Glaucoma in the Developing World

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Introduction

Glaucoma is the most common cause of irreversible vision loss and the third most common cause of vision loss worldwide after cataracts and refractive error.[1] [2] In developing countries, those affected with the disease are at a particular disadvantage in comparison to persons with glaucoma in developed nations; they have a higher incidence of disease, more advanced disease at presentation, and a higher risk of progressing to blindness.[3] [4][5] Glaucoma prevention and treatment has been a major focus of international directives, including the World Health Organization’s Vision 2020 campaign. While this initiative saw a successful decrease in worldwide blindness, most of the improvement was due to widespread adoption of cataract surgery and spectacles provision. Stated goals regarding number of ophthalmologists and optometrists in developing nations remain unfulfilled.[6] [7] [8]

There are several unique challenges to addressing glaucoma in the developing world. Glaucoma is difficult to diagnose in any context; it is almost always asymptomatic until late in the disease course. This painless, insidious vision loss results in late diagnosis unless patients are screened for glaucoma early on. Access to eye care in developing countries remains a major issue, particularly in rural areas. Most ophthalmologists are concentrated in urban areas, leaving many people in resource-limited countries unable to obtain the regular eye exams and glaucoma treatment necessary to prevent permanent vision loss. Understanding or even awareness of glaucoma is virtually nonexistent in some populations, leading to unrealistic expectations of vision restoration through surgery.[9] While this type of surgical outcome is attainable with reversible causes of vision loss such as cataracts, it is impossible for patients with advanced glaucoma to regain functional vision. This misunderstanding is prevalent across the developing world and is only one symptom of a widespread lack of education regarding eye health.[10] [11] Misinformation regarding eye diseases and treatment options also discourages many from seeking any eye care at all.[12]

In resource-limited countries, glaucoma care providers tend to favor a more aggressive treatment approach than that of developed countries. Reliable follow-up is less likely and patients are often unable to obtain or afford medications. Consequently, incisional glaucoma surgery typically is first-line treatment, instead of being reserved for those who fail medical management.[13] [14]

The majority of glaucoma data are collected from European and North American studies. Information from the developing world is limited, but has increased in recent years. This article examines the state of glaucoma in the developing world, with particular attention given to epidemiology, approach to treatment, and outlook for the future.

Epidemiology

The prevalence of glaucoma in developing countries is difficult to pinpoint because of differences in defining glaucoma, variable expertise of diagnosticians, and frequent unavailability of necessary diagnostic equipment. Much of the available epidemiology likely underestimates the true glaucoma burden in developing countries due to reliance on visual acuity thresholds for diagnosing glaucoma.[15] The estimated number of people with glaucoma worldwide is expected to rise from 76 million in 2020 to 111 million in 2040, with Africa and Asia being affected more heavily than the rest of the world.[2][16] The estimated number of glaucoma worldwide is 76 million in 2020, with 8 million suffer from moderate and severe visual impairment (MSVI) and blindness. The total number is expected to increase to 111 million in 2040, with Africa and Asia being affected more heavily than the rest of the world. .[2][16] The total amount of glaucoma care has increased worldwide in recent years, but rapid growth in the global population coupled with demographic shifts toward older populations has limited the impact of this expansion of care on a global per capita basis.[1]

Figure 1: Prevalence of MSVI and blindness due to glaucoma[5] [17] [18] [19] [20] [21]

Figure 1: Estimated regional prevalence of moderate and severe visual impairment (MSVI) and blindness due to glaucoma in 2020. MSVI is defined as visual acuity < 6/18 but ≥3/60 in the better seeing eye and blindness is defined as <3/60 in the better seeing eye. Adapted from contemporary prevalence studies.[22] [23] [24] [25] [26] [27]


Figure 2: Glaucoma blindness as a percentage of all causes of blindness in each country[5] [17] [18] [19] [20] [21]

Figure 2: Estimated percentage of the total burden of blindness due to glaucoma by country in 2020. blindness is defined as <3/60 in the better seeing eye. Data adapted from contemporary prevalence studies.[22] [23] [24] [25] [26] [27]

