Corneal Diseases in the Developing World

Key Concepts

Corneal diseases are a major cause of unilateral as well as bilateral blindness.
The magnitude of corneal blindness is highest in countries of Asia and Africa.
Causes vary between adults and children, and also between developed and developing countries. Hence different strategies are needed to address the problems of each group.
In adults, the main causes are infectious keratitis, trauma, dystrophies, and neglected tropical diseases (trachoma, onchocerciasis, and leprosy).
In children, the causes are vitamin A deficiency, ophthalmia neonatrum, infections, and ocular trauma.
Globally, vitamin A deficiency as well as causes due to neglected tropical diseases like trachoma, onchocerciasis, and leprosy are on the decline due to better implementation of corrective strategies for these conditions.
The areas with the greatest need for corneal transplantation have the fewest resources available for proper execution.

According to recent global estimates, there are 253 million people who are visually impaired (VI). Among them, 217 million live with moderate to severe visual impairment (MSVI) and 36 million are blind. Nearly 55% of those affected are women; 89% live in low or middle income countries; and 75% of the blindness is avoidable. There are 19 million VI in the age group 0–14 years, of which 1.4 million are blind. Those 50 years and older contribute to major cause of VI and blindness. Globally, the principal causes of MSVI are uncorrected refractive errors affecting 116 million and cataract affecting 53 million, while the principal causes of blindness are cataract affecting 12.6 million and refractive errors affecting 7.4 million. ^, Overall, cataract is responsible for 25.8% and refractive error is responsible for 49% of all VI. Nearly 90% of the world’s VI people live in low- and middle-income countries. Except in the most developed countries, cataract remains the leading cause of blindness. The global distribution of blindness and low vision by seven global burden of disease (GBD) “Super” regions is shown in Table 83.1 . These regions are classified based on their geographic location and also on country gross domestic product (GDP). The good news is that up to 75% of all blindness in adults is avoidable through prevention or treatment.

TABLE 83.1

Global Visual Impairment by Global Burden of Disease Sever “Super” Regions (2015)

From Bourne RRA, Flaxman SR, Braithwaite T, et al. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob Health 2017 Sep; 5 (9):e888–97.

GBD Region	Blindness in Millions (%)	Low Vision in Millions (%)	Visual Impairment in Millions (%)
South East Asia, East Asia, and Oceania	9.767 (27.1)	73.848 (34.1)	83.615 (33.1)
South Asia	11.76 (32.7)	61.192 (28.3)	72.952 (28.9)
Central Europe, Eastern Europe, and Central Asia	1.639 (4.6)	10.754 (5)	12.393 (4.9)
North Africa and Middle East	3.472 (9.6)	18.262 (8.4)	21.734 (8.6)
Sub-Saharan Africa	4.28 (11.9)	17.359 (8)	21.639 (8.6)
Latin America and Caribbean	2.167 (6)	10.934 (5)	13.101 (5.2)
High Income Countries	2.927 (8.1)	24.248 (11.2)	27.175 (10.8)
World	36.012 (100)	216.597 (100)	252.617 (100)

GBD , Global Burden of Disease.

There is a strong correlation between aging and blindness, and only 3.8% of the global total are between 0 and 14 years. The prevalence of blindness in children also varies according to socioeconomic status and under-5 mortality rates, and ranges from 0.3 to 0.4 per 1000 children in economically developed countries, to 1.2 per 1000 in underdeveloped countries. However, this prevalence data underestimates the magnitude of the problem, because the mortality rate among blind children, particularly in the developing world, is high compared to their sighted counterparts, and 60% of children die within 1 year of becoming blind. In addition, childhood blindness becomes a priority because blind children have many years of blindness ahead of them and the visual loss affects all aspects of their development. Approximately three-quarters of the world’s blind children live in developing countries, and 51% of childhood blindness is avoidable.

