A Patients Guide to Glaucoma

Table of Contents. A Patient's Guide to Glaucoma

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By Young H Kwon, MD, PhD; John H Fingert, MD, PhD; and Emily C Greenlee, MD

Edited by Young H Kwon, MD, PhD

Illustrated and copyedited by Trish Duffel, RPh, MA
The University of Iowa

Chapter 1. Glaucoma: Optic Nerve Disease

Section 1-A. Optic nerve disease
Section 1-B. The meaning of optic nerve “cupping”
Section 1-C. Understanding peripheral vision loss from glaucoma
Section 1-D. Implications of a glaucoma diagnosis & Chapter References

Chapter 2. Epidemiology of glaucoma

Section 2-A. Introduction
Section 2-B. The epidemiology of primary open-angle glaucoma
Section 2-C. The epidemiology of primary angle closure glaucoma & Chapter References

Chapter 3. The glaucoma eye

Section 3-A. Normal ocular anatomy
Section 3-B. Aqueous fluid production and drainage angle
Section 3-C. Optic nerve damage in glaucoma & Chapter References

Chapter 4. Types of glaucoma

Section 4-A. Introduction to types of glaucoma
Section 4-B . The glaucoma suspect
Section 4-C. Open-angle glaucoma
Section 4-D. Angle closure glaucoma
Section 4-E. Childhood glaucoma & Chapter References

Chapter 5. Glaucoma Risk factors

Section 5-A. For primary open-angle glaucoma
Section 5-B. For primary angle closure glaucoma
Section 5-C. For childhood glaucoma & Chapter References

Chapter 6. The glaucoma eye examination and diagnosis

Section 6-A. What to expect
Section 6-B. Intraocular pressure and corneal pachymetry
Section 6-C. The drainage angle
Section 6-D. Peripheral vision (visual field testing)
Section 6-E. Optic nerve exam & Chapter References

Chapter 7. Medical treatment of glaucoma

Section 7-A. Aqueous Production and Outflow
Section 7-B. Topical Glaucoma Medications
Section 7-C. Glaucoma Medication Classes
Section 7-C (1). Prostaglandin Analogs
Section 7-C (2). Beta-blockers
Section 7-C (3). Alpha-Adrenergic Agonists
Section 7-C (4). Carbonic Anhydrase Inhibitors (CAIs)
Section 7-C (5). Cholinergic Agents
Section 7-D. Using Glaucoma Medications & Chapter References

Chapter 8. Surgical treatment of glaucoma

Section 8-A. Glaucoma Laser treatment
Section 8-A (1). Laser Trabeculoplasty
Section 8-A (2). Laser Peripheral Iridotomy (LPI)
Section 8-A (3). Laser Iridoplasty
Section 8-B. Trabeculectomy: a filtering procedure
Section 8-C. Glaucoma Drainage Devices (Glaucoma Tube or Seton Implant)
Section 8-D. Ciliary body ablation (cycloablation) & Chapter References

Chapter 9. Glaucoma emergency: Acute angle closure glaucoma

Section 9-A. Introduction to acute angle closure glaucoma
Section 9-B. Risk Factors for acute angle closure glaucoma
Section 9-C. Diagnosis of acute angle closure glaucoma
Section 9-D. Treatment of acute angle closure glaucoma
Section 9-E. Prevention & Chapter References

Chapter 10. Childhood (pediatric, congenital) glaucoma

Section 10-A. Types of Pediatric Glaucoma
Section 10-B. Diagnosis of congenital glaucoma
Section 10-C. Treatment of congenital glaucoma
Section 10-D. Importance of team approach in pediatric glaucoma
Section 10-E. Chapter References

Chapter 11. TheGenetics of Glaucoma

Section 11-A. The Genetic Basis of Glaucoma
Section 11-B. Research Methods for Studying Glaucoma Genetics
Section 11-B(1). Candidate Gene Approach to Glaucoma
Section 11-B(2). Positional Cloning Approach to Glaucoma (Linkage Analysis)
Section 11-C. The Genetics of Specific Types of Glaucoma
Section 11-C(1). Juvenile Open Angle Glaucoma
Section 11-C(2). Primary Open Angle Glaucoma
Section 11-C(3). Normal Tension Glaucoma
Section 11-C(4). Primary Congenital Glaucoma
Section 11-D. Genetic Testing for Glaucoma
Section 11-E. The Benefits of Studying Glaucoma Genetics
Section 11-F. Chapter References

Chapter 12. Living with glaucoma

Section 12-A. Using glaucoma medications regularly
Section 12-B. Adherence to glaucoma medication
Section 12-C. Low vision aids
Section 12-D. Minimizing the impact of glaucoma on lifestyle
Section 12-E. Glaucoma societies and organizations
Section 12-F. References

updated 03-05-2007

Section 12-E: Glaucoma Societies and Organizations

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Numerous glaucoma resources are available to patients and eye doctors alike. The following is a list of the larger national organizations. They each provide links to other organizations and support groups.

The American Academy of Ophthalmology (www.aao.org) is the national organization for ophthalmologists. Its membership and resources are extensive. A special Patient section is provided which answers many questions about glaucoma. In addition to providing information on various Eye Health Topics, it contains helpful sections regarding glaucoma.

The American Glaucoma Society (www.glaucomaweb.org) is a nationally recognized society whose members are practicing glaucoma specialists. It also provides patients with basic information about glaucoma and its treatment. It is a nice resource for patients who are looking for a glaucoma specialist in their geographical location.

The Glaucoma Foundation (http://www.glaucomafoundation.org/) is a not-for-profit organization which provides patients information about their diagnosis and treatment and provides funding for glaucoma research. Information is presented in an easy to understand format. A PDF of their Patient Guide is available for downloading. Information about support groups for both adult and children is given in associated links.

The Glaucoma Research Foundation (www.glaucoma.org) provides funding for glaucoma research. The Foundation provides access to support services and discusses issues regarding financial assistance with glaucoma medications.

Research to Prevent Blindness (http://www.rpbusa.org/) is a non-government organization which provides generous funding for eye research. Basic concepts of glaucoma are discussed and presented. Downloadable articles are also available detailing recent research developments within the field of glaucoma.

Several international groups exist. The Association of International Glaucoma Societies (http://www.globalaigs.org/), of which the American Glaucoma Society is a regional member, is an international organization which facilitates collaboration among many glaucoma societies throughout the world. It attempts to distribute and consolidate information regarding the standard practice of glaucoma. The Association of International Glaucoma Patient Organizations (http://www.aigpo.org/) arose from The Association of International Glaucoma Societies and provides patients with regional support groups and references regarding patient education.

Finally, this entire book, “A Patient’s Guide to Glaucoma,” is available for free online at http://www.medrounds.org/glaucoma-guide/2006/02/table-of-contents-patients-guide-to.html.

Section 12-F: References

Busche S, Gramer E. [Improved eyedrop administration and compliance in glaucoma patients. A clinical study]. Klin Monatsbl Augenheilkd. 1997 Oct;211(4):257-62.

