Aniridic Fibrosis Syndrome in a Child with Ahmed Glaucoma Valve: Report of a Case and Review of the Literature

Abstract

Purpose:

To report a case of aniridic fibrosis syndrome (AFS) after Ahmed glaucoma valve (AGV) surgery.

Methods:

Case report.

Results:

Two years post-AGV surgery in both eyes, a 3-year-old aniridic female presented with grayish discoloration of the right eye for the past 3 months. A slit-lamp examination of the right eye revealed an aniridic, hypotonic eye with a totally edematous cornea. A tube of the AGV was in place with a mature cataract subluxed superiorly. In addition, a thick, whitish vascularized membrane originating from the rudimentary iris to the inferior part of the subluxed lens was observed. Ultrasound biomicroscopy investigation confirmed a thick fibrotic membrane originating from the iris root and extending to the posterior part of the cataractous lens. The intraocular pressure of the right and left eye was 0 and 11 mmHg, respectively. A B-scan of the right eye revealed an axial length of 21 mm, optic disc swelling, and shallow choroidal detachment in the anterior 2/3 of the posterior segment without retinal detachment. With the diagnosis of AFS, a pars plana vitrectomy, lensectomy, and membranectomy under keratoprosthesis and penetrating keratoplasty were planned.

Conclusions:

Aniridic patients may undergo multiple ocular surgeries during their lifetime. One of the rarest surgical complications in these patients is AFS. Early diagnosis can be possible with serial slit-lamp examination and ultrasonographic studies to detect the disease in the early stages and prompt intervention. Here, in our case, the parents declined any surgical intervention.

INTRODUCTION

Aniridia is a panocular disease with a partial or total absence of iris tissue and various degrees of foveal hypoplasia.1 The occurrence is 1:64,000–1:96,000.2 Ninety percent of cases are due to the mutation in paired-box gene 6 (PAX6) located on the short arm of chromosome 11 (11p13).1 Mutations in FOXC1, PITX2, and CYP1B1 have also been reported.3,4 Two-thirds of cases are familial, and one-third are sporadic.5 Its inheritance pattern is autosomal dominant with high penetrance.6 The ocular findings of aniridia include corneal stem cell deficiency and corneal opacity (78%–96%), dry eye (56%–95%), glaucoma (46%–70%), cataract (50%–85%), lens subluxation (42%), nystagmus (64%–95%), foveal hypoplasia (79%–86%), and optic nerve hypoplasia (11%–29%). Vision is limited due to multiple pathologies and is usually about 20/100–20/200.1,7,8 Congenital aniridia cases may have reduced olfaction, auditory malfunction, and abnormalities in the structure of the central nervous system.1,7 The PAX6 gene and its product as a DNA-binding transcription factor are a major regulator of eye, brain, and pancreas development;9 so, even isolated congenital aniridia may be associated with other systemic conditions. PAX6 homozygous gene mutations lead to anophthalmia and perinatal death, but heterozygous mutations result in aniridia syndrome.8

Aniridic patients may undergo multiple ocular surgeries during their lifetime that may be associated with surgical complications due to comorbidities. One of these comorbidities is aniridic fibrosis syndrome (AFS), in which a fibrotic membrane develops after intraocular surgeries of cataract extraction and intraocular lens implantation or tube shunt surgery. The authors of the initial report believed that it originated from rudimentary iris tissue stimulated by foreign hardware.10

Here, we report a case of AFS and review the etiology, diagnosis, and management of this rare condition.

CASE REPORT

Two years post-Ahmed glaucoma valve (AGV) surgery in both eyes, a 3-year-old aniridic female presented with grayish discoloration of the right eye for the past 3 months.

In examination, the patient had photophobia in the right eye and did not follow the light despite fixation. The left eye had fixation and followed the light well. A slit-lamp examination of the right eye revealed an aniridic, hypotonic eye with a totally edematous cornea. The tube of the AGV was in place with a mature cataract subluxed superiorly with inferior zonulysis. A thick, whitish, and vascularized membrane originating from the rudimentary iris to the inferior part of the subluxed lens was observed.

The left eye examination revealed a clear cornea and lens that were subluxed superiorly. The AGV was in the supratemporal quadrant with a good tube position in the anterior chamber. The intraocular pressure (IOP) of the right and left eyes was 0 and 11 mmHg, respectively. Both eyes were receiving a fixed combination of dorzolamide/timolol BID.