Primary open-angle glaucoma

Primary open-angle glaucoma (POAG) is the most common form of the disease worldwide. The highest prevalence of POAG is in African countries and in communities of African descent, such as African American and Afro-Caribbean populations.[16][28] [29] 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.[16] Another study based in West Africa showed a POAG prevalence of nearly 15% in individuals over the age of 80.[28] Among Asian populations, the prevalence of POAG ranges from 0.5% in a Mongolian population to 3.9% in a Japanese population.[30] [31] [32]

Although several genetic loci have been identifed 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 likely play a role in disease development.[33] [34] [35]

Primary angle-closure glaucoma

Angle-closure glaucoma is the second most 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 POAG. Asia bears the greatest burden of PACG with reported prevalence reaching as high as 2.5% in Myanmar.[30] [36]Females are more likely to have PACG, with a 1.5:1 female to male ratio observed in Asians.[37] Angle closure disease is much less common outside of Asia.

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.[38] Findings from this study are consistent with previous PACG studies from India and Singapore, in which 50% and 59% of siblings were affected, respectively.[39] [40] [41] 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.[37][42] [43] A study evaluating the course of angle closure glaucoma in different ethnic groups living in Malaysia found that Malays presented to clinic with higher intraocular pressures (IOPs), worse vision, more advanced optic disc changes, and at an older age than Chinese living in Malaysia. The Malay group also experienced faster glaucoma progression than the Chinese group.[44] [45]

Childhood glaucomas

Childhood blindness is a much larger problem in the developing world than in the developed world. About three-quarters of the world’s blind children live in impoverished areas of Africa and Asia alone.[46] Poorer countries are also more likely to have a larger percentage of blindness in children due to avoidable causes.[46] 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.[47] Accordingly, the prevention and treatment of diseases that cause blindness during childhood are of particular concern to the WHO. The concept of blind years also highlights the importance of addressing childhood blindness; despite its relative rarity, the total number of blind years due to childhood blindness is almost equal to the number of blind years due to adult cataracts.[46]

The most common type of infantile glaucoma in the world is primary congenital glaucoma (PCG), although it is still rare with an incidence of about 1 in 10,000 to 18,000 live births. Significantly higher PCG prevalence has been reported in populations where consanguineous relationships are common.[48] [49] [50] Late diagnosis and advanced disease at presentation are common. One study from Ethiopia found the mean age at diagnosis of PCG to be 3.3 years.[51] This is in contrast to the developed world, where the diagnosis is almost always made within the frst year of life.[49][52] In this Ethiopian case series, the authors suspected a poor long-term prognosis for their patients despite appropriate surgical intervention because of inadequate follow-up and unavailability of medications.

Post-cataract surgery 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 assess for complications is often not feasible. As pediatric cataract surgery rates increase, there is an increasing incidence of related secondary glaucoma. A study conducted at a Tanzanian tertiary pediatric eye center found a 6.5% risk for glaucoma at three years post cataract extraction in children under age 18.[53] Previous studies have reported significantly higher rates of glaucoma development when children are followed for longer time periods after surgery.[47][54] [55] [56] [57]

Secondary glaucomas

Lens-induced glaucoma (LIG) is the most common form of secondary glaucoma in many resource-limited countries. For example, LIG accounted for 5.3% of all causes of glaucoma presenting to a tertiary eye hospital in Nepal between 2007 and 2008.[58] This relatively high prevalence is a refection of the large backlog of advanced cataracts in the developing world.

