FormalPara Key Summary Points

Why carry out this study?

Cyst formation of the epibulbar tissues is a rare but distinct complication after ophthalmic surgery, especially strabismus surgery.

An extraordinarily high incidence of these postoperative cysts in our patients between January 2019 and August 2022 allowed for a detailed classification of this entity.

What was learned from the study?

Three types of cysts could be characterized consistently according to examination in slit-lamp photography, anterior segment optical coherence tomography and histopathological sections.

Postoperative cyst formation correlated strongly to the form of strabismus, patient age and type of surgical procedure.

Introduction

Strabismus is a disorder of various etiologies and classifications. With an enormous impact on binocular vision, a distinct burden on quality of life, and a prevalence between 2.8% and 2.9% in the Caucasian population [1, 2], its surgical correction is one of the most common procedures in the field of ophthalmology in the industrialized world. Even though for most indications there is no equally effective procedure available to treat manifest or intermittent forms of strabismus, in selected cases such as sixth nerve palsy or early restrictive strabismus in Graves’ orbitopathy, the application of Botulinum Toxin (Botox) can pose a minimally invasive alternative [3,4,5]. Strabismus surgery is a generally safe and effective procedure, and little has changed about the technical principles since its beginnings back in 1839 [6], although the instruments and suture materials have changed considerably. Due to its quality as an extraocular procedure, strabismus surgery is less prone to sight-threatening infections like endophthalmitis—or even loss of the operated eye itself—than intraocular procedures [7,8,9]. In a recent French nationwide 5-year cross-sectional analysis of all strabismus surgeries, Colas et al. reported an endophthalmitis rate of 0.0053% [10], comparing to an average rate of 0.03 to 0.2% worldwide for cataract surgery [11,12,13]. Nevertheless, the spectrum of possible complications comprises not only double vision and unsatisfactory cosmetic results but also serious loss of function, e.g., from retinal detachment. Various observations of disturbed wound healing after strabismus surgery are reported in the literature, including inflammatory reactions like granuloma of the conjunctiva, necrotizing scleritis [14, 15], as well as epithelial inclusion cysts, intrascleral cysts, and orbital cysts [16,17,18].

Postoperative Cyst Formation After Strabismus Surgery

Several case reports and case series of cyst formation after strabismus surgery have been reported in the literature [17,18,19]. The three largest series [20,21,22] included 12, seven, and six cases, respectively. Alas, a clear etiological explanation for the occurrence of postoperative cysts after strabismus surgery could not yet be found, which partly can be explained by the rarity of this complication [22, 23]. A better understanding of factors contributing to the development of such cysts is much-needed, considering their possible consequences for our patients, such as ocular surface damage, cosmetic implications, and the potential for reintervention including the risks of general anesthesia.

We present here a comprehensive study of consecutive patients who underwent strabismus surgery, during which cases of postoperative cyst development within a 44-month period were closely followed. To the best of our knowledge, our collective is the largest reported so far in the literature. Moreover, we are introducing a classification system based on the findings in slit-lamp examination, anterior segment optical coherence tomography (AS-OCT), and histopathology.

Methods

All 822 consecutive patients who underwent strabismus surgery at one surgical center (Medizinische Hochschule Hannover) between January 2015 and August 2022 were included in the study. Patients in which cyst formation as a postoperative complication was observed, were later followed prospectively, with detailed work-up. All surgeries were performed as described below by one specialist (K. H.) and two residents (O. G. and C. R.), in cases of resident surgeries usually under specialist assistance and supervision. From 2015 until the end of 2018, 90% of cases were operated on by the specialist; from January 2019 until August 2022, the specialist was a surgeon in 74% of cases. In the affected group, 13 cases (68%) had been operated on by the specialist, three cases (16%) by one resident surgeon (O. G.), and three cases (16%) by the other resident surgeon (C. R.). Except for one second surgery for consecutive exotropia (XT), all cases affected by postoperative cyst formation were primary strabismus surgeries. Two of the cases have had surgery for intermittent exotropia (X(T)) on the other eye years before at our clinic. In one case, an additional Faden suture (see Sect. “Surgical procedure”) was used for additional correction of hypotropia in high myopia.

