Trachoma is a recurrent ocular surface infection caused by Chlamydia trachomatis. It is the most common infectious cause of blindness worldwide and one of the leading causes of preventable blindness1).
C. trachomatis is an obligate intracellular Gram-negative bacterium1). It has a biphasic developmental cycle alternating between infectious elementary bodies and non-infectious reticulate bodies1). Ocular serotypes A, B, Ba, and C cause trachoma. Genital serotypes D to K cause inclusion conjunctivitis and neonatal conjunctivitis but usually do not lead to blindness.
Based on clinical differences, conjunctivitis caused by C. trachomatis is broadly divided into trachoma and inclusion conjunctivitis. In Japan, trachoma is now rarely seen. However, it remains endemic in countries with poor sanitation and is one of the target diseases of WHO’s Vision 2020.
In 1956, Professor Feifan Tang and Professor Xiaolou Zhang first identified C. trachomatis as the causative agent of trachoma.
According to WHO reports, trachoma is endemic in more than 38 countries, with the majority of blindness cases concentrated in Africa. An estimated 21 million people have active trachoma, and 1.9 million have visual impairment or blindness. 7.3 million people suffer from trichiasis and are at risk of blindness. The number of visually impaired people due to trachoma has significantly decreased from 4.4 million in 1990 to 2.5 million in 2019.
Active trachoma is most common in young children. Prevalence decreases with age. Scarring and trichiasis are more common in women, likely due to prolonged exposure through caring for children.
Both trachoma and inclusion conjunctivitis are caused by C. trachomatis, but the serotypes involved differ. Trachoma results from repeated infection with ocular serotypes A to C, leading to conjunctival scarring and potential blindness. In contrast, inclusion conjunctivitis is caused by genital serotypes D to K 1), occurs in adults as a sexually transmitted infection, and generally does not lead to blindness. Differentiation between the two is possible by ompA genotyping 1). In Japan, trachoma has almost disappeared, but inclusion conjunctivitis (chlamydial conjunctivitis) remains a problem as a sexually transmitted infection.
Many patients are asymptomatic or have only mild symptoms.
The clinical findings of trachoma are broadly divided into active disease and cicatricial (scarring) stages.
Findings of active disease
Findings of the cicatricial stage
| Grade | Finding |
|---|---|
| TF (Trachomatous inflammation—follicular) | Five or more follicles (>0.5 mm) on the upper tarsal conjunctiva |
| TI (Trachomatous inflammation—intense) | Thickening of the tarsal conjunctiva obscuring more than half of the deep tarsal vessels |
| TS (Trachomatous Scarring) | Scarring of the tarsal conjunctiva |
| TT (Trachomatous Trichiasis) | One or more eyelashes touching the eyeball |
| CO (Corneal Opacity) | Corneal opacity over the pupillary area |
The traditional clinical classification includes the following four stages: (1) Incipient trachoma, (2) Established trachoma (follicular type, papillary type), (3) Cicatricial trachoma, (4) Healed trachoma. Trachoma typically has an incubation period of about one week and then presents acutely.
Ocular serotypes A, B, Ba, and C of C. trachomatis cause trachoma. Strains can be classified based on the diversity of the outer membrane protein A (ompA) gene sequence1). ompA genotypes A–C cause trachoma, while D–K cause urogenital infections1).
Infection is transmitted through direct contact with ocular discharge or by flies.
The ompA gene encodes the major outer membrane protein of C. trachomatis and has extensive sequence diversity in four variable regions (VS I–IV)1). Genotyping based on this diversity allows differentiation of strains. Genotypes A–C correspond to trachoma-causing strains, and D–K to urogenital infection strains1). ompA genotyping in pediatric chlamydial conjunctivitis is reported to be useful for distinguishing trachoma from sexual abuse1).
Clinical Diagnosis
WHO Grading: In endemic areas, clinical stages are classified into five grades from TF to CO. Eversion of the upper eyelid is particularly important.
MacCallan Classification: Clinical course is evaluated in four stages: initial, established, cicatricial, and healed.
Specific Findings: Herbert’s pits (depressions after absorption of limbal follicles) are specific to trachoma. Arlt’s line (horizontal linear scar of the tarsal conjunctiva) is also a diagnostic clue.
Laboratory Tests
Cytology: Giemsa or Diff-Quick staining of conjunctival scrapings reveals intracytoplasmic inclusions (Prowazek bodies) in epithelial cells. Polymorphonuclear leukocytes predominate over mononuclear cells, and Leber cells and plasma cells are also seen.
