Mittendorf dot

Key Points at a Glance

Key Points of This Disease

• Mittendorf dot is a congenital anomaly in which the anterior end of the fetal hyaloid artery fails to regress and remains on the posterior lens capsule.
• It is considered the mildest change in persistent fetal vasculature (PFV).
• Observed as a small, round opacity on the inferonasal side of the posterior lens capsule.
• Found in 1–2% of normal individuals, non-progressive, and usually does not affect vision.
• In premature infants, up to 95% have hyaloid remnants, but only about 3% persist.
• Therapeutic intervention is rarely needed; follow-up with regular eye examinations is recommended.

1. What is Mittendorf dot?

Mittendorf dot is a congenital vascular remnant where the anterior end of the fetal hyaloid artery fails to regress and remains on the posterior lens capsule. It was described by William Frederick Mittendorf.

It is recognized as a small, round opacity in the inferonasal quadrant of the posterior lens capsule. It is present in 1–2% of normal individuals and is non-progressive. In most cases, it does not affect vision.

This condition is part of a group of disorders that occur when the fetal hyaloid vascular system fails to regress, known as persistent fetal vasculature (PFV). PFV includes persistent hyperplastic primary vitreous (PHPV), Bergmeister papilla, persistent hyaloid artery, and persistent pupillary membrane, among others. Mittendorf dot is the mildest change among them.

Traditionally, Mittendorf dot was thought to attach to the posterior lens capsule itself. However, recent reports suggest it may also be located posterior to the lens within the anterior vitreous. It is believed to exist posterior to Erggelet’s space (the space between the posterior lens capsule and the vitreous).

Q I hear it is common in premature infants. Does it persist after growth?

A

In premature infants, up to 95% have some form of vitreous remnant, including Mittendorf dot. However, as infants grow, these usually disappear, and only about 3% persist.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

Mittendorf dot alone usually does not cause subjective symptoms. Since it is a congenital opacity, patients rarely notice floaters. In rare cases where the opacity is large, patients may complain of floaters or blurred vision.

Clinical Findings

Characteristic findings include a white, cord-like remnant of the hyaloid artery with its anterior end attached to the posterior lens capsule and its posterior end floating in the vitreous.

• Location: Observed in the inferonasal quadrant of the posterior lens capsule.
• Size: Small and easily overlooked.
• Morphology: Appears as a round, localized opacity. Rarely, it may present as a large opacity extending over the entire posterior lens capsule.
• Brittle-star formation: When anastomosed with other persistent fetal vessels, it may show a star-shaped morphology called “brittle-star”.

Q Does it affect vision?

A

Mittendorf dot is non-progressive and rarely affects vision alone. However, when associated with extensive PFV, complications such as cataract or vitreous hemorrhage may cause visual impairment. For details, see the “Standard Treatment” section.

3. Causes and Risk Factors

The cause of Mittendorf dot is incomplete regression of the anterior end of the hyaloid artery during the embryonic period.

The normal development and regression of the hyaloid artery follow the process below.

• Embryonic weeks 4–6: The hyaloid artery branches from the internal carotid artery via the dorsal ophthalmic artery. It enters the primary vitreous through the embryonic fissure and reaches the posterior surface of the lens.
• From embryonic week 6 onward: The secondary vitreous forms from the retinal side.
• Embryonic weeks 13–15: Regression of the hyaloid artery begins.
• Late embryonic period to before birth: The hyaloid artery loses function and regresses. The primary vitreous is compressed and remains as the Cloquet canal.

The mechanism of regression is thought to be apoptosis due to a combination of macrophage activation and cessation of blood flow in the hyaloid artery. The signaling pathways controlling regression are not yet fully understood.

VEGF, FGF, angiopoietin 2, tumor suppressor genes, and type 18 collagen are estimated as molecules involved in the onset of PFV.

Prevention and Daily Care

Mittendorf dot is a congenital abnormality and there is no prevention method. Even if pointed out during a child’s eye examination, it is often a benign finding that does not affect visual function. Please follow your doctor’s instructions and undergo regular follow-up.

4. Diagnosis and Examination Methods

Mittendorf dot can be diagnosed by direct observation using slit-lamp microscopy due to its origin. It is identified by a small opacity on the inferonasal side of the posterior lens capsule.

Auxiliary examination methods used when direct observation is difficult are shown below.