The research adhered to the tenets of the Helsinki Declaration of 1964 and its later amendments (10/2013). Written informed consent was obtained from all patients or, in the case of minors, from both parents. Informed consent regarding the risks of strabismus surgery was taken in written form prior to surgery in all cases—for children from the parents. Retrospective patient information elaborated on our special interest in the documentation and classification of a wide spectrum of postoperative findings and surgical modalities regarding surgical outcome, especially the features of wound healing. The study's conduction was approved by the Ethics Committee of Hannover Medical School, Germany, Ethics approval Nr. 100,040.

Ophthalmological Examination

All patients received a complete ophthalmological and orthoptic examination before surgery as well as on the first postoperative day and 3 months post-operatively. Relevant systemic or ocular comorbidities were documented and treated, e.g., dry eye, prior to surgery, if advisable. In cases of suspected complications or surgery-related complaints, earlier—or additional—post-operative examination at our department was warranted. Best-corrected visual acuity (BCVA; Snellen chart or Lea Chart) was measured mono- and binocularly, with cycloplegic refraction or spectacle correction applied for all subjects. Eye alignment was assessed with spectacle correction using the alternate cover and prism test at 5 m for distance and at 0.33 m for near, or, in cases where this measurement was not applicable, Krimsky prism test was performed. This orthoptic examination was repeated at least once preoperatively with an interval of at least 14 days to cover daily variations.

In all patients, slit-lamp biomicroscopy and ophthalmoscopy were conducted. Slit-lamp photography was obtained with the BX900 slit-lamp unit (Haag-Streit, Koeniz, Switzerland), connected to an EOS 7D Mark II single lens reflex camera (Canon, Ota, Japan). AS-OCT was obtained with SPECTRALIS® spectral domain optical coherence tomography (Heidelberg Spectralis II (Heidelberg Engineering GmbH, Heidelberg, Germany; Acquisition Software Version 6.12.4.0).

Surgical Procedure

Surgery was performed under general anesthesia and standard sterile conditions using povidone-iodine (PVP-I) for disinfection of the skin and conjunctiva and adhesive draping with transparent foil to cover the lashes and the lid skin on the site of the operation. The eye was moved into position using a 5-0 double-armed disposable suture (5-0 polyester, braided polyethylene terephthalate (PET), non-absorbable, white, Catgut, Markneukirchen, Germany) going through two opposite points of the episclera near the limbus as intraoperative traction suture. This suture was discarded at the end of the surgery. A limbal incision was made in most cases to access the rectus muscle as well as in all cases of transpositions and superior oblique surgery [24]. This approach was also chosen in combined surgery of the lateral rectus and the inferior oblique muscle, while in isolated inferior oblique surgery a meridional incision, starting at the limbus, was created. In selected cases of rectus muscle surgery, e.g., contact lens wear or smaller surgical distance in patients older than 10 years of age, a modified Park’s conjunctival incision was made in parallel above and below the muscle insertion [5, 25]. From January 2015 through October 2021, all rectus muscle sutures were 6–0 sized absorbable sutures with a quarter-circle shaped micro lancet (VLM) 20-6 spatula needle (6-0 MARLIN® violet multifilament coated polyglycolic acid (PGA), Catgut, Markneukirchen, Germany). Scleral fixation of the loose end or the tucking part of the muscle was accomplished using a single suture technique on each side of the muscle rim / insertion rim. Closure of the conjunctival incision was performed as separate single-button suture using absorbable 9-0 (9-0 MARLIN® violet monofilament uncoated PGA, Catgut, Markneukirchen, Germany) in rectus muscle and combined surgery or, in patients > 60 years of age, 8-0 Marlin (8-0 MARLIN® violet coated PGA, Catgut, Markneukirchen, Germany). For single oblique muscle procedures, conjunctival closure was performed using a running 7-0 suture (7-0 MARLIN® violet coated PGA, Catgut, Markneukirchen, Germany). In cases of retroequatorial myopexy (Faden operation), a 4-0 suture (4-0 MERSILENE™ Polyester, non-absorbable, Ethicon, Johnson & Johnson Medical, Norderstedt, Germany) was used in single-button technique [26]. From November 2021, the muscle suture was changed to a 6-0 unstained absorbable suture with a VLM 33-8 spatula needle (6-0 MARLIN® unstained multifilament coated PGA, Catgut, Markneukirchen, Germany). In January 2022, the muscle suture was again exchanged, this time for a 6-0 absorbable unstained suture with a S-14 8 mm spatula needle (6-0 Coated VICRYL™ unstained multifilament coated PGA, Ethicon, Johnson & Johnson Medical, Norderstedt, Germany).

