Aniridic fibrosis syndrome (AFS) is a rare complication that occurs after intraocular surgery in patients with congenital aniridia 1).
A fibrous membrane forms from the rudimentary iris root and can extend to the intraocular lens, ciliary body, and anterior retina. In 2005, Tsai et al. first reported 7 eyes of 6 patients as “progressive anterior segment fibrosis syndrome after surgery in congenital aniridia” 1). As of the case report (Banifatemi et al. 2024) underlying this article, only 19 cases have been reported worldwide 1).
Congenital aniridia is a pan-ocular disease characterized by partial to complete absence of iris tissue 1).
The incidence is reported to be 1:64,000 to 1:96,000 1). 90% of cases are due to mutations in the PAX6 gene (11p13), with an autosomal dominant inheritance pattern (high penetrance) 1). Two-thirds of cases are familial, and one-third are sporadic 1).
Congenital aniridia presents with various ocular complications in addition to iris defects.
| Ocular Complications | Incidence |
|---|---|
| Corneal stem cell exhaustion / corneal opacity | 78–96% |
| Dry eye | 56–95% |
| Nystagmus | 64–95% |
| Macular hypoplasia | 79–86% |
| Cataract | 50–85% |
| Glaucoma | 46–70% |
| Lens subluxation | 42% |
| Optic nerve hypoplasia | 11–29% |
Visual acuity is typically limited to 20/100 to 20/2001). Due to the fragility of the zonules of Zinn, intraocular lens implantation requires careful consideration.
The PAX6 gene product is adjacent to the tumor suppressor gene WT1 on chromosome 11p13, and as a contiguous gene syndrome, it can present as WAGR syndrome (Wilms tumor, aniridia, genitourinary abnormalities, intellectual disability).
Aniridia fibrosis syndrome occurs after intraocular surgery, but it is a rare complication that does not occur in all cases. A systematic review of artificial iris implantation reported an incidence of 3.1% 1), and the mechanism of onset has not been fully elucidated.
The main complaint in aniridia fibrosis syndrome is painless, progressive vision loss from baseline 1). Because it is painless, patients often delay seeking medical attention. In advanced stages, observant patients may notice the presence of a membrane.
Early Findings
Fibrous membrane originating from the iris root: A membrane formed from the rudimentary iris root can be observed with slit-lamp microscopy. It often affects the intraocular lens.
Anterior displacement of the intraocular lens: The membrane traction moves the intraocular lens forward, and in advanced cases, it may contact the cornea.
Advanced Findings
Hypotony: Occurs when the membrane extends over the ciliary body. In this case, the right eye IOP was recorded as 0 mmHg 1).
Corneal endothelial failure: Ultimately leads to edema and endothelial damage of the entire cornea. In this case, total corneal edema was observed 1).
Retinal detachment: May occur when the membrane extends to the anterior retina.
In the case reported by Banifatemi et al. (3-year-old girl, 2 years after bilateral Ahmed glaucoma valve surgery), the following findings were observed in the right eye 1).
Hypotony occurs because the fibrous membrane covers the ciliary body, impairing its function and reducing aqueous humor production1). Corneal edema is caused by contact of the intraocular lens with the cornea or corneal endothelial damage associated with hypotony.
The cause of aniridia fibrosis syndrome is unknown. However, all reported cases have occurred after intraocular surgery.
Risk factors include the following:
Tsai et al reported 7 eyes of 6 patients with surgical history1): 7 eyes with cataract surgery and posterior chamber intraocular lens, 6 eyes with tube shunt, and 4 eyes with corneal transplant. Bakhtiari et al reported 9 cases1): all cases had cataract surgery with intraocular lens implantation, 7 cases with tube shunt, and 7 cases with corneal transplant/corneal limbal allograft.
Two theories have been proposed regarding the mechanism of onset.
Notably, recurrent progressive fibrosis has been reported in an 8-month-old infant after Descemet stripping automated endothelial keratoplasty (DSAEK)1), suggesting that it can occur without intraocular devices.
The diagnosis of aniridia fibrosis syndrome is made through clinical observation in patients with congenital aniridia who have a history of intraocular surgery.
Regular slit-lamp examination is the cornerstone of diagnosis 1). It can reveal a fibrous membrane originating from the iris root and enveloping the intraocular lens. In the early stage when the cornea is clear, detailed evaluation of the anterior segment is possible.
This examination is essential when there is anterior segment media opacity such as corneal opacity1).
In this case, ultrasound biomicroscopy was performed under chloral hydrate anesthesia, and a thick fibrous membrane extending from the iris root to the posterior part of the cataractous lens was confirmed1).
The following diseases need to be differentiated.
Treatment of aniridic fibrosis syndrome is primarily surgical. Early diagnosis and intervention lead to improved visual prognosis 1).
