Postoperative Full-Thickness Macular Hole Formation after Vitrectomy for the Removal of Epiretinal Membrane

Abstract

Purpose

To evaluate the incidence, clinical features, risk factors, and outcomes of full-thickness macular hole (MH) formation after pars plana vitrectomy (PPV) for the removal of epiretinal membrane (ERM).

Methods

This retrospective study reviewed the medical charts of the 309 eyes of 306 patients with PPV for ERM removal from 2012 to 2024 using clinical data warehouse search. Patients were categorized into two groups: one group with development of MH and the other without MH development after ERM surgery. Baseline demographics and clinical parameters were compared between the two groups. Risk factors for MH formation were analyzed using univariate and multivariate logistic regression. Surgical outcomes of the cases with MH formation were also analyzed.

Results

A total of 141 eyes were included. Five cases (3.5%) developed MH after PPV for ERM removal. In all five cases (100%), ERM was observed at MH detection. In four of the five patients (80%), cystoid macular edema (CME) was present at MH detection. ERM with lamellar hole was significantly associated factors for MH formation (odds ratio [OR], 13.11; p = 0.018). Pre-operative central macular thickness (CMT) showed a marginal association (OR, 0.98; p = 0.075). Among the four patients who underwent surgery, macular hole was successfully closed in three cases. There was no significant difference in best-corrected visual acuity before and after MH surgery.

Conclusions

ERM with lamellar hole was a significant factor for MH formation, while thin preoperative CMT showed a marginal association. At the time of MH detection, ERM and CME were observed in most cases, suggesting that tangential traction caused by postoperative ERM or, postoperative CME may represent possible etiologies for MH formation. In patients with ERM with lamellar hole or thin CMT, the possibility of MH formation after ERM surgery should be taken into account and careful monitoring is needed.

Epiretinal membrane (ERM) is a fibrocellular proliferation on the inner surface of the retina, over the internal limiting membrane (ILM) [1,2]. ERM is a common condition which results in significant patient’s quality of life affecting symptoms such as distortion and blurred vision, which is shown to have incidence rate as 7% to 11.8% [3–6]. Surgical intervention of pars plana vitrectomy (PPV) is frequently employed to improve vision for symptomatic ERM. However, complications such as a postoperative cataract, retinal detachment, recurred ERM, and rarely infection and full-thickness macular hole (FTMH) would result in worse vision and be followed by patient’s dissatisfaction [3,7–10]. Jain et al. [11] reported that FTMH rarely occurs after vitrectomy for ERM compared to other indications such as retinal detachment or vitreous hemorrhage, and noted that vitrectomy for myopic maculopathy may increase the risk of FTMH. Although little is known about the incidence of FTMH following vitrectomy for ERM, it is being reported as 0.95% to 5.6% in previous studies [12–16]. Sandali et al. [15] reported that five patients (1.0%) developed a paracentral MH among 509 patients who underwent PPV with ERM removal. Rush et al. [13] reported 11 patients (2.6%) developed postoperative MHs among 423 patients who underwent PPV and ERM/ILM peeling. In their study, the incidence of the central FTMH was 0.5%, and the incidence of the eccentric (nonfoveal) FTMH was 2.1%. The two previous studies either did not include central FTMHs or included only a very small number of such cases.

There have been few studies that have systematically investigated the formation of FTMH following PPV for ERM removal. In addition, even among these rare studies, most have reported atypical cases of paracentral or eccentric FTMH following ERM surgery. Considering that central FTMH at fovea may affect patient’s vision quality of life more than eccentric FTMH, identifying possible preoperative, intraoperative and postoperative factors associated with the development of postoperative foveal FTMH may have important clinical significance.

The purpose of the present study is to investigate the clinical characteristics of the central FTMH formation after vitrectomy for ERM removal and to identify the associated risk factors of postoperative FTMH formation. Additionally, we aimed to assess the anatomical and functional outcomes of FTMH formation.

Materials and Methods

Ethics statement

This study was approved by the Institutional Review Board of Ewha Womans University Mokdong Hospital (No.2025-04-009). The requirement for informed consent was waived due to the use of deidentified data and the retrospective nature of the study. All study procedures were conducted in compliance with the Declaration of Helsinki.

