Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are characterized by loss of pigment from the posterior surface of the iris and excessive pigment release throughout the anterior segment of the eye. The essential diagnostic signs include a unique pattern of mid-peripheral iris transillumination defects and pigment deposits on the corneal endothelium, the trabecular meshwork (TM), the iris, and the lens. Individuals with PDS may have normal or elevated intraocular pressure (IOP) without glaucomatous optic nerve damage. Patients with these same findings who demonstrate optic nerve damage and/or visual field defect are classified as having pigmentary glaucoma.
PDS and pigmentary glaucoma are more prevalent in males and typically present in the third or fourth decade of life. Contact of the posterior iris against the lens is thought to produce excessive pigment release into the anterior segment. Pigment accumulation in the trabecular meshwork impairs aqueous outflow, elevating IOP, and may subsequently cause chronic outflow dysfunction, optic nerve damage, and visual loss.
Treatment options are similar to those for primary open-angle glaucoma and include medical therapy, laser iridotomy, laser trabeculoplasty, and invasive surgical interventions.
Pigment dispersion is a fascinating cause of secondary open-angle glaucoma, recognized by its distinctive ophthalmic examination findings. Originally considered a rare condition, PDS was introduced around 1900 when Krukenberg described the characteristic corneal pigment. Over time, the condition became defined by the clinical triad of this signature pigment deposition on the corneal endothelium (Krukenberg spindle), radial mid-peripheral transillumination defects of the iris, and hyperpigmentation of the trabecular meshwork.
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Krukenberg spindle.
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Characteristic iris transillumination defects.
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Hyperpigmentation of the trabecular meshwork.
Although PDS and pigmentary glaucoma are now routinely recognized, much remains unproven about the exact causative pathophysiologic mechanism, whether damage to the trabecular meshwork can be prevented, and how to best minimize optic nerve injury.
Although PDS and pigmentary glaucoma are now widely recognized, the exact cause is still debated.
The release of pigment granules from the iris pigment epithelium is the underlying hallmark in these disorders. There is often a posteriorly concave contour of the iris and a posterior insertion of the iris root into the ciliary body.[1, 2] Many believe that this exacerbates physical contact of the posterior iris surface against the anterior lens zonules and results in excessive pigment release into the aqueous fluid.
In 1979, David G. Campbell, MD, proposed that pigment is released from the pigment epithelium of the iris when it rubs against the lens and the anterior lens zonules during normal pupil movements.[3] This contact, Campbell argued, is brought about by a posterior bowing of the iris that is not present in most eyes. Others suspect that it is not the to-and-fro rubbing, but simply the appositional contact between the iris and the lens, that causes disruption in the iris pigment epithelial cell membranes and release of pigment granules into the aqueous fluid.[4] Regardless of the exact mechanism of iris pigment loss, a unique pattern of iris transillumination defects manifests over time.
Reverse pupillary block has been termed to explain the concave iris configuration in eyes with PDS and pigmentary glaucoma. During an eye blink, a small aliquot of aqueous is burped from the posterior chamber to the anterior chamber, resulting in increased pressure in the anterior chamber. This pressure gradient produces posterior bowing of the iris and increases iridolenticular contact. The increased area of iris-lens contact creates a flap-valve effect, maintaining the pressure differential and the posteriorly concave iris configuration. This process is similar to the change in iris and angle configuration that occurs during indentation gonioscopy. Similar iris concavity has also been observed with accommodation and in myopia. This concept of reverse pupillary block is supported by studies showing laser iridotomy reverses concave configuration. Despite this, laser iridotomy has not been demonstrated to stop the progression of pigmentary glaucoma. This leads some researchers to suggest an alternative, inherent factor that causes or contributes to iris pigment loss not directly caused by physical contact.
Liberated iris pigment granules are carried by aqueous fluid and deposited throughout the anterior segment of the eye. On the corneal endothelium, the pigment typically settles in a characteristic shape consistent with aqueous convection currents (Krukenberg spindle). The spindle tends to be slightly decentered inferiorly and wider at its base than its apex. It generally appears as a central, vertical, brown band up to 6 mm long and 3 mm wide. With time, Krukenberg spindle becomes smaller and lighter and often requires careful examination for identification. Pigment deposits are also observed on the anterior surface of the iris, the trabecular meshwork, the lens, and other anterior segment structures.
