Glaucoma in the Developing World
Introduction[edit | edit source]
Glaucoma is the second most common cause of vision loss worldwide behind cataracts, but, unlike cataracts, the vision loss associated with glaucoma is largely irreversible. Those afflicted with the disease and living in developing countries are at a particular disadvantage; they have a higher risk of progressing to blindness, present with more advanced disease, and often have higher incidence of disease than developed nations.[2, 3] Glaucoma prevention and treatment has been a major focus of international directives including the World Health Organization’s Vision 2020 campaign. While this initiative has seen a decrease in worldwide blindness, most of the improvement has been due to cataract surgery. Stated goals regarding number of ophthalmologists and optometrists present in developing nations remain unfulfilled.[4-6]
There are several unique challenges that exist in the approach to glaucoma in the developing world. Access to care remains a major concern, particularly in rural areas, as most ophthalmologists are concentrated in urban areas. This leaves many people without access to regular eye exams or treatment, which is vital in preventing permanent vision loss in the setting of glaucoma. Understanding of the disease process is virtually nonexistent in some populations, leading to unrealistic expectations of treatment. In parts of the world where eye surgeries are commonly done by medical missionaries, patients often expect their vision to be restored and their disease cured by surgery. While this type of outcome is attainable in more commonly encountered causes of vision loss such as cataracts, it is unrealistic for glaucoma patients. In Kenya, about 30% of glaucoma patients expected a full cure from medical or surgical treatment. This mindset is prevalent across the developing world and is only one part of a widespread lack of education regarding eye health.[8, 9] This environment has led providers to favor a different approach than normally seen in the United States. Because the likelihood of reliable follow up is low and patients are often unable to afford medications, surgery is often seen as a first line treatment, instead of generally being reserved failing medical treatment.[10, 11]
The majority of glaucoma data are collected from European and North American studies. Information from the developing world is limited, but has been increasing in recent years. We will examine the state of glaucoma in the developing world, with particular attention given to epidemiology, approach to treatment, and outlook for the future.
Epidemiology[edit | edit source]
The number of people with glaucoma worldwide is expected to rise from 64 million to 76 million in 2020 and 111 million in 2040, with Africa and Asia being affected more heavily than the rest of the world.[12, 13] Primary open angle glaucoma is the most common form of the disease worldwide. The highest prevalences of Primary Open Angle Glaucoma (POAG) are in African countries. This is not surprising since the increased risk of glaucoma among people of African descent has been widely accepted for many years. [14, 15] Genetic studies suggest that, although several loci have been identified as “glaucoma genes”, inheritance of POAG is usually multigenic and multifactorial, having no identified association with a particular gene in most populations. Environmental factors and modifying genes are likely playing a part in disease development.[16-18]
Glaucoma prevalence is difficult to pinpoint due to differences in defining disease, expertise of measurer, and diagnostic equipment. A 2014 review of worldwide POAG prevalence among people aged 40-80 years showed estimates of 2.31% in Asia, 3.65% in Latin America and the Caribbean, and 4.20% in Africa. A review that focused on multiple Asian populations found that the prevalence of POAG ranged from 0.5% in a Mongolian population to 3.9% in a Japanese group.[19-21] Another study, based in West Africa showed a POAG prevalence of nearly 15% in individuals over the age of 80.
One of the major challenges facing providers is the delay in patient presentation commonly seen in developing countries, particularly in more rural areas. A study in an urban population in Ghana revealed that nearly 24% of those diagnosed with POAG presented blind Best Corrected Visual Acuity <3/60 in the better eye), and the average BCVA was between 6/24 and 6/36.  This is an improvement over statistics reported from other, more rural areas. The authors suggest that this improvement may be related to better access to care in a larger city. A study conducted in a rural population in North Eastern Ghana showed bilateral blindness in 34% and unilateral blindness in half of patients receiving an initial glaucoma diagnosis. In Southwest China, where angle closure glaucoma is much more common, POAG was found in 0.86% of randomly selected people over the age of 50; 74.5% were unilaterally and 14% were bilaterally blind due to glaucoma.