Nucleic Acid Amplification Test (NAAT): Excellent sensitivity and specificity. Used in clinical research, but evidence for use in national elimination programs is still insufficient.
ompA Genotyping: PCR identifies the ompA genotype of C. trachomatis strains, distinguishing trachoma strains (A–C) from urogenital strains (D–K)1).
| Differential Disease | Key Points for Differentiation |
|---|---|
| Inclusion conjunctivitis | Serotypes D–K, associated with sexually transmitted infections |
| Adenoviral conjunctivitis | Acute onset, epidemic, difficult to differentiate in early stage |
| Toxic conjunctivitis | Long-term use of eye drops, improves with discontinuation |
The WHO grading system is used for epidemiological surveys and treatment decisions in endemic areas. The upper eyelid is everted to observe the conjunctiva. TF (5 or more follicles, >0.5 mm) and TI (more than half of deep vessels invisible) indicate active infection and are indications for antibiotic treatment. TS (conjunctival scarring) indicates progression to the scarring stage. TT (trichiasis) is an indicator for surgical intervention. CO (corneal opacity in the pupillary area) assesses the degree of visual impairment. Grades may overlap.
Medical Treatment
Single oral dose of azithromycin: First-line treatment for active trachoma. It is simple and has high compliance. Azithromycin eye drops (twice daily for 3 days) have also been reported to be equally effective.
Tetracycline eye ointment: A historically used topical treatment that requires long-term administration.
Mass antibiotic therapy: In endemic areas, mass drug administration is implemented. Although significant results have been achieved, antibiotic resistance is also being recognized.
Surgical Treatment
Trichiasis surgery: This is a procedure to move the eyelashes and eyelid margin away from the cornea. The tarsal fracture technique is representative.
Posterior lamellar augmentation: Considered as an additional surgical intervention for recurrent cases.
Epilation and electrolysis: As an alternative to invasive surgery, this is a simple method to reduce ocular surface damage in certain patients.
Maintain cleanliness of the eyelids and ocular surface, actively use artificial tears, and administer antibiotics for secondary infections. In cases of severe corneal opacity, corneal transplantation may be indicated, but access is limited in endemic areas.
The SAFE strategy is a comprehensive approach for trachoma elimination developed by WHO in 1997. S stands for Surgery for trichiasis, A for Antibiotics for infection, F for Facial cleanliness, and E for Environmental change. It integrates therapeutic interventions (antibiotics and surgery) with preventive interventions (hygiene and environmental improvement) and is promoted globally as GET2020 (now GET2030).
Blindness from trachoma results from repeated active infections over months to years. Initial infection is confined to the conjunctival epithelium, inducing an immune response that appears as conjunctival follicles. Inflammatory reactions from repeated infections cause tissue destruction and fibrosis. Contraction of fibrous tissue leads to cicatricial entropion, causing eyelashes to contact the cornea. Corneal erosion, ulceration, scarring, and neovascularization progress, ultimately leading to corneal opacity and blindness.
In the active inflammatory phase, diffuse mixed inflammatory cell infiltration of the conjunctiva and lymphoid follicles in the stroma are observed. Lymphoid follicles are a histological hallmark of trachoma. Mild to moderate epithelial proliferation is also present.
In the cicatricial phase, chronic inflammatory infiltration predominantly composed of lymphocytes is seen in the substantia propria of the conjunctiva. The conjunctival epithelium shows squamous metaplasia or atrophy. The stroma is replaced by thick, dense, avascular scar tissue.
Vascular invasion from the superior cornea (pannus) is characteristic. Herbert’s pits form after the absorption of limbal follicles. Persistent corneal irritation due to cicatricial trichiasis leads to progression of corneal erosion, ulceration, and opacification.
Through the SAFE strategy promoted by WHO and international collaborative efforts, many countries including Benin, Gambia, Ghana, Cambodia, China, and Iran have achieved elimination of trachoma as a public health problem. The number of people visually impaired by trachoma decreased from 4.4 million in 1990 to 2.5 million in 2019.
In addition to annual mass azithromycin administration in endemic areas, twice-yearly administration is being considered in high-risk areas. Monitoring of antimicrobial resistance is also a challenge.
ompA genotyping is useful for epidemiological tracking of strains, but currently remains for research purposes only 1). Its application has been reported for diagnosing trachoma in migrants from endemic areas and for differential diagnosis of childhood conjunctivitis 1).
- Mitchell A, Patel M, Manning C, Abbott J. Reducing suspicion of sexual abuse in paediatric chlamydial conjunctivitis using ompA genotyping. BMJ Case Rep. 2021;14:e238871.
