Bulging Type
Appearance: Dome-shaped or spherical bulging pigmented cysts.
Surface: Smooth and glossy, with the lumen visible through the wall.
Position: Protrudes hanging down from the pupillary margin and is exposed in the anterior chamber.
Iris mammillations
Key Points at a Glance
Section titled “Key Points at a Glance”1. What is Iris Flocculus?
Section titled “1. What is Iris Flocculus?”Iris flocculus is a congenital benign cystic lesion that occurs at the pupillary border of the iris. The term “flocculus” is derived from the Latin word floccus, meaning “tuft of wool,” describing its tufted appearance.
The lesion is essentially an iris pigment epithelium (IPE) cyst that undergoes cycles of collapse and reformation. Therefore, both an inflated spherical or teardrop appearance and a deflated flat or atrophic appearance can be observed. When multiple cysts align along the pupillary border, they form a characteristic wrinkled tufted structure.
The lesion is usually benign and rarely causes visual impairment. However, associations with mutations in smooth muscle-related genes such as ACTA2 (smooth muscle alpha-actin 2) and MYH11 (smooth muscle myosin heavy chain) have been reported. Clinically, it is important to note that patients with these mutations have a risk of developing life-threatening thoracic aortic aneurysm and dissection (TAAD).
The ICD-10 code is H21.5 (cyst of iris).
Q
Is iris flocculus a rare disease?
A
This is a relatively rare disease, with both sporadic and familial forms. A report indicated that only 6 out of 100 patients with ACTA2 gene mutations had iris flocculi, suggesting it is not frequently observed among all mutation carriers.
2. Main Symptoms and Clinical Findings
Section titled “2. Main Symptoms and Clinical Findings”Subjective Symptoms
Section titled “Subjective Symptoms”Most patients are asymptomatic. When symptoms occur, the following have been reported.
- Decreased vision and darkening of the visual field: Occurs when the cyst enlarges and obstructs the visual axis. It often progresses gradually.
- Photophobia (sensitivity to light): Caused by optical interference from the cyst.
- Accommodation disorder: In smooth muscle dysfunction associated with ACTA2 mutation, loss of accommodation may occur.
- Miosis failure: Similarly, due to smooth muscle dysfunction, congenital mydriasis may be present.
Clinical Findings
Section titled “Clinical Findings”Slit-lamp examination reveals bilateral tuft-like protrusions aligned along the pupillary margin.
Collapsed type
Appearance: Flat or atrophic, wrinkled cyst wall.
Surface: Irregular wrinkles with noticeable pigmentation.
Dynamics: Repeated collapse and re-expansion may cause the morphology to differ at each examination.
On ultrasound biomicroscopy (UBM), it appears as an anechoic cyst arising from the iris. If the cyst is large, it may contact the corneal endothelium. Anterior segment optical coherence tomography (AS-OCT) is also useful for evaluating cyst structure.
Complications may include secondary glaucoma if the cyst reaches the angle, and localized corneal edema if contact with the corneal endothelium is prolonged.
In a case report by Reddens et al., a 21-year-old male (Patient 1) and a 24-year-old female (Patient 2), who were siblings, presented with bilateral iris microcysts. In the right eye of Patient 1, a large cyst covered the upper half of the pupil, and ultrasound biomicroscopy confirmed contact of the cyst with the corneal endothelium. Patient 2 had an even larger cyst in the right eye that occluded the pupil, and best-corrected visual acuity decreased to 20/50 1).
3. Causes and Risk Factors
Section titled “3. Causes and Risk Factors”Pathogenesis
Section titled “Pathogenesis”The mechanism of iris microcyst formation is thought to involve cyst formation due to dissociation between the two layers of the iris pigment epithelium (IPE). The cyst repeatedly collapses and reforms, presenting a characteristic morphology along the pupillary margin.
Genetic Background
Section titled “Genetic Background”Iris flocculi are usually sporadic, but familial variants have also been reported. Associations with the following genes have been reported.
- ACTA2 (smooth muscle alpha-actin 2): Encodes an actin isoform that controls smooth muscle in the aorta. Mutations are associated with multisystem smooth muscle dysfunction syndrome characterized by familial TAAD, iris flocculi, congenital mydriasis with accommodative dysfunction, and patent ductus arteriosus. ACTA2 mutations account for approximately 14% of familial TAAD.