Angle closure glaucoma is the other common form of the disease. Primary Angle Closure Glaucoma (PACG) is responsible for nearly half the glaucoma-related blindness in the world, despite being much less common than open angle disease. The highest prevalence of PACG is in Asia. The highest reported prevalence of PACG was 2.5% in Myanmar. Average prevalence of PACG in Southeast Asia East Asia and South Asia were 1.16%, 1.1%, 0.66%, respectively. A female preponderance was identified in PACG, with a 1.5:1 female to male ration found in Asians. Angle closure disease is much less common outside of Asia. In a Nigerian eye clinic, new glaucoma patients were evaluated, and 9.2% were found to have angle closure or angle closure glaucoma.
Family history has been identified as a major risk factor for development of angle closure glaucoma. In an Iranian study, 58% of siblings of patients with angle closure glaucoma were found to have some degree of angle closure - from suspected primary angle closure to primary angle closure glaucoma. Primary angle closure suspect (PACS) was defined as an eye in which the trabecular meshwork was not visible in at least 270 degrees on gonioscopy without synechiae and with normal optic nerve findings and normal IOP. Primary angle closure was defined as PACS criteria plus synechiae reaching to at least the scleral spur, elevated IOP without glaucomatous nerve damage, or evidence of prior acute IOP elevation. PACG was diagnosed when there was presence of optic nerve head changes or visual field defects. Findings from this study are in line with previous studies in Indian and Singaporean studies, which found approximately 50% and 59% of siblings were affected. [30, 31] A separate Indian study also demonstrated an increased risk for angle closure in siblings of subjects with angle closure, and further found that the increased risk was higher in older and female siblings.
It has long been established that angle closure is more common in Asian populations, however there are only a few studies differentiating between ethnic groups living in a single area.[27, 33, 34] A study evaluating the course of angle closure glaucoma in different ethinic groups living in Malaysia found that Malays presented to clinic with higher Intraocular Pressure (IOP), worse vision, more advanced cup to disc changes, and at an older age than Chinese living in Malaysia. The disease also advanced at a faster rate than the Chinese group. The authors were unsure of the cause of these findings., but the authors suggested possibilities including the idea that the disease behaves and progresses differently in Malay people, the different in health education and literacy between the two ethnic groups, and differences in socioeconomic status. Other studies have found diverse associations. For instance, a study conducted in India found that angle closure glaucoma was the most common form of glaucoma in Muslims, but open angle was the most common form found in the Hindu population.
Childhood glaucoma[edit | edit source]
Childhood blindness is a much larger problem in the developing world than in developed nations. About ¾ of the world’s blind children live in the developing world. The prevention and treatment of diseases that cause blindness during childhood are of particular concern to the WHO due, in part, to the concept of increased number of blind years. Despite childhood blindness being relatively rare compared to blindness starting in adulthood, the number of blind years due to childhood blindness is almost equal to the number of blind years due to adult cataracts.  Poorer countries are also more likely to have a larger percentage of blindness in children due to avoidable causes.  . In a study conducted in Ghana, Honduras, and India, 95% of caregivers believed that it was important for children to have eye exams, but 66% had never undergone one.