Study design and participants

This was a single centered, retrospective cohort study. Inclusion criteria were as follows: (1) patients who were diagnosed with ERM and underwent PPV for ERM removal at Ewha Womans University Mokdong Hospital from January 1, 2012, to December 31, 2024; and (2) followed up for more than 6 months (i.e., the possible latest follow-up was June 30, 2025). Flowchart for eyes included in the current study is presented in Fig. 1. First, using clinical data warehouse search, we retrieved the cases of PPV performed from January 1, 2012, to December 31, 2024, for the removal of ERM. Duplicate cases resulting from multiple surgeries on the same eye were excluded by reviewing electronic medical records of the retrieved cases. A total of 309 eyes of 306 patients were extracted. Among these, 168 eyes were excluded. Exclusion criteria were as follows: (1) accompanied macular diseases which can affect visual acuity (i.e., age-related macular disease, diabetic macular edema, macular edema due to branch retinal vein occlusion or central retinal vein occlusion, etc.; n = 48); (2) follow-up period of less than 6 months (n = 42); (3) vitrectomy for indications other than ERM (n = 28); (4) prior diagnosis with FTMH prior to ERM surgery (n = 16); (5) no stored optical coherence tomography (OCT) data at either preoperative or postoperative visit (n = 13); (6) previous history of vitrectomy (n = 12); (7) intraoperative gas or air tamponade for iatrogenic lesions (retinal detachment, breaks, etc.) during ERM removal (n = 9). Cases in which intraoperative air tamponade was performed at the discretion of the surgeon during ERM surgery accompanied by vitreomacular traction syndrome, lamellar hole (LH), or foveoschisis were included. The remaining 141 eyes of 139 patients were finally enrolled and analyzed in the study.

Fig. 1.

Flowchart for eyes included in the study. CDW = clinical data warehouse; EMR = electronic medical records; ERM = epiretinal membrane; PPV = pars plana vitrectomy; AMD = age-related macular degeneration; DME = diabetic macular edema; ME = macular edema; BRVO = branch retinal vein occlusion; CRVO = central retinal vein occlusion; MH = macular hole; OCT = optical coherence tomography; RD = retinal detachment.

Standard three-port 23- or 25-gauge PPV was performed with the Accurus (Alcon Laboratories) or Constellation System (Alcon Laboratories) and the noncontact wide-angle viewing system (BIOM, Oculus; Resight 700, Carl Zeiss Meditec). A posterior vitreous detachment (PVD), if not already present, was induced using aspiration. Triamcinolone (MaQaid)-assisted ERM removal and indocyanine green dye assisted ILM peeling with ILM forceps were performed. ILM peeling was done depending on the surgeon’s preference and the case. For patients with coexisting cataract, combined phacoemulsification and intraocular lens implantation were performed concurrently with PPV. For the patients with MH formation after ERM surgery, additional PPV and ERM/ILM peeling, and pneumatic tamponade were performed.

Patients were categorized into two groups: one group with MH formation and the other without MH development (control) after PPV for ERM removal. Baseline demographics and clinical characteristics were analyzed and compared between the two groups. The two groups were compared to analyze the risk factors associated with the development of FTMH following ERM surgery. Patients were also categorized into two subgroups: one with ILM peeling and the other without ILM peeling during ERM surgery. Patients with MH formation postoperatively were compared with those without MH formation within each subgroup.

Clinical data

The collected data included age, sex, past medical history (diabetes mellitus, hypertension), preoperative axial length, preoperative best-corrected visual acuity (BCVA), preoperative OCT-based foveal configurations of the ERM, preoperative presence of epiretinal proliferation (EP), pre-operative lens status, preoperative central macular thickness (CMT), intraoperative ILM peeling, intraoperative air tamponade, surgeon’s experience, and follow-up duration from ERM surgery to last visit. During the study period, a total of four surgeons performed the surgeries. The surgeons were categorized according to surgical experience based on the time each surgeon began performing ERM surgery at our institution: three surgeons had more than 3 years of surgical experience, while one had over 10 years of experience.

These factors were analyzed and compared between the MH and non-MH groups. Foveal configurations of the ERM were classified as follows: (1) ERM only; (2) ERM with cavitary change; (3) ERM with foveoschisis; (4) ERM with vitreomacular traction syndrome; (5) ERM with macular pseudohole (MPH); and (6) ERM with LH. MPH was defined by classification established by Hubschman et al. [17]. LH was defined according to the features described by Pandya et al. [18]. Foveal configuration was classified independently by two readers, and in cases of disagreement, the classification was finalized through consensus. We also analyzed the associated risk factors for the development of FTMH after ERM surgery using univariate and multivariate logistic regression with above factors. For the MH group, the time until detection of MH after ERM surgery, basal diameter of the MH, combined features at MH detection including ERM, cystoid macular edema (CME), BCVA before and after MH surgery, and anatomical results (i.e., hole closure) after MH surgery were additionally analyzed.

