Lens Coloboma

Key Points of This Disease

• Lens coloboma is a congenital condition in which a notch-like depression occurs at the equator of the lens due to partial absence of the zonular fibers (Zinn’s zonule).
• It results from incomplete closure of the embryonic fissure, and the defect often occurs inferiorly (at the site of the embryonic fissure).
• It is typically associated with iris coloboma, ciliary body coloboma, and chorioretinal coloboma, and usually occurs unilaterally.
• Cataracts frequently coexist, and cataract surgery becomes more difficult due to the reduced number and stretching of the zonular fibers.
• Mild defects may be asymptomatic, but when cataracts are present, decreased vision and irregular astigmatism become problematic.
• In cataract surgery, the fragility of the zonules of Zinn is assessed preoperatively, and capsular support devices such as the CTR (capsular tension ring) are used depending on the degree of fragility.
• Prognosis depends on the severity of associated ocular diseases (cataract, chorioretinal coloboma, lens subluxation).

1. What is lens coloboma?

Lens coloboma is a condition in which the equatorial edge of the lens is partially irregularly indented due to malformation. Partial absence of zonular fibers (zonules of Zinn) causes a notch-like depression at the lens margin, with reduced number or stretching of the zonules at that site. Some cases are accompanied by partial coloboma of the ciliary body. It is associated with failure of embryonic fissure closure and often occurs inferiorly along with iris, ciliary body, and chorioretinal coloboma.

“Coloboma” is a Greek word meaning “defect” or “mutilation.” In the eye, it can occur in various structures such as the iris, ciliary body, choroid, and optic nerve, but when it occurs in the lens, it is specifically called lens coloboma. Lens coloboma is also frequently seen in congenital lens subluxation.

Epidemiology

Accurate prevalence data for lens coloboma are scarce. Ocular coloboma as a whole is reported to occur in approximately 1 in 10,000 to 16,000 births ¹⁾, and lens coloboma rarely occurs in isolation; it is often found as a complex type combined with other colobomas. It is usually unilateral, but if the embryonic fissure closure failure occurs bilaterally, it can be bilateral.

Ocular coloboma is one of the important causes of congenital visual impairment, and along with microphthalmia and anophthalmia, appropriate management is required ²⁾.

Q Is lens coloboma hereditary?

A

Lens coloboma is a congenital disease associated with failure of embryonic fissure closure. In addition to isolated cases, it may occur as part of overall ocular malformation related to genetic abnormalities such as PAX2, PAX6, and CHD7. It can also be associated with systemic syndromes such as CHARGE syndrome (CHD7 gene mutation) and renal coloboma syndrome (PAX2 gene mutation). Genetic counseling is recommended when other colobomas are present or systemic disease is suspected.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

Symptoms of lens coloboma vary greatly depending on the extent of the defect and associated ocular diseases.

• Asymptomatic: In mild lens coloboma, the impact on visual acuity is minimal, and it may be discovered incidentally during slit-lamp examination under dilated pupils.
• Decreased visual acuity: Occurs when cataract is present. Visual acuity decreases depending on the location and severity of opacification. In children, it is a major cause of amblyopia.
• Irregular astigmatism: Deformation of the lens equator causes irregular astigmatism that cannot be fully corrected with glasses.
• Ocular misalignment and amblyopia: In children with associated coloboma or decreased visual acuity, strabismus and amblyopia may develop.
• Visual field defect: When associated with chorioretinal coloboma, a corresponding visual field defect (often in the upper visual field) occurs.

Clinical Findings

Slit-lamp examination under mydriasis is central to diagnosis, revealing the following findings.

• Notch-shaped defect of the lens equator: A concave deformation cutting into the lens periphery is observed. It most commonly occurs inferiorly (at the site of the embryonic fissure).
• Abnormalities of the zonules of Zinn: The zonules at the defect site are reduced or stretched, making lens support unstable.
• Iris coloboma: A defect in the inferior iris (keyhole pupil) may be present.
• Lens opacity: Cataracts frequently coexist. Opacity patterns range from nuclear cataract to cortical opacity.
• Fundus findings: When combined with retinochoroidal coloboma, a defect in the lower retina and choroid is observed.

Q Does lens coloboma always cause decreased visual acuity?

A

In mild defects, the impact on visual acuity may be minimal. Decreased visual acuity becomes a problem when cataracts are present or when irregular astigmatism is significant. Additionally, when combined with retinochoroidal coloboma, visual field defects corresponding to the defect site may occur. In children, amblyopia can develop, making early detection and treatment important.