Postoperative Therapy

For the first postoperative week, dexamethasone eye drops were administered four times daily (quarter in die—qid) for 1 week in combination with gentamicin sulfate (DEXA GENTAMICIN eye drops, URSAPHARM, Saarbrücken, Germany), the respective ointment (DEXA GENTAMICIN ointment) was given over night. Subsequently, a course of prednisolone acetate 1% eye drops (Predni-POS®, URSAPHARM, Saarbrücken, Germany) was administered qid with a standard tapering scheme, reducing once per day each week over 4 weeks.

Revision Surgery for Cystic Lesions

The decision for revision surgery was made upon failure of the cystic lesion to regress under qid topical steroid eye drops (dexamethasone) over at least 2 weeks. Eleven cases were revised under general anesthesia after informed consent of patients (or parents in case of minors); in one case local anesthesia was administered. Surgically, the cyst was excised in toto where possible or at least the capsule was fully excised. If the underlying muscle had to be loosened from its former insertion, it was carefully reattached to the globe in the original position intended during the prior operation, using either an 8-0 or 6-0 absorbable coated PGA multifilament MARLIN® suture (Catgut, Markneukirchen, Germany).

Histopathological Analysis

Written informed consent was obtained by the patients or both parents prior to taking tissue samples. The tissue was processed using standard histopathological techniques, i.e., fixation in 3.8% buffered formaldehyde, alcoholic dehydration, and wax infiltration. The specimen was cut using a microtome to sections of 3-µm thickness and then stained using standard hematoxylin and eosin (H&E) stain and periodic acid–Schiff (PAS) reaction.

Microbiological Analysis

Microbiological swabs were taken during revision surgery for suspected infectious etiology of the cyst. Swabs were taken from the content of the cyst and cultured on solid and liquid, selective and non-selective culture media for 4 days according to the national guidelines of the German Association for Hygiene and Microbiology (DGHM) in our accredited laboratory (German accreditation body, D-ML-13168-03-00).

Statistical Analysis

Data obtained in this study were analyzed statistically using the Statistical Package for Social Sciences for Windows (SPSS) version 27.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics and nonparametric correlation analysis using Eta (η) correlation were utilized to determine a relationship between nominal variables (type of cyst, affected muscle, form of strabismus, type of surgery) and metric (time interval, age) variables. The Phi (φ) coefficient is used to assess the relationship between two nominal variables. It ranges from 0 to 1, where 0 means no association and 1 means perfect or strong association.

Results

Patient Characteristics

Between January 2015 and August 2022, a total of 822 patients received strabismus surgery at our department. The ratio of pediatric (under 18 years of age) to adult surgery was n = 329/493 in all surgeries (40% pediatric surgeries). Strabismus surgery involved 771 rectus muscles, comprising 407 medial rectus and 327 lateral rectus muscles, 16 superior rectus muscles, 24 inferior rectus muscles, and 101 oblique muscles (64 inferior oblique muscles, 37 superior oblique muscles). Remarkably, within the first half of consecutive cases (n = 410, January 2015 to January 2019), not a single incidence of postoperative cyst formation was observed. All detected cases with cyst formation belonged to the 412 consecutive cases (506 eyes) operated on between January 2019 and August 2022. During this period, 19 patients (13 females, six males) postoperatively developed sterile cystic lesions or granulomata in this study (Table 1). The ratio of pediatric to adult surgeries in this group was n = 16/3 (84% pediatric surgeries). The average time from surgery to first follow-up visit was 81 days, and all patients did come back for a post-operative control visit. All cases were detected within 3 months of follow-up, with a mean duration of 24 days until first detection of the cyst (range, 7–56 days).