At each visit, all patients underwent complete eye examinations, including measurement of (BCVA in decimal values), intraocular pressure, slit-lamp biomicroscopy, axial length by IOLMaster 500 (Carl Zeiss AG) or IOLMaster 700 (Carl Zeiss AG), dilated fundus examinations, wide fundus photography (Nikon, Optos), and OCT (Spectralis, Heidelberg Engineering). The diagnosis of ERM and FTMH was confirmed with dilated fundus examination, wide fundus photography and OCT. CMT is defined as the average thickness of the central 1-mm diameter ETDRS (Early Treatment Diabetic Retinopathy Study) foveal subfield of the macular, measured from the ILM and the retinal pigment epithelium by OCT.

Main outcome measures

The primary outcomes were clinical characteristics of the cases with FTMH formation after vitrectomy for ERM removal and the associated risk factors of postoperative FTMH formation. Secondary outcomes were anatomical and functional outcomes of the cases with the development of the FTMH.

Statistical analysis

We performed all statistical analyses with IBM SPSS ver. 26.0 (IBM Corp) or R ver. 4.3.3 (R Foundation for Statistical Computing). The data are presented as number (%) or mean ± standard deviation. The BCVAs were converted to logarithm of the minimal angle of resolution (logMAR) for statistical analysis. The difference between MH and non-MH groups was analyzed using the nonparametric Mann-Whitney U-test for numeric variables. To compare categorical variables between the groups, the Fisher exact test was used. To investigate the association between MH formation and clinical factors, Firth bias-reduced logistic regression analysis was performed using the “logistf ” package in R. This method provides more reliable estimates when events are rare [19]. Statistical significance was defined as a p-value of <0.05.

Results

Among the 141 eyes with PPV for ERM removal, five eyes (3.5%) developed MH postoperatively. The baseline characteristics, clinical parameters, and comparison between MH and non-MH groups are presented in Table 1. The mean age at vitrectomy for ERM was 65.70 ± 8.65 years. The mean preoperative BCVA by logMAR was 0.32 ± 0.27 (Snellen, 20 / 42). The mean preoperative CMT in OCT was 440.2 ± 94.6 μm. ILM peeling was performed during ERM surgery in 77 of 141 patients (54.6%). The mean follow-up duration was 27.28 ± 22.50 months (range, 6–112 months). The proportion of the preoperative foveal configuration of ERM was significantly different between the MH and non-MH groups (p = 0.008). The preoperative CMT was significantly thinner in the MH group (332.2 ± 77.4 μm vs. 444.6 ± 92.5 μm, p = 0.007). Age, sex, diabetes mellitus, hypertension, preoperative axial length, preoperative BCVA, preoperative EP, preoperative lens status, intraoperative ILM peeling, intraoperative air tamponade, surgeon’s experience, and follow-up duration were not significantly different between the MH and non-MH groups. In subgroup analysis, the proportion of surgeons with more than 10 years of surgical experience was significantly higher in the MH group within the ILM-peeled subgroup (100% vs. 18.7%, p = 0.041) (Supplementary Table 1). In the no-ILM peeling subgroup, the proportion of the preoperative foveal configuration of ERM was significantly different between the MH and non-MH groups (p = 0.010). The MH group showed significantly thinner preoperative CMT (283.7 ± 30.7 μm vs. 422.4 ± 91.4 μm, p = 0.003) (Supplementary Table 2).

Table 1.

Baseline characteristics, clinical parameters, and comparison between the MH and non-MH groups after ERM vitrectomy

