Flat Nevus
Appearance: Flat pigmentation on the iris surface
Elevation: None to very slight
Characteristics: The most common type. It appears as shades of pigment spreading along the iris surface.
Iris Nevus
Key points at a glance
Section titled “Key points at a glance”1. What is Iris Nevus?
Section titled “1. What is Iris Nevus?”Iris nevus is a benign pigmented tumor caused by proliferation of melanocytes in the iris. Macroscopically, it appears as a dark brown to brown pigmented lesion on the iris. It is usually stationary (non-growing) and malignant transformation is extremely rare; in most cases, only observation is needed. A large study of 1611 cases reported that transformation from iris nevus to malignant melanoma occurred in 2.6% at 5 years and 4.1% at 10 years, indicating a generally stable long-term course [1].
Iris malignant melanoma is a rare tumor arising from the iris among uveal malignant melanomas, and it is often less malignant than intraocular malignant melanomas originating from the choroid or ciliary body. Differentiation between iris nevus and iris malignant melanoma is based on size, presence of growth, and irregularity of shape.
It is more common in Caucasians and tends to occur in people with lightly pigmented irises (blue, green, gray). It is often found in middle-aged and older individuals, but can also occur in younger people. Most cases are asymptomatic and are discovered incidentally during eye examinations or examinations for other diseases.
Q
I was told I have something like a mole on my iris. Is it dangerous?
A
In most cases, it is a benign iris nevus, and malignant transformation is extremely rare. However, if growth, change in shape, vision changes, or eye pain occur, it is important to see an ophthalmologist promptly. Regular eye examinations can detect any changes early.
2. Main Symptoms and Clinical Findings
Section titled “2. Main Symptoms and Clinical Findings”
Boldu-Roig J, Sorli-Clemente E, Kuljuh-Causevic A, Loras A, Anton A, Martinez-Cadenas C. Iris Pigmented Lesions: Unraveling the Genetic Basis of Iris Freckles and Nevi. Invest Ophthalmol Vis Sci. 2025;66(4):62. Figure 1. PMCID: PMC12020957. License: CC BY 4.0.
Examples of pigmented elements of the iris in six participants photographed with a slit-lamp biomicroscope; (B) nevus on brown iris, (C) nevus (black arrow) and freckle (orange arrow) on blue iris, (D) nevus (black arrow) and freckle (orange arrow) on green iris. These correspond to the color, shape, and clinical appearance of iris nevi discussed in section “2. Main Symptoms and Clinical Findings.”
Subjective Symptoms
Section titled “Subjective Symptoms”Iris nevi are usually asymptomatic, and cosmetic concerns (changes in iris color or pattern) are often the main complaint. If infiltration occurs in the angle (the drainage pathway of intraocular fluid), it can lead to increased intraocular pressure, and eye pain or decreased vision may appear.
Clinical Findings (Findings Confirmed by a Physician)
Section titled “Clinical Findings (Findings Confirmed by a Physician)”The main findings observed with a slit lamp microscope are as follows:
- Color: Dark brown to brown (may also be yellowish brown)
- Location: Occurs at the pupillary margin or any part of the iris
- Margin: Usually well-defined
- Surface: May be smooth or nodular
- Growth: Usually not observed (stationary)
Classification by Morphology
Section titled “Classification by Morphology”Iris nevi are classified into the following three types based on morphology:
Elevated Nevus
Appearance: A lesion clearly elevated from the iris surface
Elevation: Present
Features: May require differentiation from iris malignant melanoma. Regularly check for growth.
Nodular Type
Appearance: A small nodular pigmented lesion near the pupillary margin
Elevation: Elevated as a small nodule
Features: Requires differentiation from pigmented nodules on the iris seen in Cogan-Reese syndrome.
Findings Suggesting Malignant Transformation
Section titled “Findings Suggesting Malignant Transformation”If the following findings are observed, consider the possibility of transformation to iris malignant melanoma or a malignant lesion, and further examination is necessary. Shields et al. organized the risk of malignant transformation of iris nevus into six items (ABCDEF: Age ≤40 years, Blood [hyphema], Clock hour [inferior 4–9 o’clock position], Diffuse, Ectropion uveae, Feathery margin), which is widely used as a clinical decision indicator [1].
- Rapid enlargement (confirmed by serial photographic comparison)
- Angle invasion/angle clouding (evaluated by gonioscopy and anterior segment OCT)
- Iris rubeosis (appearance of iris neovascularization)
- Local inflammatory reaction (hyperemia, anterior chamber inflammatory cells)
- Hemorrhage (hyphema, vitreous hemorrhage)
3. Causes and Risk Factors
Section titled “3. Causes and Risk Factors”Iris nevus is caused by benign proliferation of melanocytes that make up the iris. Many details of the mechanism of occurrence remain unclear.
