Trachoma is the world’s leading infectious cause of blindness. This disease causes a chronic keratoconjunctivitis resulting from the obligate intracellular bacterium Chlamydia trachomatis.[1]
C trachomatis can be spread by either direct contact with an infected person's eyes or nose or indirect contact, such as via contact with clothing or flies that have come into contact with an infected person's eyes or nose. Poor sanitation, crowded living conditions, and insufficient clean water and toilets can also increase the spread of trachoma. Disease transmission occurs primarily between children and the women who care for them. Some have characterized this transmission cycle by describing trachoma as a disease of the crèche (day nursery). Flies that transmit trachoma preferentially lay their eggs on human feces lying exposed on soil.
Repeated episodes of reinfection within the family cause chronic follicular or intense conjunctival inflammation (active trachoma), which leads to tarsal conjunctival scarring. The scarring distorts the upper tarsal plate and, in some individuals, leads to entropion and trichiasis (cicatricial trachoma). The end result includes corneal abrasions, corneal scarring and opacification, and, ultimately, blindness.
Prevention of trachoma-related blindness requires a number of interventions. The World Health Organization (WHO) and their partners endorse the surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy for trachoma control.[2] The interventions are discussed in greater detail in Treatment.
Trachoma is caused by serovars A, B, Ba, and C of C trachomatis. Different serovars predominate in different families and in different communities.
Chlamydiae are gram-negative, obligate intracellular bacteria. The species C trachomatis causes trachoma and also genital infections (serovars D-K) and lymphogranuloma venereum (serovars L1-L3). Serovars D-K occasionally cause a subacute follicular conjunctivitis that may be clinically indistinguishable from trachoma, including follicular conjunctivitis with pannus, but rarely conjunctival scarring. However, these genital serovars do not typically enter stable transmission cycles within communities. Therefore, they are not involved in the genesis of trachoma blindness.[3]
Infection causes inflammation, that is, a predominantly lymphocytic and monocytic infiltrate with plasma cells and macrophages in follicles. The follicles are typical germinal centers with islands of intense B-cell proliferation surrounded by seas of T cells. Recurrent conjunctival reinfection causes the prolonged inflammation that leads to conjunctival scarring. Scarring is associated with atrophy of the conjunctival epithelium, loss of goblet cells, and replacement of the normal, loose, vascular subepithelial stroma with thick compact bands of type IV and type V collagen.
The clinical changes are a delayed-type hypersensitivity reaction to the chlamydial antigens (thought to be HSP-60). This induces an immune response with germinal centers (seen as follicles) and intense inflammatory infiltrate and the formation of papillae. Over time, this intense inflammation leads to scar formation, which, in turn, causes contraction and buckling of the tarsal plate of the upper lid, producing entropion and trichiasis.
Trachoma was once endemic in North America and Europe, but it disappeared in these locations during the 20th century as living standards improved.
International
Trachoma is endemic in parts of Africa, Asia, the Middle East, Latin America, the Pacific Islands, and aboriginal communities in Australia.[4, 5, 6, 7, 8] Worldwide, an estimated 229 million people in 53 countries live in trachoma-endemic areas. In hyperendemic areas, most members of nearly all families may have active disease. When the overall community prevalence decreases to around 20%, active disease is clearly seen to cluster in families. In 1 of 5 families, most children have active trachoma (as opposed to 1 in 5 children in most families).
Mortality/Morbidity
Blindness from any cause is associated with increased risk of mortality in endemic communities. Approximately 1.2 million people are blind because of trachoma.
Race
A disease of poverty and poor hygiene, trachoma has no racial preponderance.
Trachoma persists in areas with poor personal and community hygiene, for example, in communities with inadequate access to water and sanitation in hot, dry, dusty climates.
Trachoma typically affects the most marginalized, deprived members of a community.
Sex
Active disease most commonly occurs in preschool children of both sexes and their care providers.
Severe blinding trachoma may be nearly twice as common in women as in men; this pattern is believed to result from women assuming more childcare responsibilities, with the proximity to children resulting in increased microbial exposure.[9]
Age
Active disease most commonly occurs in preschool children, with the highest prevalence in children aged 3-5 years.