Characteristic	Total (n = 141)	MH group (n = 5)	Non-MH group (n = 136)	p-value *
Age (yr)	65.70 ± 8.65 (41–84)	67.80 ± 10.99 (50–79)	65.62 ± 8.59 (41–84)	0.422
Sex				>0.999
Male	64 (45.4)	2 (40.0)	62 (45.6)
Female	77 (54.6)	3 (60.0)	74 (54.4)
Diabetes mellitus	42 (29.8)	0 (0)	42 (30.9)	0.322
Hypertension	62 (44.0)	2 (40.0)	60 (44.1)	>0.999
Preoperative axial length (mm)	23.99 ± 1.35 (21.11–29.33)	24.52 ± 1.43 (22.79–26.48)	23.97 ± 1.34 (21.11–29.33)	0.333
Preoperative BCVA (logMAR)	0.32 ± 0.27 (0.00–1.40)	0.46 ± 0.31 (0.22–1.00)	0.32 ± 0.26 (0.00–1.40)	0.331
Preoperative foveal configuration of ERM				0.008†
ERM only	106 (75.2)	1 (20.0)	105 (77.2)
ERM with cavitary change	2 (1.40)	0 (0)	2 (1.5)
ERM with foveoschisis	9 (6.4)	0 (0)	9 (6.6)
ERM with VMTS	4 (2.8)	0 (0)	4 (2.9)
ERM with MPH	8 (5.7)	1 (20.0)	7 (5.1)
ERM with LH	12 (8.5)	3 (60.0)	9 (6.6)
Preoperative EP	45 (31.9)	2 (40.0)	43 (31.6)	0.654
Preoperative lens status				>0.999
Phakic	121 (85.8)	5 (100)	116 (85.3)
Pseudophakic	20 (14.2)	0 (0)	20 (14.7)
Preoperative CMT (μm)	440.2 ± 94.6 (250.0–690.0)	332.2 ± 77.4 (250.0–454.0)	444.6 ± 92.5 (265.0–690.0)	0.007†
Intraoperative ILM peeling	77 (54.6)	2 (40.0)	75 (55.1)	0.659
Intraoperative air tamponade	8 (5.7)	1 (20.0)	7 (5.1)	0.257
Surgeon’s experience (yr)				>0.999
≥3	94 (66.7)	3 (60.0)	91 (66.9)
≥10	47 (33.3)	2 (40.0)	45 (33.1)
Follow-up (mon)	27.28 ± 22.50 (6.00–112.00)	38.96 ± 15.33 (13.85–54.83)	26.85 ± 22.64 (6.00–112.00)	0.091

Values are presented as mean ± standard deviation (range) or number (%).

MH = macular hole; ERM = epiretinal membrane; BCVA = best-corrected visual acuity; logMAR = logarithm of the minimal angle of resolution; VMTS = vitreomacular traction syndrome; MPH = macular pseudohole; LH = lamellar hole; EP = epiretinal proliferation; CMT = central macular thickness; ILM = internal limiting membrane.

^*Mann-Whitney U-test for continuous variables and Fisher exact test for categorical values;

^†Statistically significant ( p < 0.05).

Table 2 summarizes the clinical characteristics and surgical outcomes of the cases with MH formation in the present study. All five cases developed foveal MH. There were no eccentric MHs among the 141 eyes with vitrectomy for ERM removal. Representative cases are presented in Fig. 2A–2N (case 1) and Fig. 3A–3N (case 4). The remaining cases are shown in Supplementary Figs. 1–3. The mean age of the patients with MH formation at MH diagnosis was 67.80 ± 10.99 years. Three were female. The mean preoperative BCVA by logMAR was 0.46 ± 0.31, and the mean preoperative CMT was 332.2 ± 77.4 μm. Preoperative foveal configurations included ERM with LH in three eyes, ERM with MPH in one eye, and ERM only in one eye. EP was present in cases 1 and 2. All five patients underwent combined phacoemulsification and PPV with ERM removal; ILM peeling was performed in cases 1 and 5. In case 2, surgical induction of PVD was performed during vitrectomy, whereas all other patients had a preexisting PVD at the time of surgery. MH was diagnosed an average of 21.41 ± 23.91 months (range, 0.92–51.28 months) after the surgery for ERM removal. The average MH basal diameter was 822.40 ± 510.08 μm (range, 347–1,539 μm). In all five cases (100%), ERM was observed over time after ERM surgery and at the time of MH detection. Specifically, case 2 presented with a hazy OCT image on postoperative day 1, which made accurate evaluation difficult (Supplementary Fig. 1); however, ERM was observed 1 week after surgery and was considered residual ERM. In contrast, ERM recurrence was observed in case 1 at postoperative 3 months (Fig. 2), case 3 at postoperative 6 weeks (Supplementary Fig. 2), case 4 at postoperative 1 month (Fig. 3), and case 5 at postoperative 2 years (Supplementary Fig. 3). In four of the five patients (80%), CME was present at the MH detection. One patient (case 5) was transferred to another hospital for MH surgery at the patient’s request. Four patients underwent additional PPV and ERM/ILM peeling, and pneumatic tamponade for MH. In three out of four cases, MH was closed successfully. The patient with unclosed MH (case 2) refused to undergo reoperation. BCVA by logMAR were 0.74 ± 0.51 before MH surgery and 0.76 ± 0.49 postoperatively, with no statistical significance.

Table 2.