Pigment accumulation on the trabecular meshwork impedes aqueous outflow and can trigger acute temporary elevations in IOP. This explains the acute blurred vision associated with strenuous exercise or pupillary dilation. Over time, some pigments undergo phagocytosis by the trabecular meshwork endothelial cells. In certain eyes, this endocytosed pigment does not cause trabecular dysfunction. In others, the trabecular meshwork becomes disorganized, causing obstruction of aqueous outflow, IOP elevation, and/or resultant secondary glaucoma. It is unclear why some patients with PDS develop long-term resistance to aqueous outflow while others tolerate the accumulation of pigments with no pathologic changes of the trabecular meshwork.
Active pigment liberation typically occurs in patients in their third and fourth decades in life. Greater pigment liberation tends to occur in eyes with more pronounced iris concavity, presumably because of more contact or friction between the iris pigment epithelium and the zonules. As affected individuals age, relative pupillary block counteracts the posterior bowing of the iris and reduces its contact with lens zonules. This may lead to a decrease or resolution of active pigment release. Long-term regression of pigment deposits is sometimes seen. Lichter and Shaffer observed a definite decrease in the amount of trabecular meshwork pigment in 10% of 102 patients and concluded that the pigment could pass out of the meshwork as the patient aged.[5] Krukenberg spindle and trabecular meshwork hyperpigmentation have been observed to resolve with time in some patients. Therefore, older patients presenting with glaucoma may have only very subtle manifestations, if any, of PDS, and may be diagnosed with primary open-angle glaucoma or low-tension glaucoma. Interestingly, despite the resolution of pigment deposits in the trabecular meshwork, impairment in aqueous outflow and resultant glaucoma continues to progress.
It is also not fully understood why laser iridotomy has not been shown to slow progression of pigmentary glaucoma although it is successful at reversing iris concavity. Pigmentary glaucoma may represent a subset of patients with pigment dispersion who have additional inherent predisposition to develop chronic ocular hypertension or glaucomatous optic neuropathy that is not altered by the removal of the concave iris configuration.
The prevalence of PDS and pigmentary glaucoma in the general population is unclear. Ritch et al found a 2%-3% prevalence of PDS in a population undergoing glaucoma screening.[6] The risk of developing pigmentary glaucoma due to PDS is estimated to be 10% at 5 years and 15% at 15 years.[7]
Mortality/Morbidity
Individuals with PDS, by definition, do not have glaucomatous optic nerve damage. However, they may experience acute IOP elevations with associated temporary blurred vision or develop chronic ocular hypertension. Patients with pigmentary glaucoma can suffer progressive visual field defect and significant vision loss.
Race
PDS and pigmentary glaucoma predominately affect whites. Less than 5% of cases occur in persons of African descent.[8, 9]
Sex
While PDS is slightly more common in males than females, pigmentary glaucoma affects males 2 to 5 times more often.[7, 8, 9, 5, 10]
Age
Male patients with PDS and pigmentary glaucoma are usually diagnosed in their fourth decade of life, whereas female patients typically presents in their fifth decade of life. PDS has been reported in individuals as young as 12 years. The condition becomes more prevalent in early middle age, likely because the lens has enlarged to be in greater contact with the concave iris.
Myopia
PDS and pigmentary glaucoma are commonly associated with moderate myopia (-3 to -4 D); however, a broad range of refractive errors has been reported.
Genetics
Studies of family members suggest an autosomal-dominant inheritance pattern with incomplete penetrance.[11]
Prognosis is favorable with control of intraocular pressure (IOP).
Blindness due to pigmentary glaucoma is rare. In a study of 113 patients with PDS and pigmentary glaucoma, 3 eyes in 2 patients were blind. Progression of the disease, however, is common. Ten percent of patients with PDS progressed to pigmentary glaucoma at 5 years and 15% developed pigmentary glaucoma by 10 years. Forty percent of patients with pigmentary glaucoma had worsening of optic nerve damage over a mean follow-up period of 6 years. Elevated IOP was the only identified risk factor for progression.[7] This underscores the importance of monitoring and managing IOP in patients with PDS and pigmentary glaucoma.
