From the Glaucoma in the 21st Century Conference, Hong Kong, China, 14-17 December 1999

Epidemiology of Glaucoma Dr Ivan Goldberg Sydney Eye Hospital and Save Sight Institute Sydney, Australia

The commonest glaucomas worldwide are the primary glaucomas, which divide mechanistically into open angle (primary open angle glaucoma; POAG) and angle closure types (primary angle closure glaucoma; PACG). Secondary glaucomas are relatively uncommon and childhood glaucomas are rare, although the length of time for which children live blind increases the impact for these individuals and their communities.

Tackling Glaucoma Globally

To design effective screening and interventional strategies to minimise the tragedy of what should be preventable visual disability, information from basic and clinical sciences needs to be combined with high quality epidemiological studies. Since there is such a profound influence from both age and genetics, the concept of an overall glaucoma rate worldwide is meaningless. However with much new data becoming available, for the first time it is becoming possible to estimate a realistic global prevalence of glaucoma, and soon it will be possible to determine the incidence more accurately and to understand better the associated risk factors. Dr Harry Quigley has been a leader in this analysis.

To determine how common glaucoma is worldwide, Dr Goldberg applied published material of the prevalence of OAG and ACG among the world's major ethnic groups to population statistics. The pre-mises are based on population surveys and, in order to be of value, glaucoma prevalence reports need to fulfil certain criteria (table 1).

Table 1. Criteria for glaucoma prevalence reports

The increase in prevalence rates with age for OAG for Africans are linear, with the same rates found in Africans from Tanzania as for those from Baltimore, USA. In Europeans, the model is exponential with age. While the pattern for Asians suggests a linear relation- ship, some recent data does not fit these suggested trends. For example, glaucomatous optic neuropathies among Chinese Singaporeans look exponential with age rather than linear. OAG accounted for 49% of Chinese with glaucoma and 31% had ACG, while only 15% had secondary glaucoma.

For ACG, a number of assumptions have been made in applying the avail- able data. For example, the rate amongst Africans was assumed to be half that of Europeans. ACG is more common amongst the Chinese than in any other group, and the curve for OAG was assumed to be the same as that for ACG, but with a rate 3 times higher, although this may be excessive. A higher rate of ACG has been found in Chinese than in Europeans, but not as high as those previously reported in Mongolians. In Singapore, the incidence of symptomatic ACG rises exponentially with age and is more common among women. The prevalence curves of OAG and ACG amongst Indians were assumed to be equal, although this also may be an overestimate. A study in Southern India showed a similar OAG rate to Europeans, but less ACG than anticipated.

In Europeans, the ACG rate has been estimated to be almost 12 times less than that for OAG, although the same exponential curve is assumed. For Arab populations, the assumption model was based on hospital data, and the OAG rate was assumed to be the same as for Europeans, with a 5-fold higher rate of ACG. While the validity of some of these assumptions remains to be confirmed, there is sufficient evidence to be able to derive some conclusions. These derived prevalence rates were then applied to estimates of the world's populations by age and ethnicity (table 2). From these numbers, approximately 93 million people worldwide have glaucoma.

Table 2. Estimated prevalence of primary glaucoma worldwide

*For secondary glaucoma add 20% of open angle glaucoma 6.6 million for a total of 93.2 million

With the 'greying' of the population, the number of elderly people will increase faster than the population growth. In 1999, the world's population was estimated to be 5.9 billion, with a growth rate of 1.33% per year, meaning an extra 78 million people per year. By 2050, the world's population is likely to be between 7.3 to 10.7 billion, depending on the assumed fertility rate. The most likely medium fertility projection given by the World Health Organization estimates the world population at 8.9 billion. The fer-tility rate per couple has dropped significantly worldwide, particularly among European populations. However, the world's ageing population has increased. Between 2000 and 2050, the world's total population is expected to increase by 51%. The number of octogenarians is expected to increase 6-fold, meaning that people older than 80 years who now constitute 1.1% of the population, will constitute 4.2% of the population in 2050.