3. Causes and Risk Factors

Mechanism of Development

The main mechanism of lens coloboma is failure of embryonic fissure closure. During the 6th to 7th week of gestation, the lower edge of the optic cup (embryonic fissure) fuses and closes. If an abnormality occurs in this closure process, a defect remains in the lower part of the optic cup.

Lens coloboma occurs as a result of hypoplasia of the Zinn zonules derived from the ciliary body at the site of incomplete embryonic fissure closure. At the defect site, the zonules are reduced in number or stretched, causing asymmetric traction on the lens, leading to a concave notch at the equatorial margin. Concurrently, a defect may also occur in the ciliary body itself, forming part of the ocular phenotype of incomplete embryonic fissure closure.

Genetic Background

Multiple gene mutations have been identified as causes of ocular coloboma³⁾.

• PAX2 gene: Causative gene for renal coloboma syndrome. It combines optic nerve coloboma and renal hypoplasia. Ocular coloboma is a major feature⁴⁾
• CHD7 gene: Causative gene for CHARGE syndrome (Coloboma, Heart defect, Atresia of choanae, Retardation, Genital abnormalities, Ear defects). It is a chromatin remodeling factor, and mutations cause multiple organ malformations including ocular coloboma⁵⁾
• PAX6 gene: Major transcription factor for eye development. Mutations show diverse phenotypes such as aniridia and coloboma.
• SHH gene, FZD4 gene, etc.: Involved in eye formation; mutations can cause coloboma

In isolated lens coloboma (without other colobomas), genetic mutations are often not identified.

Associated Diseases

Lens coloboma is often associated with colobomas of other ocular structures and congenital anomalies.

• Iris coloboma: Most common association. Appears as a defect in the inferior iris (keyhole pupil)
• Ciliary body coloboma: Directly related to lens coloboma through zonular fiber hypoplasia
• Chorioretinal coloboma: Defect in the lower choroid and retina. Significantly affects visual prognosis and risk of retinal detachment
• Optic disc coloboma: Defect around the optic nerve. May be accompanied by marked visual field defects
• Congenital lens dislocation: Extensive abnormality of the zonules of Zinn may be associated with lens coloboma
• Microphthalmia: May be accompanied by microphthalmia as a severe form of embryonic fissure closure failure

For patients and families

• In children suspected of having lens coloboma, it is important to see an ophthalmologist early for refraction and amblyopia testing.
• If you have chorioretinal coloboma and experience a sudden increase in floaters, flashes of light, or partial vision loss, see an ophthalmologist immediately (possible retinal detachment).
• If systemic diseases (e.g., CHARGE syndrome, renal coloboma syndrome) are suspected, referral to other departments is necessary.

4. Diagnosis and Examination Methods

Diagnosis of lens coloboma is primarily based on slit-lamp examination under mydriasis, combined with multiple tests to evaluate associated ocular conditions. Family history and systemic abnormalities must be confirmed through history taking.

Examination Item	Purpose	Main Findings
Slit-lamp examination under mydriasis	Confirmation of lens equatorial defect and Zinn zonule evaluation	Notch-shaped defect (more common inferiorly), reduced number and stretching of Zinn zonules
Fundus examination	Confirmation of retinochoroidal coloboma and evaluation of retinal detachment	Inferior retinal and choroidal defect, optic disc coloboma
Visual field test	Evaluation of visual field defects	Superior visual field defect (corresponding to retinochoroidal coloboma)
UBM examination	Detailed evaluation of anterior segment structures	Visualization of Zinn zonule reduction and extension

Key Points of Each Examination

Slit-lamp microscopy under mydriasis is the basis of diagnosis. A notch-like concave deformation at the equator of the lens, observed inferiorly (at the site of the embryonic fissure), confirms the diagnosis. Evaluating the state of the zonules of Zinn (degree of reduction and stretching) at the defect site provides important information for planning subsequent cataract surgery.

Fundus examination evaluates the presence and extent of retinochoroidal coloboma. Confirming whether the defect involves the macula or optic disc is essential for predicting visual prognosis.

Ultrasound biomicroscopy (UBM) can evaluate the fine structure of the zonules of Zinn as tomographic images ⁶⁾, and is useful for assessing fragility before cataract surgery. It helps predict the difficulty of capsulorhexis (CCC).

Systemic evaluation: If complications such as CHARGE syndrome (heart, ear, choanae) or renal coloboma syndrome (renal function) are suspected, systemic assessment should be performed in collaboration with relevant departments.