An interesting observation is that patients eventually diagnosed with pigmentary glaucoma almost always have clinical evidence of optic nerve damage, elevated IOP, or at least some abnormality in aqueous outflow on initial presentation. Conversely, PDS with normal IOP and normal aqueous outflow has a very low probability of progressing to pigmentary glaucoma. Individuals with PDS (no glaucomatous optic nerve damage by definition) and elevated IOP or abnormal aqueous outflow coefficient show a borderline risk of developing pigmentary glaucoma. It is therefore crucial to risk stratify patients with PDS based on the presence of elevated IOP or abnormal aqueous outflow, as this group has a real probability of vision-threatening disease.
Uncommonly, pigment dispersion may also improve or regress with time. In some cases, corneal endothelial pigments, trabecular meshwork pigmentation, and even iris transillumination defects have been observed to resolve over time. Normalization of IOP has also been seen. Despite this, patients with glaucoma generally continue to progress.
Early recognition of individuals with this ocular condition and careful monitoring of IOP and optic nerve damage are crucial for ensuring the best visual outcome.
Patients with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are usually asymptomatic. Many, particularly myopes, are identified on routine eye examination. Some individuals may describe episodes of haloes and/or blurred vision associated with exercise or dark exposure (resulting from acute pigment release and temporary IOP rise).
Previous history of ocular trauma, surgeries, glaucoma, or other eye diseases that may result in abnormal pigmentation of the anterior segment structures should be noted. Some patients with subtle manifestations may have been previously diagnosed with ocular hypertension, juvenile-onset glaucoma, or primary open-angle glaucoma. Sulcus placement of intraocular lens may infrequently produce anterior chamber pigmentation similar to PDS and pigmentary glaucoma.
Family history of glaucoma or other eye conditions should also be inquired in detail.
Detailed and careful slit-lamp examination is critical to early recognition of PDS and pigmentary glaucoma. Diagnostic signs are usually bilateral and symmetric. However, on occasion, the abnormalities may be very asymmetric. The most prominent clinical findings are discussed below.
Pigment deposits on the posterior surface of the cornea
The pigment is typically densest near the corneal center and forms a characteristic shape (Krukenberg spindle) that corresponds to aqueous fluid convection currents. Krukenberg spindle generally appears as a central, vertical, brown band up to 6 mm long and 3 mm wide. It tends to be slightly decentered inferiorly and wider at its base than its apex. The amount of pigment present can be quite variable. Visual acuity is usually unaffected, as patients with PDS and pigmentary glaucoma do not appear to have thicker corneas or decreased endothelial cell counts.[11] With time, the corneal pigment becomes smaller and lighter and often requires careful examination for identification.
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Krukenberg spindle.
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Pigment on posterior surface of cornea.
Mid-peripheral iris transillumination defects
Transillumination defects appear in a radial spokelike configuration in the mid-peripheral iris and are most prominent inferiorly or inferonasally. This finding is pathognomonic for PDS and pigmentary glaucoma. Contact of the posteriorly bowed concave iris with anterior lens zonules is likely responsible for this characteristic iris transillumination pattern. Searching for iris transillumination defects prior to pupillary dilation using a small slit beam in a darkened room is best. Iris transillumination defects are present in 90% of patients with pigment dispersion. Transillumination defects may be absent in eyes with thick dark irides.
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Characteristic iris transillumination defects.
Dense trabecular meshwork pigmentation
Gonioscopy should be performed prior to pupillary dilation. The anterior chamber angle is typically wide open with a homogeneous, darkly pigmented trabecular meshwork band. Excess pigment deposits may also be noted on the Schwalbe line. In some older patients, trabecular meshwork hyperpigmentation can regress. This produces a pattern of lighter trabecular meshwork pigment band in the inferior versus superior angle. This is called the pigment reversal sign and may be the only evidence to suggest pigment dispersion.
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Trabecular meshwork hyperpigmentation.
Pigment accumulation can also be seen on the anterior surface of the iris (as concentric rings within the iris furrows or causing diffuse darkening of iris color), on the anterior lens surface, along the zonules, and between the posterior lens capsule and anterior hyaloid.
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Pigment accumulation on anterior surface of iris.
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Pigment deposits on anterior lens surface.
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Pigment accumulation on posterior lens zonules.
Patients with PDS and pigmentary glaucoma have an increased risk of retinal detachment (6%-7%). Retinal breaks and lattice degeneration also occur twice as frequently in these eyes than in age- and refraction-matched controls. Detailed fundus examination and prophylactic treatment of these retinal lesions may be indicated.