Other secondary forms of glaucoma such as neovascular and pseudoexfoliative glaucoma have not been studied widely in developing countries. A Nigerian population-based study identified a 0.9% prevalence of all forms of secondary glaucoma. Of those patients diagnosed with neovascular glaucoma, 84% of affected eyes were blind on presentation. The study also identified a 0.2% prevalence of non-neovascular open-angle glaucoma secondary to couching, which is the same prevalence of neovascular cases in the study population. This finding reflects the reality that cataract surgery by couching is still a surprisingly common practice in some developing countries, despite a similar cost and vastly inferior outcomes compared to extracapsular cataract extraction.[59] [60] [61] [62] [63] Diabetes mellitus, which is a major cause of neovascular glaucoma in the developed world, was found in only 8.3% of subjects, while 62% had systemic hypertension.[64] [65] [66] 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 reported in 65% of subjects. Less common causes included chronic retinal detachment, carotid artery stenosis, retinoblastoma, and uveitis.[67]

In a tertiary eye care center in India, common causes of secondary glaucoma included 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%).

When grouped by patient age, the most common type of secondary glaucoma for 0-20 years of age was trauma; post-vitreoretinal surgery for 21-40 years of age; neovascular glaucoma for 41-60 years of age; and pseudophakic glaucoma for those over 60 years of age.[68]

Pseudoexfoliative glaucoma is a relatively uncommon form of secondary glaucoma in most regions of the developing world. However, one clinic in Ethiopia has reported it as the most common subtype of glaucoma, identified in 35% of glaucoma patients.[69] In a South Indian population study, pseudoexfoliation was identified in 3.7% of subjects, and of these 8.3% had associated glaucoma.[70]

Psychosocial and economic impact

Poor health is strongly associated with low socioeconomic status in the developing world, and eye disease is no exception.[71] [72] Glaucoma specifically can have a potentially devastating impact on quality of life, and glaucoma’s irreversible of vision loss makes early diagnosis and treatment all the more critical. 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 U.S. citizens with glaucoma. Brazilians with glaucoma also report a range of utility values lower than their U.S. counterparts. This suggests persons with glaucoma in developing countries feel a stronger impact on their quality of life.[73] [74] Not surprisingly, the degree of impact on quality of life is closely correlated with degree of visual impairment across all areas of the developing world and severity of low vision is significant predictor of quality of life.[75] [76] [77][17]

An often-overlooked effect of blindness is the secondary impact on those around a given blind person. Caregivers of vision impaired persons often bear a significant burden related to financial stress, low education, and being forced to become a caregiver.[78] A study in India reported an increased prevalence of depression in caregivers of persons with low vision or blindness. The rate of caregiver depression increased from 16% in the 20/200 group to 48% in the no light perception group. Low income was also associated with higher rates of depression.[79]

Blindness often removes two people from the workforce: the blind patient, and a family member to care for the patient.[71] Thus, glaucoma’s impact spreads far beyond individuals and their families; vision impairment and blindness have a major impact on local and national economies.[80] [81]

Glaucoma management and its challenges

Diagnosis

Universal community screening for glaucoma in developing countries is not economically feasible due to the limited numbers of providers capable of performing screenings, as well as financial and transportation barriers.[82] [83] [84] Many patients initially present when they become symptomatic from glaucoma or another ophthalmic issue. Consequently, late diagnosis is much more common in resource-limited countries.[85] For example, a study conducted in a rural population in northeastern Ghana showed bilateral blindness in 34% and unilateral blindness in half of patients receiving an initial glaucoma diagnosis.[86] This is in line with several other studies in Sub-Saharan Africa, which report a unilateral blindness rate of up to 56% in newly diagnosed glaucoma patients.[87]

Due to limited diagnostic resources, diagnosis is often made based on IOP, vision, and examination without any ancillary testing such as formal visual fields and OCTs. One recent survey of Nigerian glaucoma management found that basic diagnostic equipment was unavailable in 15-20% of clinics.[88] Gonioscopy is not always feasible at the point of screening due to a lack of access to the necessary equipment and/or personnel trained at performing gonioscopy. Thus, the use of van Herick grading or even oblique flashlight grading is more often utilized in screening for occludable angles.[84]

Medical management

Medical management of glaucoma in developing countries is more difficult than in developed countries due to more advanced disease at time of presentation, limited access to ophthalmic medications, lack of affordability of medications, variable quality of generic ophthalmics, and poor follow-up.[89] [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. The vast majority did not have any type of insurance or reimbursement for costs of treatment.[92] As such, glaucoma medical management in the developing world typically is reserved for patients with early glaucoma whose medication adherence and follow-up are all but certain or for patients who decline surgery. It was reported that medication compliance ranged from 32.5% to 65.4% in Sub Saharan Africa countries.[18]