Cicatricial disease is most common in middle-aged adults. The age group in which cicatricial disease begins to appear depends on the intensity of transmission in the community. In areas of extremely high endemicity, rare cases of trichiasis occur in children younger than 10 years.
Because of repeat infection, aging may be accompanied by sequential worsening of disease. Young children have follicular trachoma with intense conjunctival inflammation; young adults, especially mothers, have trachomatous scarring; and middle-aged patients or grandparents have trichiasis and corneal opacity. However, these signs are not mutually exclusive. Individuals may have episodes of follicular trachoma with intense conjunctival inflammation even after cicatricial complications develop; therefore, follicles, scarring, and trichiasis may all be present in the same patient.
Two phases of the disease process exist: the active phase and the scarring (cicatricial) phase. As implied above, though, these phases are not stages along a linear pathway of disease pathogenesis; both phases may coexist in the same patient.
The active phase resembles many other diseases in which follicular conjunctivitis is a feature. Without laboratory facilities, the diagnosis is solely based on the clinical appearance of active trachoma in someone living in a community where trachoma is endemic or suspected to be endemic.
Most patients with active trachoma are relatively asymptomatic.
The cicatricial phase has unique clinical features, which lead to definitive diagnosis in most cases.
Determine the amount of time that the patient has spent in a trachoma-endemic community and/or near a pool of infection.
Conjunctival scarring alone tends to be asymptomatic, though the associated disturbance of the architecture of the tear film (due to scarring and destruction of mucous and serous glands) often leads to dry eye.
Trichiasis causes an intensely irritating foreign body sensation, as well as blepharospasm. Ultimately, it leads to corneal scarring.
Many patients self-epilate before their presentation.
Corneal opacities or scars that cover any part of the pupil impair the patient's vision.
Active trachoma is characterized by a mucopurulent keratoconjunctivitis. The conjunctival surface of the upper eyelid shows a follicular and inflammatory response. The cornea may have limbal follicles, superior neovascularization (pannus), and punctate keratitis. Infection with C trachomatis concurrently occurs in other extraocular mucous membranes, commonly the nasopharynx, leading to a nasal discharge.
Follicular trachoma
Follicular trachoma (designated TF in the WHO simplified trachoma grading scheme) is seen in the image below.
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Trachomatous inflammation, follicular (TF), is the presence of 5 or more follicles (each at least 0.5 mm in diameter) on the central part of the upper....
Follicular trachoma is defined as the presence of 5 or more follicles at least 0.5 mm in diameter in the central part of the upper tarsal conjunctiva.
Follicular trachoma indicates active disease.
This form is most commonly found in children, with a peak prevalence in those aged 3-5 years. The prevalence rapidly decreases in school-aged children as they leave the pool of re-infection (ie, their family childcare group).
Follicles are germinal centers that primarily consist of lymphocytes and monocytes.
The presence and involution of follicles at the limbus (corneoscleral border) give rise to the pathognomonic lesion of past active trachoma, Herbert pits.
Intense inflammatory trachoma
Intense inflammatory trachoma (designated TI in the WHO simplified trachoma grading scheme) is seen in the image below.
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Trachomatous inflammation, intense (TI) is pronounced inflammatory thickening of the upper tarsal conjunctiva that obscures more than one half the nor....
Intense inflammatory trachoma is defined as pronounced inflammatory thickening of the upper tarsal conjunctiva that obscures more than one half of the normal deep tarsal vessels.
The cause is an intense inflammatory response. Like follicular trachoma, intense inflammatory trachoma indicates active disease.
The normally thin tarsal conjunctiva develops a velvety thickening.
Papillae are visible under slit lamp examination.
Intense inflammatory trachoma indicates an increased potential for significant conjunctival scarring and, hence, a higher ultimate risk of blinding disease.
Surveying the prevalence of intense inflammatory trachoma in children can help in predicting the risk of future blinding trachoma in that cohort of children.