Of the 1.4 million blind children worldwide, an estimated 23.2% are blind from retinal diseases, 14.6% from corneal pathology, 13.5% due to lens-related causes, 12.3% due to optic nerve related causes, 7.4% from glaucoma, and 17.1% due to anomalies affecting the whole globe ( Table 83.2 ). The causes of childhood blindness also vary in developed countries and countries with less-developed economies ( Table 83.3 ). In poor countries of the world, corneal scarring due to vitamin A deficiency (VAD), measles, ophthalmia neonatorum, and the effects of harmful traditional eye remedies predominate, while at the other end of the socioeconomic spectrum, retinal diseases, and optic nerve affections due to genetic or perinatal causes are the main causes of blindness. ^, ^, However, there is a shift in the causes of childhood blindness in low-income countries from infectious and nutritional corneal opacities that more closely resemble the patterns seen in high income countries. Hence improving maternal and neonatal health and maintenance of national ophthalmic care infrastructure are the keys to reducing the burden of avoidable blindness.

TABLE 83.2

Global Estimate of Visual Impairment in Children According to Etiologic Classification

From Kong L, Fry M, Al-Samarraie M, et al. An update on progress and the changing epidemiology of causes of childhood blindness worldwide. J AAPOS 2012 Dec; 16 (6):501–7.

	Percentage of Population
WHO Regions	Hereditary	Intrauterine	Perinatal	Childhood	Unclassified
Africa	14	4	2	38	48
Americas	25	12	17	17	17
Eastern Mediterranean	25	1	7	43	37
Europe	44	18	2	4	24
South-East Asia	23	10	4	26	44
Western Pacific	34	3	6	12	45

WHO , World Health Organization.

TABLE 83.3

Global Estimate of Visual Impairment in Children According to Anatomic Site

From Kong L, Fry M, Al-Samarraie M, et al. An update on progress and the changing epidemiology of causes of childhood blindness worldwide. J AAPOS 2012 Dec; 16 (6):501–7.

	Site Percentage
WHO Region	Cornea	Lens	Retina	Optic Nerve	Glaucoma	Whole Globe
Africa	19	13.1	15.4	12.3	3	15.7
Americas	4.4	5.8	42.1	13.7	10	9.4
Eastern Mediterranean	16.4	13.2	26.9	8.2	10.2	17.3
Europe	NA	14.1	8.1	21.7	6.42	NA
South-East Asia	23.8	13.6	17.9	7.2	7.8	26.2
Western Pacific	9.4	21.3	28.9	10.8	6.9	17.1
Total	14.6	13.5	23.2	12.3	7.4	17.1

WHO , World Health Organization.

Global Data on Corneal Blindness

While cataract is responsible for nearly 12.6 million of the 36 million blind people in the world, 1.68 million (4.6%) are blind due to corneal diseases, including trachoma, mainly due to corneal scarring and vascularization. In terms of MSVI, corneal diseases and trachoma affect 4.5 million (2.1%). Worldwide, corneal scarring (including trachoma) as the cause of VI has shown a decline. It is now the fifth major cause of bilateral blindness, after cataract, refractive error, glaucoma, and age-related macular degeneration (ARMD). However, it remains a significant cause for unilateral blindness and VI, mainly due to ocular trauma and corneal ulceration, which may be responsible for 1.5–2.0 million new cases of monocular blindness every year. Among children, of the 1.4 million blind, 140,000 are due to corneal causes. When it affects a younger population, the disability-adjusted life years compared to cataract related blindness is much higher. In addition, only 1 in 70 individuals with treatable corneal blindness undergo surgery because of various social, economic, and political factors, and most of these surgeries are done in developed countries. ^, While efforts to encourage cornea donation must continue in all countries, there is also a need to develop alternative solutions such as corneal bioengineering.