Surgery

Surgery is generally regarded as the preferred first-line treatment for glaucoma in developing countries.[93] [94] [95] This is due to late diagnosis, poor follow-up, and the aforementioned difficulties of medical management. Small prospective trials of early glaucoma surgery in developing countries have demonstrated favorable outcomes and patient satisfaction.[96] [97] Despite this, patient acceptance of surgery in developing countries is highly variable and often low.[87][96][97] Patient-related barriers to surgery include unfamiliarity with glaucoma, absence of symptoms at time of diagnosis, and fear of complications. Due to a lack of knowledge about the disease, many newly diagnosed patients with end-stage glaucoma in their worse eye decline potentially vision-saving surgery on their better eye.

One survey of Nigerian ophthalmologists identified multiple surgeon-specific concerns that may act as barriers to surgical intervention as well, including concern about lack of patient satisfaction, complications of surgery, and negative publicity.[89] Such concerns are not unfounded. Glaucoma surgery is designed to prevent vision loss, but patients with glaucoma who lack eye health literacy often have an expectation for sight restoration, such as through spectacles or cataract surgery. In practice, performing incisional glaucoma surgery on patients in a population where there is little understanding of eye diseases can potentially discourage patients with cataract blindness and other reversible causes of vision loss from seeking eye care. Nevertheless, glaucoma surgery acceptance rates can substantially increase when patients are properly educated about the disease at the time of diagnosis.[96]

Trabeculectomy is the most common glaucoma surgery performed in the developing world.[94][98] [99] [100] When performed with antimetabolites (e.g. mitomycin C or 5-fuorouracil), the surgery has a reasonably high rate of providing significant long-term IOP reduction.[101] [102] Trabeculectomy is arguably the most cost-effective glaucoma intervention because it requires minimal equipment, does not involve the implantation of a device that may be prohibitively expensive or difficult to obtain, and often obviates the need for long-term medical management.[95] The surgery is highly effective for not only open-angle glaucoma but also for angle-closure forms of the disease; in countries with a high incidence of angle-closure glaucoma (ACG) such as China, trabeculectomy is the preferred first-line treatment for PACG with significant peripheral anterior synechiae.[14]

Modifications to what many surgeons in developed countries would consider a “standard” trabeculectomy technique are common in resource-limited parts of the world. Surgeons often employ releasable sutures due to the unavailability of lasers for suture lysis.[97] Releasable sutures also enable a tighter suturing of the scleral fap, which reduces the incidence of postoperative hypotony and its sequelae, including the acceleration of cataract formation.[103] Even with optimal technique, trabeculectomy in any form is cataractogenic, especially when antimetabolites are used. Patients in the developing world also frequently present with both visually significant cataracts and glaucoma. To address both issues, techniques have been developed that combine manual small incision cataract surgery (MSICS) with trabeculectomy.[104] Some have advocated for the use of beta radiation as an alternative to antimetabolites in developing countries because a radiation delivery device is reusable, durable, and does not depend on regular supply of medication.[85][99]

There is an increased risk of trabeculectomy failure in African eyes compared to Caucasian eyes.[105] [106] While the use of antimetabolites significantly reduce the risk of failure, this racial difference may not be present with tube-shunt surgery.[107] [108] 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.[109] In Ethiopia, a series of patients with refractory glaucoma received tube-shunt placement surgery and experienced similar success.[110] 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.[102] [111]Potential barriers to tube-shunt placement in the developing world are added cost, access to the device, and access to the donor tissues typically used to cover the tube at its entry site (e.g. cornea, sclera and pericardium). Aurolab, the nonprofit manufacturing unit of the Aravind Eye Care System, manufactures the Aravind Aqueous Drainage Device, a valveless tube-shunt that is comparable to the Baerveldt 350 glaucoma implant. This device is sold throughout the world for approximately US$50 - a fraction of the cost of other glaucoma tube-shunts.