The most common type of infantile glaucoma in the world is primary congenital glaucoma (PCG), although it is still quite rare with an incidence of about 1 in 10,000 to 18,000 live births. A much higher disease prevalence has been reported in cultures where consanguineous relationships are common,[40-42] Advanced disease is common at presentation. One study from Ethiopia found the mean age at diagnosis of primary congenital glaucoma to be 3.3 years. This is in contrast to the developed world, where the diagnosis is almost always made within the first year of life. For example, in two studies the mean age of diagnosis was 4 months in Australia and 11 months in Great Britain.[40, 44] In this Ethiopian case series, 40 eyes with PCG were treated surgically. Twelve of these eyes required secondary procedures for persistently elevated IOP, and four had serious complications. Average IOP was 54 mmHg pre-operatively and 23 post-operatively, with 43% of eyes reaching an IOP of 22 mmHg or less. This is lower than the success rates reported in studies conducted in developed countries; the authors feel that this discrepancy may be due to extremely high IOP in Ethiopian patients. The authors also suspect a poorer long-term prognosis in these patients because of the lack of available follow-up and medications. Interestingly, over half of these patients had scars on their temples, indicative of traditional folk treatment. [45-47]
Post cataract glaucoma is another type of childhood glaucoma that is particularly important in developing nations. Due to the relatively large number of cataract operations performed in a medical mission setting, long term follow-up to asses for complications is often not feasible. As cataract surgical rates increase, there is an increased incidence of this form of glaucoma. A study conducted at a Tanzanian tertiary pediatric eye center found a 6.5% risk for glaucoma at three-year post cataract extraction in children under age 18. Previous studies have reported significantly higher rates of glaucoma development when children are followed for longer time periods after surgery.[39, 49-52]
Secondary glaucoma[edit | edit source]
Secondary forms of glaucoma such as neovascular and pseudoexfoliative glaucoma have not been studied as widely as the primary forms of the disease, particularly in developing countries. A Nigerian group studied 61 patients who had been diagnosed clinically with neovascular glaucoma, most commonly secondary to retinal ischemia. Over 84% of these eyes were blind on presentation. Among those patients without occlusive disease, couching was the most commonly identified cause. Couching is still a surprisingly common practice in some developing societies, despite a similar cost and vastly inferior outcomes.[53-57] Diabetes mellitus, which is a major cause of neovascular glaucoma in the Western world, was found in only 8.3% of subjects, while 62% had systemic hypertension.[58-60]
A study on neovascular glaucoma conducted in Saudi Arabia found the most common cause of the disease to be diabetic retinopathy, followed by retinal vein obstruction. A history of diabetes was report in 65% of subjects. Less common causes included chronic retinal detachment, carotid artery obstruction, retinoblastoma, and uveitis. This study highlights the need for close monitoring of ocular complications of chronic diseases in areas where these conditions are common.
In a tertiary eye care center in India, 21.8% of referred patients who were suspected or confirmed to have glaucoma, had secondary types of the disease. Common causes of secondary glaucoma included post vitrectomy surgery (14%), trauma (13%), corneal pathology (12%), aphakia (11%), neovascular glaucoma (10%), pseudophakia (10%), steroid-induced glaucoma (8%), uveitic glaucoma (8%), and miscellaneous causes (14%). The causes were broken down by age: the most common cause for those 0-20 years old was trauma (often sports-related); for patients 21-40 , post-vitreoretinal surgery was most common; neovascular glaucoma was most common in those 41-60 and pseudophakic glaucoma was most common in those over 60.
Pseudoexfoliation syndrome causes a relatively uncommonly reported secondary form of glaucoma in many regions, although one clinic in Ethiopia reports it as the most common subtype of glaucoma, in 35% of glaucoma patients evaluated. In a south Indian population, glaucoma was associated with 8% of those with pseudoexfoliation. At 6 year follow up evaluations, all patients evaluated had developed ocular hypertension and 6% had developed glaucoma.
Management[edit | edit source]
As previously mentioned, glaucoma is often managed with surgery as the first line treatment in developing nations. It has been noted that there is an increased risk of trabeculectomy failure in African eyes compared to Caucasian eyes.[65, 66] Trabeculectomy was the most common glaucoma surgery in one Nigerian study, comprising 81% of all glaucoma procedures.
This racial difference does not seem to be present in the placement of implanted shunts.[68, 69] A small group of adult and pediatric cases receiving the Ahmed valve implant in Kenya showed IOP reduction from a mean of 36.4 mmHg to 16.7 mmHg along with a decrease in medication requirement and only one major complication. However, median follow up was only two months in this study. In Ethiopia, a series of patients with refractory glaucoma received tube shunt placement surgery and experienced similar success. The success rate according to the predetermined definition was 76.9%. Complications were encountered in 6 eyes. Given the decreased follow-up burden with tube placement as compared to trabeculectomy, decreased need for reoperation, and comparable number of medications needed to maintain goal IOP; tube placement may be a viable choice for disease management in developing countries.[72, 73] A potential barrier to tube shunt placement in the developing world is access to the donor tissues such as cornea, sclera and pericardium commonly utilized to provide coverage over the tube at its entry site.