Table 1 Clinical findings of all patients with cyst formation
Full size table

Patient age at time of surgery was significantly younger in the affected group than the average patient age of all strabismus surgeries (mean, 14.2 years vs. 27.7 years (range, between 2 and 64 years vs. 2 and 86 years, respectively). 13/19 (68%) had (X(T)) in the affected group, compared to 17% in all surgeries. All affected extra ocular muscles were horizontal recti, with a clear overweight on the strengthened muscle (15/19).

Clinical Findings

All observed postoperative cysts were located to the scleral suture at the insertion of a rectus muscle. In the affected patients, the predominant form of strabismus treated was intermittent exotropia (13/19), with the tucked rectus muscle being affected in most cases (11/19), while a recessed or resected rectus muscle was affected in 4/19 cases, respectively, the resections being modified by one anteroposition and one infraposition. No cases of two-muscle involvement were noted, with all cases being combined surgeries of agonist and antagonist. Altogether, between January 2019 and August 2022, a total of 890 extraocular muscles, dividing into 788 rectus muscles and 102 oblique muscles, have been operated at our department: 415 medial rectus muscles, 333 lateral rectus muscles, 16 superior rectus muscles, 24 inferior rectus muscles, 37 superior oblique, and 65 inferior oblique muscles.

Out of a total of 412 strabismus patients in the second collective, 75 (88/506 eyes or 17%) were operated on for (X(T)), with a mean patient age of 18.1 years. Comparing these numbers to the affected patient collective results in a significantly higher ratio of (X(T)) (13/19 or 68%) and a significantly younger age in the affected group (14.3 years). Of the affected extra-ocular muscles, all were horizontal recti, with a clear overweight on the strengthened muscle (15/19 or 78.95%), the strengthening procedure being a tuck in 11/19 muscles and a resection in 4/19 muscles, while two of the resections were combined with a transposition of the respective extraocular muscle (one anteroposition of 3 mm and one infraposition of 1 mm). In one of the affected recessed muscles, an aberrant anatomy was noted intraoperatively (patient #6), with the lateral rectus muscle showing a low insertion (Table 1).

Subjective symptoms were mild in all cases, with five patients (26.3%) reporting no symptoms at all. Mean onset of symptoms postoperatively was at 3 weeks after surgery (range, 1 day to 8 weeks), the most marked sign being redness over the affected muscle, followed by foreign body sensation and swelling.

Slit-Lamp Findings

Evaluation of form and aspect of cysts on slit-lamp photography led to three general types of cysts: type 1 presented as a single, clear cyst with varying amount of yellowish condensed material and level formation; type 2 morphology showed as multilobular cysts; type 3 was seen as granulomatous lesion with cystic component.

The examples of slit-lamp images of three types of grading are presented in Fig. 1.

Fig. 1
figure 1

Examples of slit-lamp images of three types of grading of the cysts. A–H Slit-lamp images showing type 1 single cyst; I-N represent the type 2 lesion of two or multilobular cysts. O–Q reveal the type 3 or granulomatous-like cyst lesion. Mirror formation in A, H, I, N represents fibrin-serous material (asterisk). A characteristic feature in postoperative conjunctival cysts, the formation of a superior and inferior mirror with clear center, we termed “striped billiard ball sign” (I)

Full size image

Of the total cases, 17/19 could be evaluated from slit-lamp pictures. The above grading system led to a classification of type 1 in 8/17 cases, type 2 in 6/17 cases, and type 3 in 3/17 cases.