Gurwitz JH, Glynn RJ, Monane M, Everitt DE, Gilden D, Smith N, Avorn J. Treatment for glaucoma: adherence by the elderly. Am J Public Health. 1993 May;83(5):711-6.

Kass MA, Gordon M, Morley RE Jr, Meltzer DW, Goldberg JJ. Compliance with topical timolol treatment. Am J Ophthalmol. 1987 Feb 15;103(2):188-93.

Kosoko O, Quigley HA, Vitale S, Enger C, Kerrigan L, Tielsch JM. Risk factors for noncompliance with glaucoma follow-up visits in a residents’ eye clinic. Ophthalmology. 1998 Nov;105(11):2105-11.

Muir KW, Santiago-Turia C, Stinnett SS, Herndon LW, Allingham RR, Challa P, Lee PP. Health literacy and adherence to glaucoma therapy. Am J Ophthalmol. 2006 Aug;142(2):223-6.

Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glaucoma. Ophthalmic Surg. 1995 May-Jun;26(3):233-6.

Sleath B, Robin AL, Covert D, Byrd JE, Tudor G, Svarstad B. Patient-reported behavior and problems in using glaucoma medications. Ophthalmology. 2006 Mar;113(3):431-6.

Vold SD, Riggs WL, Jackimiec J. Cost analysis of glaucoma medications: a 3-year review. J Glaucoma. 2002 Aug;11(4):354-8.

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Section 12-D: Minimizing the Impact of Glaucoma on Lifestyle

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A chronic disease requires chronic treatment. The diagnosis of glaucoma often means a lifetime of ophthalmic exams and treatment. Chronic treatment and monitoring should be incorporated into one’s life with minimal strain or stress to the patient. One of the major factors affecting how likely a patient will be adherent with medications is the impact of glaucoma treatment on a person’s lifestyle. Physically active patients would prefer not to have continual disruptions in their day to administer medications. It is important to minimize the number of medications/doses per day to adequately control glaucoma. The number of prescribed medications increases if glaucoma is uncontrolled with existing medications. Doses per day depend on the prescribed medication. Once-daily dosed medications help minimize the time requirement for administration.

Incorporating medications into a daily routine helps prevent missed doses. Once a routine is established, there is less of a chance of forgetting medications. Until a routine is established and memorized, it is helpful to have written instructions to follow. This eliminates dosing the incorrect eye or using the wrong number of doses.

When glaucoma surgery is warranted, the type of procedure chosen can be influenced by lifestyle choices. Discuss your activities with your doctor to guide surgical treatment. Input from the patient helps to maximize surgical success.

Cost becomes an issue with using glaucoma medications. The average cost per month can be significant depending on the number of medications used. Generic brands are available for some of the eye drops which can decrease their cost substantially. A prescription health plan and other benefits (e.g., veterans’ benefits) also help to defray the cost of these prescription medications. Comparing costs of medications online is another method of finding the most economical alternatives. Using drug delivery aids can prevent wasted doses by effectively delivering the medications to the eye. A discussion with your provider helps coordinate a plan for the most effective and least costly drug regimen.

Take advantage of low vision aids and existing benefits. Computer monitor settings can be changed to increase font size and appearance of the screen for advanced visual loss. In the United States, a person who has significant vision loss or is legally blind (best corrected vision less than 20/200 or visual field < 20º in the better eye) may qualify for Social Security or Supplemental Security Income (SSI) benefits (http://www.ssa.gov/) or tax benefits (http://www.irs.gov/). Directory assistance and other benefits may be available depending on the state of residence. The Library of Congress (www.loc.gov/nls) also provides free library services for the visually impaired and physically disabled. Veterans may also qualify for benefit through their Veterans Administration (http://www.va.gov/).

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Section 12-C: Low Vision Aids

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If glaucoma is undiagnosed or poorly controlled, it may result in varying degrees of visual disability. Once vision loss occurs from glaucoma, it cannot be regained. If the loss is mild, the patient may not experience any limitation in their daily activities. If moderate, there may be some visual impairment. In advanced cases, functional vision can be severely compromised to the point of legal blindness. It is, therefore, important to have periodic scheduled monitoring for glaucoma with good adherence to a prescribed drug regimen. This can minimize the visual decline resulting from glaucoma.

When functional visual disability exists, evaluation by a Vision Rehabilitation Specialist is important. A vision rehabilitation specialist is an eye doctor trained in providing low vision evaluations and presenting devices which may assist patients in their daily activities. The purpose of a Vision Rehabilitation Specialist is to improve individual’s activities of daily living (ADLs) so that the disability’s effects are minimized. These specialists can assess a person’s needs within both home and occupational settings and provide recommendations to improve their level of functioning within these areas. A consultation may provide instruction on the optimal eyeglass prescription (near and far), lighting for various tasks, and an assessment of driving. Various low vision aids may be beneficial, including high prescription reading glasses, filtered lenses, handheld and free-standing magnifiers, talking clocks/books and other appliances, large print materials, electronic reading machines, telescopes, closed circuit televisions/video magnifiers, computer access technology, and devices for braille. These aids allow patients to optimize their functioning in both home and occupational settings. For example, adequate task lighting and prescription strengths for reading may be evaluated so that reading is easier and more enjoyable. Filtered lenses can help with light sensitivity or problems with glare. Both handheld and free-standing magnifiers are helpful for patients who require increased magnification for better reading. They come in different strengths. Handheld magnifiers have the benefit of being portable but are bothersome for those with hand tremors. Free-standing magnifiers are more useful in these cases but have the disadvantage of not being easily portable. Talking clocks/books and other appliances are also helpful for visually disabled persons. They allow people to rely on their hearing to obtain information. Large print books are helpful for those who need extra magnification for easier reading. These are available in books stores and libraries. Closed circuit TVs/video magnifiers have a camera which magnifies images that are then relayed to a monitor for viewing. This is useful for reading material such as newspapers or for important activities such as reading bills or signing checks. A Low Vision evaluation aims toward improving patients’ lifestyles by analyzing their needs and providing the means and methods to meet them.

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Section 12-B(2): Measures to Improve Adherence to Glaucoma Medications

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Understand the Disease and Its Treatment. Patients are encouraged to ask questions about their diagnosis and understand the rationale behind its treatment. Obtain information on the disease from the prescribing provider, books, and online glaucoma sites (e.g. http://www.medrounds.org/glaucoma-guide/2006/02/table-of-contents-patients-guide-to.html).

Prescribing Least Number of Medications/Doses. Adherence can be improved by using the least number of medications and least number of doses per day to control glaucoma

Minimize Untoward Side Effects. Report adverse side effects from eye drops. Understand the expected side effects and identify which ones are not transient. Some medications may cause slight redness upon initial instillation of the drop which improves with time.
Get Written Instructions. Written instructions are helpful for the patient to recall the exact medical regimen prescribed by the eye doctor (Figure 12-2). Relying only on verbal instructions often leads to mistakes in administration of medications. It is difficult for the patient to remember all verbal instructions when there is so much information given during a clinic visit.