PDS is diagnosed based on the clinical triad of pigment deposit on corneal endothelium, mid-peripheral iris transillumination defects, and heavy pigmentation of the trabecular meshwork. The presence of all three findings in the absence of another cause (ie, ocular trauma or sulcus posterior chamber intraocular lens [PCIOL]) confirms this condition. The unique mid-peripheral iris transillumination defects are so pathognomonic for pigment dispersion that its lone presence is sufficient for making a presumptive diagnosis of PDS or pigmentary glaucoma. In eyes with corneal and/or trabecular meshwork pigment accumulation but without the characteristic iris transillumination defects, no formal diagnostic criteria have been established. Disease is likely present when accompanied by other consistent findings (ie, elevated IOP, zonular or posterior capsule pigment).
Pigment dispersion can occur with normal or elevated IOP.[11] IOP is usually higher in pigmentary glaucoma than in PDS. Pigmentary glaucoma is diagnosed when signs of PDS are accompanied by optic nerve cupping and/or visual field loss.
Ultrasound biomicroscopy (UBM) is useful in evaluating the iris configuration and the posterior chamber structures in patients with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG).[14] UBM may demonstrate a posterior iris insertion,[15] iris concavity, iridozonular contact, and extensive iridolenticular contact.
Anterior-segment optical coherence tomography (OCT) has been used to assess the parameters of the anterior chamber and angle dimensions in patients with pigmentary glaucoma.[16, 17]
The intraocular pressure (IOP) in pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) is subject to large spontaneous fluctuations. This tendency should be kept in mind when considering treatment and evaluating IOP response to therapies.
Despite full PDS features (iris concavity, typical transillumination defects, angle pigmentation), patients who do not have elevated IOP or any abnormality in outflow dynamics are extremely unlikely to develop pigmentary glaucoma. Animal studies have also shown that, in normal eyes, instilling vast quantities of pigment into the anterior chamber is not sufficient to produce glaucoma. An inherent predisposition to trabecular dysfunction, unrelated to pigment release, must be present to cause pigmentary glaucoma.[4]
Of the many individuals with pigment dispersion, fewer than half will develop elevated IOP or pigmentary glaucoma. However, because pigment dispersion syndrome is a risk factor for the development of ocular hypertension, all patients with this disorder should undergo periodic eye examinations. The frequency of follow-up visits may be tailored based on the severity of optic nerve damage, ocular hypertension, and degree of pigment accumulation.
Pigment dispersion syndrome is typically a bilateral disease, although asymmetry may occur. A correlation is noted between the amount of pigment lost from the posterior surface of the iris, increased degree of pigmentation in the trabecular meshwork, and degree of dysfunction in the trabecular meshwork as evidenced by elevation of the IOP. The size and density of the Krukenberg spindle does not necessarily correlate with trabecular meshwork damage. However, the amount of pigment that is presented to the trabecular meshwork does play a role in the elevation of the IOP. Markedly asymmetric disease is usually due to an additional factor, making one eye worse, such as anisometropia or the development of exfoliation syndrome or angle recession, or an additional factor acting to prevent the development of pigment dispersion syndrome, such as aphakia or Horner syndrome.
Progressive glaucomatous optic neuropathy in pigmentary glaucoma is primarily pressure-dependent, and reduction of IOP is the mainstay of therapy. In addition to monitoring of IOP, sequential ophthalmic examinations should include gonioscopy to assess the degree and progression of trabecular pigmentation, stereoscopic evaluation and photography of the optic nerve, and perimetry.
Because the degree and stage of pigment liberation, IOP, and extent of glaucomatous optic neuropathy vary among individuals, each must be evaluated to determine the proper course of intervention. As understanding of the pathogenesis of pigment liberation expands, consideration should also be given to gearing therapy toward eliminating acute pigment release, rather than just treating elevated IOP.
Initial medical therapy for pigmentary glaucoma is aqueous suppression with a topical beta-blocker, primarily because of the relatively easy dosing schedule and minimal side effects.
Prostaglandin analogues, which lower IOP by increasing uveoscleral outflow, are also effective in treating pigmentary glaucoma and offer the advantage of once daily administration. The iris surface color change that may occur during therapy appears to involve increased melanin production by iris melanocytes and is not known to affect the iris pigment epithelium (IPE) or result in pigment dispersion.