Anterior Segment Optical Coherence Tomography (AS-OCT) Findings

In 12/19 cases, AS-OCT could be obtained. AS-OCT evaluation provided a classification of three cyst types: clear single cyst (type 1) only in 5/12 cases, while 4/12 cases showed multiple cysts, sometimes with faint septae (type 2). Type 3 (3/12) lesions were dense on AS-OCT scans with microcystic edema (Fig. 2).

Fig. 2
figure 2

Anterior segment optical coherence tomography (AS-OCT) examination. A–E AS-OCTs of type 1 lesion. The lesion is characterized by a single cyst as hyporeflective layer of epithelium and underlying hyperreflective connective tissue layer (stroma). The lower reflective Tenon capsule overlying homogeneous, dark, hyporeflective subepithelial lesions with smooth borders corresponding to the serous cyst. White asterisks represent deposits of dense, homogenous material. F–I AS-OCTs of type 2 lesion showing a heterogeneous subepithelial hyporeflective lesion with two or more borders, dark lesions corresponding to serous material in #6, #10, and #17, and moderately hyperreflective fibrin deposits in #12. J–L AS-OCTs of type 3 lesion reveals an inhomogeneous, subepithelial, hyperreflective lesion with fibrillary and micro-cystic appearance of the connective tissue layer in #2, #13, and #18 elevating the overlying thin epithelium. Inset shows scan location

Full size image

The cyst sizes according to the corresponding en-face infrared picture were determined for all types. Average vertical diameter of type 1 cysts (n = 5) was 4052 µm, horizontal diameter was 4894 µm with an average area of 21 µm2 and a height of 1497 µm; type 2 cysts were 5502 µm in vertical diameter, 5599 µm in horizontal diameter, an area of 27.2 µm2, and a height of 1452 µm. Type 3 cysts showed an average vertical diameter of 4883 µm, a horizontal diameter of 5455 µm, and an average area of 37.8 µm2 with a height of 1687 µm. In four cases, measurements of cyst dimensions were not possible due to poor quality of scans.

Histopathological Findings

Specimens for histology were available from seven revision surgeries (patient #2, #4, #5, #12, #13, #15, and #16). All cysts were thin-walled with a soft capsule that easily ruptured on revision surgery. Cyst type 1 (single epithelial cyst) was found in #4, #5, #15 and #16; cyst type 2 (multilobular epithelial cyst) in #2 and #12; cyst type 3 (granulomtous cyst) in #13. Histopathologically, cyst type 1 revealed a cystic wall lined by a single to double layer of metaplastic squamous and cuboidal epithelium with chronic inflammatory reaction multifocally (Fig. 3A, B).

Fig. 3
figure 3

A, B Type 1, single epithelial cyst. A Histopathologic findings of #16 showing a complete cystic wall lined by a single to double layer of metaplastic squamous and cuboidal epithelium with chronic inflammatory reaction multifocally, measuring 0.4 × 0.4 × 0.25 cm (hematoxylin and eosin (H&E) stain, × 20). B The histopathologic section (H&E stain, × 200) of # 16. The cyst wall is lined by nonkeratinizing stratified metaplastic epithelium (asterisk) and connective tissue with chronic inflammatory reaction multifocally. C, D Type 2, multilobular epithelial cyst. C Histopathologic findings of patient #2 showing a multilobular cystic wall lined by a single to double layer of metaplastic squamous and cuboidal epithelium with chronic inflammatory reaction multifocally, measuring 0.4 cm (H&E stain, × 20). D The histopathologic section (H&E stain, × 200) of # 2 showing multilobular cyst walls lined by nonkeratinizing stratified metaplastic epithelium (asterisks) and connective tissue with chronic inflammatory reaction multifocally. E, F Type 3 granulomatous cyst. E Histopathologic findings #13 (H&E stain, × 20) showing a squamous cyst in fibrosed fat/connective tissue. F The histopathologic section (H&E stain, × 200) of patient #13 showing squamous cyst in fibrosed fat/connective tissue with multifocal chronic granulating partly resorptive inflammatory reaction (white asterisk), and focal protrusion of squamous epithelium (black asterisk) along double-breaking suture material (blue arrows), measuring 0.7 cm. Small lesions showed evidence of partially atrophic and fibrosed striated muscles

Full size image

Histopathological findings of type 2 multilobular epithelial cyst showed a multilobular cystic wall lined by a single to double layer of metaplastic squamous and cuboidal epithelium with chronic inflammatory reaction multifocally, measuring 0.4 cm (H&E stain, × 20). D. The histopathologic section (H&E stain, × 200) of patient #2 showing multilobular cyst walls lined by nonkeratinizing stratified metaplastic epithelium (asterisks) and connective tissue with chronic inflammatory reaction multifocally (Fig. 3C, D).