Figure 12-2. A medication instruction sheet is a helpful reminder to take medications as exactly prescribed (Click on image above for larger, pdf, version. © University of Iowa).

Use Colors to Identify Correct Medications. It is important to know what medications are prescribed, what they do, and how to correctly identify them. The bottles cap color provides a helpful reminder of what each bottle contains (see Chapter 7, Table 7-2).
Practice Administering Medications in the Clinic. Patients are encouraged to practice administering eye drops under the supervision of their eye doctor. This allows the eye doctor to see how well a patient is instilling their medications. It also reassures the patient that their instillation technique is correct.
Time Doses with Scheduled Activities. Dose eye drops with scheduled activities. Patients can often incorporate their medication in the morning, with meals, and at bedtime. Linking the eye drop with an activity, such as brushing teeth or taking other oral medications, is helpful.
Obtain Help from Family/Caregivers. Enlisting the help of others may be necessary for those who are unable to comprehend or self-administer eye drops. Family/caregivers’ understanding of the disease and its treatment is key to improving adherence to a prescribed drug regimen.
Perform Punctal Obstruction or Eyelid Closure. It is recommended that patients wait 15 minutes between medications to allow better absorption of each medication. If 3 eye drops have been prescribed, there would be 30 minutes of waiting time per dose. For example, if there are 3 medications that need to be taken twice daily each, more than 60 minutes of time is necessary to administer these medications each day. It is easy to see how an increase in the number of medications causes a decrease in adherence. Another method of improving absorption of eye drops is to use punctual occlusion. This maneuver allows the eye medication to absorb more effectively by obstructing the outflow from the eye. It is performed by placing digital pressure over the lower eyelid puncta by the nose (see Chapter 7, Figure 7-4, 7-5).
Use Eye Drop Delivery Aids If Necessary. Eye drop delivery aids could be useful in some patients. For those with arthritis or severe vision loss, it may be useful (Figure 12-3).

Figure 12-3. An eyedrop dispenser for Xalatan (Xal-Ease, Pfizer, NY, NY) can help those who have difficulty administering Xalatan eye drop.

Checking on Prescription Refills to Determine Adherence Level. Patients and eye doctors can check on the number of refills within a certain time period. This gives a general estimation to see if the usage seems on track.

Generics and Understanding Available Resources to Decrease Cost. Generic glaucoma medications are available which helps to defray some of the cost. The Glaucoma Research Foundation (http://www.glaucoma.org/) provides a section on financial aid and programs that assist patients with obtaining their glaucoma medications.

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Section 12-B(1): Factors Affecting Adherence

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1) Forgetfulness or Physical Limitations. Many patients report forgetfulness as one of the major reasons that they are not 100% adherent with their glaucoma medications. It is often difficult to incorporate a new drug regimen into one’s lifestyle.

2) Physical Limitations. Those with physical limitations, such as severe arthritis or significant visual disability, may have problems self-administering medications. Family or caregivers can help treat glaucoma by accompanying the patient to appointments, understanding the disease, and learning how to administer eye drops if necessary.

3) Misunderstanding the Disease and Its Treatment. This factor is easily corrected by gathering information about the disease process. Information on glaucoma is readily available at your eye doctor’s office, the library, book stores, and the internet (e.g. http://www.medrounds.org/glaucoma-guide/2006/02/table-of-contents-patients-guide-to.html). These available resources are inexpensive and easily obtained.

4) Multiple Doses Per Day. The number of doses per day and number of medications can also affect adherence. The more doses or medications prescribed, the less likely that there will be perfect adherence. Instilling numerous doses or medications can adversely affect a patient’s lifestyle. It is difficult to remember multiple drops and take time to administer eye drops throughout the day. The more frequently this occurs, the more likely there will be missed doses. Given the time necessary and other methods involved with ensuring proper glaucoma medications, it is easy to see why patients prefer once daily-dosed eye drops. The following eye drops are administered once daily: Xalatan, Travatan, Lumigan, Timolol XE, Istalol.

5.) Multiple Medications. One can improve adherence by minimizing the dosage and total number of medications that are still effective. Patients should be on the least number of eye drops necessary with the least dosing per day to control their glaucoma. Written instructions from the doctor’s office are a good reminder to be used at home, particularly for those on multiple systemic medications for other diseases. Combination eye drops [e.g., Cosopt (timolol/dorzolamide)] also exist which minimizes the number of eye drop bottles.

6.) Difficulty Administering Medications. Eye drop delivery aids are available for people who have physical difficulty administering their eye medications. The bottle can be placed in these devices, and the device allows the patient to easily squeeze the bottle in the correct position over the eye. One eye medication, Travatan, offers an aid which electronically monitors doses and offers reminders when doses are due (Figure 12-1). This aid allows providers to download the information to see how adherent a patient has been since their last visit.

Figure 12-1. The Travatan Dosing Aid (Alcon, Ft Worth, TX) reminds patients when doses are due. It also allows the eye doctor to download information about the doses taken and their timing.

7.) Intolerable Side Effects. In general, topical glaucoma eye drops are well-tolerated, especially with the newer generation of medications. Nevertheless, some people can experience untoward side effects. The various medications and the side effects are numerous and have been discussed previously (see Chapter 7).

8.) High Cost of Medications. In a 3-year review (1998 to 2000) analyzing the medication cost, the following was the cost of glaucoma medication per year (Table 12-1).

Table 12-1. Average cost of glaucoma medication per year (1998-2000)
Cosopt	$470
Betoptic-S	$370
Xalatan	$352
Trusopt	$288
Alphagan	$273
Azopt	$243
Timoptic-XE	$190
Ocupress	$183
Generic levobunolol	$138
Optipranolol	$135
Generic timolol	$133

Patients are sometimes willing to pay more for medications which increase convenience and cause minimal side effects. Others are constrained by the cost, especially when they are taking other medications for systemic diseases.

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Section 12-B: Adherence to Glaucoma Medication

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Many studies have tried to evaluate the level of adherence in patients and the risk factors for nonadherence. In general, 13.4% to 60% of patients have reported their non-adherence when asked. Numerous factors have been evaluated to determine what affects adherence. Age, race, and gender have not been found to be contributing factors. Others are contributory and discussed below.

12-B(1): Factors Affecting Adherence

12-B(2): Measures to Improve Adherence to Glaucoma Medications

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Section 12-A: Using Glaucoma Medications Regularly

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The Doctor-Patient Relationship

The most important controllable factor in glaucoma management is adherence to prescribed medications. A good doctor-patient relationship fosters knowledge of the disease process and greater likelihood of adhering with a recommended regimen. The more patients know about their disease process, the more likely they are to adhere to treatment. It is the eye care providers’ responsibility to inform patients of their diagnosis and its implications. A common misconception is that blindness is the inevitable result of glaucoma. While there is a possibility of blindness in glaucoma, it is not necessarily inevitable. With proper diagnosis and early intervention, most patients retain functional vision with limited visual disability. Asking the doctor questions and better understanding of the disease are part of effective treatment.