There was no view to the right eye retina and optic nerve, but the left eye retina looked fine with a cup-to-disk ratio of 0.4. The IOP of the right eye remained 0 after stopping the antiglaucoma drop for 3 days. A B-scan of the right eye revealed an axial length (AL) of 21 mm, optic disc swelling, and shallow choroidal detachment in the anterior 2/3 of the posterior segment without retinal detachment. The AL in the left eye was 25 mm. Ultrasound biomicroscopy (UBM) of the right eye under chloral hydrate showed a thick fibrotic membrane originating from the iris root and extending to the posterior part of the cataractous lens [Figure 1].

Figure 1.

Ultrasound biomicroscopy of the right eye shows an edematous cornea (red arrows), a cataractous lens (yellow arrows), and a thick fibrotic membrane (blue arrows) originating from the iris root (green arrows) and extending to the posterior part of the cataractous lens

With the diagnosis of AFS, a pars plana vitrectomy, lensectomy, and membranectomy under keratoprosthesis and penetrating keratoplasty were planned, but the parents declined any surgical intervention. They provided informed consent to have the case described and published.

DISCUSSION

To the best of our knowledge, this case is the 19^th reported case of AFS.10,11,12,13 This AFS was first presented in 2005 by Tsai et al., who reported 7 eyes of six patients with anterior chamber progressive fibrosis.10 The age range of the patients was 9–65 years; our case was 3 years old.10 All eyes in their report had undergone previous intraocular surgeries, and several had multiple procedures.10 Seven eyes had a history of cataract surgery with posterior chamber intraocular lens (PCIOL), six eyes had a tube shunt, and four eyes had corneal graft. All patients were female. All the eyes had sulcus IOLs, 6 of the IOLs were acrylic, and one had polymethyl methacrylate combined with iris diaphragm implantation.10 In all eyes, a thin membrane formed around the PCIOL (posterior and anterior) and eventually displaced the IOL toward the cornea.10 All cases developed corneal endothelial decompensation during follow-up. Histopathology examination revealed a fibrotic tissue originating from the rudimentary iris root, with dense hypocellular fibrous membrane and scarce vascularity. Immunohistochemistry showed a few T cells and macrophages in 2 cases, ruling out inflammation as the causative factor, except in one case where inflammatory cells were present. Electron microscopy revealed immature collagen bundles mixed with mature fibers. No glial, corneal endothelial, and lens epithelial cells or lens capsular tissue was found in the fibrotic membrane.10

In our case, there was no retrocorneal membrane, but hypotony and corneal edema had occurred due to the involvement of the ciliary body and cyclitic membrane. Tsai et al. also found hypotony and membrane extension to the ciliary body and anterior retina in 2 of their cases.10 Five of the cases underwent penetrating keratoplasty and membranectomy combined with either PCIOL explantation or exchange. Two eyes with retinal involvement had retinal detachment repair as well. No eyes had a recurrence in their study. One of the cases with hypotony recovered after excision of the membrane, and another maintained the IOP between 5 and 10 mmHg. All cases had low vision after the disease diagnosis, ranging from 20/200 to light perception, but all 5 cases that underwent surgical intervention had vision improvement. The authors postulated that the underlying mechanism in aniridic eyes is the intraocular hardware touching the rudimentary iris or immature vessels of the rudimentary iris, creating a scaffold for membrane formation.10 Another proposed theory was a predisposition to fibrosis associated with PAX6 mutation since similar progressive fibrosis conditions are seen in other congenital anterior chamber anomalies such as Peters’ anomaly associated with PAX mutations.10,14

Although previous studies have shown that PAX6 negatively regulates Wnt signaling, which the chronic upregulation of it, can drive fibrosis. In a study by Wang et al. on mouse models of aniridia, the PAX6 haploinsufficiency induced a prefibrotic state in aniridic eyes in comparison to wild types due to elevated Wnt signaling, which may cause the AFS following intraocular surgeries.15 Indeed, the authors confirmed chronic upregulation of Wnt signaling in unoperated haplo-PAX6 mice. These mechanisms could justify the membrane formation mechanism in our case, as our patient had an implant in the anterior chamber.