Recent research on the use of intracameral moxifoxacin as the last step of cataract and glaucoma surgery in the developing world has found a robust decrease in the incidence of postoperative endophthalmitis.[112] One retrospective study reported a nearly 4-fold reduction in early endophthalmitis following trabeculectomy or combined trabeculectomy/cataract extraction surgery.[113] In response, many surgeons and eye care systems throughout the world have adopted intracameral moxifoxacin as standard practice for glaucoma surgery.

For ACG, cataract extraction with or without trabeculectomy may be a reasonable surgical option. The crystalline lens plays a major mechanistic role in ACG by virtue of its size, in effect mechanically crowding anatomically narrow-angled eyes. Additionally, because trabeculectomy accelerates the development of cataract, combining the two surgeries or simply performing standalone cataract extraction may provide better long-term visual outcomes in developing regions where patient follow-up is poor. One randomized controlled trial of eyes with medically controlled primary angle-closure glaucoma (PACG) and cataract, demonstrated that phacoemulsifcation alone garnered IOP reductions similar to combined phacoemulsifcation/trabeculectomy.[114] In a related study of eyes with medically uncontrolled PACG, the combined surgery group had greater IOP reductions than the standalone phacoemulsifcation group. Notably, phaco-trabeculectomy also yielded more complications.[115]

Clear lens extraction for the treatment of angle-closure glaucoma is controversial. In younger patients, clear lens extraction results in the loss of accommodation and also confers a higher risk of rhegmatogenous retinal detachment.[116] Nevertheless, one prominent multicenter randomized controlled trial found that for the management of PACG and primary angle closure with elevated IOP, clear-lens extraction had superior outcomes and was more cost-effective than laser peripheral iridotomy.[117] Another randomized controlled trial investigating management of uncontrolled PACG in eyes without cataract found that trabeculectomy was superior to phacoemulsifcation in terms of IOP and medication reduction.[118] However, trabeculectomy also was associated with more complications in the study.

Management of neovascular glaucoma (NVG) is notoriously difficult in any setting. In general, glaucoma drainage implants are considered more effective than trabeculectomy in treating NVG because fibrovascular membranes can grow over and obstruct trabeculectomy sclerostomy sites. However, trabeculectomy can successfully treat NVG in the developing world, especially when antifibrotics and anti-VEGF agents are also used.[119] Multiple challenges limit the use of bevacizumab and other anti-VEGF agents in the developing world, including cost, availability, and the need for refrigerated storage.

Lasers

Selective laser trabeculoplasty (SLT) is popular in settings where the necessary equipment is available. In a population of African descent in St. Lucia, SLT treatment of patients with open-angle glaucoma had a success rate of 77.7%, with success defined as at least 10% reduction in IOP. About half of the successful eyes had at least a 40% reduction in IOP from post-washout baseline.[120] A Chinese study of SLT reported a success rate of 53%, using an IOP reduction of at least 20% as the cutoff for success.[121] In Africa and other developing regions of the world, SLT may be a better alternative to surgery than medical therapy because of the considerable challenges with medication compliance in resource-limited countries.[122]

Laser peripheral iridotomy (LPI), where available, is a reasonable and relatively safe alternative to surgery for the management of primary angle-closure or “early” PACG. However, there is growing evidence that PACG with definite glaucomatous optic neuropathy does not respond well to LPI. One recent review of the literature found that in 68% to 94% of PACG patients initially treated with LPI, the IOP actually increased at 6 months post-laser.[14] Reflecting this reality, Chinese medical textbooks generally recommend trabeculectomy as the first-line treatment for PACG with peripheral anterior synechiae > 180 degrees.

