A persistent pupillary membrane (PPM) is a congenital ocular anomaly. Although the exact pathophysiology is not well understood, a PPM is regarded to represent the remnants of the anterior tunica vasculosa lentis, which supplies nutrition to the developing lens during embryogenesis.1 PPMs range in appearance from fine, fragile strands to densely pigmented membranes that almost totally block the visual axis.1,2 Most PPMs require no treatment because they usually regress during the first year of life.3 However, some PPMs are large and dense enough to affect visual development, necessitating intervention. Medicine, laser, and surgical treatments have been introduced to clear the visual axis and optimize visual development.4,5 The use of a Nd:YAG laser for membranectomy has been described in previous studies and was found successful in adults and older children.4–6 However, laser therapy is technically difficult in young children and might not be effective in cases with thick, fibrotic membranes.5

Various surgical approaches involving different instruments to manipulate and remove the membranes, including micro-Vannas scissors and vitreous scissors, have been described in previous studies.2,3,7–10 Some studies have reported modified surgical methods for removing PPMs.9,10 However, most of the previous reports were case reports or case series with a few cases. To our knowledge, there has been no study summarizing PPMs with different morphologies nor describing the surgical approaches for such cases. The aim of this study was to explore the surgical methods and techniques for PPMs with different morphologies. Furthermore, the preoperative and postoperative changes in vision were evaluated.

METHODS Patients

Patients (aged from 3 to 14 years) with visually significant PPMs who needed membranectomy surgery were included from April 2020 to July 2022 at the Zhongshan Ophthalmic Center, Sun Yat-sen University in China. Patients who had a relevant ocular disease other than PPM or could not tolerate the examinations were excluded. The indications for surgery included decreased visual acuity, poor retinoscopic reflex, or impaired visualization of the fundus. Patients with bilateral PPMs underwent coinstantaneous surgery. The study adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from the parent or guardian of each patient. The original study protocol in each country was approved by the Ethics Committee of Sun Yat-sen University-Zhongshan Ophthalmic Center-Institutional Review Board.

Preoperative Examinations

Detailed ophthalmic examinations were performed preoperatively, including detailed history-taking, visual acuity, intraocular pressure (IOP), slitlamp examination, autorefraction, and fundus examination. The visual acuity as measured using a Snellen Chart was converted to logMAR for analysis. The keratometry parameters were measured with an IOLMaster 700 (Carl Zeiss Meditec AG) in all the patients. Slitlamp examination (BX900, Haag-Streit AG) was performed through natural and dilated pupils, while anterior segment photographs were obtained for morphological evaluation and classification. The morphology of the PPM and its relationship with the anterior lens capsule were evaluated under natural and dilated pupils.

Surgical Technique

Operations were performed on patients without a tight membrane adhesion with the anterior lens capsule under natural pupils. Otherwise, patients with a central membrane adhesion with the anterior lens capsule received compound tropicamide drops (0.5% tropicamide plus 0.5% phenylephrine hydrochloride, 3 doses at 10-minute intervals) 30 minutes before the surgery to dilate the pupil. An experienced pediatric ophthalmologist specialist (W.R.C.) performed all the surgeries.

All the surgeries were performed under general anesthesia with tracheal intubation. After making a 2.2 mm modified scleral tunnel incision, a cohesive ophthalmic viscosurgical device (OVD) with a blunt tip was used to gently fill the space between the PPM and the anterior lens capsule. When the tensile force of the OVD was inadequate to separate the membrane from the anterior lens capsule, the blunt tip of the OVD was used to assist the separation. Before using capsulotomy scissors to cut the attached membrane near the collarette of the iris, the OVD was inserted to lift the membrane strand to prevent injuring the normal iris tissue. The PPM was removed through the primary incision with capsulorhexis forceps only when all the membrane strands were confirmed to be severed.

In some patients with no space between the PPM membrane and the anterior lens capsule, an OVD was incapable of separating the membrane from the anterior lens capsule. In these cases, a discission needle was used to gently and carefully hook the membrane, and then, the capsulorhexis forceps was used to peel off the membrane. An additional OVD was used as needed to allow viscodissection and to protect the anterior lens capsule.