Understanding Goals of Treatment

Since glaucoma is a chronic condition, once treatment is initiated it is often continued throughout a patient’s lifetime. The goal of medications is to prevent a further decline of vision by lowering the intraocular pressure (IOP). This goal is sometimes not obvious to patients because instead of restoring previously lost vision, it aims toward preventing further vision loss. The presumed lack of direct benefit hinders adherence with glaucoma medications. When patients see no direct benefit from taking medications, they may be less inclined to take them as prescribed. In addition, the vision loss from glaucoma tends to occur slowly over time and there are usually no acute symptoms. Patients do not notice the vision loss that occurs over a long time period and fail to see this as being a result of not taking their glaucoma medications. Although the immediate benefit is not obvious, it is important to realize that taking daily eye drops is decreasing the likelihood of vision loss from glaucoma.

Worsening Glaucoma with Missed Doses

Missed doses of medications can cause vision loss as much as not taking glaucoma medications altogether. The fluctuations in IOP can be equally detrimental to the optic nerve. A study which used electronically monitored medication bottles revealed that only 83% of timolol doses were taken as prescribed. The IOP measured the day of the exam can be misleading since most patients take their eye medications shortly prior to the examination. Unfortunately, there is no available physiologic parameter which allows the eye doctor to know what the average IOP has been between visits. Glaucoma can worsen when doses are repeatedly missed despite a good measurement at the doctor’s office. The fluctuations of IOP can be detrimental to the optic nerve.

A Team Approach to Battling Glaucoma

The treatment of glaucoma is a battle which must be fought by both the eye doctor and patient. It is very difficult, if not impossible, for an eye doctor to control glaucoma without the full participation of the patient. It is the patient who is responsible for the day-to-day treatment of glaucoma. The patient should be aware of the benefits and side effects of the recommended medications as well as the disease itself. A well-informed patient is more likely to adhere to a long-term medical treatment of glaucoma.

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Chapter 12: Living with Glaucoma

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This chapter includes:
12-A: Using Glaucoma Medications Regularly
12-B: Adherence to Glaucoma Medications
12-B(1): Factors Affecting Adherence
12-B(2): Measures to Improve Adherence to Glaucoma Medications
12-C: Low Vision Aids
12-D: Minimizing the Impact of Glaucoma on Lifestyle
12-E: Glaucoma Societies and Organizations
12-F: References

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Section 11-E: Benefits of studying glaucoma genetics

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Every year, thousands of Americans are blinded by glaucoma. In most cases, the loss of vision caused by glaucoma could be limited or prevented by currently available therapies if the disease were identified in its early stages. Many cases of glaucoma are not discovered until vision has already been permanently lost, because clinical signs of early glaucoma are subtle and silent to the patient.

The discovery of glaucoma disease genes provides a method for early detection of glaucoma. Genetic testing for disease-causing mutations in these genes is capable of identifying those at highest risk for developing glaucoma years to decades before vision loss or other symptoms are manifested. Heightened surveillance and early institution of glaucoma therapy can then be provided to these patients before any vision is lost, perhaps even before any symptoms are observed.

Testing to determine the genetic causes of glaucoma will also facilitate the development and evaluation of new medical therapies and surgical interventions.

Glaucoma is a collection of distinct diseases with similar clinical appearances. Genetic testing will allow physicians to identify groups of patients with the same biochemical basis of glaucoma. Some sub-types of glaucoma may respond to certain treatments while others may not. Identification of such well-characterized groups of patients to test new medical therapies and surgical interventions will help speed the discovery of new, effective treatments.

Genetic study of inherited diseases such as glaucoma will likely promote advances in therapy as well as diagnosis. For example, methods to replace defective genes with normal functioning genes (trans-genes) are being perfected. At present, however, there are some limitations to this technology known as gene therapy. Some of the major obstacles in using gene therapy include difficulties in obtaining 1) effective delivery of the trans-genes to the right tissues of the eye, 2) control of transgene activity, 3) maintenance of transgene effect, and 4) low-cost methodology. Advances in all of these areas are being realized, and gene therapy for glaucoma may be possible in the future.

Most inherited genetic defects, however, may be treated with currently available medical and surgical therapies. As the functions of disease-causing genes are discovered, conventional treatments may also be tailored to mitigate disease-causing defects. In one form or another, genetic research opens the promise of a new generation of sight-saving therapies.

Section 11-F: References

Fingert JH, Anderson, MG. Chapter 144: Glaucoma. In Emery and Rimoin’s Principles and Practice of Medical Genetics. 5th Ed. Elsevier, Philadelphia, 3133-3156, 2006.
Allingham RR, et al., editors. Shields’ Textbook of Glaucoma, ed. 5. Philadelphia: Lippincott Williams & Wilkins, 163-169, 2005.
Fingert JH, Stone EM, Sheffield VC, Alward WLM. Myocilin Glaucoma. Survey of Ophthalmology, 47: 547-561, 2002.
Sheffield VC, Alward WLM, Stone EM. Chapter 242: The Glaucomas. In Scriver CR, et al, eds. The Metabolic & Molecular Basis of Inherited Disease. 8th Ed. MacGraw-Hill, St. Louis, 6063-6075, 2001.
Johnson AT, Alward WLM, Sheffield VC, Stone EM. Chapter 2: Genetics and Glaucoma. In Ritch R, Shield MB, Krupin T, eds. The Glaucomas. 2nd Ed. Mosby, Chicago, 39-54, 1996.
GeneTests http://www.genetests.org
GeneReviews . see http://tinyurl.com/34eks3(http://www.genetests.org/servlet/access?id=8888892&key=3L1fqyZufuJdP&fcn=y&fw=29qT&filename=/reviewsearch/searchdz.html)
The John and Marcia Carver Non-profit Genetic Testing Laboratory http://www.carverlab.org.

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Section 11-D: Genetic testing for glaucoma

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Incredible progress in being made in the field of genetic research and important discoveries and innovations are being made at an increasingly rapid pace. In the last few years, several landmark discoveries have been made in ophthalmic genetics. The Online Mendelian Inheritance in Man (OMIM, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM) is a catalog of heritable diseases and syndromes. At the beginning of 2007, this database had 813 entries of heritable conditions that affect the eye and 171 conditions in which glaucoma is a feature. As new genes that cause various types of glaucoma are discovered, there will be more opportunities for genetic testing to enhance all aspects of patient care including diagnosis, prognosis, treatment, and family planning. Currently, genetic testing is available for several glaucoma genes including myocilin (MYOC), optineurin (OPTN), and cytochrome P450 1B1 (CYP1B1).