Cyclodestructive procedures generally are viewed as last-line treatment for patients with poor vision due to their side-effect profle (i.e. uveitis, cataract, ischemia, hypotony, phthisis), but there has been some support for using cyclophotocoagulation as frst-line treatment in developing countries.[123] In Malawi,47 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 3 months.[124] Similar results were reported in Tanzania and Cameroon.[125] [126] The development of micropulse transscleral diode lasers such as the MicroPulse P3 (Iridex, Mountain View, CA) offers an additional alternative to medication and incisional surgery.[127] Because micropulse lasers are less destructive than traditional continuous wave diode lasers, they have a better safety profile, but the IOP-lowering effects are not as robust and may not be as sustained.

Potential solutions and future directives

Diagnosis

Despite recent efforts such as the VISION 2020 global initiative to eliminate avoidable blindness, most people with glaucoma remain undiagnosed.[15] Because population-based screening is resource-prohibitive, the WHO and many global ophthalmology experts advocate for enhanced opportunistic screening.[83] For example, a cost-effective strategy at improving glaucoma diagnosis rates is the promotion of comprehensive eye examinations for people all above 40 years of age.[84] The development of novel technologies and the repurposing of existing technologies offer considerable promise for improving glaucoma diagnostics in the developing world.

Teleglaucoma

The SARS-CoV-2/COVID-19 pandemic has had a profound impact on global healthcare, and ophthalmology is one of the most impacted medical specialties.[128] [129] With social distancing measures in place, ophthalmology practices in both developing and developed countries have rapidly adopted telemedicine out of necessity.[130] [131] [132] [133] [134] [135] [136]

Notable advantages of teleophthalmology, not necessarily limited to times of crisis, include decentralization of care, cost-efficiency, time-efficiency and high patient satisfaction.[130] [131] [132] [133] [134][137] [138] [139] [140] Potential advantages unique to resource-limited and remote areas worldwide include expanded access to expert eye care, facilitation of medical management as an alternative to surgery, and improved disease outcomes.[141] [142] [143] [144] [145] [146] These benefits are particularly relevant for the subspecialty of glaucoma due to its heavy reliance on testing to guide management decisions.[147]

Teleophthalmology has been implemented in some developing countries with success, albeit on a limited scale. This important technology is convenient and can potentially decrease the cost and reduce the number of patients with advanced glaucoma. [19][20] Two commonly employed telemedicine models are “real-time” and “store-and-forward.” In a “real-time” model, healthcare professionals and patients directly interact via audio or audiovisual communications. This interaction may include live collection of objective data such as visual acuity. In a “store-and-forward” model, patients receive a diagnostic workup at a remote ophthalmic testing center or primary health care center equipped with the necessary diagnostic equipment. This workup is then sent electronically to healthcare professionals elsewhere, such as in major eye centers, where the data is interpreted at a later time.[148] [149] [150] [151] For example, a store-and-forward teleglaucoma program utilizing Van Herick angle grading in combination with pachymetry has been shown to have an acceptable sensitivity and specificity for diagnosing occludable angles.[152] Store-and-forward teleophthalmology has been successfully implemented in long-term, remote care of glaucoma patients.[153] Real-time video visits with data from remote testing centers can help guide management without the need to bring the patient in office, unless there are signs of worsening.[147][154]

Widespread implementation teleophthalmology remains a considerable challenge in resource-limited regions of the world, in part due to inadequate telecommunications infrastructure and poor integration of ophthalmology with existing healthcare systems.[141] [142] [143] [144] [145] [146][21]

Smartphone-based testing

Smartphone-based glaucoma testing is a promising area of diagnostics. Such technology’s portability, relatively low cost, and potential use without the physical presence of an ophthalmic specialist make smartphone-based testing attractive for serving rural and under-resourced populations. Furthermore, the increasing ubiquity and sophistication of smartphones potentially enables widespread adoption of such technologies in developing countries.[137] [138] [139] [140]

The use of smartphone photography for ocular imaging has been validated as safe.[155] Smartphone photography for anterior segment screening examination,[156] [157] gonio-imaging,[158] and fundus and disc assessment[137][159] [160] [161] [162] [163] [164] [165] has been described in the literature. Smartphone and tablet-based visual field applications such as Melbourne Rapid Fields (MRF) have been developed and offer screening comparable to tangent screen testing.[166] Virtual reality based visual field testing also may be a portable alternative to office based visual field testing, with the added benefits of gaze tracking capabilities.[167] Proof-of-concept smartphone systems have even demonstrated the potential to estimate IOP with reasonable accuracy.[168]