If the pigment severely blocked the visual axis and could not be removed by applying a balanced salt solution or an OVD, an OVD with a blunt tip was used to gently polish the anterior lens capsule. Whether the anterior lens capsule was injured during the operation should be confirmed before miosis. Irrigation/aspiration was performed to remove the remaining OVD from the anterior chamber after miosis. Intraoperative complications were also recorded.

Postoperative Examinations

Postoperative follow-up was performed on the first day, 1 week, 1 month, 3 months, 6 months, and then every 3 months postoperatively. The follow-up period was at least 6 months. Detailed ocular examinations were performed at each visit, including visual acuity, IOP, slitlamp examination, and fundus examination. The axial length and keratometry parameters were measured, and refraction was examined at 3 months postoperatively. Postoperative complications, including traumatic cataract, suspected glaucoma, and glaucoma, were also recorded.

Data Analysis

Statistical analysis was performed using SPSS statistical software (v. 24.0, SPSS, Inc.). Continuous variables are shown as the mean ± SD. Categorical variables such as sex, PPM type, and intraoperative complications were described as percentages. The normality of data distribution was assessed with the Shapiro‒Wilk test. A mixed model was used to compare continuous variables before and after the operation. A P value of 0.05 or less was considered statistically significant.

RESULTS

This study comprised 31 eyes from 19 patients. The mean age of the patients was 7.2 ± 3.3 years (range from 3 to 14 years). Twelve patients (24 eyes) underwent bilateral surgery. Slitlamp examination and anterior segment photographs under natural and dilated pupils were used to assess the morphology of the PPM, especially its relationship with the anterior lens capsule. Three morphologic variants of the PPM were observed (Table 1).

Table 1. - Clinal characteristics in varied morphological characteristics of PPMs Characteristics Type I Type II Type III Age (y), mean ± SD (range) 7.1 ± 3.0 (3, 14) 7.4 ± 2.8 (4, 13) 7.3 ± 0.8 (6, 8) Proportion of cases, % (n) 48.4 (15/31) 41.9 (13/31) 9.7 (3/31) Follow-up (mo), mean ± SD 6.7 ± 2.4 8.6 ± 5.0 14.5 ± 6.8 Morphological characteristics of PPM evaluated under natural and dilated pupil Spider-like appearance with plenty of fine iris strands attached to iris collarette, without tight adhesion to the anterior lens capsule Central membrane loosely adhered to the anterior lens capsule, with partially thick iris strands attached to iris collarette Central membrane tightly adhered to the anterior lens capsule, with a few silk-like iris strands attached to iris collarette Pupil dilation preoperatively No Yes Yes Surgical approaches to separate the central membrane from the anterior lens capsule No adherence; viscoelastic injection to increase the surgical space Separated by viscoelastic injection Discission needles and capsulorhexis forceps were used to peeled off the central membrane Anterior lens capsule polish for the pigment residue, (%) n 13.3 (2/15) 69.2 (9/13) No Iris injury (%) 0 0 0 Lens injury (%) 0 0 0 Transient increase of IOPa after surgery, % (n) 26.7 (4/15) 30.8 (4/13) 0 (0/0)

PPM = persistent pupillary membrane

aIOP increased after surgery and decreased to the normal range within a month postoperatively

Type I was characterized by a spider-like appearance with plenty of fine iris strands attached to the iris collarette; however, there was no tight adhesion between the PPM and the anterior lens capsule (Figure 1, A–C). Type II was a PPM that had a central membrane loosely adhered to the anterior lens capsule and partially thick iris strands attached to the iris collarette (Figure 1, D–I). There were 2 subtypes of type II PPMs according to the different distributions of iris strands. In type IIa PPMs, iris strands were distributed in all quadrants of the pupil, as shown in Figure 1, D–F, while in type IIb PPMs, iris strands were distributed in only 1 to 2 quadrants of the pupil, as shown in Figure 1, G–I. In type III PPMs, a central membrane is tightly adhered to the anterior lens capsule, but only a few silk-like iris strands are attached to the iris collarette (Figure 1, J–L).