Will the acquired immunodeficiency syndrome (AIDS) epidemic change these predictions? The average life expectancy is 7 years less in the 29 hardest-hit African countries than it was without AIDS. Botswana has the highest pre- valence of human immunodeficiency virus- (HIV-) positivity, with 1 in 4 adults affected, and the life expectancy has dropped by 20 years in a decade. The population in 2025 will be 23% smaller than it would have been without AIDS. However, since the fertility rate is also high, the population is expected to double in the next 50 years. Therefore, AIDS is not likely to interfere significantly with the glaucoma numbers presented in this article.

Assessment of the number of people blind owing to glaucoma may be confounded by concomitant pathology (cataract, macular degeneration). In European populations, bilateral blindness rates range from 2 to 8% of patients with glaucoma. In less developed regions where fewer people have access to treatment, the blindness rate may be higher, and a worldwide rate for glaucoma blindness of 10% seems reasonable although probably conservative. Therefore, including both primary and secondary glaucoma, worldwide bilateral glaucoma blindness can be estimated at about 9.3 million people.

In Conclusion

Second only to cataract, glaucoma is the largest cause of bilateral blindness. Unlike cataract, however, the disability caused is irreversible. By not considering unilateral blindness, loss of stereopsis, or reduction of mid-peripheral vision in one or both eyes, these figures do not reflect the world's real visual disability from the glaucomas.

"Everywhere, the glaucomas are a major public health problem, causing personal tragedy, and denial of human dignity. For most patients, detection and reduction of raised IOP remains the key to halting or slowing the disease process," concluded Dr Goldberg.

Clinical Use of Xalatan Professor T Zimmerman University of Louisville Kentucky, USA

Xalatan has been shown to have a more potent IOP lowering effect for a longer time period than b-blockers. Guidelines suggest aiming for an individualised target intraocular pressure (IOP) of 21 mm Hg for control of glaucoma. The target pressure is usually determined by lowering the IOP to a given level or reducing the IOP by a given percentage.

A meta-analysis of latanoprost and timolol trials performed in the UK, Scandinavia, and the UK shows the percentage of patients reaching a specific target IOP. The results favoured latanoprost over timolol, particularly for the lower range of IOP (table 3). Similarly, the percent of patients achieving a higher percentage reduction is higher with latanoprost. Furthermore, a meta- analysis of 1200 patients throughout the world treated with latanoprost found a 2 mm Hg difference in IOP in favour of latanoprost versus timolol.

Table 3. Percentage of patients reaching a specific target IOP in a meta-analysis of trials performed in Europe and the USA

* p < 0.001 latanoprost vs timolol; ** p < 0.002 latanoprost vs timolol

In the past, prescribing for glaucoma involved monotherapy with a b-blocker, with the addition of another drug if the IOP reduction was not sufficient. However, there is mounting evidence that this may not be the best course of action. Instead, a change to a different monotherapy could be a better alternative for these patients.In this scenario, latanoprost is more potent at lowering IOP and is more likely to bring the IOP within the target range. An additional drug may then be added if the IOP is not sufficiently lowered.

A trial of switch therapy randomised patients not controlled with b-blockers alone to receive either additional pilocarpine or latanoprost monotherapy. Latanoprost alone was superior to timolol plus pilocarpine (p < 0.004). In a similar trial, latanoprost alone was shown to be as effective as combination treatment with timolol and dorzolamide (figure 3).

Figure 3. Diurnal intraocular pressure (IOP) reduction (mean ± SEM) at 3 months compared with baseline.

Preliminary results of an efficacy and safety evaluation of replacement of dual therapy (one drug being a b-blocker) with latanoprost monotherapy found that after 3 months of treatment these patients had achieved, on average, an additional 0.8 mm Hg IOP decrease. Of the 225 patients who switched to latanoprost monotherapy and completed the study, 92% achieved the predefined IOP level, indicating a successful switch.

In Conclusion

Latanoprost is as effective as first-line treatment with b-blockers. Latanoprost consistently lowers IOP over 3 years with no evidence of long-term drift. Latanoprost provides an additive IOP lowering effect in combination with b-blockers.

A switch from timolol to latanoprost monotherapy achieves the same or better diurnal IOP reduction as adding dorzolamide or pilocarpine to timolol in patients not adequately controlled by timolol alone. In patients inadequately controlled on b-blockers, switch to latanoprost monotherapy can be attempted before combination therapy is initiated.

"For more than 20 years we have used timolol first then added other medications. Is it now time to use latanoprost first and add other medications if necessary? I think it is now time to change this 20-year paradigm."