DEFINING GLAUCOMA FOR STANDARDIZED ASSESSMENT
Unlike VISION 2020's five enumerated causes of worldwide visual suffering—each singular either in its causation or curative strategy—the term glaucoma refers to a wide spectrum of diseases and mechanisms resulting in a common endpoint: structural damage to the optic nerve with functional loss of the visual field. This focus, bypassing reference to IOP, was advocated by Foster et al in defining glaucoma in international prevalence studies.4 Structural damage is simply defined as a vertical cup-to-disc ratio beyond the 97.5 percentile (ie, a cup-to-disc ratio of >0.7 by direct ophthalmoscopic estimation). The functional correlate is evidence of the loss of visual field in the 24-2 threshold test of the Humphrey Field Analyzer (Carl Zeiss Meditec Inc., Dublin, CA), defined by the conjunction of an abnormal Glaucoma Hemifield Test alert with three contiguous points at the 5% level on the pattern deviation probability map. Early disease, in which visual field defects occur with vertical cup-to-disc ratios of <0.7, are neglected by this disease definition, which is weighted to detect significant, sight-threatening damage.
Recognizing the realities of ophthalmic assessment in the developing world, Foster et al proposed three levels of evidence to be indicated in surveys: the highest category of diagnostic precision demonstrates vertical disc damage with a corresponding visual-field defect; the intermediate category detects a damaged disc, but no visual field data are available; and, in the default category, neither the optic nerve nor visual field can be assessed. Nevertheless, vision is <20/400 with an IOP of >99.5mmHg, and/or there is evidence of prior glaucoma surgery or treatment. Conforming with this definition and qualification of evidence of glaucoma should facilitate international efforts to quantify the reality of the disease's worldwide presence. Technological innovations, such as the use of portable and sensitive frequency-doubling technology (FDT) perimetry devices,5 will continue to refine efforts to achieve comparable data sets for compilation.
PRIMARY ANGLE CLOSURE AND PRIMARY ANGLE-CLOSURE GLAUCOMA
The historical American-European bias in the classical ophthalmic literature has only recently acknowledged the manifestation of glaucoma in eyes if nonwhite subjects. There is a new appreciation that primary angle closure disease—now categorized4 as primary angle closure (PAC)-suspect, PAC (ie, occludable or damaged angle with elevated IOP, but without optic nerve damage), and primary angle-closure glaucoma (PACG)(ie, PAC with damaged disc and visual field)—varies widely among populations, in contrast to the rather constant prevalence of primary open-angle glaucoma (POAG) among large population groups.6 Among whites, Hispanics, Japanese, and blacks, the ratio of POAG:PACG is 9:1; yet the ratio among Mongolians is 1:3, and among Asian Indians and Chinese it is 3:2. The methodology for discriminating these forms of PAC is also in evolution: low-tech assessments, such as oblique-flashlight testing, van Herick estimation of the limbal anterior chamber depth at the slit-lamp, and biometric gonioscopy,7 can be quantitatively improved with an optical axial-anterior chamber depth measurement,2 ultrasonic biomicroscopy,8 or infrared gonioscopy.9 However, the application of these technologies in the developing world remains problematic.
The evolving literature on PACG has generated several surprises. First is the finding among Chinese and Mongolian populations that there are approximately 10 cases of PAC to every one case of PACG. At present, there is no way to predict which eyes with compromised angles and elevated IOP will develop actual glaucomatous damage. In other words, we do not know who might benefit from an intervention such as laser iridotomy.6 Moreover, the morbidity of PACG is truly appalling: it is responsible for 90% of bilateral blindness due to glaucoma in China, although POAG is nearly as common a disease.10 Apparently, only 25% of PACG cases are acute attacks,6 and laser iridotomies restore normal IOP in only 40% of such eyes.11 Moreover, acute PACG leads to optic nerve damage in more than half of such eyes as well as blindness in one out of six.12
The obverse of this statistic is that 75% of PACG cases are chronic and without symptoms, and hence subject to detection by the same optic nerve and visual field assessments as is POAG. Once detected, however, which intervention for either acute or chronic PACG is most efficacious?13 Laser iridotomy?14 Trabeculectomy? Cataract extraction with IOL implantation? Goniosynechialysis? Refining the predictive factors for PACG progression and clarifying which interventions are effective are among the most compelling issues in managing glaucoma for public health.