Laser treatment is popular in settings where the necessary equipment is available. In a population of African descent in St. Lucia, medically treated patients with open angle glaucoma underwent bilateral 360 degree selective laser trabeculoplasty (SLT) after a 30 day medication washout period. The authors reports a success rate of 77.7%, with success defined as at least 10% reduction in IOP at multiple follow up visits up to 12 months after treatment. About half of the successful eyes had at least a 40% reduction in IOP from post-washout baseline. The author stressed that in developing nations, IOP-lowering medications are not easily affordable for most individuals, so surgery should be favored if it is found to be equally efficacious. A Chinese study found a success rate of 53% for SLT treatment, using an IOP reduction of at least 20% as the cutoff for success. Predictors of success in this study were high pre-treatment IOP, thin retinal nerve layer, lower IOP on post-SLT day 1, and use of topical carbonic anhydrase inhibitor. Use of three topical IOP-lowering medications was associated with SLT failure.
SLT is also gaining popularity as a treatment option for angle closure. A multicenter trial conducted in Hong Kong, Singapore, and Indonesia reported a success rate of 60% of eyes with primary angle closure or primary angle closure glaucoma after treatment with SLT. This was lower than the 84% success reported with use of prostaglandin analog. Success in this trial is defined as IOP reduction to 21mmHg or less at 6 months follow up, without the use of medication. Recent meta-analysis of SLT outcomes in open angle glaucoma treatment worldwide reports from 6.9% to 35.9% IOP reduction at ≥12 months post treatment, and concludes that SLT offers comparable outcomes to argon laser trabeculoplasty and medication. The majority of trials analyzed were conducted in developed nations.
Management of neovascular glaucoma is notoriously difficult in any setting. In a retrospective review conducted in Thailand, six treatment groups were compared: A medical treatment group, an intraocular bevacizumab injection group, a trabeculectomy with mitomycin C group, a trabeculectomy with mitomycin C plus adjunctive intraocular bevacizumab injection group, a glaucoma drainage device group, and a transscleral cyclophotocoagulation group. Trabeculectomy with mitomycin C plus bevacizumab injection proved to be the most successful treatment, at 54% of eyes being treated successfully. Adjuvant bevacizumab was associated with a lower complication rate.
Cyclodestructive procedures vary in their acceptance in developing countries. In Malawi, forty seven eyes with primary open angle or pseudoexfoliative glaucoma were treated with low dose transscleral diode laser cyclophotocoagulation. Half of these patients maintained an IOP reduction of at least 25% at three month follow up. Similar results were reported in Tanzania, where 51% of patients had a 50% or greater reduction in IOP at the first post operative appointment. Primarily destructive procedures are viewed as last line treatment, but there has been some support for using cyclophotocoagulation as first line treatment in primary open angle glaucoma, based on positive results (average IOP reduction of 24% from baseline at 12 month follow up) from Cameroon. A prospective study conducted in Brazil compared cyclophotocoagulation with Ahmed drain implantation in eyes with refractory glaucoma and found similar success for both treatments. The post operative IOP, number of medications required post operatively, and post operative visual acuity were not statistically different. However, the group with the valve implant experienced more side effects, leading the authors to suggest that cyclophotocoagulation may be a safer way to treat these refractory patients.
An analysis of medical and surgical treatment in Nigeria found no difference in cost over three years. However, this study only measured direct medical costs and excluded indirect costs such as travel expenses which can be significant, especially for those living in rural areas. All Nigerians surveyed still refused surgery. Other studies have shown 46% of patients in east Africa accepted early surgery when offered and over one third accepted surgery in India.[84-86] In India, surgery is often viewed as a “one shot” treatment and trabeculectomy is preferred. However, there is still a need for post-operative monitoring and often continued use of topical or systemic medicine, necessitation and individualized approach to the decision of whether surgery or medical management is preferred for patients in developing areas.[87, 88]
Current Limitations[edit | edit source]
There are many reasons why glaucoma more commonly progresses to blindness in developing countries. In Ethiopia, a study showed that 67.5% of patients who had been using topical glaucoma medications were noncompliant with their medicine. Noncompliance was associated with older age, financial hardships, advanced disease, and less frequent follow up.
Generally poor health is associated with a depressed socioeconomic status in the developing world, and eye disease is no exception.[90, 91] A study from India highlighted the significant economic burden caused by anti-glaucoma drug regimens, particularly on poorer people from rural areas. The monthly cost of glaucoma medications represented 13%-123% of monthly income for the patients in the lowest socioeconomic groups. This did not take into account the lost income or costs of travel for their appointments, which are often greater than the cost of the medicine itself. Those with higher incomes were allowed to contribute a significantly smaller percentage of their income to glaucoma medication, but were still required to devote a significant fraction of their pay to maintain medication compliance. The vast majority did not have any type of insurance or reimbursement for costs of treatment. 