Figure 1.:

Representative images of 3 morphological variants of PPMs are presented. A type I PPM is characterized by a spider-like appearance with plenty of fine iris strands attached to the iris collarette (A-C). Type II PPMs are characterized by a central membrane that is loosely adhered to the anterior lens capsule and with partially thick iris strands attached to the iris collarette (D-I). There are 2 subtypes of type II PPMs. Type IIa PPMs are distributed in all quadrants of the pupil, as shown in D-F, while type IIb PPMs are distributed in only 1 to 2 quadrants of the pupil, as shown in G-I. Type III PPM is characterized by a central membrane tightly adhered to the anterior lens capsule and with a few silk-like iris strands attached to the iris collarette (J-L). A, D, G, and J were filmed under dispersed light with natural pupils, B, E, H, and K were filmed under slit light with natural pupils, and C, F, I, and L were filmed under dispersed light with dilated pupils. PPM = persistent pupillary membrane

Type I PPMs were observed in 15 eyes (48.4%), type II was observed in 13 eyes (41.9%), and type III was observed in 3 eyes (9.7%). Patients with type I PPMs were 3 to 14 years of age, those with type II PPMs were 4 to 13 years of age, and those with type III PPMs were 6 to 8 years of age (Table 1).

Patients with type I PPMs were operated on under natural pupils. The OVD was used to fill the space between the membrane and the anterior lens capsule, and then, capsulotomy scissors were used to cut each iris strand attached near the iris collarette. After each attached iris strand was severed, the PPM was removed through the primary incision with capsulorhexis forceps (Figure 2).

Figure 2.:

Surgical procedures for type I PPM. PPM before surgery with natural pupil (A). OVDs were injected under the PPM to create a surgical space and separate possible adhesions between the PPM and the anterior lens capsule (B). The attachment of the PPM and iris were cut with capsular scissors (C, D). PPMs were removed, and few pigmentations remained on the anterior capsule (E). The pupil was constricted by injection of carbachol into the anterior chamber (F). PPM = persistent pupillary membrane

Patients with type II PPMs were operated on under dilated pupils. The OVD was inserted to separate the central membrane from the anterior lens capsule. Then, capsulotomy scissors were used to cut each iris strand attached near the iris collarette (Figure 3). In some cases, there was residual pigment on the center surface of the anterior lens capsule in which the anterior lens capsule was polished and cleaned with a viscoelastic material through injection (Figure 3, C–E).

Figure 3.:

Surgical procedures for type II PPM. PPM before surgery with dilated pupil (A). OVDs were injected under the PPM to create a surgical space and separate possible adhesions between the PPM and the anterior lens capsule. The attachment of the PPM and iris were cut with capsular scissors (B). PPMs were removed, and few pigmentations remained on the anterior capsule (C). Dense pigmentations remained on the anterior lens capsule (C). A blunt pinhead was used to polish the anterior lens capsule to remove the pigmentations (D). The floating pigmentations and remaining OVD were cleared by inspiration/aspiration (E). The lens remained clear and intact after surgery (F). PPM = persistent pupillary membrane

Patients with type III PPMs were operated on under dilated pupils. There was no space between the central membrane and the anterior lens capsule; therefore, using an OVD was incapable of separating the membrane from the anterior lens capsule. In these cases, a discission needle was used to gently and carefully hook the membrane, and then, capsulorhexis forceps were used to peel off the membrane (Figure 4).

Figure 4.:

Surgical procedures for type III PPM. PPM firmly adhered to the anterior lens capsule before surgery in a dilated pupil (A). Discission needles were used to hook the PPM (B), and capsulorhexis forceps were used to peel the central membrane from the anterior lens capsule (C). Scissors were used to cut the silk-like attachment between the PPM and the iris (D). The isolated PPM and remaining OVD were cleared by inhalation/aspiration (E). The lens remained clear and intact after surgery (F). PPM = persistent pupillary membrane

As summarized in Table 2, the postoperative corrected distance visual acuity (CDVA) was significantly better at the final visit (0.19 ± 0.12) than the preoperative CDVA (0.34 ± 0.18) (P < .001). Vision in patients with type I and type II was significantly improved, although the improvement was not significant in patients with type III. There were 3 eyes with type III, 2 eyes with improved CDVA, and 1 eye with no postoperative change in vision. Moreover, corneal astigmatism was not changed postoperatively (P = .13).

