Congenital cystic eye (CCE) is an extremely rare congenital ocular malformation in which a cyst replaces the eyeball within the orbit. It is thought to result from complete or partial failure of invagination of the primary optic vesicle at the 2–7 mm stage of embryonic development (around the 4th week of gestation).
The first case was reported by Taylor and Collins in 1906. In 1939, Ida Mann described the clinical features in detail and established the concept of “anophthalmos with cyst.” It is classified under ICD-10 code Q11.0.
Orbital cystic lesions account for 10–30% of non-thyroid orbital lesions, but CCE is the rarest among them. Only 53 cases have been reported in the English literature from 1966 to 2022. It is usually unilateral, but bilateral cases have also been reported.
CCE is an orbital cyst lined by neuroepithelium that usually does not form a lens, ciliary body, or optic nerve. However, there is variability in the degree of differentiation of intraocular tissues, and cases with incomplete but partial ocular structures have been reported 1).
It is an extremely rare disease, with only 53 cases reported in English literature from 1966 to 2022. It is the least common among orbital cystic lesions.
The clinical presentation of CCE varies depending on the time of detection.
No clear risk factors for CCE have been identified. Both the inheritance pattern and causative genes are unknown.
In related diseases such as microphthalmia and anophthalmia, many causative genes including SOX2, OTX2, PAX6, and RAX have been identified. Environmental factors such as rubella, toxoplasma, cytomegalovirus, thalidomide, alcohol, and radiation are known risks for microphthalmia, but no specific risk factors for CCE have been established.
The diagnosis of CCE proceeds in three stages.
Physical examination of the eye and whole body is the first step. Check for absence of the eyeball, palpable cystic mass in the orbit, eyelid abnormalities, and presence of systemic associated malformations.
Histopathology is essential for definitive diagnosis.
Congenital Cystic Eye
Invagination disorder of the primary optic vesicle: Occurs at the 2–7 mm stage.
Absence of surface ectoderm-derived structures: Lacks surface ectoderm-derived elements such as the cornea and lens.
Cyst wall: Lined by glial tissue.
Microphthalmia with cyst
Failure of embryonic fissure closure: Occurs at the 7–14 mm stage.
Presence of microphthalmos: Ocular structures exist, albeit incompletely.
Cyst wall: May contain neuroretinal tissue.
Other differential diagnoses include epithelial cysts, orbital cystic teratoma, ectopic brain tissue, meningocele, optic nerve meningocele, and lymphangioma.
Evaluation of microphthalmia involves measurement of axial length, corneal diameter, and palpebral fissure width, as well as A-scan and B-scan ultrasonography and optical biometry.
In CCE, the key differentiating feature is the complete absence of structures derived from the surface ectoderm, such as the cornea and lens. In microphthalmia with cyst, ocular structures are present, albeit incompletely. Histopathological evaluation is essential for definitive diagnosis.
Treatment of CCE is centered on surgical intervention, and pharmacotherapy has no role in long-term management.
A staged surgical approach is standard.
Cyst Excision
First stage: Complete excision of the cyst is performed. The eyelid is preserved.
Preoperative evaluation: Screening for meningocele is performed preoperatively to prevent cerebrospinal fluid leakage.
Implant Insertion
Second stage: Insert a spherical silicone orbital implant or bioceramic implant.
Orbital volume maintenance: Contributes to facial symmetry.
Prosthetic Eye Fitting
Third stage: After an orbital conformer, finally fit a prosthetic eye.
Enucleation at a young age: Insertion of an orbital expander before long-term prosthesis is beneficial.
In severe microphthalmia with asymmetry, conjunctival expanders or contact prostheses may be used to promote orbital growth. Early intervention is desirable as fitting becomes difficult after age 3.
Most orbital development is complete by age 2. Asymptomatic cysts can promote orbital bone expansion and help maintain facial symmetry, so there is an option to preserve them until age 2. Observation is acceptable if there is no cyst enlargement or complications.
Eye development is regulated by the coordinated expression of eye field transcription factors (EFTFs). Pax6, Rax, Six3, and Lhx2 are expressed in cells of the eye field and drive eye morphogenesis.
The molecular mechanisms of development are organized as follows.
CCE results from complete or partial failure of invagination of the primary optic vesicle. The disturbance occurs at the 2–7 mm stage of embryonic development (around the 4th week of gestation).
Cyst size is related to the patency of the optic stalk. If the optic stalk is patent, fluid within the cyst drains, resulting in a small cyst; if closed, fluid accumulates and forms a large cyst. It has also been shown that individual intraocular tissues may partially continue to develop after the invagination failure, and variations in tissue differentiation are explained by this phenomenon 1).
Since inflammatory cells are observed on histopathology, an inflammation-mediated etiology has also been proposed as a hypothesis, but the detailed mechanism remains unknown. No specific gene mutation for CCE has been identified to date.
Traditionally, CCE has been defined as a cyst containing almost no intraocular tissue. However, in recent years, cases with partial differentiation of the lens or ciliary body within the cyst wall have been accumulating, and there is debate over whether the definition of CCE should be expanded 1).
Sano et al. (2025) reported a case of bilateral CCE in a horse, with neuroepithelial lining within the cyst wall and incomplete formation of the lens, ciliary body, and optic nerve 1). The variability in the degree of differentiation of intraocular tissues suggests that individual tissue development may continue even after impaired invagination of the primary optic vesicle.
The genetic cause of CCE remains unknown. In related diseases such as microphthalmia and anophthalmia, causative genes such as SOX2, OTX2, PAX6, and RAX have been identified, and their association with CCE is a topic for future research. With the widespread use of next-generation sequencing, identification of CCE-specific gene mutations is expected.