- MYH11 (smooth muscle myosin heavy chain): Encodes smooth muscle myosin heavy chain. Similar to ACTA2, it affects smooth muscle in the aorta and iris.
In the cases reported by Reddens et al., a pathogenic ACTA2 gene mutation (c.445C>T, p.Arg149Cys) was identified in both patients 1 and 2 and their biological mother. This mutation has been repeatedly reported in families characterized by TAAD, premature coronary artery disease, iris flocculi, and livedo reticularis1).
Patient 2 exhibited cutaneous livedo reticularis (livedo reticularis). This is useful as an auxiliary clinical sign of ACTA2 mutation1).
Systemic Risk
Section titled “Systemic Risk”The overall penetrance of aortic events due to ACTA2 mutations is reported to be approximately 48%, with a cumulative risk of aortic events by age 85 estimated to reach 75% 1).
Q
Are people with iris mammillations more likely to develop aortic disease?
A
Not necessarily, but associations between ACTA2 or MYH11 gene mutations and iris mammillations have been reported, and these mutations increase the risk of aortic aneurysm and aortic dissection. If iris mammillations are found, cardiac evaluation and genetic testing should be considered. In the case reported by Reddens et al., only the sister among siblings had aortic valve abnormality, suggesting that even with the same mutation, phenotypes may differ 1).
4. Diagnosis and Examination Methods
Section titled “4. Diagnosis and Examination Methods”Clinical Diagnosis
Section titled “Clinical Diagnosis”Diagnosis is based on direct observation with a slit-lamp microscope. Key findings include bilateral frond-like structures along the pupillary margin and temporal changes between the distended and collapsed types.
Imaging Tests
Section titled “Imaging Tests”- Ultrasound Biomicroscopy (UBM): Evaluates the morphology, size, and positional relationship of the cyst with the angle and corneal endothelium. In the case reported by Reddens et al., UBM confirmed that the cyst in the right eye of patient 1 was in contact with the corneal endothelium, providing a basis for treatment intervention1).
- Anterior Segment Optical Coherence Tomography (AS-OCT): Non-invasively visualizes the structure of the cyst.
Genetic Testing
Section titled “Genetic Testing”Testing using a 15-gene panel including ACTA2 is performed. In the case reported by Reddens et al., panel testing was conducted at a certified clinical laboratory accredited by Accreditation Canada and in accordance with ACMG guidelines 1).
Cardiac Evaluation
Section titled “Cardiac Evaluation”Transthoracic echocardiography is recommended to evaluate the aortic valve and ascending aorta. In the case reported by Reddens et al., patient 2 was found to have a bicuspid aortic valve with fusion of the left and right coronary cusps and mild dilation of the ascending aorta (3.4 cm) 1).
Differential Diagnosis
Section titled “Differential Diagnosis”| Disease | Features | Key Differentiating Points |
|---|---|---|
| Iris pigment epithelial cyst | Common at the iris root | Differentiated by location and shape |
| Iris stromal cyst | Common after trauma or surgery | Differentiated by history and ultrasound biomicroscopy |
| Lisch nodules | Neurofibromatosis type 1 | Systemic findings/solid nodules |
| Iris melanoma | Solid/tendency to enlarge | Shape/growth rate |
Q
Is genetic testing essential for diagnosing iris mammillations?
A
Clinical diagnosis is possible based on slit-lamp microscopy findings, but genetic testing is recommended for all cases to confirm the presence of mutations in ACTA2 or MYH11 genes. If a mutation is confirmed, cardiac evaluation and genetic counseling for the patient and family are necessary 1).
5. Standard Treatment
Section titled “5. Standard Treatment”Observation
Section titled “Observation”For cases without visual symptoms, observation is the principle. If there is no hyphema, corneal opacity, ocular inflammation, or elevated intraocular pressure, ophthalmic follow-up every 6 months is considered a guideline. Cysts may fluctuate naturally and may resolve spontaneously.
Laser Treatment
Section titled “Laser Treatment”Intervention is considered when visual symptoms occur or when contact with the corneal endothelium is confirmed by ultrasound biomicroscopy. A stepwise approach from less to more invasive treatment options is recommended.