Table 2. - The comparison between descriptive statistics of PPM eyes before and after surgery Variables Preop Postop P value CDVA (logMAR) 0.34 ± 0.18 0.19 ± 0.12 <.001*  Type I (n = 15) 0.36 ± 0.20 0.23 ± 0.11 .007*  Type II (n = 13) 0.34 ± 0.17 0.18 ± 0.12 <.001*  Type III (n = 3) 0.25 ± 0.13 0.17 ± 0.04 .25 ΔK (D) −2.06 ± 1.20 −1.78 ± 1.55 .13 K1 (D) 42.14 ± 1.95 42.35 ± 1.78 .01* K2 (D) 44.24 ± 2.24 44.13 ± 2.53 .18 Sph (D) 3.48 ± 3.25 3.36 ± 3.26 .20 Cyl (D) −1.33 ± 1.56 −1.50 ± 1.52 .13

PPM = persistent pupillary membrane; LLCI = lower limit of CI; ULCI = upper limit of CI; ΔK = corneal astigmatism; K1 = flat keratometry; K2 = steep keratometry; Sph = sphere; Cyl = cylinder

*Statistically significant

In this study, the PPM was successfully removed from all the eyes without causing any severe complications during 9.5-month follow-up. No iris or lens injuries were observed during surgery. Transient hypertension presented in 8 of 31 (25.8%) eyes, including 4 of 15 (26.7%) with type I and 4 of 13 (30.8%) with type II. However, the IOP of these eyes decreased to a normal range within 1 month postoperatively.

DISCUSSION

The present prospective study was intended to define the morphology of PPMs and explore the appropriate surgical approaches for different morphologies of PPMs. We examined PPMs with 3 different morphologies based on their anatomical relationship with the anterior lens capsule. PPMs with a spider-like appearance but no adhesion to the anterior lens capsule were found in 15 eyes (48.4%, type I). PPMs with a central membrane loosely adhered to the anterior lens capsule, and partially thick iris strands were found in 13 eyes (41.9%, type II). PPMs with a central membrane tightly adhered to the anterior lens capsule, but only a few silk-like iris strands were found in 3 eyes (9.7%, type III). For different morphological variants of PPMs, different surgical approaches were performed to remove the membranes. PPMs were successfully removed from all the eyes without causing any severe complications. After surgery, the postoperative CDVA was significantly better than the preoperative CDVA.

A PPM is usually an isolated finding, and most PPMs are asymptomatic. However, some PPMs that impair visual acuity can produce deprivation amblyopia.11 A thick membrane that covers the entire pupil or leaves a pupillary opening less than 1.5 mm usually requires surgical removal.8,11 In previous studies, successful surgical management of PPMs has been reported. In the study of Lee et al., the long-term lens complications in 32 eyes of 26 children with PPM after removal were evaluated retrospectively.8 Only 2 patients presented with lens changes during the 6.5 ± 3.3-year postoperative follow-up period. Hu et al. also reported that surgical membranectomy was successfully performed in 8 eyes of 6 PPM patients with a low risk of complications.9 However, most of the previous studies were retrospective studies or case reports with a few cases. To our knowledge, this is the first study to summarize the various morphologies of PPM and elaborate the surgical approaches for such cases.

In this study, a PPM without a central membrane adhered to the anterior lens capsule (type I) was the most common type, which was found in 15 eyes (48.4%). The surgical methods for removing a PPM with a similar morphology were described in previous case reports. Most of the authors suggested performing the surgery through a dilated pupil.9,12,13 Tsai used carbachol 0.01% to constrict the pupil before surgery.3 However, in this study, patients with type I PPMs were operated on through their natural pupils. A type I PPM was characterized by multiple iris strands attached to the iris collarette in all quadrants. Therefore, surgery performed through an undilated pupil was better for avoiding the scissor and the tips to contact with the crystalline lens. The reason why the pupil was not constricted was that there was a pigment residue on the surface of the anterior lens capsule in some patients (13.3%) with this type. The anterior lens capsule could be polished through the natural pupil.