Trachomatous scarring
Trachomatous scarring (designated TS in the WHO simplified trachoma grading scheme) is seen in the image below.
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Trachomatous conjunctival scarring (TS) is the presence of easily visible scars in the tarsal conjunctiva.
Trachomatous scarring is defined as the presence of easily visible scars in the tarsal conjunctiva.
Trachomatous scarring indicates past inflammatory disease and a risk of future trichiasis. The more severe the scarring, the higher the risk of subsequent trichiasis.
This form may be associated with the development of dry eye syndrome, but chronic, low-grade bacterial conjunctivitis and dacryocystitis may also lead to a weeping eye.
Trichiasis
Trichiasis (designated TT in the WHO simplified trachoma grading scheme) is seen in the image below.
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Trachomatous trichiasis (TT) is defined as the presence of at least 1 eyelash rubbing on the eyeball or evidence of recent removal of in-turned lashes....
Trichiasis is defined as at least 1 eyelash rubs on the eyeball or evidence of recent removal of in-turned eyelashes.
This is a potentially blinding lesion that can lead to corneal opacification.
Trichiasis is due to subconjunctival fibrosis over the tarsal plate that leads to lid distortion.
Some vision can be restored with the successful correction of trichiasis.
Corneal opacity
Corneal opacity (designated CO in the WHO simplified trachoma grading scheme) is seen in the image below.
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Easily visible corneal opacity over the pupil; it is so dense that at least part of the pupil margin is blurred when viewed through the opacity. Photo....
Corneal opacity is defined as easily visible corneal opacity over the pupil that is so dense that it blurs at least part of the pupillary margin when it is viewed through the opacity.
Corneal opacity or scarring reflects the prevalence of vision loss and blindness resulting from trachoma.
This condition includes pannus, epithelial vascularization, and infiltration only if it involves the central cornea.
Trachoma is caused by repeated conjunctival infection with C trachomatis. Important individual-level risk factors for active trachoma include having siblings with active disease, having a dirty face, and crowded sleeping arrangements. At the community level, adequate water access for personal hygiene, sanitation, and fly control determine the risk of endemic trachoma.
In endemic areas, the diagnosis is almost always based on the clinical appearance.
Laboratory assays are principally used in research.
To confirm that the clinical diagnosis of active trachoma is the result of ocular C trachomatis infection, the best laboratory techniques are the nucleic acid amplification tests (NAATs), of which the polymerase chain reaction (PCR) is one example.
The NAATs have high sensitivity and specificity but are too expensive and too technically complex to be widely available in most settings where trachoma is endemic.
On any assay, apparent false-positive and false-negative results (compared with the clinical signs of active trachoma) may be related to the natural history of infection and disease. Individuals become infected several weeks before specific clinical signs appear, and evidence of conjunctival inflammation persists for weeks to months after the infection resolves.
Other useful techniques are direct fluorescein-labeled monoclonal antibody (direct fluorescent antibody [DFA]) assay and enzyme immunoassay (EIA) of conjunctival smears. These tests are less sensitive than the NAATs. However, to determine whether antibiotics are needed by a community, the prevalence of infection may be an important parameter, so a test with high specificity may be useful even if it has lower sensitivity.
Newer diagnostic methods have superseded cell culture, which was the criterion standard for laboratory diagnosis. Cell culture requires a highly specialized laboratory and is expensive and technically demanding. Cell culture has virtually 100% specificity but only moderate sensitivity.
Giemsa cytology is microscopic examination of stained conjunctival scrapings for intracytoplasmic inclusions. Giemsa cytology is technically demanding. This test has high specificity but low sensitivity.
The key to the treatment of trachoma is the SAFE strategy developed by the WHO. The surgical ("S") component of this strategy is described in Surgical Care below. Antibiotics ("A"), facial cleanliness ("F"), and environmental improvement ("E") are described in this section.
Antibiotic therapy
The WHO recommends 2 antibiotics for trachoma control: oral azithromycin and tetracycline eye ointment. Azithromycin eye drops have also been shown to be very effective.
