Long-term outcomes of “open iridectomy” for secondary anterior chamber epithelial iris cysts

Epithelial cysts run a high risk of recurrence and conversion to sheet-like ingrowth after surgical intervention. In this retrospective study, we introduced a modified iridectomy for treatment of secondary epithelial iris cysts (EICs) in the anterior chamber. Twenty-nine patients (29 eyes) aged 2–61 years received “open iridectomy” for EICs between April 1995 and July 2019. After viscodissection, most of the cyst wall was cut using a 20-gauge aspiration cutter via a 2.5-mm clear corneal incision. The residue closely adhering to the iris stroma was remained to avoid photophobia and diplopia. At 3 months, best corrected visual acuity was ≥ 20/100 in 55.5% (15/27, except two pediatric patients with poor cooperation) of patients. Among the eight patients suffering partial corneal edema preoperatively, six patients received surgery treatment at 3–6.5 months, and the cornea in the other two patients became transparent after medication. In a mean follow-up of 47.4 months, recurrence occurred in 3 patients at 7, 37, and 118 months, respectively. The percentage of treatment success was 96%, 87%, and 65% at 1, 5, and 10 years, respectively. “Open iridectomy” was effective for EICs, with a minimal invasion, less damage to the corneal endothelium, and a low recurrence rate.

www.nature.com/scientificreports/ All cyst extractions were performed by the same surgeon (LX). Inclusion criteria were: (1) enlarged cysts obstructing the visual axis, (2) ultrasound biomicroscopy (UBM) or anterior segment optical coherence tomography (As-OCT) showing cyst attachment to the anterior chamber angle and corneal endothelium, possibly accompanied with partial corneal edema, (3) repeated iridocyclitis, secondary glaucoma, complicated cataract, or lens subluxation, and (4) cysts in the anterior chamber allowing a transcorneal approach.
The "open iridectomy" technique. Local or general anesthesia was performed according to the patient cooperation. A side incision was created for injection of carbachol 0.1 mg/ml (Bausch & Lomb, Jinan, China) to induce miosis and sodium hyaluronate 15 mg/ml (Qisheng, Shanghai, China) to maintain the depth of the anterior chamber. Then a 2.5-mm limbal incision was made, through which sodium hyaluronate 15 mg/ml was filled to separate the cyst wall from the adjacent intraocular structure (corneal endothelium and anterior chamber angles) till to the cyst base. Normal tissues were preserved when a 20-gauge aspiration cutter (DP4400-6, Bausch & Lomb, Rochester, New York, USA) was introduced to aspirate and resect most of the cystic content and collapse the cyst wall. The suction vacuum was set at 200 mmHg, the cutting rate at 800 cuts per minute (cpm), and the BSS bottle at 70 cm. Because of the perfusion during the aspiration cutting, an anterior chamber maintainer was not necessary. To avoid photophobia and diplopia related to excessive iridectomy, the residual cyst wall/base closely adhering to the iris stroma was remained. The cystic fluid and viscoelastic substance were removed by irrigation and aspiration (MVS1063C, Bausch & Lomb, Rochester, New York, USA) with a BSS bottle set at 70 cm through the limbal incision. The incision could be self-sealed or sutured with one stitch (Fig. 1). The resected walls of the iris cysts were histopathologically examined. The surgical procedure is shown in Supplementary video 1.

Postoperative therapy.
Postoperatively, all patients were administered with tobramycin 0.3% and dexamethasone 0.1% eyedrops (Alcon, Fort Worth, Texas, USA) four times a day for 2 weeks and pranoprofen eyedrops (Senju, Osaka, Japan) four times a day for 1 month. The follow-up visits were scheduled at 2 weeks, 1 month, 3 months, and as necessary thereafter.   www.nature.com/scientificreports/ Statistical analysis. Statistical analysis was carried out with SPSS software version 17.0 (SPSS, Inc., Chicago, IL, USA). The age and follow-up time were described as mean ± standard deviation (SD) after Kolmogorov-Smirnov test. Kaplan-Meier analysis was used to assess the recurrence.
Ethical approval. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Results
Histopathological examination. Histopathological examination of the cyst tissue demonstrated iris stroma and pigment granules lining several layers of non-keratinised squamous epithelial cells (Fig. 2). The fluid aspirated from the cyst was also found to contain some epithelial cells. In the two patients with recurrence (patients 1 & 2 in Table 2), fewer than 3 layers of squamous epithelial cells were seen to be extensively adherent to the iris stroma.  (Table 1). Further surgical interventions were required in 14 (48.2%) patients. In the 8 eyes with concurrent preoperative corneal edema, 6 eyes developed endothelial decompensation, which was treated by corneal surgeries. One eye suffered sheet-like ingrowth after the cyst excision (Fig. 3). The eye had received congenital cataract surgery 20 years before and iris cyst extraction 2 years before in a local hospital. The patient first visited our institution in December 2013 for the recurrence of an EIC at the 7-8 o' clock positions. UBM showed suspected sheet-like ingrowth at the 4-5 o' clock positions. For the enlarged cyst, "open iridectomy" was performed in May 2014 with a histopathological examination. In May 2018, the progressive epithelial sheet-like ingrowth with corneal edema was resected, and scleral transplantation was performed. No recurrence or aggravated corneal edema was found during the 6 months of follow-up.
Recurrence and treatment. Repeated excisions were required in three eyes at 7, 37, and 118 months, respectively. The details of the cases are listed in Table 2. Except one patient (case 3) who received repeated excision combined with cataract extraction in another hospital, the other two patients received a second "open iridectomy", with no recurrence observed during the follow-up of 19 and 27 months, respectively. The cumulative percentage of treatment success in all 29 patients was 96%, 87%, and 65% at 1, 5, and 10 years, respectively (Fig. 4).