Artificial intelligence (AI) and deep learning

New avenues with automated glaucoma screening and diagnostics are being explored using machine learning and AI. In settings where specialist care is scant, artificial intelligence may provide potentially powerful screening and diagnostic tools that can be integrated with existing primary care delivery models in the developing world.[169] [170] [171] The division of machine learning that focuses on imaging is deep learning. Possible barriers to widespread application include cost of development and implementation as well as a lack of an ethnically diverse data set.[172]

Automated Screening and Diagnostics

AI-based systems have demonstrated remarkable capabilities in analyzing retinal images, optic nerve scans, and visual field tests to detect signs of glaucoma with high accuracy.[173] By employing machine learning algorithms, these systems can identify subtle changes indicative of glaucomatous damage at early stages, enabling timely intervention and management.[174][175] Moreover, AI-powered tools can streamline the screening process, reducing the burden on healthcare providers and improving patient access to essential eye care services.[173]

Integration with Primary Care Delivery Models

One of the key advantages of AI-driven glaucoma screening is its potential for integration with existing primary care delivery models prevalent in the developing world.[176] By deploying AI-enabled devices in community health centers, mobile clinics, and telemedicine platforms, primary care providers can enhance their capacity to detect and manage glaucoma cases at the grassroots level. This decentralized approach ensures broader coverage and facilitates proactive management of ocular health in underserved populations.

Deep Learning and Imaging Analysis

Deep learning, a subset of machine learning, has emerged as a powerful tool for image analysis in glaucoma diagnosis.[177] By training neural networks on large datasets of retinal scans, optical coherence tomography (OCT) images, and visual field examinations, deep learning algorithms can discern intricate patterns and subtle abnormalities indicative of glaucomatous damage. This advanced level of analysis complements traditional diagnostic methods and enhances the accuracy of glaucoma detection, especially in cases where expertise is limited.[178]

Challenges and Considerations

Despite the potential benefits of AI and deep learning in glaucoma detection, several challenges hinder their widespread implementation in the developing world. The cost of developing and deploying AI-based solutions, including hardware, software, and training, poses a significant barrier, particularly in resource-constrained settings.[179][180] Moreover, the lack of ethnically diverse datasets for algorithm training raises concerns about the generalizability and accuracy of AI models across different populations.[181] Addressing these challenges requires collaborative efforts among researchers, healthcare providers, policymakers, and technology developers to develop cost-effective and culturally sensitive AI solutions tailored to the needs of diverse communities.

Patient education and awareness

One of the largest barriers to eye care in developing countries is the lack of community awareness about common eye diseases and their treatment. Currently there is widespread lack of understanding regarding glaucoma’s causes, symptoms, and natural history. 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.[98] 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.[9] 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.[182] [183] All of these numbers are much lower than the awareness and understanding of disease reported from developed countries.[184] [185] Lack of patient knowledge about glaucoma has been linked to refusal of surgery, poor medication adherence, more psychological depression, and a lower quality of life.[186] [187] [188] To address this knowledge gap, glaucoma experts have called for the development of culture-specific marketing and other local glaucoma public service awareness programs that increase general knowledge about glaucoma and promote routine vision screening.[84]

Medical management

As in developed countries, medication adherence in the developing world is a major obstacle to nonsurgical management of glaucoma. The recent development of sustained-release drug delivery systems such as bimatoprost SR (Allergan, Dublin, Ireland) portends considerable promise, although the current cost and availability of such medications all but preclude their use in resource-limited settings.[189] Lowering the cost and improving the quality of generic ophthalmic medications throughout the developing world is critical to more widespread medical management of glaucoma. Earlier diagnosis and improved monitoring such as via emerging teleglaucoma technologies may increase the role of medications worldwide.