The impact of glaucoma on the quality of life for the patient is potentially devastating. The irreversible nature of vision loss inherent to the disease process makes early diagnosis and treatment vital to maximizing vision potential. On a quality of life scale from 0 to 1, where 0 represents death and 1 represents perfect health, an Indian population with glaucoma reported a mean utility value of 0.64, much lower than the score reported a similar study in Americans with glaucoma. Brazilians with glaucoma also report a range of utility values lower than their American counterparts. This suggests patients in those developing countries feel a stronger impact on their quality of life when they suffer with glaucoma.[93, 94] Not surprisingly, the degree of impact on quality of life is closely correlated with degree of visual impairment in all areas, including Brazil, China, and India. [95-97]
An often overlooked effect of blindness and low vision in a population is the impact on those around the blind person. Increased burden for caregivers has been shown to be associated with financial stress, low education, and being forced to become a caregiver. A study in India showed an increased prevalence of depression in caregivers of blind people or those with low vision. Rate of caregiver depression increased from 16% in the 20/200 population to 48% in the no light perception group. Low income was also associated with higher rates of depression.
Glaucoma’s impact spreads far beyond individuals and their families. Blindness and vision impairment has a major impact on local and national economies. However, a larger economic impact is typical in developed nations due to longer life expectancy and greater per capita GDP.  In developing countries, blindness often removes two people from the workforce: the blind patient, and a family member to care for the patient.
One of the largest hurdles facing health care providers in developing nations is educating the populace about health and disease processes. There currently seems to be a widespread lack of understanding regarding the causes, symptoms, and progression of glaucoma. In a multicenter study from Nigeria, only 46% of patients were aware that glaucoma causes vision loss and 73% believed that vision loss due to glaucoma was reversible.  In Botswana, 11.5% of patients with previously diagnosed glaucoma had ever heard of the disease before the diagnosis and 36% still did not understand the disease after being diagnosed. In India, awareness, or being familiar with the term glaucoma, was found to be 2.3% in an urban population and 0.32% in a rural population. A later study indicated that 13% of a random sample of respondents were aware of the disease, perhaps representing an improvement in education about glaucoma.[103-105] All of these numbers are much lower than the awareness and understanding of disease reported from developed countries. [106, 107] Poor understanding of disease has been linked to refusal of surgery, poor medication adherence, more psychological depression, and a lower quality of life. [108-110] A recent report clarifies the lack of evidence of eye health in African primary care, and advocates for further inclusion of eye care into the public health system. Clearly, public health education should be a high priority in the prevention of vision loss due to glaucoma, particularly in dealing with a treatable disease like glaucoma.
The use of screening eye exams is a controversial subject. There is some support for the implementation of widespread screening, while others recommend focused screening efforts. A Nepalese study confirmed the association of primary open angle glaucoma with hypertension and diabetes. The authors suggest screening individuals with these diseases for glaucoma. Others imply that screening family members of those with glaucoma would be more cost effective than wide spread screening. In Nigerian school children ages 4-15, a screening program identified pathology in 19.9% of subjects with 1.4% having definite or suspected glaucoma.
Conclusion[edit | edit source]
Glaucoma continues to pose a challenge to eye care professionals in developing countries. Unlike surgical treatment of cataracts and other vision robbing maladies, glaucoma management typically requires years of regular follow up visits and medication adjustments. Since a medical missionary surgeon model for glaucoma treatment is not ideal, emphasis should be placed on training and retaining native eye surgeons. An African study gives a hint about how to increase retention: professional development and continued training. The opportunity for further training and professional development was the most common response when asked why an African ophthalmologist might consider migration, at 46%. A continued effort through initiatives like VISION 2020, public health education, professional training programs, and programs focused on early disease detection and treatment is needed for vision loss to be decreased in the developing world. Since glaucoma is more prevalent in many developing countries than in the developed world, it should be a primary focus of any campaign aimed at improving eye health.
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