Histopathologic findings of type 3 granulomatous cyst showed a squamous cyst in fibrosed fat/connective tissue with multifocal chronic granulating partly resorptive inflammatory reaction and focal protrusion of squamous epithelium along double-breaking suture material (Fig. 3E, F).

The highly differentiated epithelium such as conjunctival epithelium with proven mucus-producing cells was detected. It was primarily assumed that the cyst was originally lined by this epithelium. A chronic inflammatory reaction was found multifocally, which could explain a transition into metaplastic squamous epithelium or flat cuboid epithelium. No evidence of malignancy was found in any specimen.

Microbiological Findings

In 7/12 patients receiving revision surgery (patient #1, #2, #3, #4, #10, #15 and #16), a microbiological swab test was taken. In all investigated cases the result was negative concerning fungi and aerobic as well as anaerobic bacteria.

Revision Surgery Results

Twelve of nineteen patients received revision surgery, with the achievement of a sustained removal of the cyst in all cases. In one case (patient #2) a smaller residual cyst was noted 3 weeks after revision surgery, which regressed spontaneously after 6 months. Average time until revision surgery was 15.67 weeks (range, 3–26 weeks). Because of their thin wall, total surgical excision of the cyst without rupture was successful only in two cases (#13 and #16), and this was associated with a significantly longer duration of revision surgery (40 vs. 16 min). No changes in muscle position had to be performed during revision surgery, since no muscle disinsertions were seen. In one case, we found a cyst out of squamous epithelium in fibrotic fat and connective tissue with multifocal chronic- granulating partly resorptive inflammation. An expansion of squamous epithelium could be found alongside birefringent suture material. Also, small samples of atrophic or fibrotic striated muscle could be found (Fig. 4).

Fig. 4
figure 4

Revision surgery of the medial rectus muscle in patient #13 showing a type 3 cyst measuring 9 mm × 5 mm

Full size image

Correlation Analysis

Eta nonparametric correlation analysis could show a correlation between time of clinical appearance and type of cyst (Eta = 0.63). Most cysts developed within 20 days after surgery. Not only did cysts more frequently affect the medial rectus muscle, which in most cases underwent a shortening procedure (11/19 tucks, 4/19 resections), the cyst also formed earlier in these muscles than in the lateral rectus muscle (Eta = 0.45). No correlation could be shown between the type of surgical procedure and time of cyst occurrence (Eta = 0.1). Patient age and cyst type correlated strongly (Eta = 0.47)—most cysts were type 1 in patients under the age 20 years. The underlying form of strabismus did not correlate with the type of cyst observed (Phi = 0.226).

Grading System

Clinical evaluation using slit lamp, AS-OCT, as well as histological analysis resulted in a classification of three types of cysts: type 1 single hyporeflective cyst, lined by a single or multi-layer of metaplastic epithelium; type 2 multilobular cyst of two or more hyporeflective compartments and histologically a multilobular cystic wall; type 3 a dense hyperreflective granulomatous-like cyst consisting of squamous epithelium in fibrosed fat and connective tissue with a multifocal chronic granulating, partly resorptive inflammatory reaction. Detailed analysis of the cysts led to a grading system, which is summarized in Table 2.