Eye care professional education

The expansion of professional eye care education is critical to adequately addressing glaucoma in the developing world. While most countries have increased their total number of eye care professionals in recent years, the number of ophthalmologists, optometrists, and other eye care professionals remains inadequate.[83] In particular, increasing the numbers of ophthalmic paraprofessionals in resource-limited countries is essential to providing the routine vision screenings necessary to detect and treat glaucoma. Improved distribution of eye care professionals is also needed to address the world’s uneven distribution of glaucoma and other eye diseases. One global survey found that two thirds of the world’s ophthalmologists reside in just 13 countries.[190]

To improve quality of ophthalmic training in developing countries, which can be variable, some countries such as several in Eastern, Central, and Southern Africa have made recent efforts at standardizing training curricula.[191] The expanded use of structured wet lab courses and specialized artificial eyes also may play a key role in the improved quality and volume of eye surgeon training in areas of greatest need.[192] Some ophthalmology institutions including Aravind Eye Hospitals in India, Tilganga Institute of Ophthalmology in Nepal, LV Prasad Eye Institute in India, Byers Eye Institute at Stanford University, and Moran Eye Center at the University of Utah have created global ophthalmology fellowships and international observership programs as a means of improving ophthalmology training in developing countries. Orbis International, a nonproft organization based out of the United States, fosters skills transfer to eyecare professionals in developing countries via its “Flying Eye Hospital” MD-10 aircraft and via Cybersight, Orbis’s teleophthalmology and online education platform.[193]

Eye care integration into existing systems

Since 1984, the WHO has recommended integrating eye care into existing healthcare systems.[194] Specifically, many experts advocate for expanding the role that primary care systems play in detecting common eye diseases such as glaucoma.[15] Such an approach is not necessarily straightforward, and unfortunately in places like Africa, little ground has been gained since 1984 toward these ends.[194] Most primary health workers worldwide have poor knowledge of glaucoma. Existing healthcare systems are often resource-limited as it is, so the added burden of screening for eye diseases may not be feasible without additional financial and material resources. Even when primary care physicians in developing countries identify vision issues, referral pathways to an eye care specialist are often lacking.[90]

Successful, self-sustaining models for comprehensive eye care in the developing world do exist, such as LV Prasad Eye Institute, Tilganga Institute of Ophthalmology, and Aravind Eye Hospitals.[90][195] These eye care systems are multi-tiered and have excellent referral pathways, from village screenings to dedicated eye hospitals. Eye care for the poor is cross-subsidized by eye care for those who can pay and elect for premium services. Organizing glaucoma care into multiple levels of care such that screening is performed at a primary level, medical care is performed at a secondary level, and surgery is performed a tertiary level, enables a broader reach of eye care into rural and resource-limited regions.[84] The Indian government’s m-Health mobile telemedicine system may constitute a viable model for glaucoma management in developing countries, especially as internet access becomes more ubiquitous.[196] Artificial intelligence- and machine learning algorithm-assisted interpretation of ophthalmic imaging may play a critical role in making glaucoma screening affordable and accessible in remote parts of the world.[172]

Conclusion

Glaucoma continues to pose a major challenge in developing countries. Unlike blindness related to vitamin A deficiency, onchocerciasis, and other vision-impairing diseases that have been addressed through public health initiatives, glaucoma management requires one-on-one care from an eye care specialist. Unlike cataract blindness, which can be reversed permanently with a single surgery, glaucoma care generally necessitates routine follow-up for monitoring of disease progression, medication adjustments, procedures, and/or surgeries. Emphasis should be placed on training, educating, and mobilizing existing non-ophthalmology health care systems. Improved training and retention of eye care specialists in developing countries is critical to expanding global access to glaucoma care. Further development of teleglaucoma and its successful integration into existing models of healthcare delivery may dramatically improve access to eye care in resource-limited countries. Continued efforts through multinational initiatives, public health education, professional training programs, and programs focused on early disease detection and treatment are all 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 core focus of any campaign aimed at improving eye health.

Additional Resources

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