Azithromycin is better than tetracycline, but it is more expensive.
National trachoma control programs in a number of countries are fortunate to be beneficiaries of a philanthropic donation of azithromycin.
Azithromycin is the drug of choice because it is easy to administer as a single oral dose.[10] Its administration can be directly observed. Therefore, compliance is higher than with tetracycline and can actually be measured, whereas, with the home administration of tetracycline, the level of compliance is unknown.
Azithromycin has high efficacy and a low incidence of adverse effects. When adverse effects occur, they are usually mild; gastrointestinal upset and rash are the most common adverse events.
Infection with C trachomatis occurs in the nasopharynx; therefore, patients may reinfect themselves if only topical antibiotics are used.
Beneficial secondary effects of azithromycin include its treatment of genital, respiratory, and skin infections.
Current WHO recommendations for antibiotic treatment of trachoma are as follows:
Determine the district-level prevalence of follicular trachoma in 1- to 9-year-old children. If the prevalence is 10% or higher, conduct mass treatment with antibiotic of all people throughout the district. If the prevalence is less than 10%, conduct assessment at the subdistrict or community level in areas of known disease.
If assessment at the subdistrict or community level is undertaken in subdistricts or communities where the prevalence of follicular trachoma in 1- to 9-year-old children is 10% or more, conduct mass treatment of all people with antibiotics.
If assessment at the subdistrict or community level is undertaken in subdistricts or communities where the prevalence of follicular trachoma in 1- to 9-year-old children is 5% or more but less than 10%, targeted treatment should be considered. Targeted treatment could involve the identification and treatment of all members of any family in whom one or more members have follicular trachoma.
If assessment at the subdistrict or community level is undertaken in subdistricts or communities where the prevalence of follicular trachoma in 1- to 9-year-old children is less than 5%, antibiotic distribution may not be necessary, though targeted treatment can be considered.
Where the baseline prevalence of follicular trachoma in children aged 1-9 years is 10% or more, annual treatment should be undertaken for at least 3 years before review. Where the baseline prevalence of follicular trachoma in children aged 1-9 years is 30% or more, annual treatment should be undertaken for at least 5 years before review.
Development of significant resistance to either azithromycin or tetracycline has not yet been demonstrated in C trachomatis.
Macrolide resistance may be induced in Streptococcus pneumoniae by the mass distribution of azithromycin for trachoma, but multiple rounds of treatment and/or the presence of macrolide resistant isolates at baseline may be necessary for epidemiologically significant resistance to emerge.
Facial cleanliness
Epidemiologic studies and community-randomized trials have shown that facial cleanliness in children reduces both the risk and the severity of active trachoma.[11]
To be successful, health education and promotion activities must be community based and require considerable effort.
Environmental improvement
General improvements in personal and community hygiene are almost universally associated with a reduction in the prevalence—and eventually the disappearance—of trachoma. This is true not only in Europe, the Americas, and Australia but also in Africa and Asia.
Environmental improvement activities are the promotion of improved water supplies and improved household sanitation, particularly methods for safe disposal of human feces.
These activities should be prioritized.
The flies that transmit trachoma preferentially lay their eggs on human feces lying exposed on the soil. Controlling fly populations by spraying insecticide is difficult. Studies on the impact of fly control on trachoma have had variable results. Trials undertaken to evaluate the installation of pit latrines suggested that the prevalence of trachoma was reduced but failed to demonstrate a statistically significant effect.
The key to the treatment of trachoma is the SAFE strategy. “S” stands for trichiasis surgery. The antibiotics (“A”), facial cleanliness (“F”), and environmental improvement (“E”) components of this strategy are described in Medical Care.
Eyelid surgery to correct trichiasis is important in people with trichiasis, who are at high-risk for trachomatous visual impairment and blindness. Eyelid surgery to correct entropion and/or trichiasis may prevent blindness in individuals at immediate risk.
Eyelid rotation limits the progression of corneal scarring. In some cases, it can result in a slight improvement in visual acuity, probably due to restoration of the visual surface and reductions in ocular secretions and blepharospasm.