The main risk factors include the following:
- Light-colored iris: More common in Caucasians with blue, green, or gray irises. In irises with less pigment, changes in melanocytes are thought to become more apparent. In a population study of 1014 cases, the frequency of iris nevus was 4-6% in adults, associated with aging, female sex, green iris, and pigmentary cataract, and involvement of pigment-related gene mutations such as IRF4 and HERC2 has been reported [3].
- Aging: More common after middle age. However, it can also occur in younger individuals.
- Risk of morphological abnormality increase: The risk of malignant transformation of an existing iris nevus is very low. Growth rate, irregular shape, and angle invasion are suggestive findings of malignancy.
As a rare association, an association with BAP1 tumor predisposition syndrome has been reported. Families with BAP1 gene mutations are thought to have an increased risk of uveal melanoma, and caution may be needed in the observation of iris nevi.
4. Diagnosis and Examination Methods
Section titled “4. Diagnosis and Examination Methods”Slit-lamp Microscopy
Section titled “Slit-lamp Microscopy”The basic diagnostic test for iris nevus is detailed observation of the anterior segment using a slit-lamp microscope. Record the size, color, shape, borders, and degree of elevation of the lesion. Taking high-resolution photographs regularly and tracking changes over time is the core of management.
Anterior Segment OCT
Section titled “Anterior Segment OCT”Anterior segment OCT is a useful test for quantitatively evaluating the depth and height of iris nevi. It can quantify tumor thickness and width and objectively record changes over time. Combined with slit-lamp photography, early detection of growth is possible. Anterior segment OCT has been reported to capture 96% of iris melanocytic tumors, and for evaluating pure iris tumors, it is a useful non-contact and simple method, while UBM is superior for detecting ciliary body invasion [4].
Ultrasound Biomicroscopy (UBM)
Section titled “Ultrasound Biomicroscopy (UBM)”Ultrasound biomicroscopy (UBM) is useful for evaluating invasion of the ciliary body and angle using anterior segment ultrasound. It is performed when a raised iris nevus or extension to the ciliary body is suspected. It assesses the presence and extent of angle invasion and evaluates glaucoma risk.
Intraocular Pressure Measurement
Section titled “Intraocular Pressure Measurement”When an iris nevus invades the angle, pigment dispersion to the trabecular meshwork can cause elevated intraocular pressure. Regular intraocular pressure measurement enables early detection of secondary glaucoma.
Differential Diagnosis
Section titled “Differential Diagnosis”Important differential diagnoses of iris nevus are shown in the table below.
| Disease | Key Points for Differentiation |
|---|---|
| Iris malignant melanoma | Rapid growth, irregular shape, ciliary body invasion, angle seeding, rubeosis iridis. May be small and locally resectable. |
| Cogan-Reese syndrome | Unilateral pigmented nodules on the iris with pigmentation, accompanied by slowly progressive peripheral anterior synechiae and glaucoma. A variant of the iridocorneal endothelial syndrome. |
| Metastatic iris tumor | Often white to milky white in color. May be multiple. Check history of primary tumor in other organs. |
| Juvenile xanthogranuloma (JXG) | Common in infants and young children. Yellow to orange iris nodules. May present with hyphema. |
Cogan-Reese syndrome is characterized mainly by pigmented nodular elevated lesions or pigmentation on the iris of one eye, resembling iris nevus, and gradually causes peripheral anterior synechiae leading to glaucoma. Morphologically, it is difficult to distinguish from iris nevus, and sometimes differentiation from malignant melanoma is necessary.
Q
How to differentiate iris nevus from iris melanoma?
A
If there is rapid enlargement, irregular shape or indistinct borders, angle infiltration, iris rubeosis (iris neovascularization), local inflammatory reaction, or hemorrhage, iris malignant melanoma should be suspected. Combine quantitative evaluation with anterior segment OCT/UBM and regular photographic documentation, and consider referral to an ocular oncology center if changes are observed.
5. Standard Treatment
Section titled “5. Standard Treatment”Small, Stable Iris Nevus
Section titled “Small, Stable Iris Nevus”For small iris nevi without enlargement, observation is the basic policy. Regular slit-lamp photographic documentation tracks changes in lesion size and shape. Combining quantitative evaluation with anterior segment OCT allows objective recording of even minute changes.
General guideline for observation intervals (may vary depending on facility policy):
- Re-evaluate 3 to 6 months after initial observation; if no change, continue regular observation every 6 to 12 months thereafter.
- If changes occur, shorten the observation interval and consider further examination and treatment.
When There Is a Tendency to Enlarge or Findings Suggesting Malignancy
Section titled “When There Is a Tendency to Enlarge or Findings Suggesting Malignancy”If findings suggest malignancy, referral to an ocular oncology center is appropriate. The following treatments may be selected.
- Local resection (iridectomy): Chosen when the tumor is relatively small and localized. Pathological examination of the resected specimen provides a definitive diagnosis.
- Biopsy: Performed when resection is difficult or a definitive diagnosis is needed.
