An anomalous iris finding: A case of Wölfflin nodules
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Wölfflin nodules are light-colored, peripheral iris nodules that are found in 10% of healthy individuals and almost exclusively in patients with light irides.
The nodules are a variant of Brushfield spots, which have a known association with Down syndrome. Wölfflin nodules have no confirmed association to systemic conditions, but recent research has found a possible link to psychological conditions like schizophrenia (Schmidt I).
Case report
A 53-year-old white man presented for his eye exam with complaints of blurred near vision. Medical history included insomnia and depression, for which he received no treatment. He was a former smoker. Ocular history was unremarkable — this was his first comprehensive eye exam — and family ocular history was unremarkable.
Best corrected visual acuity was 20/20 in each eye. Ocular motilities, pupils and confrontation visual fields were all normal. Slit lamp examination revealed blue irides with yellow-white nodules in a circumferential pattern in the peripheral iris of each eye. Anterior segment exam was otherwise unremarkable, and IOP was 20 mm Hg in each eye.
Dilated fundus examination revealed a cup-to-disc ratio of 0.55, flat macula, normal vasculature and intact peripheral retina in each eye. Optic nerve OCT was performed due to borderline pressure with moderate optic nerve cupping and revealed healthy retinal nerve fiber layer in each eye.
The nodules were photographed, and the patient was asked to return in 6 months to monitor. Anterior segment OCT and ultrasound biomicroscopy of the lesions will be considered to monitor for size and depth at that time. The patient also was referred for mental health services for his insomnia and depression.
Discussion
Wölfflin nodules are composed of condensed collagen with atrophy of the iris stromal layer. Nodules become visible after the development of the iris stroma, usually within the first year of life, and the initial presentation typically remains unchanged. There is no association with corneal, conjunctival or other anterior segment abnormalities; the nodules are often found in eyes that are “white and quiet.”
They are often bilateral, with 10 to 20 elevated nodules in the peripheral iris of each eye. They appear whitish or yellow in light irides and tan in brown eyes and can be round, oval, star-shaped or triangular and range in size from 0.1 mm to 2 mm. Less commonly, they appear as numerous, tiny nodules arranged regularly near the iris root or as rod-shaped spots close to the pupillary margin. Different variations of nodules may present concurrently in one or both eyes.
Wölfflin nodules can be classified as category 1, or no nodules; category 2, with nodules that extend less than 180 degrees around the iris; or category 3, with nodules that extend more than 180 degrees around the iris. The iris feature classification system established by Edwards and colleagues also can be used to document iris crypts, contractures, pigmented lesions and nodules. Photographs also are ideal for documenting iris nodule presentation.
Although Wölfflin nodules are considered rare and associated with light-colored irides, newer studies suggest that prevalence may be underestimated, as they are difficult to detect in dark irides (Schmidt I). The heavier pigment of dark irides may mask the iris trabeculae and the contraction needed for full nodule formation.
Wölfflin nodules in heavily pigmented eyes also may be obscured by melanin. A study that used near-infrared light to identify Wölfflin nodules found that 19% were found in dark colored irides (Postolache L, et al).
A relationship between the PAX6 gene, which regulates iris stromal adhesion and influences variability in iris crypts and furrows, and the anterior cingulate cortex has recently been established, which suggests a relationship between iris characteristics and brain function (Trixler D, et al). PAX6 mutations within a family have been linked to higher rates of unusual behavior, impulsive behavior, impaired social understanding and impaired verbal inhibition.
Trixler and colleagues studied iris structure in schizophrenia and found that Wölfflin nodules were seen significantly more often in patients with schizophrenia, the proposed mechanism being a shared ectodermic origin of the iris and extension of the brain.
Differentials
Like Wölfflin nodules, Brushfield spots are variably sized — 0.1 mm to 1 mm — but appear as coalesced, mottled or marbled whitish to yellow pinpoint nodules on the outer two-thirds of the iris periphery. Brushfield spots occur at the junction of the middle and outer third of the iris, while Wölfflin nodules typically are located at the junction of the outer four-fifths of the iris and tend to be smaller and arranged in a more regular formation. Brushfield spots are often present at birth and are commonly associated with Down syndrome in 90% of cases. Although iris hypoplasia is common in 80% to 95% of those with Brushfield spots, only 9% have been seen with Wölfflin nodules (Brooke Williams RD).
Other differentials for iris nodules include Lisch nodules, Koeppe nodules, Busacca nodules and iris mammillations. Lisch nodules are melanocytic hamartomas associated with neurofibromatosis type 1 and are present in roughly 90% to 100% of patients with the disease (Senthilkumar VA, et al). They are brown and have a dome shape. Their presence, along with café au lait skin spots in adolescence, can be the first indicators of neurofibromatosis. This condition is autosomal dominant and characterized by hamartomas of neural crest-derived tissue.
Koeppe and Busacca nodules are a result of ocular inflammation and are located at the pupil border and on the iris surface, respectively. While Koeppe nodules can be present in nongranulomatous or granulomatous uveitis cases, Busacca nodules are only present in granulomatous cases. The nodules usually resolve after treatment.
Iris mammillations are small, dark brown domelike lesions on the anterior surface of the iris. They can be uniform or increase in size as they approach the pupil border. These lesions can be found in patients with darker irides diagnosed with ocular melanocytosis, oculodermal melanosis or as an isolated finding.
This case reminds practitioners to be cognizant of iris nodule presentations so appropriate recommendations can be made.
References:
- Antoniolli LP, et al. An Bras Dermatol. 2021;doi:10.1016/j.abd.2020.09.007.
- Brooke Williams RD. Dev Med Child Neurol. 1981;doi:10.1111/j.1469-8749.1981.tb02047.x.
- Busacca nodules. https://www.columbiaeye.org/education/digital-reference-of-ophthalmology/cornea-external-diseases/non-infectious/bussaca-nodules. Accessed Feb. 8, 2022.
- Edwards M, et al. R Soc Open Sci. 2016;doi:10.1098/rsos.150424.
- Gündüz K, et al. Arch of Ophthalmol. 2000;doi:10.1001/archopht.118.5.716.
- Postolache L, et al. Sci Rep. 2018;doi:10.1038/s41598-018-36348-6.
- Ragge NK, et al. Eye. 1996;doi:10.1038/eye.1996.13.
- Schmidt I. Optom Vis Sci. 1971;doi:10.1097/00006324-197107000-00006.
- Senthilkumar VA, Tripathy K. Lisch Nodules. StatPearls Publishing; 2023.
- Shaikh N, et al. Indian J Ophthalmol. 2019;doi:10.4103/ijo.IJO_2105_18.
- Trixler D, et al. Psychiatry Res. 2017; doi:10.1016/j.psychres.2017.07.004.
For more information:
Danielle Kalberer, OD, MBA, FAAO, practices at the Northport VA Medical Center in Northport, New York. Chanpreet Kataria, OD, practices at The Eye Center of Northern Virginia. Shephali Patel, OD, MS, FAAO, is residency supervisor at Northport VA Medical Center and an adjunct associate clinical professor at State University of New York College of Optometry.
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