In contrast to type I PPMs, type II PPMs are characterized by a central membrane that is adhered to the anterior lens capsule. Pupil dilation was recommended during surgery to increase traction of the central membrane, which helped to lyse the central adhesions. The central adhesion between the PPM and the anterior lens capsule could be relatively easily separated by injecting a viscoelastic material in most cases. The surgical treatment of PPMs with a morphology similar to type II PPMs has been reported in previous studies. In the report of Ramappa et al., a 12-year-old PPM patient with a bilateral hyperplastic membrane adhering to the lens underwent surgical treatment. At the last visit 16 months postoperatively, the lens remained clear in this case.14 Similarly, in the study of Kraus and Lueder, the visual axis in 10 eyes of 6 patients was clear, and there were no significant complications after a mean postoperative follow-up of 5.3 years.2 It is worth mentioning that the pigment residue was found on the surface of the anterior lens capsule in more patients (69.2%) with this type than in those with type I PPMs. In most of these cases, a viscoelastic material was applied through a blunt tip to polish the surface of the anterior lens capsule and remove the pigment. After a mean follow-up of 9.6 months, the lenses of these patients remained clear.

The adhesion between the central membrane and the anterior lens capsule in patients with type III PPMs was the tightest among the 3 types of PPMs. There was no gap between the central membrane and the anterior lens capsule, so blunt separation with a viscoelastic injection was unfeasible. In these cases, a discission needle and capsulorhexis forceps were used to peel the membrane from the anterior lens capsule. Care was taken to avoid disruption of the lens capsule. This type of PPM was observed in only 3 eyes (9.7%) in this study. To our knowledge, no similar cases have been previously reported. In this type of PPM, the central pigmented membrane was tightly adhered to the anterior lens capsule. However, the PPM was derived from the tunica vasculosa lentis, while the lens capsule originated from the epidermal ectoderm. The different embryonic development of the 2 tissues might make it possible to separate them. In this study, there were no lens opacities during a mean follow-up of 14.5 months.

Some authors believe that there is no visual advantage to be gained by removing these membranes after the sensitive period for visual development is over, although modest improvements have been reported in teenagers.5,14 Similarly, in this study, vision was significantly improved after surgical treatment of PPMs. The visual acuity in patients with type III PPMs was not significantly improved after the surgery. However, vision was better after surgery in 2 eyes, and the vision in 1 eye with a type III PPM remained the same as before. The small sample size of patients with type III PPMs might limit the discovery of positive results. Although the visual outcomes improved in most of the cases, transient increases in IOP occurred in 25.8% of eyes postoperatively. The reason for the transient increase in IOP in these cases might be that we constricted the pupils before aspirating the viscoelastic agents, which might lead to the residues of viscoelastic agents. However, after topical treatment with medicine, the IOP in all these cases was reduced to the normal range within 1 month postoperatively.

A modified superior scleral tunnel incision was made in all the eyes in this study, which would be better protected by the upper eyelid. In addition, corneal astigmatism was found in all the study cases, which was similar with the previous report.15 Therefore, the superior incision would not increase corneal astigmatism after surgery. In this study, corneal astigmatism decreased slightly postoperatively, although the difference was not statistically significant. It is worth mentioning that some authors recommend multiple corneal incisions for removing an extensive PPM.3 If the surgeon is not very experienced and feels it difficult to operate through a single incision, multiple incisions can be considered. In this study, the senior surgeon used capsule scissors to cut the attached membrane near the collarette of the iris. In previous reports, some authors recommended the use of vitreous scissors, which might be more suitable for surgeons with less experience.2,14 However, it was recommended that PPM removal surgeries should be performed by experienced surgeons. The surgical procedure carries the risk for cataract formation, especially in patients with type II and type III PPMs.