Alpha-agonists are useful in pigmentary glaucoma, but the development of allergy in as many as 50% of patients precludes the long-term use of dipivefrin, epinephrine, and apraclonidine in many individuals. Brimonidine tartrate 0.2% may provide satisfactory IOP with less allergic reaction than other drugs in this class.
Topical carbonic anhydrase inhibitors are useful agents for treating pigmentary glaucoma and are generally well tolerated. Systemic agents should be reserved for particularly difficult circumstances or when the risks of surgery are unacceptably high.
Miotic therapy
Parasympathomimetics may also be administered.
Pupillary miosis increases resistance to aqueous flow from the posterior chamber, past the lens surface, and through the pupil into the anterior chamber. This increased resistance allows aqueous pressure to build within the posterior chamber (ie, relative pupillary block) and forces the iris to move anteriorly, away from the zonules, and assume a convex configuration. The relief of iridozonular contact following miotic therapy has been demonstrated with ultrasound biomicroscopy (UBM).
However, miotics are poorly tolerated in young individuals because of the associated spasm of accommodation and blurring of vision. An extended-release pilocarpine delivery system (Ocusert) was often effective without disabling adverse effects; however, it is no longer commercially available.
A careful peripheral retinal examination should be performed before and after the institution of or change in miotic therapy because of the higher incidence of retinal breaks and detachment in these patients.
Laser iridectomy eliminates the iris concavity in most patients with pigment dispersion syndrome by permitting equalization of pressures between the anterior and posterior chambers. This causes the iris to flatten, thereby decreasing iridozonular contact and resultant pigment dispersion. Anecdotal evidence suggests that this can prevent continued pigment liberation, result in a reversal of trabecular pigmentation, and, subsequently, lower IOP. However, long-term lowering of IOP and stabilization of glaucomatous optic neuropathy and visual field loss have not been demonstrated conclusively. Although theoretically sound, laser iridectomy should be used with caution because of the paucity of data regarding the long-term efficacy of this procedure.
Laser trabeculoplasty
Argon laser trabeculoplasty may be offered as a treatment in the management of uncontrolled pigmentary glaucoma. Although the initial result is often good, a larger proportion of patients can lose control of IOP when compared to patients with primary open-angle glaucoma (POAG), and the loss of control can occur in less time. In contrast to other forms of open-angle glaucoma, younger patients appear to respond better to trabeculoplasty than older individuals. Selective laser trabeculoplasty has been reported to result in marked and sustained IOP elevation, necessitating trabeculectomy in a few eyes with pigmentary glaucoma; therefore, it should be used with great caution.[18]
Filtering surgery
The surgical management of patients with pigmentary glaucoma follows the same principles and considerations used in the management of primary open-angle glaucoma. The appearance and change in the optic nerve along with visual field defects should be the principal guidelines used in deciding whether surgery is needed. Most patients respond well to standard filtration operations, although antifibrosis agents may be indicated to achieve a low target pressure or for reoperation. No unusual problems are typically encountered during cataract surgery.
Although glaucoma is not simply a disease of elevated intraocular pressure (IOP), current medical therapy remains directed at lowering IOP.
A rational approach to choosing antiglaucoma medication should minimize the number of medications and probability of significant adverse effects.
As mechanisms of axonal death by apoptosis become better understood, therapies may be developed to protect nerve fibers from ongoing damage and death. This has been termed neuroprotection.
Agents currently under investigation as neuroprotective include glutamate receptor blockers, calcium channel blockers, inhibitors of nitric oxide synthase, free radical scavengers, and drugs to increase blood flow to the optic nerve.
Bimatoprost (Lumigan), travoprost (Travatan), and unoprostone (Rescula) are new ophthalmic prostaglandin analogs recently approved in the United States. Bimatoprost is a prostamide analog with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Travoprost and unoprostone are prostaglandin F2-alpha (ie, dinoprost) analogs similar to latanoprost. They are selective FP prostanoid receptor agonists believed to reduce IOP by increasing uveoscleral outflow. They are indicated for the lowering of IOP in patients with open-angle glaucoma or ocular hypertension who are intolerant of other IOP-lowering medications or who are insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another IOP-lowering medication.