Genetic testing may be useful for patients with specific types of glaucoma and particular clinical features of the disease. Patients that are interested in testing should discuss it with their physician and/or a genetic counselor. Along with discussing whether genetic testing is appropriate for a particular type of glaucoma, physicians and counselors may discuss the implications of these investigations. Genetic testing for inherited diseases may provide information that is useful for a patient’s medical care; however, this information may also affect other family members. Consequently, it is possible that genetic testing may be a source of stress or anxiety for the patient and for family members. Additionally, the results of genetic tests are complex, and should be interpreted by experienced physicians and genetic counselors. The meaning of positive or negative results is not always obvious, and must be carefully explained for genetic testing to be helpful to the patient. For example, there are likely many more glaucoma-causing genes than what have been discovered so far. If a patient is tested for defects in the known glaucoma genes (i.e. myocilin and optineurin) and no disease-causing mutations are detected, it is still possible that this patient has as yet unidentified alterations in genes that play a crucial role in glaucoma development. A patient’s physician or counselor is best equipped to explain the meaning and consequences of such genetic test results.

Some general guidelines for who may benefit most from some specific types of genetic testing are provided below.

Myocilin genetic testing for JOAG.

The patients with the highest likelihood of having glaucoma that is associated with a defect in the myocilin gene are patients with an early onset of disease (< 40 years of age); extremely high intraocular pressure (> 30 mm Hg); and a strong family history of disease. Most patients with these characteristics have familial juvenile-onset primary open angle glaucoma (JOAG) that is due to a mutation in the myocilin gene. Genetic testing may provide patients with familial JOAG and their physicians useful information to help solidify a diagnosis of this form of glaucoma.

Myocilin (MYOC) genetic testing for POAG.

Mutations in the myocilin gene account for a smaller proportion of POAG cases (3-4%) than JOAG. At present, due to the relatively low prevalence of myocilin-associated POAG and the labor-intensive nature of the mutation detection tests, large-scale testing of the general population for myocilin defects are not feasible. However, testing those individuals who are at extremely high risk for developing myocilin-associated POAG may be warranted. Such patients would include family members of patients with known myocilin-associated glaucoma and members of families with a strong history of inherited POAG.

Optineurin (OPTN) genetic testing for NTG.

Most cases of normal tension glaucoma (NTG) occur sporadically, without a family history of disease. However, there are rare familial cases of NTG and testing these patients for mutations in the optineurin gene may be warranted.

Cytochrome P450 1B1 (CYP1B1) testing for PCG.

Many cases of PCG are due to mutations in the CYP1B1 gene. In certain European populations of patients, as much as 87% of family cases of PCG and 27% of sporadic cases of PCG are caused by mutations of the CYP1B1 gene. However, the frequency of CYP1B1 mutations in cases of PCG in the United States is not precisely known. Based on this information, it is usually reasonable to test for CYP1B1 mutations in PCG patients with a positive family history of disease. While the likelihood of detecting a CYP1B1 mutation in a PCG patient is lower when there is no family history of disease, genetic testing may be warranted in some of these sporadic cases.

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Section 11-C(4) Primary congenital glaucoma (PCG)

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Many cases of primary congenital glaucoma (PCG) appear to be sporadic; however, as many as 10-40% cases are familial with autosomal recessive inheritance. Many large PCG pedigrees with clear autosomal recessive inheritance have been reported. In addition, twin studies have provided strong evidence that PCG has a genetic basis. Twins with identical DNA (identical, monozygotic twins) tend to both have PCG at a much higher rate than twins with only 50% identical DNA (fraternal, dizygotic twins). This difference in concordance indicates that genes have important roles in the development of PCG.

Research studies of several large families have shown that mutations in the gene cytochrome P450 1B1 (CYP1B1) cause many cases of PCG. Most patients with PCG (87% of familial cases and 27% of sporadic cases) have glaucoma due to variations in the CYP1B1 gene.

The CYP1B1 gene encodes a protein that metabolizes or breaks down certain molecules or drugs. The mechanism by which defects in the CYP1B1 gene causes PCG is unknown. However, it has been theorized that mutations in this gene may alter its ability to break down factors that are vital to the normal development of drainage angle. A defective CYP1B1 gene might, therefore, result in an abnormal concentration of these developmental factors and lead to the abnormal formation of the drainage angle and PCG.

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Section 11-C(3): Normal tension glaucoma

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Most cases of normal tension glaucoma (NTG) are sporadic with no clear family history. However, rare cases of families with many affected members have been reported. In these families, NTG is inherited as an autosomal dominant trait. Genetic studies have shown that mutations in a gene known as optineurin (OPTN) are responsible for a significant fraction of familial NTG cases. A single optineurin mutation has been associated with glaucoma in several large NTG families. The role of the optineurin gene in sporadic cases of NTG has not been clearly defined.

More is known about the optineurin gene than the myocilin gene. The optineurin gene produces a protein that appears to have many functions. Some studies suggest that optineurin is involved in apoptosis, which is a process by which cells self-destruct or “commit suicide”. It is possible that the optineurin gene may cause optic nerve damage and glaucoma by promoting apoptosis of this tissue. Current studies are exploring the precise mechanism by which defects in the optineurin gene lead to glaucoma.

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Section 11-C(2): Primary open angle glaucoma

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Primary open angle glaucoma (POAG) is the most common form of glaucoma in the United States. Like juvenile onset open angle glaucoma (JOAG), there is also a genetic basis to POAG. However, there are important differences between the genetics of POAG and JOAG. POAG runs in families, but the pattern of inheritance is more difficult to recognize. Due to the relatively late onset of disease in POAG (after the age of 40), most of the families with this condition only include one or two generations of affected family members that are alive. Parents of affected family members are often deceased and offspring of affected members are frequently too young to show signs of the disease. Consequently, families with inherited forms of POAG are generally small with only a few affected members and are difficult to distinguish from sporadic (non-familial) cases (Figure 11-3).

Figure 11-3 POAG pedigree. This diagram shows an example of the pattern of inheritance of glaucoma may occur in a POAG pedigree. The squares represent male family members, while the circles represent female family members. Darkly shaded symbols indicate an affected family member, while unshaded symbols indicate an unaffected family member. Grey symbols indicate a family member with unknown glaucoma status. Diagonal lines (through a square or circle) indicate that a particular family member is deceased. Notice that the founders of the family are deceased and it is unknown whether they were affected with POAG (indicated by grey boxes). Similarly, most of the grandchildren of the founders are younger than the age at which most people develop glaucoma. It is unknown whether these family members will later develop glaucoma so they are shaded grey to indicate their unknown glaucoma status. The majority of family members affected with POAG are in a single generation.

Although research has indicated that POAG is heritable, most of the genes that cause this disease have not yet been identified. It is likely that some cases of POAG will be due to defects in a single gene, while other cases will be due to the combined effects of mutations in several genes and other environmental factors.

The identification of disease-causing genes has been an active focus of research studies of POAG. The approximate position in the genome, or locus, of many genes that can cause POAG has been determined by linkage analysis (Table 11-3). Loci for genes that cause POAG are designated by the a code beginning with the letters “GLC1” and ending in a suffix letter for each new glaucoma loci in chronologic order of discovery. For example, GLC1A was the first open angle glaucoma locus to be discovered. The glaucoma genes in two of these loci have been discovered (myocilin at the GLC1A locus and optineurin at the GLC1E locus). Research to find the disease-causing genes at the other loci is ongoing.

