Persistent pupillary membrane (PPM) is a congenital anomaly in which the fetal anterior tunica vasculosa lentis fails to disappear, leaving a mesh-like tissue in the pupillary area. PPM is a common congenital anomaly with varying degrees and forms.
It is common, with remnants of the membrane found in about 95% of newborns and about 20% of adults. It is more common in preterm infants, with no sex difference. It may be unilateral or bilateral. Most cases are mild and rarely cause visual impairment. However, severe cases can lead to form deprivation amblyopia.
Persistent pupillary membrane is a rare congenital anomaly, so most past literature consists of case reports and photographs. 1) It is emphasized that optimal visual acuity can be achieved through medical management with mydriatics and full correction with glasses. 1)
Duke-Elder Classification
Type I (Iris attachment type): Membrane attached only to the iris
Type II (Iris-lens adhesion type): Adhesion between the iris and anterior lens capsule. Includes a subtype characterized by pigmented stellate deposits on the anterior lens capsule called “chicken tracks”
Type III (Corneal attachment type): Membrane attached to the cornea. Seen in Axenfeld-Rieger syndrome
Basic Disease Characteristics
Frequency: About 95% of newborns and about 20% of adults
Symmetry: May be unilateral or bilateral
Sex difference: None
Genetics: Mostly sporadic. Familial cases have also been reported
Spontaneous regression: Considerable atrophy within the first year after birth
Persistent pupillary membrane is usually asymptomatic. However, symptoms may appear in the following situations:
Slit-lamp microscopy findings are diverse.
| Finding | Characteristics |
|---|---|
| Strands | One or several lace-like strands partially bridging the pupil. The periphery always attaches to the iris collarette. |
| Pigment stellate deposits | Deposits of iris melanocytes on the anterior lens capsule, also called “chicken tracks.” |
| Extensive membrane | Rarely, an iris membrane sheet occluding the pupil is seen. |
| Hyphema | Rare complication from strands. |
Under mydriasis, check the extensibility of the strand-like tissue and the presence of adhesion to the lens.
Yes, remnants of the pupillary membrane are seen in about 95% of newborns, but in most cases they are mild and regress spontaneously. They usually atrophy considerably within the first year after birth and rarely require treatment. However, if a dense membrane persists beyond one year, spontaneous regression is unlikely, and there is a risk of amblyopia, so ophthalmologic follow-up is necessary.
During the embryonic period, the lens is surrounded by a vascular membrane. Around the 9th week of gestation, mesenchymal cells derived from neural crest cells develop along the anterior surface of the optic cup, forming the anterior tunica vasculosa lentis, which is continuous with the vessels of the iris stroma. As iris development begins around the 12th week of gestation, the anterior tunica vasculosa lentis becomes smaller and forms the pupillary membrane. The pupillary membrane regresses and disappears around the 8th to 9th month of gestation via macrophage phagocytosis.
Remnants that persist after birth are called persistent pupillary membrane.
VEGF (vascular endothelial growth factor) and basic fibroblast growth factor in the aqueous humor decrease with the regression of the pupillary membrane. These factors are suggested to be involved in ocular development, including the persistence of the pupillary membrane. Abnormalities in the process of selective apoptosis of vascular endothelial cells may underlie the persistence of fetal vasculature. 1)
Diagnosis is primarily clinical. Without dilation, the extent and transparency of the membrane covering the pupillary area are assessed. With dilation, the extensibility of the strands and the presence of adhesions to the lens are examined.
Anterior segment optical coherence tomography (OCT) non-invasively obtains cross-sectional images and is useful for visualizing anterior chamber depth, angle width, structural abnormalities of the cornea and iris, and persistent pupillary membrane. 1) In a case from Okayama University, OCT visualized iris processes adhering to the inner surface of the cornea, supporting the diagnosis of Peters anomaly. 1)
| Examination | Purpose |
|---|---|
| Slit-lamp microscopy | Evaluation of distribution, characteristics, and adhesion sites of strands |
| Retinoscopy (skiascopy) | Evaluation of lenticular astigmatism if localized lens opacity is present |
| Anterior segment optical coherence tomography | Evaluation of the relationship between the membrane, lens capsule, and iris. High-resolution OCT visualizes the relationship with the anterior border layer of the iris. 1) |
| High-frequency ultrasound | Evaluation of the relationship between the membrane and lens capsule when there is extensive membrane |
| Iris angiography | Vascular perfusion is only 0.3%. Fluorescein angiography is not indicated in most membranes. |
| Visual acuity and refraction tests | Evaluation for amblyopia and refractive errors |
| Fundus examination | Check for posterior segment complications |
Both may appear together as anterior segment dysgenesis, but they have different embryological origins. Peters anomaly is an anterior segment dysgenesis characterized by central corneal opacity, iridocorneal adhesions, and defects in Descemet membrane and posterior stroma, arising from neural crest-derived mesenchyme. In contrast, persistent pupillary membrane results from incomplete regression of the anterior tunica vasculosa lentis of mesodermal origin. In a case from Okayama University, Peters anomaly and persistent pupillary membrane coexisted in the same eye, but OCT confirmed adhesion of iris processes to the corneal endothelium, supporting the diagnosis of Peters anomaly.