Bimatoprost and travoprost are each administered once daily at bedtime (ie, 1 gtt in affected eye[s] hs), whereas unoprostone must be administered bid. They have not been studied in pediatric patients.
These medications are contraindicated if hypersensitivity has been documented. No drug interactions have been reported. All are classified as pregnancy category C (ie, safety for use during pregnancy has not been established).
Like latanoprost, all demonstrate the unusual adverse effect of permanent increase in pigment of the iris (ie, increases brown pigment) and eyelid, and they may increase eyelash growth. Bacterial keratitis may occur. Use is cautioned in uveitis or macular edema. They should not be used if inflammation is present.
Clinical Context:
Brimonidine is a relatively selective alpha2 adrenergic-receptor agonist that decreases IOP by dual mechanisms, reducing aqueous humor production and increasing uveoscleral outflow. Brimonidine has minimal effect on cardiovascular and pulmonary parameters. A moderate risk of allergic response to this drug exists. Caution should be used in individuals who have developed an allergy to Iopidine. IOP lowering of up to 27% has been reported.
Clinical Context:
Apraclonidine is a potent alpha adrenergic agent that is selective for alpha2 receptors, with minimal cross-reactivity with alpha1 receptors. It suppresses aqueous production and reduces elevated, as well as normal, IOP, whether accompanied by glaucoma or not. Apraclonidine does not have significant local anesthetic activity. It has minimal cardiovascular effects.
Clinical Context:
Nonselective beta-blocker. Timolol may reduce elevated and normal IOP, with or without glaucoma, by reducing the production of aqueous humor. Timolol gel-forming solution (Timoptic XE) usually is administered at night, unless it is used concurrently with latanoprost therapy. Used as 0.25% or 0.5% solution and applied topically to the eye 1-2 times per day.
Clinical Context:
This agent selectively blocks beta1 adrenergic receptors, with little or no effect on beta2 receptors. It lowers IOP by reducing the production of aqueous humor. The drug may have less effect on the pulmonary system. Its IOP-lowering effect is slightly less than that of nonselective beta blockers. It may increase optic nerve perfusion and confer neuroprotection.
Clinical Context:
Blocks beta1-receptors and beta2-receptors and has an intrinsic sympathomimetic activity (partial agonist activity), with possibly less adverse effect on cardiac and lipid profiles.
Clinical Context:
Beta-adrenergic blocker that has little or no intrinsic sympathomimetic effects and membrane stabilizing activity. Has little local anesthetic activity. Reduces IOP by reducing production of aqueous humor.
Topical beta-adrenergic receptor antagonists decrease aqueous humor production by the ciliary body. Adverse effects are due to systemic absorption of drug (decreased cardiac output and bronchoconstriction). In susceptible patients, this may cause bronchospasm, bradycardia, heart block, or hypotension. Monitor patient's pulse rate and blood pressure; patients may be instructed to perform punctal occlusion after administering the drops. Depression or anxiety may be experienced in some patients, and sexual dysfunction may be initiated or exacerbated.
Clinical Context:
Used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one ophthalmic drug is being used, administer the drugs at least 10 min apart. Presumably, it slows bicarbonate ion formation, producing a subsequent reduction in sodium and fluid transport. In addition, reversibly inhibits CA, reducing hydrogen ion secretion at renal tubule, and increases renal excretion of sodium, potassium bicarbonate, and water to decrease production of aqueous humor.
Clinical Context:
Catalyzes reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. May use concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, administer drugs at least 10 min apart.
Reduce secretion of aqueous humor by inhibiting carbonic anhydrase (CA) in the ciliary body. In acute angle-closure glaucoma, administer systemically; apply topically in patients with open-angle glaucoma. These drugs are less effective, and their duration of action is shorter than many other classes of drugs. Adverse effects are relatively rare but include superficial punctate keratitis, acidosis, paresthesias, nausea, depression, and lassitude.
Clinical Context:
Also available as Pilogel, a naturally occurring alkaloid, pilocarpine mimics muscarinic effects of acetylcholine at postganglionic parasympathetic nerves. Stimulates salivary glands and smooth muscle, decreasing aqueous production and increasing outflow.
Constriction of the pupillary sphincter increases relative pupillary block and reduces iridolenticular contact. These drugs also contract the ciliary muscle, tightening trabecular meshwork and allowing increased outflow of aqueous. Adverse effects include brow ache, induced myopia, and decreased vision in low light.