Chromosomal Loci	Locus Name	Known Gene	Glaucoma
Chromosome 1q	GLC1A	MYOC	JOAG, POAG
Chromosome 2q	GLC1B	-	POAG
Chromosome 3q	GLC1C	-	POAG
Chromosome 8q	GLC1D	-	POAG
Chromosome 10p	GLC1E	OPTN	NTG
Chromosome 7q	GLC1F	-	POAG
Chromosome 5q	GLC1G	-	POAG
Chromosome 2p	GLC1H	-	POAG
Chromosome 15q	GLC1I	-	POAG
Chromosome 9q	GLC1J	-	POAG
Chromosome 20p	GLC1K	-	POAG
Chromosome 2p	GLC3A	CYP1B1	PCG
Chromosome 1p	GLC3B	-	PCG
Table 11-3. Known loci (chromosome location) for primary forms of glaucoma. The chromosomal locations of 13 genes that cause glaucoma have been discovered. The type of glaucoma associated with each loci is indicated: Primary open angle glaucoma (POAG), juvenile-onset open angle glaucoma (JOAG), normal tension glaucoma (NTG), or primary congenital glaucoma (PCG). The disease-causing gene at three of these loci are known, while the remaining ten are as yet undiscovered.

At present, only one gene that causes POAG has been discovered (the myocilin gene at the GLC1A locus). As discussed above, one set of mutations in the myocilin gene are known to cause early onset glaucoma (JOAG). A different set of mutations in the same myocilin gene can cause POAG. In fact mutations in the myocilin gene have been shown to be responsible for approximately 3-4% of worldwide cases of POAG. Myocilin associated glaucoma is inherited as an autosomal dominant trait and offspring of affected parents have a 50% chance of inheriting an abnormal myocilin gene, which confers a high risk for developing glaucoma.

Myocilin defects have been identified in patients with POAG from different races and ethnicities including Caucasians from Midwestern America; Caucasians from Canada; Caucasians from Australia; African Americans from New York City; and Asians from Gifu, Japan. In all populations approximately 1 in 25 cases of POAG are due to abnormalities of the myocilin gene. One set of defects in the myocilin gene cause JOAG while a different set of defects cause POAG. In many cases, when a particular defect in the myocilin gene is detected, the severity of the associated glaucoma (age of onset and maximum intraocular pressure) may be accurately predicted.

Myocilin mutations account for approximately 1 in 25 cases of primary open-angle glaucoma. It is likely that many additional genes are involved in the development of glaucoma. The search for these genes is an area of ongoing research.

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Section 11-C(1): Juvenile open angle glaucoma

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Juvenile open angle glaucoma (JOAG) is a rare form of glaucoma that accounts for approximately 1% of total cases. The clinical features of JOAG are the same as those of more common forms of glaucoma (such as POAG). JOAG differs from POAG mainly in the severity of disease and age of onset. Patients with JOAG develop disease at a much earlier age than patients with POAG (between 3 and 40 years of age). JOAG patients also have very high intraocular pressures that frequently exceed 40 mm Hg in the absence of treatment.

In many cases, JOAG clearly runs in families as a dominant trait. Due to the early age of onset and the strong clinical signs of JOAG, several large pedigrees with many generations of affected family members have been recognized (Figure 11-2).

Figure 11-2. Juvenile open angle glaucoma (JOAG) pedigree. JOAG is an early-onset form of open angle glaucoma that is inherited as an autosomal dominant trait. Offspring of a parent with JOAG have up to a 50% chance of inheriting JOAG. This diagram shows the pattern of inheritance of glaucoma through an actual JOAG pedigree.

Genetic studies of large families (like the one shown in Figure 11.2) demonstrated that defects or mutations in the myocilin gene are a cause of JOAG. Most cases of JOAG that have a strong family history of disease are associated with defects in the myocilin gene (MYOC). Myocilin associated glaucoma is inherited as an autosomal dominant trait. That is, patients carrying a myocilin mutation that causes JOAG have a 50% chance of passing the gene (and high risk for glaucoma) to their children. Several specific defects or mutations in the myocilin gene that cause JOAG have been identified.

Some patients have the typical clinical features of JOAG but do not have a family history of disease. The myocilin gene has a less important role in these sporadic cases of JOAG.

The myocilin gene directs tissues of the eye to produce a protein that is released into the aqueous humor. The myocilin protein has an unknown function; however, glaucoma develops when its structure is altered by a mutation. Studies are underway to investigate role of the myocilin gene in healthy eyes and the process by which defects in this gene lead to glaucoma.

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Section 11-C: The genetics of specific types of glaucoma

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Several forms of glaucoma have been investigated in search of disease causing genes. In the last 10 years, genes associated with juvenile open angle glaucoma, primary open angle glaucoma, primary congenital glaucoma, and many forms of secondary glaucoma have been identified (Table 11-2). The genes associated with juvenile open angle glaucoma, normal tension glaucoma, and primary congenital glaucoma are reviewed below.

Gene	Chromosomal location	Type of Glaucoma
Myocilin (MYOC)	Chromosome 1q24.3-q25.2	JOAG or POAG
Optineurin (OPTN)	Chromosome 10p15-p14	NTG
Cytochrome P450 1B1 (CYP1B1)	Chromosome 2p22-p21	PCG
Paired homeodomain transcription factor 2 (PITX2)	Chromosome 4q25-q26	Glaucoma associated with ARS
Forkhead Box C1 (FOXC1)	Chromosome 6p25	Glaucoma associated with ASD and ARS
Paired box 6 (PAX6)	Chromosome 11p13	Glaucoma associated with aniridia

Table 11-2 Known glaucoma-causing genes. Several genes have been associated with various forms of glaucoma including juvenile open angle glaucoma (JOAG), primary open angle glaucoma (POAG), primary congenital glaucoma (PCG), Axenfeld-Rieger’s syndrome (ARS), anterior segment dysgenesis syndrome (ASD), and aniridia.

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Section 11-C(1). Juvenile Open Angle Glaucoma

Section 11-C(2). Primary Open Angle Glaucoma

Section 11-C(3). Normal Tension Glaucoma

Section 11-C(4). Primary Congenital Glaucoma

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Section 11-B(2): Positional cloning approach to glaucoma (linkage analysis)

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Linkage analysis is a method for identifying glaucoma-causing genes that is dependent solely on the availability of large families with several members that have glaucoma. DNA is collected from each member of these families and is tested to see which segments of the DNA are always passed down through the family along with glaucoma. Genes that cause glaucoma are located within these linked regions of DNA (Figure 11-1).

Figure 11-1. Linkage analysis of glaucoma. These diagrams represent the family tree of a family affected with glaucoma. The males in the family are represented by squares and the females are represented by circles. Deceased family members have a diagnonal line across the symbol. Family members affected with glaucoma are indicated by shading the pedigree symbols black. Most spouses were omitted from the diagram. In linkage analysis the inheritance of genetic markers (represented in the diagrams of a family tree with colored squares) is compared to inheritance of glaucoma (represented by darkly shaded pedigree symbols). The inheritance of a genetic marker on chromosome 1 is represented by the green boxes. Notice that the green boxes are always passed down through the family together with glaucoma. The gene causing glaucoma in this family is located near this genetic marker on chromosome 1.