The WHO has produced a training manual on the bilamellar tarsal rotation procedure.[12] Details are as follows:
This procedure involves a full-thickness incision of the scarred lid and external rotation of the distal margin by using 3 sutures.
In regions where access to ophthalmologists is limited, well-trained and well-supported health workers can perform bilamellar tarsal rotation.
Results of randomized clinical trials have confirmed the superiority of this method over other techniques.
Even after successful surgery, patients remain at risk for recurrence. Therefore, long-term follow-up care and intermittent screening are important after surgery.
Recurrence rates vary greatly between surgeons. Ongoing audit is an essential element of trichiasis surgery programs.
Evidence supports the adjuvant use of single-dose azithromycin to patients at the time of surgery.
Long-term, intermittent follow-up care is required for patients with active or cicatricial disease.
One episode of infection may be treated adequately, but reinfection from the community pool of infection is likely unless an effective mass treatment campaign is implemented. When mass treatment is undertaken, antibiotic coverage should be as high as possible, with 80% being an absolute minimal target. It is important to treat all family members, especially the younger children.
Some studies suggest a great benefit if coverage in excess of 95% can be achieved.
Surgical patients require annual follow-up care because of the potential for recurrence.
The aim in treatment is to reduce the amount C trachomatis in the infection reservoir in the family. Treating an individual and not treating infected family members leaves the individual at risk for repeat infection. All family members, including infants, should be treated.
The antibiotic of choice for treating active trachoma is azithromycin. The dose for children is 20 mg/kg in a single dose; adults receive a single dose of 1 g. The second-line treatment is topical tetracycline eye ointment 1%. Topical tetracycline is applied to both eyes twice a day for 6 weeks.
If the patient lives in a hyperendemic area, the whole district (or whole community) is eligible for antibiotic treatment.
Clinical Context:
Azithromycin is a macrolide antibiotic and is the drug of choice for trachoma. Plasma concentrations are low, but tissue concentrations are higher, giving it value in treating intracellular organisms. It has a long tissue half-life. A single dose is recommended.
Clinical Context:
Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit. Use if azithromycin is unavailable. Minimal systemic adverse effects.
Clinical Context:
Azithromycin ophthalmic is an ophthalmic macrolide antibiotic indicated for bacterial conjunctivitis caused by CDC coryneform group G bacteria, Haemophilus influenzae, Staphylococcus aureus, Streptococcus mitis group, and Streptococcus pneumoniae.
Andrew G Lee, MD, Chair, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital; Clinical Professor, Associate Program Director, Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch School of Medicine; Clinical Professor, Department of Surgery, Division of Head and Neck Surgery, University of Texas MD Anderson Cancer Center; Professor of Ophthalmology, Neurology, and Neurological Surgery, Weill Medical College of Cornell University; Clinical Associate Professor, University of Buffalo, State University of New York School of Medicine
Disclosure: Received ownership interest from Credential Protection for other.
Coauthor(s)
Michael Duan, Baylor College of Medicine
Disclosure: Nothing to disclose.
Rahul T Pandit, MD, Associate Professor of Clinical Ophthalmology, Weill Cornell Medicine, Blanton Eye Institute; Medical Director, Houston Methodist Hospital Ophthalmology Operating Room; Methodist Eye Associates
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Johnson and Johnson Vision; Bausch and Lomb.
Specialty Editors
Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Disclosure: Nothing to disclose.
Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Avedro; Bio-Tissue; Shire<br/>Received income in an amount equal to or greater than $250 from: AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab.
Chief Editor
Michael Taravella, MD, Director of Cornea and Refractive Surgery, Rocky Mountain Lions Eye Institute; Professor, Department of Ophthalmology, University of Colorado School of Medicine
Disclosure: Received income in an amount equal to or greater than $250 from: J&J Vision (Consultant)/Proctor<br/> for: Coronet Surgical (Consultant), no income received.