Test	Features
B-mode ultrasound	Can detect cord-like structures
OCT angiography	Confirms patency of persistent hyaloid artery
CT/MRI	Visualization of persistent hyaloid artery

When a precorneal lens is used in conjunction with a slit-lamp microscope, it may be possible to directly observe cord-like tissue extending from the posterior lens capsule to the vitreous body.

Differential Diagnosis

Mittendorf dot is the mildest change in PFV, but differentiation from more extensive PFV (persistent hyperplastic primary vitreous) is necessary. When presenting with leukocoria, differentiation from retinoblastoma is important.

• Persistent hyperplastic primary vitreous: Accompanied by microphthalmia and extensive fibrovascular tissue on the posterior lens capsule. Classified into anterior, posterior, and mixed types.
• Retinoblastoma: Confirm intraocular calcification with CT. Usually not associated with microphthalmos.
• Norrie disease / Familial exudative vitreoretinopathy: Differential diagnosis is needed when there is bilateral total retinal detachment or retrolental fibroplasia.

5. Standard Treatment

Mittendorf dot usually does not require therapeutic intervention. It is non-progressive and the prognosis is extremely good.

Regular ophthalmologic examinations (including gonioscopy) for follow-up are recommended.

Rare Complications

Complications from an isolated Mittendorf dot are rare. However, when associated with more extensive PFV, the following complications may occur.

• Vitreous hemorrhage: This may occur when the posterior remnant of the hyaloid artery maintains blood circulation.
• Retinal detachment
• Lens intumescence
• Glaucoma

In anterior PFV, good visual acuity may be achieved with lens surgery and anterior vitrectomy. Posterior and mixed types often involve macular degeneration and have a poor visual prognosis.

Q Is treatment necessary?

A

An isolated Mittendorf dot is non-progressive and generally does not require treatment. Regular ophthalmic examinations are used to monitor the condition. Only in rare cases where complications arise from extensive PFV pathology is intervention such as surgery considered.

6. Pathophysiology and Detailed Mechanism

The hyaloid artery is a temporary vessel that extends from the optic disc to the posterior pole of the lens during fetal development. It supplies nutrients to ocular tissues in early embryogenesis and forms the primary vitreous. From the hyaloid artery, a dense network of intraocular vessels branches and proliferates, anastomosing with the vascular membrane covering the lens (tunica vasculosa lentis).

The regression process of this vascular system is summarized chronologically.

• End of 4th gestational week: Internal carotid artery → dorsal and ventral ophthalmic arteries → hyaloid artery is formed.
• 5–6 weeks of gestation: The hyaloid artery advances through the primary vitreous and reaches the posterior surface of the lens. It anastomoses with the vascular membrane covering the anterior lens surface to form the vascular network around the lens.
• After 6 weeks of gestation: The secondary vitreous forms from the retinal side, surrounding the primary vitreous.
• 13–15 weeks of gestation: Regression of the hyaloid vessels begins.
• Before birth: The hyaloid artery regresses and disappears, leaving the perivascular sheath as Cloquet’s canal.

The basic mechanism of regression is theorized to be macrophage activation followed by apoptosis due to blood flow cessation in the hyaloid artery. The details of the cell signaling leading to macrophage activation are not yet fully understood.

Mittendorf’s dot results from failure of regression of only the anterior end of the hyaloid artery. The anterior end remains as a small white opacity on the posterior lens capsule, while the posterior end floats in the vitreous. In contrast, when the posterior end of the hyaloid artery fails to regress, it remains as Bergmeister’s papilla on the optic disc. Both may be observed in continuity.

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8. References

1. Zeydanli EO, Ozdek S. Persistent Fetal Vasculature: Current Insights and Future Directions. Semin Ophthalmol. 2024;39(8):599-609. doi:10.1080/08820538.2024.2344026. PMID: 38628063. PubMed
2. Prakhunhungsit S, Berrocal AM. Diagnostic and Management Strategies in Patients with Persistent Fetal Vasculature: Current Insights. Clin Ophthalmol. 2020;14:4325-4335. doi:10.2147/OPTH.S236117. PMID: 33335385. PubMed
3. Mehta A, Singh SR, Dogra M, Ram J. Persistent fetal vasculature – Clinical spectrum. Indian J Ophthalmol. 2018;66(12):1860. doi:10.4103/ijo.IJO_1042_18. PMID: 30451201. PubMed
4. Jeon H, Kim J, Kwon S. OCT angiography of persistent hyaloid artery: a case report. BMC Ophthalmol. 2019;19(1):141. doi:10.1186/s12886-019-1155-5. PMID: 31272412. PubMed