This study has limitations. First, the sample size was small, thus limiting our power to detect statistically significant differences in parameters, especially in patients with type III PPMs. Second, the follow-up time was not long enough to observe any long-term complications, although no postoperative complications have been found thus far. Despite these limitations, to our knowledge, this is the first study to summarize the various morphologies of visually significant PPMs. Moreover, we present safe and effective surgical approaches for 3 different morphologies of PPMs. With these surgical approaches, PPMs can be removed without leaving the pigment residue on the visual axis, which benefits visual improvement after surgery.WHAT WAS KNOWN Persistent pupillary membrane (PPM) is a congenital ocular anomaly with various morphological manifestations, some of which are large and dense enough to affect visual development, necessitating intervention. What different surgical methods and techniques could be applied to different morphological forms of PPMs have not been summarized.

WHAT THIS PAPER ADDS PPM was assessed and categorized into 3 types according to its morphology and the anatomic relationship with the anterior lens capsule. Appropriate surgical approaches and techniques for different types of PPMs were beneficial to improve surgical safety and reduce surgical complications. REFERENCES 1. Viswanathan D, Padmanabhan P, Johri A. Hyperplastic persistent pupillary membranes with congenital corneal anomalies. J Cataract Refract Surg 2007;33:1123–1126 2. Kraus CL, Lueder GT. Clinical characteristics and surgical approach to visually significant persistent pupillary membranes. J AAPOS 2014;18:596–599 3. Tsai Y, Chiang C, Tsai C. Surgical technique for removing an extensive persistent pupillary membrane. J Cataract Refract Surg 2004;30:1622–1625 4. Kumar H, Sakhuja N, Sachdev M. Hyperplastic pupillary membrane and laser therapy. Ophthalmic Surg 1994;25:189–190 5. Gupta R, Kumar S, Sonika, Sood S. Laser and surgical management of hyperplastic persistent pupillary membrane. Ophthalmic Surg Lasers Imaging 2003;34:136–139 6. Wang J, Wu C, Lai P. Sequential argon-YAG laser membranectomy and phacoemulsification for treatment of persistent pupillary membrane and associated cataract. J Cataract Refract Surg 2005;31:1661–1663 7. Reynolds J, Hiles D, Johnson B, Biglan A. Hyperplastic persistent pupillary membrane: surgical management. J Pediatr Ophthalmol Strabismus 1983;20:149–152 8. Lee H, Kim J, Kim S, Yu Y. Long-term lens complications following removal of persistent pupillary membrane. Korean J Ophthalmol 2018;32:103–107 9. Hu H, Nie D, Zou Y, Du B, Fang M, Yang M, Wang J, Liu X. Surgical membranectomy with modified incision and capsulotomy microscissors for persistent pupillary membrane. Ann Palliat Med 2021;10:5619–5626 10. Serafino M, Trivedi R, Wilson M, Ramappa M, Achanta D, Nucci P. Outcomes after surgical removal of anterior epi-capsular plaque associated with persistent pupillary membranes in children. Eur J Ophthalmol 2022;32:729–731 11. Miller S, Judisch G. Persistent pupillary membrane: successful medical management. Arch Ophthalmol 1979;97:1911–1913 12. Banigallapati S, Potti S, Marthala H. A rare case of persistent pupillary membrane: case-based approach and management. Indian J Ophthalmol 2018;66:1480–1483 13. Iida M, Mimura T, Goto M, Kamei Y, Kondo A, Saito Y, Okuma H, Matsubara M. Letter to the editor: excision of congenital bilateral persistent pupillary membrane in a child with exotropia. Open Ophthalmol J 2015;9:33–35 14. Ramappa M, Murthy S, Chaurasia S, Singhla R, Rathi VM, Vemuganti GK, Sangwan VS. Lens-preserving excision of congenital hyperplastic pupillary membranes with clinicopathological correlation. J AAPOS 2012;16:201–203 15. Hu H, Yang M, Du B, Fang M, Liu X, Wang J. Evaluation of corneal curvature and astigmatism in patients with persistent pupillary membrane by partial coherence interferometry measurements. Ophthalmic Res 2020;63:314–319