If visual acuity is good, no treatment is needed. However, treatment is considered in the following cases:
Within the first year of life, many pupillary membrane remnants naturally atrophy, so observation is the principle. For persistent dense membranes after one year, the likelihood of spontaneous regression is low, so treatment indications should be considered.
Mydriatics:
Refractive correction and amblyopia treatment:
Elderly patients with a thin, sparse membrane may be candidates for Nd:YAG laser membranotomy. If there is no adhesion between the persistent pupillary membrane and the anterior lens capsule, argon laser or YAG laser goniopuncture may be performed. Rarely, there are risks of hyphema, cataract formation, iritis, and pigment dispersion.
Indications:
Surgical technique (Okayama University):1) The anterior chamber is filled with hyaluronic acid (1%) to maintain anterior chamber space. Scissors are inserted through a side port at the corneal limbus to cut the root of the pupillary membrane on the iris surface. The dissected pupillary membrane is extracted through the side port with 25G forceps. Then, the anterior chamber is irrigated using a 25G vitreous cutter in aspiration mode.
Surgical complications:
Treatment Options
Observation: For good vision and mild symptoms
Mydriatics: To secure the pupillary area and prevent amblyopia. Can be continued long-term from 6 months of age1)
Refractive correction and occlusion: Management of refractive error and amblyopia
Nd:YAG laser: For thin membranes, elderly patients, and no lens adhesion
Surgical excision: For dense membranes, cases with lens adhesion, and infants
Key Points from Okayama University Cases
Case 1: Photophobia as main complaint with good vision. Surgical excision at age 6 → maintained visual acuity 1.2 at age 171)
Case 2: Complicated by Peters anomaly. Deemed not indicated for surgery → mydriatics alone, right eye visual acuity 0.7 at age 121)
Case 3: First symptoms at age 49 due to cataract. Pupillary membrane excision combined with cataract surgery at age 561)
During the fetal period, the tunica vasculosa lentis surrounds the lens and supplies nutrients. It is composed of anterior ciliary arteries and mesenchymal-derived vessels, and anastomoses with the posterior hyaloid vessels on the dorsal side to form the lens vascular membrane.
Involution begins around the 6th month of gestation via macrophage phagocytosis and is complete by the 8th month. During involution:
Impairment of the process by which vascular endothelial cells selectively die via apoptosis is thought to be a factor in persistence. 1)
Pathological examination of excised pupillary membranes from Okayama University cases 1 and 3 revealed vascular structures containing red blood cells within the lumen. 1) This finding histopathologically supports the fact that persistent pupillary membrane is a remnant of the fetal vasculature. 1)
Immunostaining (after melanin removal) showed:
CD31- and retinal electrogram-positive cells were arranged in a fascicular pattern, likely representing longitudinal sections of blood vessels. 1) It has been confirmed that there are no lymphatic vessels in intraocular tissues (lens, iris, ciliary body, retina, choroid), and persistent pupillary membrane is not associated with lymphatic vessels. 1)
The pupillary membrane arises from mesodermal vascular elements, whereas the iris stroma and anterior border layer arise from neural crest-derived mesenchyme. Although they originate from different germ layers, structural associations are observed due to anatomical proximity during embryonic development. 1)
Optical coherence tomography of the anterior segment is increasingly useful for non-invasive evaluation of persistent pupillary membrane. 1) High-resolution OCT may detect abnormalities in the iris layers, particularly signal attenuation in the anterior border layer of the iris. 1) Future high-resolution anterior segment OCT with intensity mapping may clarify the correlation with histological features of persistent pupillary membrane. 1)
A case report from Okayama University demonstrated that a personalized approach is essential for managing persistent pupillary membrane, a rare congenital anomaly. 1) Whether surgery, mydriatic agents, or observation is appropriate depends on the patient’s age, visual acuity, complications, and the extent of the membrane. A strict risk-benefit assessment is necessary when considering surgical indications. 1)
Immunostaining findings using CD31 and electroretinogram markers confirmed that persistent pupillary membrane possesses true vascular structures. 1) Deeper understanding of the regression regulatory mechanisms via vascular endothelial growth factor and basic fibroblast growth factor may lead to future exploration of pharmacologically induced regression.
The main risk of surgical excision is cataract formation due to damage to the anterior lens capsule. In children, the lens is soft, and extreme care is needed to avoid injuring the lens capsule during scissor manipulation. Other risks include intraocular inflammation, elevated intraocular pressure, and postoperative infection. In the Okayama University case, safe excision was achieved by filling the anterior chamber with hyaluronic acid to maintain space during surgery. When visual acuity is good, the necessity of surgery and the risk of complications must be carefully considered.