Linkage analysis identifies where glaucoma genes are located within the genome. The next step is testing members of the family for disease-causing defects in the genes that are located with the linked regions.

Linkage analysis has some advantages that make it particularly well-suited for searching for glaucoma genes. This approach to finding disease-causing genes is possible even when little is known about the basic biological mechanisms of the disease being studied (such as glaucoma). This research is dependent on the identification and enrollment of large families with many members that are affected with glaucoma. Most of the known glaucoma genes were discovered with linkage analysis of large glaucoma families.

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Section 11-B(1): Candidate gene approach to glaucoma

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The core features of the candidate gene approach are:
1) making a list of candidate genes that might cause glaucoma if their normal function was altered and
2) testing a large group of unrelated glaucoma patients for defects in these candidate genes.

Identifying candidate genes.
Several types of genes are suspected of having a role in the development of glaucoma. Some of the best candidate genes have functions that suggest they may be important in glaucoma such as 1) genes that are active in the drainage angle where fluid leaves the eye;
2) genes that are active in the ciliary body where fluid enters the eye;
3) genes with functions that suggest they regulate the intraocular pressure; and
4) genes that may be important in maintaining the health of the optic nerve.

Testing candidate genes.
Candidate genes are evaluated for a possible role in causing glaucoma by testing the DNA of large numbers of unrelated glaucoma patients for disease-causing defects. Candidate gene screening is a useful research approach to discover disease-causing genes. This research is dependent on the enrollment of hundreds of volunteer subjects that have glaucoma. By participating in candidate gene studies of glaucoma, patients may learn something about the reasons why they developed glaucoma as well as help with research efforts to study the disease.

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Section 11-B: Research methods for studying glaucoma genetics

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Two general approaches to study the genetics of glaucoma are candidate gene screening and positional cloning. The advantages of each of these types of investigations are discussed below.

Section 11-B(1). Candidate Gene Approach to Glaucoma

Section 11-B(2). Positional Cloning Approach to Glaucoma (Linkage Analysis)

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Section 11-A: Genetic basis of glaucoma.

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Several lines of evidence indicate that glaucoma has a genetic basis, that is, glaucoma is caused in part by defects in specific genes (Table 11-1). First, although many cases of glaucoma occur with no family history of disease, glaucoma appears to be clearly heritable in some families. A number of large families have been reported in which glaucoma is inherited as a simple Mendelian trait (usually with autosomal dominant inheritance). Studies of the epidemiology of glaucoma also support the notion that there is a significant genetic component. Relatives of individuals affected with glaucoma have a much higher risk of developing glaucoma when compared to the general public. Additionally, many of the individual signs of glaucoma are heritable themselves, including cup to disc ratio and IOP. When these key features of glaucoma are examined individually, they appear to run in families. Lastly, the frequency of glaucoma varies greatly between different ethnic and racial groups. For example, the prevalence of glaucoma in African Americans is significantly higher than that of whites, which suggests that African Americans have a higher risk of developing glaucoma due to a heritable factor that is more prevalent in this racial group.

Table 11-1. Evidence that glaucoma is caused at least in part by genes.

Evidence that glaucoma has a genetic basis

Families that show clear inheritance of glaucoma

Relatives of glaucoma patients have a higher rate of developing glaucoma themselves

Features of glaucoma (large cup to disc ratio and high intraocular pressure) are heritable

Glaucoma is more common in some ethnic and racial groups than others

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Chapter 11: The Genetics of Glaucoma

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Heredity plays an important role in most forms of glaucoma. In some types of glaucoma, such as in juvenile open angle glaucoma, disease clearly runs in families. However, the contribution of genetic factors to other types of glaucoma, such as primary open angle glaucoma, may be less obvious. Many genetic factors that are involved in the development of glaucoma are discussed in more detail below.

Section 11-A. The Genetic Basis of Glaucoma

Section 11-B. Research Methods for Studying Glaucoma Genetics

Section 11-B(1). Candidate Gene Approach to Glaucoma

Section 11-B(2). Positional Cloning Approach to Glaucoma (Linkage Analysis)

Section 11-C. The Genetics of Specific Types of Glaucoma

Section 11-C(1). Juvenile Open Angle Glaucoma

Section 11-C(2). Primary Open Angle Glaucoma

Section 11-C(3). Normal Tension Glaucoma

Section 11-C(4). Primary Congenital Glaucoma

Section 11-D. Genetic Testing for Glaucoma

Section 11-E. The Benefits of Studying Glaucoma Genetics

Section 11-F. Chapter References

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Section 10-D: Importance of team approach in pediatric glaucoma

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It takes a whole team of physicians, nurses, and family to provide an optimal treatment for patients with pediatric glaucoma. For example, a glaucoma specialist may provide care for pediatric glaucoma, while a pediatric ophthalmologist may simultaneously treat a “lazy eye” (amblyopia). Lazy eye is a condition in which the visual part of the child’s brain does not develop properly due to abnormalities of the eye (for example, glaucoma) or eye alignment (strabismus). Pediatric glaucoma patients are at a high risk for development of amblyopia, unless they are closely monitored and treated. If amblyopia is detected, he/she needs to be promptly treated because the amblyopia becomes irreversible and not amenable to treatment after the age of approximately 10 years.

It is critical to have a total commitment of the family as well. The family is asked to bring the patient to multiple doctors over many months or years for the treatment of glaucoma. The child may undergo multiple sedations or anesthesia, just to check the intraocular pressure and perform adequate ocular examination. The family is often asked to administer multiple eye drops every day as part of the glaucoma treatment. All of these activities can add a significant amount of stress to the family as well as the patient. On the other hand, when everyone works together to provide an optimal treatment, there is a good chance that the child with glaucoma can grow up with good eyesight.

Section 10-E: References

Allingham RR, Damji K, Freedman S, Moroi S, Shafranov G. Ch 13: Congenital Glaucomas. In: Shield’s Textbook of Glaucoma. 5th Ed. Lippincott Williams and Wilkins, Philadelphia, p235-251, 2005.
Alward, WLM. Ch 9: Glaucomas of Infancy and Childhood. In Glaucoma: The Requisites in Ophthalmology, Mosby, St. Louis, p111-127, 2000.