Additional Contributors
Anthony W Solomon, MBBS, DTM&H, PhD, MRCP, Wellcome Trust Intermediate Clinical Fellow, Senior Lecturer, Department of Clinical Research, London School of Hygiene and Tropical Medicine; Honorary Consultant Physician, The Hospital for Tropical Diseases, UK
Disclosure: Received grant/research funds from International Trachoma Initiative for researcher; Received member of trachoma expert committee from International Trachoma Initiative for review panel membership; Received member of scientific advisory board from Queen Elizabeth Diamond Jubilee Trust for review panel membership.
Hugh Ringland Taylor, AC, MD, MBBS, BMedSc(Melb), DO(Melb), FRANZCO, FRACS, FAAO, FACS, FAICD, Harold Mitchell Professor of Indigenous Eye Health, Melbourne School of Population and Global Health, University of Melbourne
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Eclipse, Galderma, Mertz.
Acknowledgements
Anastasios J Kanellopoulos, MD Assistant Program Director, Clinical Associate Professor, Department of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, New York University
Anastasios J Kanellopoulos, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Eye Bank Association of America, and International Society of Refractive Surgery
Disclosure: Nothing to disclose.
Denise Mabey, FRCOphth, MBBS Consulting Staff, Department of Ophthalmology, St Thomas Hospital of London
Reacher M, Foster A, Huber J. Trichiasis surgery for trachoma: the bilamellar tarsal rotation procedure. WHO/PBL 93.29. Geneva: World Health Organization;. 1993.
Trachomatous inflammation, follicular (TF), is the presence of 5 or more follicles (each at least 0.5 mm in diameter) on the central part of the upper tarsal conjunctiva. Images from the Slides/Text Teaching Series, No. 7, Trachoma, published by The International Centre for Eye Health, Institute of Ophthalmology, 11-43 Bath St, London EC1V 9EL, United Kingdom. Photograph courtesy of John D. C. Anderson, MD.
Trachomatous inflammation, intense (TI) is pronounced inflammatory thickening of the upper tarsal conjunctiva that obscures more than one half the normal deep tarsal vessels. Photograph courtesy of Allen Foster, MD.
Trachomatous conjunctival scarring (TS) is the presence of easily visible scars in the tarsal conjunctiva.
Trachomatous trichiasis (TT) is defined as the presence of at least 1 eyelash rubbing on the eyeball or evidence of recent removal of in-turned lashes. Photograph courtesy of John D. C. Anderson, MD.
Easily visible corneal opacity over the pupil; it is so dense that at least part of the pupil margin is blurred when viewed through the opacity. Photograph courtesy of John D. C. Anderson, MD.
The image on the left shows intense inflammatory trachoma, and the image on the right shows allergic conjunctivitis with the typical cobblestone papillae. Courtesy of John D. C. Anderson, MD, and Murray McGavin, MD.
Trachomatous inflammation, follicular (TF), is the presence of 5 or more follicles (each at least 0.5 mm in diameter) on the central part of the upper tarsal conjunctiva. Images from the Slides/Text Teaching Series, No. 7, Trachoma, published by The International Centre for Eye Health, Institute of Ophthalmology, 11-43 Bath St, London EC1V 9EL, United Kingdom. Photograph courtesy of John D. C. Anderson, MD.
Trachomatous inflammation, intense (TI) is pronounced inflammatory thickening of the upper tarsal conjunctiva that obscures more than one half the normal deep tarsal vessels. Photograph courtesy of Allen Foster, MD.
Trachomatous conjunctival scarring (TS) is the presence of easily visible scars in the tarsal conjunctiva.
Trachomatous trichiasis (TT) is defined as the presence of at least 1 eyelash rubbing on the eyeball or evidence of recent removal of in-turned lashes. Photograph courtesy of John D. C. Anderson, MD.
Easily visible corneal opacity over the pupil; it is so dense that at least part of the pupil margin is blurred when viewed through the opacity. Photograph courtesy of John D. C. Anderson, MD.
The image on the left shows intense inflammatory trachoma, and the image on the right shows allergic conjunctivitis with the typical cobblestone papillae. Courtesy of John D. C. Anderson, MD, and Murray McGavin, MD.
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