The relative importance of diseases causing blindness varies greatly by region, and corneal diseases are an important cause in nations with less-developed economies, which are already burdened by a higher prevalence of blindness. The most common causes in developed countries like the United States are Fuchs endothelial dystrophy, pseudophakic bullous keratopathy (PBK); and in developing countries, the most common is keratitis in Asia and keratoconus in Africa. Among children, the causes of corneal blindness include measles, VAD, ophthalmia neonatorum, traditional eye medicine, and less frequently seen ocular diseases such as herpes simplex virus infections and vernal keratoconjunctivitis.

The prevalence of these disorders and the effects they have on visual disability in developing countries is significant for two reasons. First, the epidemiology of corneal diseases varies widely based on geography and local environmental conditions compared to more developed nations. The second and more important reason is the inadequate level of eye care available in most of the developing nations, which further magnifies the impact of these disorders on visual outcome. Medical and surgical interventions are usually inadequate and are accessible only to a small minority of patients needing them.

Causes of Corneal Blindness

The epidemiology of corneal blindness is complicated and encompasses a wide variety of infectious and inflammatory eye diseases that cause corneal scarring, which ultimately leads to functional blindness. The causes are varied and largely depend on the ocular diseases that are endemic to each geographical area. Traditionally, important diseases that are responsible for corneal blindness include xerophthalmia, trachoma, onchocerciasis, leprosy, and ophthalmia neonatorum. ^,

Xerophthalmia

Xerophthalmia, caused by VAD, is still the leading cause of childhood blindness. Of the estimated 1.4 million children blind and 5 million visually disabled worldwide, 250,000–500,000 are blinded every year as a result of VAD. The subsequent high mortality in these children explains the relatively low prevalence of xerophthalmia seen in developing countries in spite of its high incidence. In other words, most of the children with severe VAD leading to bilateral corneal melting, perforation, and blindness associated with xerophthalmia die within the first year. An even more tragic aspect of xerophthalmia is its close association with measles epidemics. Malnourished children who are susceptible to xerophthalmia frequently develop this disease after contracting measles from a sibling or a classmate. However, there is a declining trend in VAD. Recent information from 134 population representative data from 83 countries, which studied serum retinol levels, found that the prevalence of VAD declined from 39% in 1991 to 29% in 2013. The decline was significant in East and South-East Asia and Oceania followed by Latin America and the Caribbean. However, it was still highly prevalent in sub-Saharan Africa (SSA; 48%) and South Asia (44%), and there is little change in past two decades. This might be due to insufficient dietary diversification, unsuccessful food fortification, and restricted effect of vitamin A on serum retinol. Despite such high prevalence of VAD in SSA and South Asia, there were only 2% deaths related to VAD in these regions as compared to 50% in 2000. This decline is due to improvement in nutritional status, water and sanitation, and vaccination for measles.

Clinical Features

Xerophthalmia is a term that describes the ocular changes resulting from VAD. Xerosis implies drying of the conjunctival or corneal epithelium. While conjunctival xerosis may signal mild disease, corneal xerosis indicates more severe deficiency. Other clinical findings in the spectrum include Bitot spots on the conjunctiva, fundus changes, and nyctalopia (night blindness). Keratomalacia is the most severe ocular form of VAD, resulting in rapid sterile melt of the cornea, leading to corneal perforation and secondary infection often resulting in permanent blindness. Children with VAD are also likely to suffer from systemic illnesses such as diarrhea, respiratory illnesses, and measles. The presence of keratomalacia indicates a poor prognosis for health and life, with more than 50% of children with xerophthalmia dying due to associated poor nutritional status and susceptibility to diseases.

Management

Xerophthalmia should not be considered an isolated ocular disease, because it generally occurs with generalized malnutrition and it is both an ocular and a medical emergency.

Xerophthalmia treatment regimen for children between 1 and 6 years of age is as follows: ^,

Immediately on diagnosis: 200,000 IU of vitamin A orally
Following day: 200,000 IU of vitamin A orally
4 weeks later: 200,000 IU of vitamin A orally.