Iris malignant melanoma is often less malignant than intraocular malignant melanoma originating from the choroid or ciliary body, but appropriate management is necessary due to the risk of infiltration and metastasis. Iris malignant melanoma accounts for about 4% of uveal malignant melanoma, with reported mean tumor diameter at diagnosis of 5.5 mm, seeding in 28%, and secondary glaucoma in 35%, highlighting the importance of early management [2].
Cases with Glaucoma
Section titled “Cases with Glaucoma”If secondary glaucoma due to angle infiltration is present, glaucoma treatment should be performed concurrently. Topical medication for intraocular pressure control is the first choice; if control is poor, surgical therapy should be considered.
Prognosis
Section titled “Prognosis”Most iris nevi follow a benign course. Malignant transformation is very rare, and it is important to detect changes early through regular follow-up. If no growth or morphological changes are observed, the condition often remains stable over the long term.
6. Pathophysiology and Detailed Mechanisms
Section titled “6. Pathophysiology and Detailed Mechanisms”Benign Proliferation of Melanocytes
Section titled “Benign Proliferation of Melanocytes”Iris nevi are formed by benign proliferation of melanocytes in the iris stroma. Melanocytes are cells that produce pigment (melanin) and determine the color of the iris. In nevi, cell proliferation is localized and does not show invasive growth, which is the essential difference from malignant lesions.
Most iris nevi are stationary, but rarely they may undergo malignant transformation to iris malignant melanoma. The mechanism of malignant transformation is thought to involve molecular abnormalities such as GNAQ/GNA11 mutations found in uveal melanoma overall, but many details of the specific malignant transformation mechanism of iris nevi remain unknown.
Effects on the Angle
Section titled “Effects on the Angle”Pigment granules shed from an iris nevus may be dispersed into the angle (anterior chamber angle). When these dispersed pigments deposit on the trabecular meshwork (the intraocular aqueous humor drainage pathway), outflow resistance may increase, leading to elevated intraocular pressure. Secondary glaucoma due to this mechanism can be detected early by intraocular pressure measurement and regular gonioscopy.
Pathophysiology of Cogan-Reese Syndrome
Section titled “Pathophysiology of Cogan-Reese Syndrome”Cogan-Reese syndrome is a type of iridocorneal endothelial (ICE) syndrome. ICE syndrome is a unilateral disease common in middle-aged women and is classified into three types: essential iris atrophy, Chandler syndrome, and Cogan-Reese syndrome [5]. Abnormally proliferated corneal endothelial cells cover the anterior surface of the iris, and compression or traction on the iris forms nodular lesions resembling iris nevi and pigmentation. Gradually, peripheral anterior synechiae progress, leading to glaucoma. Morphologically, it may be difficult to distinguish from iris nevi; evaluation of corneal endothelial cell abnormalities (by specular microscopy) aids in differentiation [5].
7. Latest Research and Future Perspectives
Section titled “7. Latest Research and Future Perspectives”Quantitative observation using anterior segment OCT
Section titled “Quantitative observation using anterior segment OCT”Quantitative longitudinal evaluation of iris nevi using anterior segment OCT is attracting attention as a method to objectively capture minute changes in tumor thickness, width, and volume. Compared to conventional slit-lamp photography, it may reduce inter-observer variability and enable early detection of growth.
Development of diagnostic criteria
Section titled “Development of diagnostic criteria”Establishment of quantitative criteria to accurately differentiate iris nevi from iris malignant melanoma based on imaging findings is needed. Development of risk stratification criteria specific to iris lesions, similar to the TFSOM-UHHD criteria for choroidal nevi, is considered a future challenge.
Accumulation of epidemiological data
Section titled “Accumulation of epidemiological data”Large-scale, long-term data on the prevalence and malignant transformation rate of iris nevi are limited, and accumulation of epidemiological data, especially in Asian populations, is needed. Multi-center, long-term cohort studies are required to identify risk factors for malignant transformation and determine optimal follow-up intervals.
8. References
Section titled “8. References”- Shields CL, Kaliki S, Hutchinson A, et al. Iris nevus growth into melanoma: analysis of 1611 consecutive eyes: the ABCDEF guide. Ophthalmology. 2013;120(4):766-772. PMID: 23290981.
- Cherkas E, Kalafatis NE, Marous MR, Shields CL. Iris melanoma: Review of clinical features, risks, management, and outcomes. Clin Dermatol. 2024;42(1):62-70. PMID: 37865279.
- Boldu-Roig J, Sorli-Clemente E, Kuljuh-Causevic A, Loras A, Anton A, Martinez-Cadenas C. Iris Pigmented Lesions: Unraveling the Genetic Basis of Iris Freckles and Nevi. Invest Ophthalmol Vis Sci. 2025;66(4):62. PMID: 40261663. PMCID: PMC12020957.
- Razzaq L, Emmanouilidis-van der Spek K, Luyten GPM, de Keizer RJW. Anterior segment imaging for iris melanocytic tumors. Eur J Ophthalmol. 2011;21(5):608-614. PMID: 21218392.
- Das S, Tripathy K. Iridocorneal Endothelial Syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. PMID: 37603618.