Differential Diagnosis

• Traumatic lens subluxation: Differentiate based on history of trauma and pattern of zonular rupture (often acute and unidirectional).
• Congenital lens subluxation (Marfan syndrome, Weill-Marchesani syndrome, etc.): Differentiate based on presence of systemic disease or skeletal abnormalities. Often involves extensive zonular defects with characteristic displacement direction (superior displacement common in Marfan syndrome).
• Spherophakia: A condition where the entire lens becomes spherical. Differentiate in relation to Weill-Marchesani syndrome and Alport syndrome.

Q Are special tests needed to diagnose lens coloboma?

A

Diagnosis is possible if a notch-shaped defect at the lens equator is confirmed by slit-lamp microscopy under mydriasis. Fundus examination is also essential to evaluate associated chorioretinal coloboma. When planning cataract surgery, UBM examination to assess the detailed condition of the zonules is useful for surgical planning. If systemic disease (e.g., CHARGE syndrome) is suspected, collaboration with a pediatrician is important.

5. Standard Treatment Methods

There is no fundamental treatment for lens coloboma itself. Treatment focuses on managing complications (cataract, irregular astigmatism, amblyopia, retinal detachment).

Conservative Treatment

• Refractive correction: For irregular astigmatism, prescription glasses are the basic approach. If glasses do not provide sufficient correction, hard contact lenses are used. Hard contact lenses correct irregular astigmatism by uniformly covering the anterior corneal surface.
• Amblyopia treatment: In pediatric cases with visual acuity differences, amblyopia training using occlusion of the healthy eye (eye patch) is performed. Intervention within the critical period of vision (generally up to around age 10) is key to preventing irreversible vision loss.
• Regular fundus examination: In cases with chorioretinal coloboma, there is a risk of retinal detachment, so fundus examinations every 6 to 12 months are performed for early detection.

Cataract Surgery

When cataracts complicate and visual impairment progresses, surgery is indicated. In cases with lens defects, the support of the lens is unstable due to reduction and stretching of the zonules of Zinn, making cataract surgery more difficult than usual.

Key points of preoperative evaluation:

• Evaluate the condition of the zonules of Zinn using slit-lamp microscopy and UBM.
• Assess the degree of zonular weakness by the extent of lens movement during capsulorhexis (CCC).
• Prepare capsular support devices (CTR, M-CTR, CTS, etc.) in advance according to the degree of weakness.

The choice of surgical technique according to the degree of zonular weakness is as follows.

Zonular weakness	Recommended procedure	Capsular support device
Mild (grade 1)	Phacoemulsification (PEA)	CTR “pre-insertion”
Moderate (grade 2)	PEA	Consider CTR + CE (capsule expander)
Severe (grade 3 or higher)	Consider extracapsular cataract extraction (ECCE)	M-CTR/CTS (scleral sutured type)
Extensive defect	Lens extraction	Scleral-fixated IOL / Iris-sutured IOL

Points for using CTR (Capsule Tension Ring):

CTR is a device inserted into the lens capsule during cataract surgery in cases with weak zonules to maintain the capsule in a circular shape and reduce stress on the zonules. Use of CTR can prevent posterior capsule rupture and enlargement of zonular dialysis ⁷⁾.

In mild to moderate weakness cases, it is useful to insert the CTR “first” after creating the CCC and before nuclear emulsification with the ultrasound (US) tip. Sufficiently expanding the capsule with an ophthalmic viscosurgical device (e.g., hyaluronic acid preparation) before CTR insertion can reduce stress on the capsule during insertion. Caution is needed in cases with hard nuclei, as the cortical layer may be thin, making CTR insertion difficult.

In cases of severe zonular weakness, capsule support devices such as a modified CTR (Cionni ring) that can be fixated to the sclera are an option ⁷⁾. By supporting the entire capsular bag to the sclera, the IOL can be stabilized within the bag. If the posterior capsule and zonules are significantly insufficient, methods to fixate the IOL outside the bag (scleral-fixated IOL, iris-sutured IOL) are chosen. In pediatric cases, refractive correction as an aphakic eye may be performed.

Precautions in Cataract Surgery

• Always assess zonular weakness during CCC before creating the main incision
• Sufficiently expand the capsule with viscoelastic material before CTR insertion
• In hard nuclei, the cortical layer is thin, requiring caution during CTR insertion
• Long-term follow-up is necessary for the risk of postoperative IOL decentration or dislocation
• Surgery by an experienced surgeon is recommended

Management of Retinal Detachment

In cases with chorioretinal coloboma, the risk of retinal detachment is high. The retina and choroid are absent at the coloboma site, and retinal detachment tends to occur around it. Retinal detachment associated with coloboma is often refractory, and vitrectomy is performed, but visual prognosis depends on the extent and location of the defect ¹⁾.

Q Is cataract surgery difficult when there is a lens defect?