The most effective method for diagnosing aniridic fibrotic membrane is through a detailed slit-lamp examination and using UBM when dealing with media opacity conditions such as aniridic-associated keratopathy. UBM allows evaluation of the ciliary bodies, the extent of the fibrotic membrane, and the formation of cyclitic membranes.16

Bakhtiari et al. reported 9 cases of AFS; all had undergone cataract surgery and IOL implantation. Seven cases had tube shunt surgery, and 7 cases had previous corneal transplantation or keratolimbal allograft surgery.12 All of the cases presented with retrocorneal and retrolenticular membrane formation and subsequent IOL displacement and corneal decompensation. One patient had corneal melting and perforation due to displaced IOL into the cornea. Two of the patients had an extension of the membrane posteriorly, leading to tractional retinal folds. The age range of their patients was 11–71 years (mean: 33.8). They followed the patients for 6–48 months (mean: 26.1).12 The management of AFS cases in this study included IOL explantation in 7 out of 9 cases, removal of fibrosis and anterior vitrectomy in 1 case, removal of fibrosis with pars plana vitrectomy in eight patients, and implantation of a type I Boston KPro in all cases, even primarily or secondarily. Vision improved in all eyes, ranging from hand motions/counting fingers preoperatively to 20/200–2/500 postoperatively.12 Postoperative complications of KPro implantation included retroprosthetic membrane in 5 eyes, suprachoroidal hemorrhage in 1 eye, and tractional retinal detachment in 1 eye. The authors recommended IOL explanation and complete pars plana vitrectomy instead of anterior vitrectomy to prevent the recurrence of membrane formation. Early detection and intervention are also key factors to success.12 They also concluded that initiation and progression of fibrosis can occur in the absence of clinically detectable inflammation, a finding that was also observed by Tsai et al. The fibrotic membrane of AFS arises from the iris root and grows toward the cornea. This membrane is similar to the fibrous membrane enveloping the IOL after cataract surgery in chronic uveitis but without any inflammation.10

Another study by Dyer et al. evaluated the survival of Boston type 1 keratoprosthesis in congenital aniridic eyes. A common postoperative complication in their patients was retroprosthetic membrane formation in 8 of 12 cases (66%). They found an overall retention rate of 83.3% with a mean follow-up time of 58.7 months.17 In another study by Shah et al. on Boston type 1 KPro in 46 aniridic eyes of 34 patients, the rate of retroprosthetic membrane formation was 61%, and the KPro retention rate was 87% in 54 months of follow-up.18

The incidence of retroprosthetic membrane formation after Boston KPro 1 was studied in other cases without aniridia, and it was 26.7%–39%.19,20 The rate of retroprosthetic membrane formation in aniridic eyes is higher than in other eyes that underwent Boston KPro type 1 implantation.19,20 This retroprosthetic membrane may be another presentation of AFS.21 In a study by Muzychuk et al., aniridia was found to be an important risk factor for losing vision after a Boston KPro operation.22 Bakhtiari et al. believe that the KPro is far from the iris root, where pathology begins, and cannot irritate the iris to reform the membrane in AFS.12 However, it is necessary to review the results of other studies about KPro implantation in aniridic eyes. A systematic review by Romano et al. of artificial iris implantation in congenital aniridia showed that in only one study by Figueiredo and Snyder on 96 aniridic eyes, the complication of AFS was noted with an incidence of 3.1%.23,24 All these previously published studies used intraocular hardware such as IOL, tube shunts, or artificial iris. However, recurrent and progressive anterior segment fibrosis following Descemet’s stripping automated endothelial keratoplasty surgery was reported in an 8-month-old infant with congenital aniridia.11 This case report may confirm the predisposition of aniridic eyes to intraocular fibrosis even without any intraocular implant.

The exact mechanism of AFS is unknown; it may be that the rudimentary iris is the site of the launch of fibrosis in aniridic eyes. The fibrosis may be triggered by intraocular hardware touching the anomalous iris or even by manipulation during surgery such as trabeculotomy or trabeculectomy.22 In addition, fibrosis may be started before any operation in pockets of fibrosis.15

In conclusion, the occurrence of AFS is higher in aniridic patients, and these patients need close follow-up after intraocular surgery. Early diagnosis is possible with serial slit-lamp examination and ultrasonographic studies to detect the disease at early stages and intervene. The recommended interventions include intraocular implant removal, complete pars plana vitrectomy with concomitant membranectomy, and aphakic keratoprosthesis in the presence of corneal decompensation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.