VAD is not an isolated entity and is dependent on many dietary, social, and economic factors. Community interventions and education therefore play equally important roles in the prevention and management of this disease. Some of the preventive strategies include increasing awareness about breast-feeding, dietary fortification, and improvement of general nutrition. Measles also contributes significantly to the morbidity and mortality of VAD syndromes by precipitating acute deficiency and unmasking borderline malnutrition. Immunization of children against measles is also an important health strategy in the prevention of VAD states. ^,

Trachoma

Trachoma is a chronic keratoconjunctivitis caused by the bacterium Chlamydia trachomatis (A, B, Ba, and C) and primarily affects the superior and inferior tarsal conjunctiva and the cornea. Recurrent episodes of conjunctival infection and inflammation lead to corneal scarring and irreversible blindness. Trachoma is a disease of overcrowded and unclean living environments and is spread by poor hygiene, contaminated water, and houseflies. Patients most severely affected by trachoma are usually infected early in childhood and remain infected most of their lives.

Trachoma was one of the world’s leading causes of blindness and ocular morbidity. However, there has been a significant decline in its prevalence, and recent global data showed that there are 2 million people who are either blind or moderate to severely VI due to trachoma in 41 endemic countries. Overall, the age standardized prevalence of VI due to trachoma has decreased from 0.105% in 1990 to 0.03% in 2015, a 74% decline in prevalence. The highest prevalence is still seen in SSA, and the highest in SSA is seen in Ethiopia, which carries 30% of the global prevalence. ^,

The critical factors for success of Trachoma control were establishment of an evidence-based common approach and urgency towards shared goals, with the common approach being a common methodology for “Global Trachoma Mapping Project” (GTMP), the goals of which were defined as “Global Elimination of Trachoma” (GET) through the “SAFE” strategy (Surgery, Antibiotics, Facial cleanliness and Environmental change). The GTMP is the largest infectious disease survey in history. It collected data from 2.6 million individuals across 29 countries representing a global population of 224 million. There were more than 550 teams involved in the survey, in almost 2000 districts over a period of 3 years. ^, There were also intersectoral collaborations between governments, scientists, partners and donors with financial support from UK Aid, United States Agency for International Development (USAID), The Queen Elizabeth Diamond Jubilee Trust and Azithromycin donation by Pfizer. As we come closer to the elimination of trachoma, the future challenge is reaching the last mile and finding those with active disease and trachomatous trichiasis (TT) and ensuring quality of services. There is also a need to create strong partnership with water and sanitation (WASH) approaches.

GET was established in 1997 by the World Health Organization (WHO) to eliminate trachoma by year 2020. The 1998 World Health Assembly (WHA) adopted a resolution to eliminate trachoma by 2020 through SAFE strategy. Elimination is defined as the prevalence of active trachoma less than 5% in children younger than 10 years and less than one case of trichiasis per 1000 population. With implementation of SAFE strategy, elimination of trachoma is achieved in 10 countries and its validated by the WHO in Mexico, Morocco, and Oman.

Clinical Diagnosis

Trachoma is nearly always bilateral. Active trachoma is seen in young children, and conjunctival scaring is seen in 2nd to 3rd decade of life followed later by entropion, trichiasis, and corneal opacity. The infection begins in the upper tarsal conjunctiva but also involves the lower fornix. Initial response to infection includes a widespread papillary reaction and a diffuse follicular response, which indicates active infection. Follicles also appear at the limbus and, when healed, leave characteristic scars known as Herbert’s pits. It often results in corneal scarring with dense vascularization, ocular surface problems, and invariable presence of entropion and trichiasis. Corneal changes during the acute stage include development of superior pannus and punctuate keratitis eventually resulting in cornea scarring. Chronic disease results in conjunctival scarring, which results in entropion and trichiasis, with further damage to the cornea. Trachoma often leads to an increased susceptibility to microbial keratitis and dacryocystitis.

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