Trematode-induced uveitis is a disease in which cercariae of trematodes living in freshwater invade ocular tissues and form granulomas in various parts of the eye. It is frequently reported in some developing countries.
The causative trematodes have a complex life cycle. They use shellfish, freshwater fish, and crustaceans as intermediate hosts, and water birds as definitive hosts. Humans become accidental hosts when they come into contact with contaminated water. DNA of Procerovum varium (family Heterophyidae) has been identified from intraocular granulomas of affected children in South India and from cercariae derived from the freshwater snail Melanoides tuberculata [1]. Similar reports exist from rural Egypt [3].
All age groups can be affected, but it is more common in children and adolescents. The disease is particularly aggressive in younger children, and delayed consultation leads to severe visual sequelae.
QIn which regions does trematode-induced uveitis occur?
A
It is mainly reported in developing countries (such as India and Egypt) that have freshwater areas where trematodes are prevalent. Contact with shallow, slow-moving water, such as river tributaries or brackish ponds, serves as the infection trigger.
Findings vary depending on the location of granuloma formation. Lesions tend to become more severe when located posteriorly. Multiple granulomas may be observed in the same eye, or lesions may occur in different locations in both eyes.
Anterior Segment Lesions
Conjunctival and episcleral nodules: Small, well-defined nodules form within 180 degrees inferiorly in one or both eyes.
Corneal granuloma: A yellowish-white granuloma forms near the corneal limbus, accompanied by localized interstitial keratitis. After healing, fibrous scarring remains.
Anterior chamber granuloma: The most common type. Pearly, yellowish-white nodules are observed in the inferior angle (4 to 8 o’clock).
Posterior Segment Lesions
Ciliary body granuloma (CBG): The most vision-threatening form. It forms in the ciliary body of the inferior quadrant and causes severe vitritis and retinal vasculitis.
Anterior chamber granulomas are classified into nodular and membranous types.
Nodular type: Pearl-like nodules are seen in the inferior angle. It is accompanied by severe granulomatous anterior chamber reaction and granulomatous keratic precipitates (KPs). Size varies from small nodules to large cheese-like granulomas occupying several clock hours of the anterior chamber.
Membranous type: More common in chronic cases. It forms a retrocorneal membrane with neovascularization. It adheres firmly to the adjacent iris, causing peaking of the pupil and poor dilation.
Gonioscopy is important in all cases to detect microgranulomas in the angle.
Direction of progression of ciliary body granuloma (CBG)
Anterior progression: Involves the iris root and peripheral lens, causing localized cataract. If untreated, it progresses to total cataract.
Circumferential progression: Leads to supraciliary effusion, cyclitic membrane, choroidal detachment, and refractory hypotony. These cases are the most difficult to treat and have a poor prognosis.
Posterior and radial progression: Causes traction on the peripheral retina, leading to tractional retinal detachment (TRD). Subretinal fibrous bands may extend from the CBG toward the optic disc.
QWhich is more serious: anterior chamber granuloma or ciliary body granuloma?
A
Ciliary body granuloma (CBG) is more serious. Involvement of the retina increases the risk of vision loss, and progression to tractional retinal detachment leads to a poor prognosis. If untreated, it may result in phthisis bulbi. Anterior chamber granuloma is the most common type but is manageable with appropriate treatment.
The cause of this disease is a trematode that inhabits freshwater. Infection is thought to occur when cercariae in contaminated water directly penetrate the eye tissue.
Contact with contaminated water: Bathing, swimming, or working in contaminated water can trigger infection. The risk is high in shallow freshwater areas such as river tributaries and brackish ponds.
Age: More common in children and adolescents. Younger children tend to develop more severe symptoms.
Region: Concentrated in developing countries where trematodes are endemic.
Hematogenous dissemination (after drinking contaminated water or consuming undercooked fish) has also been suggested, but stool tests in ophthalmic patients are usually negative for trematode eggs, making this route unlikely.
The gold standard for diagnosis is a high clinical suspicion based on the clinical presentation of granulomatous uveitis in a young patient with a history of exposure to contaminated fresh water. The diagnosis is relatively easy if characteristic anterior chamber granulomas or retrolental membranes are present.