Discussion
It is a challenge to strike a balance between minimally invasive surgery and a low recurrence rate for the management of secondary EICs. The "open iridectomy" technique we used was to open the cyst wall to the anterior chamber through a small incision with simple instruments. Most of the cyst wall and content were cleaned by an aspiration cutter, and the few production of the remained tissue was excreted by aqueous humor circulation. The open area was made large enough to avoid cyst reclosing, and the normal tissue could be protected by precision cutting. All patients in this study achieved favorable visual function recovery with a low recurrence rate during the mean follow-up of 4 years.
According to previous reports, non-invasive procedures by laser with a small open area and content cleaning just through the aqueous humor circulation may result in recurrence and sheet-like ingrowth 3,17 . Actually, we do observe rapid proliferation of cysts after laser treatment, and the recurrent cysts are liable to cause secondary complications like glaucoma, corneal edema, and structural changes in the anterior chamber over time. Cyst  www.nature.com/scientificreports/ aspiration combined with endodiathermy 7 or endolaser photocoagulation 6 at the excision site for devitalization of residual cells has been tried in a small number of cases with a short period of follow-up. Injection of chemicals, such as ethalnol 8 , into the cyst requires a precise judgment of the cyst status by the surgeon. Once the procedure fails, the chemicals may be leaked and induce a disaster in the eyeball. Invasive surgery, like EIC excision combined with corneal or corneoscleral grafting, has been used in treating progressive cystic or diffuse epithelial ingrowth of the anterior chamber 14,18 as a permanent solution compared with conservative methods. Although the epithelial tissue could be completely removed to avoid recurrence, serious complications, including hemorrhage, secondary glaucoma, inflammation, and rejection of the graft tissue, may occur. The visual function is inevitably deteriorated because of the pupil defect and astigmatism.
Anterior chamber EICs, usually with delineated margins, can be visible during the surgical procedure. Hence we treated the cyst by lamellar iridectomy instead of sector iridectomy for prevention of glare and dicoria. Our modified technique possesses the following advantages in the treatment of secondary EICs. First, the 20-gauge instrument for vacuum aspiration could maintain a stable anterior chamber. The EIC is amenable via a localized, more conservative, and less destructive excision, which has the potential for commensurately less collateral damage to the delicate ocular structures and thus less visual disturbance. Second, a 2.5-mm incision allows combined surgical procedures, like phacoemulsification or trabeculectomy. Third, the procedure could be safely repeated.
In this study, there were 8 eyes with coexisting corneal edema before the excision surgery, 6 of which received penetrating keratoplasty or amniotic membrane transplantation months after the intervention, while 2 eyes had transparent corneas after medication, with no new onset of corneal decompensation during the follow-up. In the viscodissection of the cyst wall from the corneal endothelium, our approach did help to preserve the corneal endothelium and eliminate the corneal edema. Moreover, postoperative glaucoma was found in 4 eyes, reminding us that even if the cysts are successfully eradicated, IOP should be monitored for a long period of time.
The recurrence time of iris cysts was reported to range from 6 weeks to 5 years depending on different surgical treatment methods [19][20][21] . To avoid recurrence, Shields et al. 22 advised to perform an aspiration and light cryotherapy, and recommended a non-vitrectomy technique to prevent the inflammatory reaction and epithelial Epithelial sheet-like ingrowth is a potentially disastrous complication following anterior segment surgery and penetrating ocular injuries. The sheet-like growth in anterior chamber structures and posteriorly over the ciliary body and even the retina can place a burden on the en bloc section. As early as in 1978, Stark et al. 24 described 10 consecutive cases treated by photocoagulation to define the extent of epithelial involvement, followed by excision of the involved iris tissue and vitreous, and cryotherapy of the epithelium remaining on the posterior surface of the cornea, ciliary body, and in the anterior chamber. During the 23-month follow-up, eight patients achieved improved vision, two had controlled IOP with medication, and one had an IOP of 6 mmHg. In 1992, Naumann and Rummelt 18 reported a block excision without cryotherapy in 32 consecutive patients with an average follow-up of 60.1 months, demonstrating no recurrence and visual acuity ≥ 20/60 in 37.5% of patients. The major postoperative complication was corneal endothelial decompensation in 9 patients, among whom 4 received antiglaucomatous medication. With the development of modern microsurgery, epithelial ingrowth has been uncommon. The sheet-like ingrowth in one of our patients (Fig. 3) seeded in the former operative incision for anterior chamber iris cysts was successfully treated by "open iridectomy" surgery with no recurrence observed over 4 years of follow-up. However, the sheet-like ingrowth located in the sclera progressed slowly for 20 years after the previous surgery. We performed the resection and partial allograft scleral transplantation at the area according to As-OCT images. Antiglaucomatous eyedrops were administered for 5 months to control the IOP. During the 10-month follow-up after the secondary surgery, corneal endothelial decompensation did not become aggravated, and thereby corneal transplantation was not needed.
Because of the low occurrence rate of iris cysts, this study was limited as the retrospective design. The pathological findings and influencing factors of the recurrence also need further clarifications based on more clinical cases. Nevertheless, we provided a new idea for repeatable and minimally invasive treatment with ample information of the etiology, postoperative complications, and recurrence from a comparatively large number of patients with a long-term period of follow-up. The "open iridectomy" can be effective in the treatment of secondary anterior chamber EICs, with a low rate of recurrence and favorable preservation of the corneal epithelium.