The surveys of nearly 30 international prevalence studies of POAG reveal key features of this disease.2,15 First, as in PACG, there is a marked racial diversity of POAG: its prevalence is four times greater among blacks than whites in Baltimore; intermediate among whites in America, Europe, and Australia; and lowest among Mongolians and Inuits. Second is its steadily increasing prevalence with age; POAG's incidence doubles every decade past the sixth. In other words, people older than 80 years demonstrate 10 times the rate of POAG of those between 40 and 50 years of age.15 Third is the dose-response curve of IOP and its effect on POAG's prevalence, incidence, and progression.16
A more exhaustive investigation of each of these risk factors—race, age, and IOP—reveals multiple complexities. For example, race may serve as a clinical marker for surveys, but in actuality, it remains genetically unsubstantiated and likely functions as a “congruence marker” for a variety of factors (eg, blacks statistically show thinner corneas, larger optic discs, and differential responses to glaucoma drops). Age, too, is a “temporal surrogate”17 for many factors: the aging of tissues, duration of exposure to risk factors, age of onset or interval since diagnosis, etc. Even IOP needs be considered not as a static parameter, but as a mean value or a range of fluctuation.
The diagnosis and effective treatment of POAG by reducing IOP have been demonstrated at a clinical level, yet their application to public health remains frustratingly elusive. Even in a developed society such as the US, approximately 50% of POAG remains undetected. In the underdeveloped world, the burden is even greater. Here, in addition to the epidemiologic challenges alluded to earlier, there is also the “negative social marketing” of glaucoma intervention: patients often present with advanced vision loss and may undergo a “successful” procedure to reduce IOP, but they do not experience any restoration of visual function. Such an outcome results in (understandably) negative feedback from the afflicted individual's family and community.
The timely elaboration of applicable diagnostic criteria, appropriate testing strategies, and effective, preventive interventions are a creative challenge to the glaucoma community, which, faced with the enormity of a heretofore unavoidable blinding disease, must urgently and effectively reverse this international scourge.
Marc F. Lieberman, MD, is Director of Glaucoma Services at California Pacific Medical Center and serves as Clinical Professor of Ophthalmology at University of California, San Francisco. He is also Founder and Medical Director of the Tibet Vision Project, established in 1995. He did not disclose financial interest in any product or company presented herein. Dr. Lieberman may be reached at (415) 771-4020; email@example.com.
1. Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol. 1996;80:389-393.
2. Johnson G, Quigley H. The glaucomas. In: Johnson G, Minassian D, Weale R, West S, eds. The Epidemiology of Eye Disease. 2nd ed. London: Arnold; 2003: 222-239.
3. Pizzarello L, Abiose A, Ffytche T, et al. VISION 2020: the right to sight: a global initiative to eliminate avoidable blindness. Arch Ophthalmol. 2004;122:615-620.
4. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002;86:238-242.
5. Mansberger SL, Johnson CA, Cioffi GA, et al. Predictive value of frequency doubling technology perimetry for detecting glaucoma in a developing country. J Glaucoma. 2005;14:128-134.
6. Quigley HA, Congdon NG, Friedman DS. Glaucoma in China (and worldwide): changes in established thinking will decrease preventable blindness. Br J Ophthalmol. 2001;85:1271-1272.
7. Congdon NG, Spaeth GL, Augsburger J, et al. A proposed simple method for measurement in the anterior chamber angle: biometric gonioscopy. Ophthalmology. 1999;106:2161-2167.
8. Congdon NG, Friedman DS. Angle-closure glaucoma: impact, etiology, diagnosis, and treatment. Curr Opin Ophthalmol. 2003;14:70-73.
9. Sugimoto K, Ito K, Matsunaga K, et al. New gonioscopy system using only infrared light. J Glaucoma. 2005;14:264-266.
10. Foster PJ, Johnson GJ. Glaucoma in China: how big is the problem? Br J Ophthalmol. 2001;85:1277-1282.
11. Aung T, Ang LP, Chan SP, Chew PT. Acute primary angle-closure: long-term intraocular pressure outcome in Asian eyes. Am J Ophthalmol. 2001;131:7-12.
12. Aung T, Friedman DS, Chew PT, et al. Long-term outcomes in Asians after acute primary angle closure. Ophthalmology. 2004;111:1464-1469.
13. Chew PT, Aung T. Primary angle-closure glaucoma in Asia. J Glaucoma. 2001;10(suppl):7-8.
14. Nolan WP, Baasanhu J, Undraa A, et al. Screening for primary angle closure in Mongolia: a randomised controlled trial to determine whether screening and prophylactic treatment will reduce the incidence of primary angle closure glaucoma in an east Asian population. Br J Ophthalmol. 2003;87:271-274.
15. Allingham R, Damji K, Freedman S, et al. Clinical epidemiology of glaucoma. In: Allingham R, ed. Shiled's Textbook of Glaucoma. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins. 2005: 170-190.
16. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the early manifest glaucoma trial. Arch Ophthalmol. 2002;120:1268-1279.
17. Quigley HA. Risk factors for glaucoma: ones that aren't, ones that are, and dealing with risk fators for risk, onset, progression, and response to treatment.Paper presented at: The 54th Annual Symposium of the New Orleans Academy of Ophthalmology; Friday, February 18, 2005; New Orleans, LA.