In infectious uveitis in general, a high clinical suspicion is required because various pathogens can present with similar clinical features.
Toxocariasis: The most important disease to differentiate in the differential diagnosis of ciliary body granuloma.
Tuberculous uveitis: In areas where trematodes are endemic, tuberculosis is also often prevalent, and a positive QuantiFERON does not necessarily indicate tuberculous etiology.
Toxoplasmosis: Requires differentiation as a cause of granulomatous uveitis.
Masquerade syndrome: In young patients with an externally “white” and quiet eye, exclude leukemic infiltration, etc.
Ultrasound biomicroscopy (UBM): The most important test for detecting ciliary body granuloma. It can visualize granulomas of the iris, lens, and ciliary body, and assess the extent of anterior, circumferential, and posterior spread. In a study of 30 children in rural Egypt, UBM confirmed localized granulomas with ciliary body edema and anterior chamber granulomas in all cases, and lens opacities were found in 30% [4]. UBM is considered essential in all cases with vitritis.
B-scan ultrasonography: Detects posterior segment complications when media opacities are present.
Metagenomic analysis of resected specimens has low positivity rates and is expensive, so intraocular specimen collection is not routinely performed for research purposes.
QWhy is ultrasound biomicroscopy important?
A
Ciliary body granuloma (CBG) is the most vision-threatening form, yet it is difficult to detect on routine examination. Ultrasound biomicroscopy is the only noninvasive test that can assess the presence, extent, and direction of spread of the granuloma, and is essential for determining treatment strategy.
Topical steroid eye drops: Used for anterior chamber inflammation, hyperemia, and pain. Symptoms respond well to topical steroids, but tend to recur upon tapering. In low-severity cases, steroid monotherapy has been reported to achieve a good response in approximately 94% of cases [2].
Antiparasitic drugs: A single dose of praziquantel (40 mg/kg) combined with metronidazole is used. In cases with small granulomas (<2.5 mm²), drug therapy alone is effective [3].
Systemic steroid administration: Short-term systemic steroid administration has been reported to resolve inflammation in atypical cases complicated by dacryoadenitis.
Pars plana vitrectomy: Performed for tractional retinal detachment (TRD) associated with CBG and refractory PTIGIU. Combined lensectomy and PPV achieved corrected visual acuity of 20/40 or better in the active phase with attached retina, but remained at 20/70 or worse in cases with TRD and scar changes [5].
Active phase (when the retina is still attached) is expected to have a relatively good visual prognosis.
Cicatricial stage (after TRD onset) carries a risk of retinal detachment recurrence after initial surgery and has a poor prognosis.
Cataract surgery: Surgery for complicated cataracts has been reported to provide good visual improvement (preoperative 0.09 → postoperative 0.37), with no vision-threatening complications observed [6].
Surgical excision of granuloma: Granulomas within the iris stroma are difficult to excise and tend to recur after steroid tapering. For large granulomas (≥2.5 mm²), surgical aspiration is effective as an adjunctive therapy [3].
As a general complication of uveitis, if posterior synechiae become circumferential, intraocular pressure may rise due to pupillary block. It is important to correctly assess the mechanism of intraocular pressure elevation and select an appropriate treatment strategy.
The exact route of entry into the eye has not been elucidated. The most plausible hypotheses are as follows.
Direct penetration theory: Cercariae in contaminated water directly penetrate ocular tissues. Cercariae are known to have the ability to penetrate skin and mucous membranes. Complaints of generalized itching or swelling of the oral mucosa after swimming support this route.
Hematogenous dissemination theory: Eggs or cercarial antigens may be hematogenously disseminated into the eye after drinking contaminated water or consuming undercooked fish. The possibility of this route is considered low because stool examinations of ophthalmic patients are usually negative for trematode eggs.
Granulomatous inflammatory reactions to trematode antigens occur at various sites within the eye. Granulomas can form in locations ranging from the conjunctiva to the choroid, with the following characteristics.