Clinical Context:
Latanoprost may decrease IOP by increasing the outflow of aqueous humor. Patients should be informed about possible cosmetic effects to the eye/eyelashes, especially if uniocular therapy is to be initiated.
Clinical Context:
This agent is a prostamide analogue with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Bimatoprost ophthalmic solution is used to reduce IOP in open-angle glaucoma and ocular hypertension.
Clinical Context:
This agent is a prostaglandin F2-alpha analogue. It is a selective FP prostanoid receptor agonist that is believed to reduce IOP by increasing uveoscleral outflow. Travoprost ophthalmic solution is used to treat open-angle glaucoma and ocular hypertension.
Prostaglandin analogs increase uveoscleral outflow of aqueous. One mechanism of action may be through the induction of metalloproteinases in the ciliary body, which breaks down the extracellular matrix, reducing resistance to outflow through the ciliary body. They can be used in conjunction with beta-blockers, alpha-agonists, or topical CA inhibitors. Many patients respond well to these agents; others do not respond at all. Adverse effects include iris pigmentation, cystoid macular edema, and uveitis.
Clinical Context:
CA inhibitor that may decrease aqueous humor secretion, causing a decrease in IOP. Presumably slows bicarbonate ion formation with subsequent reduction in sodium and fluid transport.
Timolol is a nonselective beta-adrenergic receptor blocker that decreases IOP by decreasing aqueous humor secretion. Both agents administered together bid may result in additional IOP reduction compared with either component administered alone, but reduction is not as much as when dorzolamide tid and timolol bid are administered concomitantly.
Jim C Wang (王崇安), MD, Vitreo-Retinal and Cornea/Anterior Segment Subspecialist, Department of Ophthalmology, Kaiser Permanente Fontana Medical Center
Disclosure: Nothing to disclose.
Coauthor(s)
Robert Ritch, MD, FACS, FARVO, Shelley and Steven Einhorn Distinguished Chair in Ophthalmology, Professor of Ophthalmology, Surgeon Director Emeritus, New York Eye and Ear Infirmary of Mount Sinai
Disclosure: Received none from Sensimed for board membership; Received none from iSonic Medical for board membership; Received consulting fee from Aeon Astron for consulting; Received honoraria from Pfizer for speaking and teaching; Received honoraria from Allergan for speaking and teaching; Received honoraria from Ministry of Health of Kuwait for speaking and teaching; Received honoraria from Aeon Astron for speaking and teaching; Received royalty from Ocular Instruments for other.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Martin B Wax, MD, Professor, Department of Ophthalmology, University of Texas Southwestern Medical School; Vice President, Research and Development, Head, Ophthalmology Discovery Research and Preclinical Sciences, Alcon Laboratories, Inc
Disclosure: Nothing to disclose.
Chief Editor
Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Additional Contributors
Andrew I Rabinowitz, MD, Director of Glaucoma Service, Barnet Dulaney Perkins Eye Center
Disclosure: Nothing to disclose.
Yaniv Barkana, MD, Consulting Staff, Glaucoma Unit, Department of Ophthalmology, Assaf Harofe Medical Center
Ramulu P. Pigmentary glaucoma and pigment dispersion syndrome. http://eyewiki.aao.org/Pigmentary_glaucoma_and_Pigment_Dispersion_Syndrome. Available at http://eyewiki.aao.org/Pigmentary_glaucoma_and_Pigment_Dispersion_Syndrome . Accessed: July 19, 2016.
[Guideline] U.S. Preventive Services Task Force (USPSTF). Screening for glaucoma: recommendation statement. Rockville (MD): Agency for Healthcare Research and Quality (AHRQ); 2005 Mar.
Chew SJ, Tello C, Wallman J, Ritch R. Blinking indents the cornea and reduces anterior chamber volume as shown by ultrasound biomicroscopy. Invest Ophthalmol Vis Sci. 1994. 35 (Suppl):1573.
Cantor L. Section 10: Glaucoma. Basic and Clinical Science Course. American Academy of Ophthalmology: 1996-1997.
Chaudry I, Wong S. Recognizing glaucoma. A Guide for the Primary Care Physician. 1999. Vol 99.: 247-64.
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