To prevent further membrane proliferation and tissue destruction, early surgical membrane excision via penetrating keratoplasty (PKP) is recommended.
In the study by Tsai et al., among 7 eyes of 6 patients, 5 cases underwent surgery 1):
Tsai et al (initial report)
Surgical technique: Full-thickness corneal transplant + membranectomy. Some cases combined with intraocular lens removal/exchange.
Recurrence: Recurrence was observed only in cases that underwent intraocular lens removal/exchange. Simultaneous intraocular lens removal was concluded to be effective in preventing recurrence.
Visual outcomes: All 5 operated cases showed visual improvement1).
Bakhtiari et al (9 cases)
Surgical technique: All cases received Boston KPro type 1 implantation (primary or secondary). Intraocular lens removal was performed in 7 of 9 cases, and vitrectomy in 8 cases.
Postoperative complications: Retroprosthetic membrane in 5 eyes, suprachoroidal hemorrhage in 1 eye, and tractional retinal detachment in 1 eye.
Visual outcomes: All cases improved from preoperative hand motion to light perception to postoperative 20/200 to 2/5001).
Boston type 1 keratoprosthesis is a viable treatment option that has not been associated with recurrence of aniridia fibrosis syndrome 1). Since the KPro is placed away from the iris root (the origin of the lesion), it is thought to cause less irritation to the iris.
However, it should be noted that in aniridic eyes, the incidence of retroprosthetic membrane (RPM) formation is high (61–66%). This is significantly higher than the incidence in non-aniridic eyes (26.7–39%) 1), and this retroprosthetic membrane may be a phenotype of aniridia fibrosis syndrome 1).
Dyer et al reported a retention rate of 83.3% (mean follow-up 58.7 months) for Boston KPro type 1 in aniridic eyes, while Shah et al reported 87% (54 months follow-up)1).
Bakhtiari et al. recommend not only anterior vitrectomy but also complete vitrectomy to prevent recurrence1).
Outcome data for cases with a confirmed diagnosis of AFS that did not undergo surgery are limited. In this case report (Banifatemi et al. 2024), surgery was not performed due to parental refusal 1). In general, without treatment, progression of corneal endothelial failure, hypotony, and retinal detachment is a concern. Tsai et al. reported visual improvement in all surgically treated cases, emphasizing the importance of early intervention 1).
The exact pathogenesis of aniridic fibrosis syndrome remains unclear, but multiple lines of evidence support the iris root as the origin of fibrosis.
Pathological analysis by Tsai et al. confirmed the following 1):
Banifatemi et al. (2024) state that “the fibrous membrane is similar to the membrane around intraocular lenses after surgery in chronic uveitis, but differs in that it is not accompanied by inflammation”1).
Two mechanisms have been proposed.
Mechanical irritation hypothesis
This theory suggests that the intraocular device contacts residual iris tissue or immature iris vessels, providing a scaffold for membrane formation1). This is consistent with the clinical observation that aniridia fibrosis syndrome occurs in association with different intraocular devices such as intraocular lenses, tube shunts, and artificial irises.
PAX6 mutation-related Wnt signaling elevation hypothesis
PAX6 is a transcription factor that negatively regulates Wnt signaling. The theory suggests that chronic activation of Wnt signaling due to PAX6 mutations creates a predisposition to intraocular fibrosis1). In a mouse model study, Wang et al. confirmed that PAX6 haploinsufficiency (haploPAX6) induces a prefibrotic state even in unoperated eyes compared to wild-type1).
Similar progressive fibrosis has been reported in other congenital anterior segment anomalies such as Peters anomaly, suggesting that PAX6 mutations are broadly associated with a fibrotic predisposition1).
The rate of retroprosthetic membrane formation after Boston KPro type 1 implantation in aniridic eyes is 61–66%, significantly higher than in non-aniridic eyes (26.7–39%) 1).
Yang et al. have suggested that this high rate of retroprosthetic membrane formation may be a phenotype of aniridia fibrosis syndrome 1). Meanwhile, Muzychuk et al. reported that aniridia is a significant risk factor for vision loss after Boston KPro surgery 1).
In a systematic review of artificial iris implantation by Romano et al., the incidence of aniridia fibrosis syndrome was reported as 3.1% in a study of 96 aniridic eyes by Figueredo and Snyder 1). Since artificial iris implantation functions as an intraocular device similar to intraocular lenses and tube shunts, it carries a potential risk of developing aniridia fibrosis syndrome.
Wang et al.’s mouse model study is one of the first systematic studies to elucidate the molecular mechanism of aniridia fibrosis syndrome 1). Selective inhibition of the Wnt signaling pathway has been suggested as a potential future therapeutic target, but it has not yet reached clinical application.