Tendency to occur in the lower area (conjunctival nodules in the inferior 180 degrees, anterior chamber granulomas at 4 to 8 o’clock, CBG in the inferior quadrant)
Multiple granulomas are often observed in the same eye
Granulomas enlarge during the active phase and heal with fibrosis
Pathophysiology of CBG progression and complications
Progressive enlargement and fibrosis of CBG cause complications through the following mechanisms.
Cataract formation: Anterior progression involves the peripheral lens, leading to localized cataract. Anterior bulging of the iris corresponding to the CBG provides a diagnostic clue.
Tractional retinal detachment: Posterior and radial progression pulls the peripheral retina toward the CBG. Contraction of the fibrous components of the granuloma causes TRD.
Hypotony and phthisis bulbi: Circumferential progression leads to ciliary membrane and supraciliary effusion, reducing aqueous humor production and resulting in refractory hypotony. If untreated, it eventually progresses to phthisis bulbi.
In treated CBG cases, there is a risk of epiretinal membrane formation causing tangential traction on the inner retina in some patients.
QWhy are granulomas more common in the lower part?
A
The exact reason is not known. It is speculated that when exposed to contaminated water, cercariae tend to accumulate in the lower part due to gravity, or that they preferentially invade the lower conjunctiva, angle, and ciliary body, but there is no definitive explanation.
7. Latest Research and Future Perspectives (Research-stage Reports)
Ribosomal DNA analysis of surgically excised intraocular specimens and cercariae has identified sequences of digenetic trematodes, including Procerovum varium [1]. However, the positivity rate is low and does not always lead to a definitive diagnosis. The development of highly sensitive molecular diagnostic methods remains a future challenge.
Staging of CBG and optimization of surgical treatment
Amin et al. classified ciliary body granuloma cases into an “active phase” (with attached retina) and a “scarring phase” (after the onset of TRD), showing that the timing of surgical intervention significantly affects visual prognosis [2]. The effectiveness of early surgical intervention in the active phase and the establishment of measures to prevent TRD recurrence in the scarring phase are needed.
Amin and Abdullatif also defined a condition characterized by vitritis and retinal vasculitis associated with CBG as “presumed trematode-induced granulomatous intermediate uveitis (PTIGIU)” and reported the usefulness of early lensectomy-PPV in cases resistant to medical treatment [5]. This concept is expected to contribute to the refinement of diagnosis and classification.
Arya LK, Rathinam SR, Lalitha P, Kim UR, Ghatani S, Tandon V. Trematode Fluke Procerovum varium as Cause of Ocular Inflammation in Children, South India. Emerg Infect Dis. 2016;22(2):192-200. doi:10.3201/eid2202.150051. PMID: 26812231.
Amin RM, Radwan AE, Goweida MB, El Goweini HF, Bedda AM, Lotfy WM, Ahmed ARH. Management of presumed trematode induced granulomatous uveitis in pediatric patients. Jpn J Ophthalmol. 2019;63(1):119-125. doi:10.1007/s10384-018-0632-3. PMID: 30386949.
El Nokrashy A, Abou Samra W, Sobeih D, Lamin A, Hashish A, Tarshouby S, Lightman S, Sewelam A. Treatment of presumed trematode-induced granulomatous anterior uveitis among children in rural areas of Egypt. Eye (Lond). 2019;33(10):1525-1533. doi:10.1038/s41433-019-0428-9. PMID: 30944459.
El Hefny E, Sabry D, Sewelam A, El Nokrashy A. Characteristics of Childhood Presumed Trematode-Induced Granulomatous Anterior Uveitis Using Ultrasound Biomicroscopy. Ocul Immunol Inflamm. 2022;30(7-8):1604-1608. doi:10.1080/09273948.2021.1922709. PMID: 34014799.
Abdallah M, Al-Hussaini AK, Soliman W, Saleh MGA. Outcome of cataract surgery in children with presumed trematode-induced granulomatous anterior uveitis. BMC Ophthalmol. 2024;24(1):21. doi:10.1186/s12886-023-03273-w. PMID: 38225542.
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