Table 2 Grading system of postoperative cysts according to clinical findings
Full size table

Discussion

What is Known About Postoperative Cyst Formation from the Literature

So far, no clear association with either the surgical technique or specific disturbance of wound healing or infection has been made. Some could clearly be identified as epithelial inclusion cysts, their position varying from the anterior superficial aspect of the operated muscle to below the muscle belly, or even distantly anterior to the muscle insertion or deep within the orbit [22]. Neither was there any evidence for a specific suture material to be prone to cause this complication.

What is Known from Observations in Animal Models

In 1966, Ingram had studied wound healing after strabismus surgery in the Macaca rhesus monkey and proposed the term “pseudotenon” for the scar tissue he found around the operated muscles [27]. His observation was confirmed in the human in 1976, when Swan described wound healing around the operated extraocular muscle from a specimen after revision strabismus surgery [23]. Ingram had already noted that the original tenon layer was not needed for safe reattachment of the muscle, but recommended diligent wound closure with respect to all tissue layers for regular healing. Later, Kushner described such a “pseudotenon” membrane on the undersurface of the operated extraocular muscle in a case series of subconjunctival cysts he had surgically revised years after the initial strabismus surgery [22].

Theories About the Etiology of the Cysts

Since then, several reports add to the characterization of the course, localization, and morphology of postoperative cysts after strabismus surgery. The suspected etiological mechanism, the implantation of epithelial cells into the canal of the scleral suture by dragging with the suture material, has been questioned [22], and could be excluded in some cases, e.g., in a case where the cyst located to the muscle belly, 2 mm from the insertion [28]. Moreover, other ophthalmo-surgical procedures also involve scleral tunnels and sutures, but with a significantly lower reported incidence of conjunctival inclusion cysts [29,30,31].

Anatomical and Physiological Considerations

Hence, additional factors for cyst formation can be postulated regarding the distinctive anatomical features of the extraocular muscles’ soft tissue sheaths along with mechanical strain during muscle action. Occurrence of the cysts years after strabismus surgery is associated with larger size of the cysts and a different localization according to the literature—the cyst lying between the site of the intended new position of the extraocular muscle during initial surgery and the anterior edge of the now posteriorly displaced muscle [17, 22, 32]. The fornix and bulbar conjunctiva consist of a three-layered epithelium, whereas the limbal conjunctiva consist of 8–10 layers of stratified squamous epithelium. The goblet cells are more common in the inferior and nasal parts, particularly near the fornix. It can be hypothesized that formation of cysts in the nasal bulbar region are due to the histologically unique presence of more epithelial layers and dense goblet cells in this region. Histopathologically, the origin of the cysts in most cases appears to be from conjunctival tissue, that by implantation during the surgical procedure forms cysts adjacent to the operated eye muscle.

Surgical Alternatives and their Anatomical Advantages or Disadvantages

Although cyst formation has not been described in the literature postoperatively after Botox injection, it can also cause serious complications such as vitreous hemorrhage and retinal detachment [33]. Another procedure to minimize surgical burden on patients, the combined resection of Müller’s muscle and conjunctiva with tarsectomy and horizontal strabismus surgery, did not show an increased risk of the formation of postoperative cysts in a small collective [34].

Characteristics of the Cysts in our Collective

In all of our 19 cases, however, cysts developed early after surgery (mean detection time 24 days postoperatively), and revision surgeries showed a cyst localized to the surface of the anterior aspect of the operated muscle. No cases of submuscular cyst formation and no infected cysts were found. Characterization by slit-lamp aspect, AS-OCT, and histopathological examination resulted in three categories. In the more translucent cysts—mostly in type 1, but also in several type 2 cysts, deposits of dense homogenous material can be seen in slit-lamp examination as a pseudohypopyon. In contrast to a real hypopyon or other forms of pseudohypopyon, postoperative conjunctival cysts often feature a double layer where the center is clear, their aspect resembling that of a striped billiard ball. AS-OCT enhances visualization of the interior of especially the denser cysts and in many cases reveals a significant number of fibrin-like deposits inside the cyst.

Comparison to Cysts After Different Ophthalmo-Surgical Procedures

Parallels in the clinical picture of postoperative cysts can be seen both between early and late-type cysts and between different surgeries. Even after pars plana vitrectomy, Bourcier et al. showed a case of postoperative cyst [30] with the typical formation of a double-layered pseudohypopyon (“striped billiard ball”) as best seen in our patient #2 (Fig. 1I).