Nd:YAG laser is positioned as the least invasive treatment. It improves visual symptoms by disrupting and shrinking the cyst wall. In the case by Reddens et al., a single session (energy: 1.0 mJ, single shot) disrupted the wall of the largest cyst, resulting in immediate cyst shrinkage and visual improvement. No postoperative intraocular pressure spike was observed, but pigment dispersion into the anterior chamber was noted. Stability was maintained during 2 years of follow-up1).
In two cases by Reddens et al. (2025), after Nd:YAG laser treatment, both patients experienced improvement in visual discomfort, and the corrected visual acuity in the right eye of patient 2 improved from 20/50 to 20/25. No recurrence was observed at the 2-year follow-up1).
Surgical Treatment
Section titled “Surgical Treatment”If laser treatment is ineffective or if angle compression or corneal opacity progresses, fine-needle aspiration or surgical excision may be considered.
Systemic Management
Section titled “Systemic Management”For patients with confirmed ACTA2 mutations, cardiac imaging at least once a year is recommended based on a diagnostic flowchart according to patient age1).
6. Pathophysiology and Detailed Pathogenesis
Section titled “6. Pathophysiology and Detailed Pathogenesis”The iris flocculus is essentially an iris pigment epithelium (IPE) cyst, formed by dissociation between the two layers of the IPE (anterior and posterior epithelial layers), creating a cystic cavity. The cyst repeatedly collapses and reforms, so its appearance varies depending on the time of observation even in the same patient.
The ACTA2 gene encodes α-actin in vascular smooth muscle and is involved in the function of the iris sphincter and aortic wall smooth muscle. MYH11 encodes myosin heavy chain and regulates the contraction-relaxation functional unit. Mutations in these genes are thought to cause contractile dysfunction of the iris smooth muscle and structural weakness of the aortic wall.
The former produces ocular symptoms such as iris flocculi, accommodative dysfunction, and congenital mydriasis, while the latter causes cardiovascular abnormalities including thoracic aortic aneurysm/dissection (TAAD), premature coronary artery disease, and patent ductus arteriosus.
In the case reported by Reddens et al. (2025), among siblings with the same ACTA2 pathogenic variant (c.445C>T, p.Arg149Cys), only the sister showed aortic valve abnormalities (bicuspid aortic valve, mild ascending aortic dilation). The difference in phenotype despite the same variant suggests the involvement of other unidentified genetic variants1).
Additionally, a variant of uncertain significance in the FBN2 gene (c.6439G>A, p.Asp2147Asn) was identified in patient 2, but its clinical significance is unknown1).
7. Latest Research and Future Prospects
Section titled “7. Latest Research and Future Prospects”Phenotypic Diversity of Genetic Mutations
Section titled “Phenotypic Diversity of Genetic Mutations”Even with the same ACTA2 mutation (e.g., p.Arg149Cys), the presence and severity of aortic changes can vary within families, and research into modifier genes continues. MYH11 and other genes may be involved in phenotypic diversity1).
Need for Systematic Screening
Section titled “Need for Systematic Screening”There is growing opinion that all patients with iris mammillations should undergo screening to evaluate for aortic changes. The European Reference Network for Rare Vascular Diseases (VASCERN) has published a consensus statement on the management of patients with ACTA2 pathogenic variants 1).
Long-term laser treatment outcomes
Section titled “Long-term laser treatment outcomes”Data on long-term management with Nd:YAG laser are limited, and large case series are needed. Existing reports show stability for over two years 1), but protocols for additional treatment upon recurrence have not been established.
8. References
Section titled “8. References”- Redden LD, Lakosha H, Riaz KM. Successful treatment of bilateral familial iris flocculi associated with aortic valve abnormalities. American journal of ophthalmology case reports. 2025;39:102386. doi:10.1016/j.ajoc.2025.102386. PMID:40718499; PMCID:PMC12296538.
- Brisson R, Stålhammar G. Iris Flocculus. Ophthalmol Retina. 2024;8(11):e37. PMID: 38613528.
- Ueberroth JA, Ratanasit A, Grunstein L. Spontaneous Hyphema from Dislocation of an Iris Pigment Epithelium Flocculus. Ophthalmology. 2024;131(2):248. PMID: 37318414.