cell culture. Perhaps transplantation of normal trabecular cells into a glaucomatous eye may become feasible. A cure for glaucoma ultimately depends on finding the cause of glaucoma. Although ideas abound, the search continues.
- Vision Research, a National Plan. Vol 2. National Institutes of Health, Bethesda, Maryland1983: 1 (Part 4)
- Thoughts on reading “Immortal Words.”.Dartmouth Medical School Alumni Magazine. Spring 1985; : 32
- Glaucoma; classification, causes, and surgical control: results of microgonioscopic research.Am J Ophthalmol. 1938; 21: 1099-1117
- Absence of a feedback controller of intraocular pressure mediated through aqueous flow (abstract).Inv Ophthal Vis Sci. 1985; 26: 108
- Value of prophylactic peripheral iridectomy on the second eye in angle-closure glaucoma.Trans Ophthalmol Soc UK. 1977; 97: 189-191
- System of Ophthalmology. Vol 11. CV Mosby Company, St. Louis1969: 389
- Interocular comparison of contrast sensitivities in glaucoma patients and suspects.Br J Ophthalmol. 1980; 64: 858-862
- Psychovisual disturbances in glaucoma: a study of temporal and spatial summation.Arch Ophthalmol. 1974; 91: 463-468
- The early psychophysical disturbances in chronic open-angle glaucoma: a study of visual functions with asymmetric disc cupping.Arch Ophthalmol. 1982; 100: 1632-1634
- Acquired color vision changes in glaucoma: use of 100-Hue test and Pickford anomaloscope as predictors of glaucomatous field change.Arch Ophthalmol. 1981; 99: 829-831
- Chromatic extrafoveal dark adaptation function in normal and glaucomatous eyes.Mod Probl Ophthalmol. 1976; 17: 304-310
- The pathogenesis of glaucoma.Arch Ophthalmol. 1925; 54: 20-37
- A clinicopathologic study of four cases of primary open-angle glaucoma compared to normal eyes.Am J Ophthalmol. 1981; 91: 88-105
- The anatomic basis for glaucoma.Ann Ophthalmol. 1978; 10: 397-411
- Electron microscopic studies on the trabecular meshwork in glaucoma simplex.Graefes Arch Clin Exp Ophthalmol. 1972; 183: 251-266
- Why is intraocular pressure elevated in chronic simple glaucoma? Anatomical considerations.Ophthalmology. 1983; 90: 758-765
- Calculations of flow resistance in the juxtacanalicular meshwork (abstract).Invest Ophthalmol Vis Sci. 1983; 24: 135
- The importance of the mucopolysaccharides in intraocular pressure regulation (editorial).Invest Ophthalmol Vis Sci. 1975; 14: 173-176
- Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals.Ophthalmology. 1984; 91: 564-579
- The basement membrane exfoliation syndrome.Arch Ophthalmol. 1979; 97: 510-515
- Pseudoexfoliation of the lens capsule. II. Development of the exfoliation syndrome.Acta Ophthalmol. 1969; 47: 161-173
- Dimensions of the anterior chamber in pigment dispersion syndrome.Arch Ophthalmol. 1983; 101: 81-83
- Pigmentary dispersion and glaucoma: a new theory.Arch Ophthalmol. 1979; 97: 1667-1672
- Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy.Arch Ophthalmol. 1982; 100: 135-146
- The optic disc in glaucoma. II. Correlation of the appearance of the optic disc with the visual field.Br J Ophthalmol. 1977; 61: 107-113
- Lea & Febiger, Philadelphia1979: 66 Glaucoma. Second edition.
- Why do some people go blind from glaucoma?.Ophthalmology. 1982; 89: 991-998
- Optic nerve damage in glaucoma.Surv Ophthalmol. 1981; 26: 128-148
- Regional differences in the structure of the lamina cribrosa and their relation to glaucomatous optic nerve damage.Arch Ophthalmol. 1981; 99: 137-143
- Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage.Arch Ophthalmol. 1981; 99: 635-649
- Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma.Am J Ophthalmol. 1983; 95: 673-691
- The importance of disc hemorrhage in the prognosis of chronic open angle glaucoma.Arch Ophthalmol. 1977; 95: 226-228
- Williams & Wilkins, Baltimore1982: 144 A Study Guide for Glaucoma.