The Search for Reasons for the Massive Increase in Postoperative Cysts from January 2019

Remarkably, in our collective of 822 patients, not a single cyst formation was noted during the first 4 years or within the first 410 consecutive cases, while in the second period of three and a half years or within the following 412 consecutive cases a total of 19 postoperative cysts were observed.

As we pointed out in the Introduction, postoperative cyst formation is a known complication of especially strabismus surgery, but incidence in previous reports moved between 0.25% [20] and 0.4% [21], whereas it reaches an almost tenfold amount in our second collective (4.5% in the second 412 cases), and an overall value of 2.3%, which still is unparalleled. Several potential weak points make comparing those incidences difficult, the two most important being a variable rate of routine follow-up and a high variability in subjective symptoms. The fact that all of our 822 patients received a standard follow-up visit 3 months after surgery fairly excludes point one in our study, and the possibly higher awareness and sensitivity for cosmetically eye-catching alterations post-surgery should satisfactorily remove point two. Hence, we really do think that the extremely high incidence of cysts in collective two was real.

The Potential Role of Technique

One possible mechanism of postoperative cyst formation is implantation of epithelial cells into the deeper tissues, which then form inclusion cysts. When we observed the occurrence of the first postoperative cysts in our collective, we did not essentially change the manner of conjunctival closure, since we had always been using the same technique and instruments. We did, as always, pay attention to meticulous conjunctival closure and keeping the suture thoroughly clear of any adhering tissue. This was also considered in cases where the surgeon was a resident.

The Potential Role of Suture Material and Instruments

The first idea of how to explain this sudden increase in incidence was a change in the chemical properties of the suture material. However, the company confirmed no changes in the material had been made at all. Still, since the raised incidence remained, we asked the company to provide us the unstained pendant of our standard muscle suture—which we switched to since January 2021. Even with the unstained material, however, we still observed the same elevated incidence of cysts, which made us again change the suture material, this time to a 6/0 absorbable unstained multifilament coated PGA suture with a S-14 8-mm spatula needle (VICRYL™, Ethicon, Johnson & Johnson Medical, Norderstedt, Germany). After having contacted the company providing the suture material, we also extended our instrument scanning and documentation system to the systematic tracking of all sutures being used during our strabismus surgeries. Thus, specifications like the charge number and material properties could easily be looked up in case of another complication. This seemed to make even more sense, as the cysts appeared in clusters of two or three patients operated on within a matter of weeks, further emphasizing the potential role of suture material as a specific culprit. In addition, a long-planned replacement of the surgical instruments took place in November of 2021. Even though switching to newer instruments should generally reduce the risk of complications like epithelial implantation, we successively replaced the 10-mm spatula (Castroviejo, G-15480, Geuder, Germany) used for muscle tucking by a model with a wider 15-mm end (Castroviejo, G-15475, Geuder, Heidelberg, Germany) to prevent tissue dragging on the distal end of the spatula.

Strengths and Limitations of the Study

The large number of patients compared to other studies in the field is our major strength. Moreover, our study features a detailed and multimodal imaging approach, enabling a comprehensive comparison and clinical classification of this entity. The systematic follow-up visits at fixed points in time contribute to the reproducibility of our research. Limitations are the rarity of this complication itself as well as the lack of insight into the process of wound healing on a biochemical level.

Conclusions

In conclusion, our study includes a period of significantly increased incidence of postoperative cyst formation after strabismus surgery, compared to our previous collective and reports in the literature. Diligent rework led to adaptations of the surgical procedure including a change in suture material, instruments, and the implementation of continuous scanning of the suture material used. The particularly high number of cases and AS-OCT as a new imaging modality allowed for a detailed description of the cysts, leading to a classification system for early postoperative epithelial inclusion cysts into three types. In the future, our multimodal approach may contribute to a better understanding and individualized management of these cases.