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Section 10-C: Treatment of congenital glaucoma

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Unlike adult glaucoma, the initial treatment for congenital glaucoma is often surgical. A “drainage angle surgery” is often recommended for congenital glaucoma. The most common surgical procedures for congenital glaucoma are goniotomy and trabeculotomy. While they are considered to have similar rates of success (80-90%), some surgeons prefer one technique over the other. One advantage of trabeculotomy over goniotomy is that a clear cornea is not necessary to perform the procedure, while a reasonably clear cornea is necessary for goniotomy. The goniotomy surgery involves entering the anterior chamber with a sharp goniotomy knife and making an opening incision through the abnormally developed trabecular meshwork to allow greater outflow of the aqueous fluid and thereby, lower the IOP (Figure 10-5). Often 120 degrees (out of 360 degrees total) of the trabecular meshwork can be treated with goniotomy in a single setting. Trabeculotomy surgery involves making an external incision and identifying the Schlemm’s canal from the outside, inserting a fine instrument into the Schlemm’s canal, and breaking through the trabecular meshwork to increase the aqueous outflow (Figure 10-6). Typically, 120-140 degrees of trabecular meshwork can be treated by trabeculotomy in a single surgery. If one surgical technique is unsuccessful in decreasing the IOP, the other technique can be utilized in a fresh area of the trabecular meshwork (the area not previously operated upon) to increase the success of the surgery. Even after initial control of the intraocular pressure is established with surgery, a periodic monitoring is necessary to ensure the IOP doesn’t increase again and the glaucoma go out of control.

Figure 10-5. Goniotomy. A fine surgical knife is used to open the drainage angle (trabecular meshwork) in order to lower the intraocular pressure.

Figure 10-6. Trabeculotomy. A trabeculotome instrument is used to open the drainage angle (trabecular meshwork) in order to lower the intraocular pressure.

Medications can be used as an adjunct therapy either before or after the surgical treatment. Medications may be utilized temporarily after the diagnosis until surgery can be performed. If the initial surgery fails to completely control the IOP, topical medications can be used to bring the glaucoma under control. The systemic side effects of topical medications are greater in infants than in adults because of the smaller body mass. Because of potential systemic side effects, the first line of medications that are commonly employed is the topical carbonic anhydrase inhibitors (CAI, see Chapter 7). After the CAI, the next choices are topical prostaglandin analogs or beta-blockers (Chapter 7). The prostaglandin analogs appear to be safe in children; however, there are no long-term data on the safety of these medications in children. Topical beta-blockers should be used with caution in children because of the well-known systemic side effects (Chapter 7). Finally, topical alpha-2 agonist (brimonidine, Chapter 7) should be AVOIDED in infants because it’s been associated with severe respiratory depression (breathing difficulty).

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Section 10-B: Diagnosis of congenital glaucoma

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Congenital glaucoma occurs in infants up to 3 years of age. Most commonly, patients are diagnosed between 3-6 months of age. In the US, boys are slightly more commonly affected than girls. Approximately 70% of congenital glaucoma patients have both eyes affected, while the remaining 30% have only one eye affected. There are 3 common symptoms associated with congenital glaucoma (Table 10-2). These include tearing (epiphora. Figure 10-1), light sensitivity (photophobia, Figure 10-2), and spasm and closure of the eyelids (blepharospasm, Figure 10-2) due to the patient’s sensitivity to light.

Figure 10-1. Light sensitivity and tearing in a teenage patient with a long history of congenital glaucoma. He also has misalignment of the eyes (strabismus).

Figure 10-2. Spasm and closure of the eyelids (blepharospasm) and light sensitivity (photophobia) of a patient with congenital glaucoma.

Common symptoms of congenital glaucoma	Common signs of congenital glaucoma
Tearing (epiphora)	Elevated intraocular pressure (IOP)
Light sensitivity (photophobia)	Enlarged cornea
Spasm and closure of eyelids (blepharospasm)	Cloudy, hazy cornea (corneal edema)
	Tears in Descemet’s membrane in cornea (Haab’s striae)
	Enlarged length of the eye (buphthalmos)
	Optic nerve damage (cupping)

Table 10-2. Common symptoms and signs of primary congenital glaucoma

On eye examination, there are certain features that are commonly associated with congenital glaucoma (Table 10-2). Patients often avoid bright lights because they are very sensitive to light. This is from the cloudy, hazy cornea that disperses the light and causes glare. Instead of a normally clear cornea, these patients develop a thick, cloudy, and hazy cornea (frosted glass appearance) from elevated intraocular pressure (IOP). In severe cases, the patient’s pupil may not even be visible due to the cloudy cornea. Over time, the elevated IOP can cause “stretch marks” in the cornea from excessive stretching (Haab’s striae, Figure 10-3), and also enlarge the size of the eye itself (buphthalmos, Figure 10-4, same as 4-10).

Figure 10-3. Stretch marks in the cornea (Haab’s striae) from the high intraocular pressure in a patient with congenital glaucoma (need cropping and arrows).

Figure 10-4. The left eye of this congenital glaucoma patient is noticeably larger than the right eye. The patient has buphthalmos of the left eye (same as Figure 4-10).

Abnormal enlargement of one or both eyes in an infant is an important sign of congenital glaucoma and should not be ignored. Eventually, as in adult glaucoma, the optic nerve will become damaged (cupping, see Chapter 1). However, unlike adult glaucoma, the optic nerve damage in congenital glaucoma is considered reversible in the early stages if the glaucoma is treated promptly and effectively.

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Chapter 10: Pediatric Glaucoma

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Section 10-A: Types of pediatric glaucoma

Pediatric glaucoma (also referred to as childhood glaucoma, infantile glaucoma or congenital glaucoma) is a relatively rare disease, as most patients with glaucoma are adults. However, pediatric glaucoma can lead to loss of vision and blindness in a young child and will profoundly affect the child’s life, if not diagnosed promptly and treated appropriately. Pediatric glaucoma can include a number of different diagnoses. Primary congenital glaucoma occurs in the first three years of life (usually within the first 6 months of life) without associated ocular or systemic abnormalities. Other pediatric glaucomas are associated with ocular and/or systemic abnormalities, or due (secondary) to another disease (Table 10-1). The remainder of this chapter describes the primary congenital glaucoma.

Primary pediatric glaucoma associated with ocular abnormalities	Primary pediatric glaucoma associated with systemic abnormalities	Secondary pediatric glaucoma
Aniridia	Axenfeld-Rieger syndrome	Trauma
Axenfeld-Rieger syndrome	Congenital rubella	Intraocular tumors (e.g., retinoblastoma)
Congenital hereditary endothelial dystrophy (CHED)	Cutis marmorata telangiectasia congenita	Uveitis (ocular inflammation)
Congenital microcornea with myopia	Marfan syndrome	Lens-induced
Congenital ocular melanosis (Nevus of Ota)	Neurofibromatosis 1	Aphakic (after cataract surgery without lens implant)
Peters anomaly	Oculocerebrorenal (Lowe) syndrome	Steroid-induced
Posterior polymorphous dystrophy (PPMD)	Stickler syndrome	Ocular infection
Sclerocornea	Sturge-Weber syndrome	Angle-closure (e.g., retinopathy of prematurity)

Table 10-1. Different types of pediatric glaucomas.

The primary congenital glaucoma is thought to be an autosomal recessive disease and can be associated with positive family history. However, in many cases of primary congenital glaucoma, there is no obvious family history. It occurs approximately one in 30,000 live births, and the risk for congenital glaucoma is increased if there is a pre-existing family history. Recently, molecular genetic studies have identified CYP1B1 gene as a cause for congenital glaucoma in patients with positive family history (see Chapter 11 for more).

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