- Risk factors favoring the development of glaucomatous visual field loss in ocular hypertension.Surv Ophthalmol. 1980; 25: 155-162
- Genetic determination of cup/disc ratio of the optic nerve.Arch Ophthalmol. 1967; 78: 35-43
- Diabetes mellitus and primary open-angle glaucoma.Am J Ophthalmol. 1971; 71: 1-16
- Family history in primary open-angle glaucoma.Arch Ophthalmol. 1977; 95: 598-600
- Family studies in glaucoma.Br J Ophthalmol. 1974; 58: 529-535
- Open angle glaucoma, ocular hypertension, low-tension glaucoma, and refraction.Arch Ophthalmol. 1982; 100: 1464-1467
- Effect of myopia on prognosis in treated primary open-angle glaucoma.Am J Ophthalmol. 1982; 93: 622-628
- Racial influences in open-angle glaucoma.Ann Ophthalmol. 1978; 10: 1398-1402
- Recent advances and future prospects in the medical treatment of ocular hypertension.Br J Ophthalmol. 1954; 38: 742-746
- Immediate effect of epinephrine on aqueous formation in the normal human eye as measured by fluorophotometry.Invest Ophthalmol Vis Sci. 1980; 19: 256-266
- Improvement of the coefficient of outflow in glaucomatous eyes: prolonged local treatment with epinephrine.Arch Ophthalmol. 1961; 66: 314-317
- The effect of topical anti-glaucoma drugs on the synthesis of glycosaminoglycans in the cat trabecular meshwork (abstract).Invest Ophthalmol Vis Sci. 1983; 24: 5
- The mechanism of timolol in lowering intraocular pressure: in the normal eye.Arch Ophthalmol. 1978; 96: 2045-2048
- The effects of timolol maleate and acetazolamide on the rate of aqueous formation in normal human subjects.Am J Ophthalmol. 1982; 93: 232-237
- Aqueous humor flow during sleep.Invest Ophthalmol Vis Sci. 1984; 25: 776-778
- Carbonic anhydrase inhibitor side effects: serum chemical analysis.Arch Ophthalmol. 1977; 95: 1378-1382
- Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study findings.Ophthalmology. 1978; 85: 82-104
- Laser photocoagulation of the iris.Arch Ophthalmol. 1970; 84: 193-199
- Outpatient argon laser iridectomy for angle closure glaucoma: a two-year study.Trans Am Acad Ophthalmol Otol. 1975; 79: 529-538
- Laser iridotomy: current concepts in technique and safety.Int Ophthalmol Clin. 1981; 21: 137-144
- Histologic studies of angle structures after laser iridotomy in primates.Arch Ophthalmol. 1982; 100: 1665-1670
- Threshold for retinal damage associated with the use of high-power neodymium-YAG lasers in the vitreous.Am J Ophthalmol. 1983; 96: 153-159
- Glaucoma treatment by trabecular tightening with the argon laser.Int Ophthalmol Clin. 1981; 21: 69-78
- Long-term control of adult open angle glaucoma by argon laser treatment.Ophthalmology. 1981; 88: 197-202
- Laser therapy for open angle glaucoma.Ophthalmology. 1981; 88: 213-217
- Argon laser trabecular surgery in uncontrolled phakic open angle glaucoma.Ophthalmology. 1981; 88: 203-212
- Effect of trabecular photocoagulation on the aqueous humor dynamics of the human eye.Am J Ophthalmol. 1983; 96: 139-147
- Trabeculectomy vs full-thickness filtering operation for control of glaucoma.Ophthalmol Surg. 1980; 11: 498-505
- Surgical management of chronic glaucoma in aphakia.Ophthalmology. 1983; 90: 807-813
- Combined cyclodialysis and cataract extraction.Ophthalmol Surg. 1976; 7: 62-73
- Cyclocryotherapy: recent experience using a standardized technique (abstract).Invest Ophthalmol Vis Sci. 1984; 25: 43
- Argon laser photocoagulation of the ciliary processes in cases of aphakic glaucoma.Arch Ophthalmol. 1979; 97: 2135-2138
- Transscleral laser cyclocoagulation (abstract).Invest Ophthalmol Vis Sci. 1984; 25: 45
- The effect of therapeutic ultrasound on aqueous humor dynamics (abstract).Invest Ophthalmol Vis Sci. 1985; 26: 158
- Valve implants in filtering surgery.Am J Ophthalmol. 1976; 81: 232-235
- New implant for drainage in glaucoma: clinical trial.Br J Ophthalmol. 1969; 53: 606-615
- Forskolin lowers intraocular pressure by reducing aqueous inflow.Invest Ophthalmol Vis Sci. 1984; 25: 268-277
- Intraocular pressure and aqueous flow are decreased by cholera toxin.Invest Ophthalmol Vis Sci. 1981; 20: 371-381
- Three-dimensional computer graphic display and correlation of optic disc pallor with cupping (abstract).Invest Ophthalmol Vis Sci. 1985; 26: 223
- Evaluation of nerve fiber layer assessment.Arch Ophthalmol. 1984; 102: 1766-1771
- Diffuse and localized nerve fiber loss in glaucoma.Am J Ophthalmol. 1984; 98: 566-571
- Visual field and retinal nerve fiber layer comparisons in glaucoma.Arch Ophthalmol. 1985; 103: 205-207
- Neuroretinal rim area and retinal nerve fiber layer in glaucoma.Arch Ophthalmol. 1985; 103: 203-204
- Loss of blue-cone sensitivity in glaucoma (abstract).Invest Ophthalmol Vis Sci. 1982; 22: 95
- Flicker threshold and pattern VEP latency in ocular hypertension and glaucoma.Invest Ophthalmol Vis Sci. 1983; 24: 1524-1528
- Arden contrast sensitivity testing in glaucoma.Arch Ophthalmol. 1982; 100: 947-950
- VEP latency in ocular hypertension and glaucoma (abstract).Invest Ophthalmol Vis Sci. 1982; 22: 95
© 1986 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.