A

Due to the reduction and stretching of the Zinn zonules, the difficulty is higher than in normal cataract surgery. During CCC, the fragility of the Zinn zonules is assessed, and capsular support devices such as CTR (capsular tension ring) are used according to the fragility. In mild to moderate fragility cases, phacoemulsification with CTR “pre-insertion” is performed. In severe cases, scleral sutured capsular support devices such as M-CTR or CTS, or extraocular IOL fixation are selected. Surgery by an experienced surgeon is recommended.

6. Pathophysiology and Detailed Pathogenesis

Embryological Background

During eye development, the retina, choroid, iris, ciliary body, and zonules of Zinn are all structures that differentiate from the optic cup (secondary optic vesicle). If an abnormality occurs when the lower edge of the optic cup (fetal fissure) closes at 6–7 weeks of gestation, various colobomas form depending on the degree and location of the incomplete closure ²⁾.

Lens coloboma results from hypoplasia of the zonular fibers derived from the ciliary body at the site of incomplete fetal fissure closure. Normally, zonular fibers extend radially from the ciliary body to the lens equator evenly, but at the defect site, the number of fibers is reduced (hypoplasia) or the fibers are elongated (stretching). This asymmetric traction creates a concave deformation (notch) at the lens equator. At the same time, a part of the ciliary body may be absent (ciliary coloboma), and in more extensive incomplete closure of the fetal fissure, the defect may extend to the iris, retina, choroid, and optic nerve.

Molecular Genetic Mechanisms

The molecular genetic background of ocular coloboma is complex, and abnormalities in multiple transcription factors and signaling pathways involved in eye development have been reported ³⁾.

PAX2 and PAX6 are major transcription factors in eye development and are also involved in signals that control fetal fissure closure. PAX2 mutations primarily cause optic nerve coloboma and renal hypoplasia (renal coloboma syndrome), while PAX6 mutations lead to various phenotypes including aniridia and coloboma ⁴⁾. CHD7 is a chromatin remodeling factor, and as the causative gene of CHARGE syndrome, it causes multiple organ malformations including ocular coloboma ⁵⁾.

Structure and Function of the Zonule of Zinn

The zonule of Zinn (ciliary zonule) is a bundle of fibers that extends radially from the ciliary body to the equator of the lens, serving to suspend and support the lens within the eye. The fibers are composed of microfibrils primarily made of fibrillin-1 (the protein responsible for Marfan syndrome).

In cases of lens coloboma, the zonule of Zinn is reduced or stretched, leading to unstable lens support. This instability contributes to irregular astigmatism and reduces capsular stability during cataract surgery. When performing anterior capsulotomy (CCC) intraoperatively, the lens may wobble unstably at sites of zonular weakness, increasing the risk of reduced capsulotomy precision. The CTR was developed to address this issue; it is inserted into the capsular bag to support it circularly from within, equalizing the load on the zonule of Zinn.

7. Prognosis and Course

Natural Course

Lens coloboma itself is usually not progressive. The size and shape of the defect often do not change significantly with growth. When a mild lens coloboma exists in isolation, its impact on visual function may be minimal. However, visual prognosis varies greatly depending on the presence and extent of associated colobomas, so the status of comorbid conditions determines the prognosis.

Complications and Prognosis

• Cataract cases: Early cataract surgery can be expected to improve vision. However, due to problems with the zonules of Zinn, surgical risk is high, and thorough preoperative evaluation and preparation are important.
• Choroidal coloboma cases: Visual prognosis is determined by the extent and location of the coloboma (whether it involves the macula or optic nerve). If the defect extends to the macula, significant visual impairment remains. There is a risk of retinal detachment at the edge of the coloboma, requiring long-term follow-up ¹⁾.
• Amblyopia: If early detection and treatment are not performed in pediatric cases, irreversible visual impairment may result. Starting appropriate refractive correction and amblyopia treatment before the critical period of vision (generally around age 10) greatly influences visual prognosis.
• Postoperative IOL decentration/dislocation: Due to the fragility of the zonules of Zinn, there is a risk of IOL decentration or dislocation over the long term after cataract surgery. Regular postoperative follow-up is necessary.

Long-term Management Plan

• Monitor the progression of complications through regular eye examinations (every 6 to 12 months).
• In cases with chorioretinal coloboma, do not omit fundus examinations for early detection of retinal detachment.
• Regularly assess the progression of cataracts and consider surgical indications when visual acuity is affected.
• In pediatric cases, maintaining compliance with amblyopia treatment is important; thorough explanation and support for guardians are required.
• When systemic diseases (such as CHARGE syndrome or renal coloboma syndrome) are present, coordinate management with relevant departments.

8. References

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