Clinical characteristics and surgical outcomes of the cases with MH formation after ERM removal

Case no.	Age (yr)	Sex	Before ERM surgery				During ERM surgery (ILM peeling)	Time to MH detection after ERM surgery (mon)	MH basal diameter (μm)	Combined features at MH detection	Before MH surgery		During MH surgery (gas injection)	After MH surgery			Total follow-up (mon)†
			BCVA (decimal)	CMT (μm)	Foveal configuration	EP					BCVA (decimal)	Lens status		BCVA (decimal)	MH closure	Follow-up (mon)*
1	71	Female	0.4	306	ERM with LH	Yes	Yes	51.28	1,539	ERM, CME	0.1	Pseudophakia	C3F8 14%	0.04	Yes	3.55	54.83
2	73	Female	0.4	291	ERM with LH	Yes	No	0.92	676	ERM, CME	0.04	Pseudophakia	C3F8 14%	0.3	No	44.68	45.60
3	50	Female	0.1	250	ERM with LH	No	No	1.38	1,146	ERM, CME	0.15	Pseudophakia	C3F8 14%	0.6	Yes	36.51	37.89
4	79	Male	0.57	310	ERM with MPH	No	No	10.82	347	ERM, CME	0.5	Pseudophakia	SF6 18%	0.4	Yes	3.03	13.85
5	66	Female	0.6	454	ERM only	No	Yes	42.64	404	ERM	0.67	Pseudophakia	NA	NA	NA	NA	42.64

MH = macular hole; ERM = epiretinal membrane; ILM = internal limiting membrane; BCVA = best-corrected visual acuity; CMT = central macular thickness; EP = epiretinal proliferation; LH = lamellar hole; CME = cystoid macular edema; NA = not applicable.

^*Interval time from MH surgery to last follow-up;

^†Interval time from ERM surgery to last follow-up.

Fig. 2.

Sequential widefield fundus photography and optical coherence tomography images of a representative case of full-thickness macular hole (FTMH) development after epiretinal membrane (ERM) surgery with internal limiting membrane (ILM) peeling (case 1, 71-year-old female patient). (A, B) Preoperative images show macular ERM and lamellar hole. (C, D) Relatively well-restored foveal contour is shown at 1 month postoperatively (E, F) New-onset foveal thinning is observed at 3 months postoperatively. Recurred parafoveal ERM (arrow) is seen. Progressive foveal thinning and ERM are shown (G, H) at 1 year postoperatively and (I, J) at 2 years and 5 months postoperatively. (K, L) The images at 4 years and 3 months postoperatively show FTMH. Large cystoid macular edema and ERM (arrows) are seen around the macular hole. (M, N) The MH was closed at the most recent visit, 3.5 months after additional vitrectomy and ERM/ ILM peeling with ILM graft, and intravitreal gas injection (C₃F₈ 14%).

Fig. 3.

Sequential widefield fundus photography and optical coherence tomography images of a representative case of full-thickness macular hole (FTMH) formation after epiretinal membrane (ERM) surgery without internal limiting membrane (ILM) peeling (case 4, 79-year-old male patient). (A, B) Preoperative images show macular ERM and macular pseudohole. (C, D) The images at 6 days postoperatively show well-removed ERM and relatively good foveal contour. Progressive foveal thinning with extended recurred ERM (arrows) is shown at postoperative (E, F) 1 month, (G, H) 3 months, and (I, J) 6 months. (K, L) The images at 11 months postoperatively show FTMH. Small cystoid macular edema and ERM (arrow) are seen around the MH. (M, N) The MH was closed at the latest visit, 3 months after additional vitrectomy and ERM/ILM peeling, and intravitreal gas injection (SF₆ 18%).

In univariate Firth bias-reduced logistic regression analysis, MH formation after PPV for ERM removal was significantly associated with the preoperative foveal configuration of ERM with MPH (odds ratio [OR], 14.07; 95% confidence interval [CI], 1.05–190.53; p = 0.046), ERM with LH (OR, 25.91; 95% CI, 3.82–288.85; p = 0.001), and preoperative CMT (OR, 0.98; 95% CI, 0.96–0.99; p = 0.002) (Table 3). The variance inflation factor (VIF) was also calculated to check the possible multicollinearity among the factors. The VIF values derived from the Firth regression analysis were 1.46 for ERM with MPH, 1.63 for ERM with LH, and 1.08 for preoperative CMT, all well below the cutoff of 10. Since no variables exceeded a VIF of 10, multicollinearity was considered absent. Consequently, ERM with MPH, ERM with LH, and preoperative CMT were included in the Firth logistic regression multivariate analysis model. In multivariate analysis, the preoperative foveal configuration of ERM with LH remained significantly associated with the MH formation (OR, 13.11; 95% CI, 1.56–160.50; p = 0.018). Preoperative CMT showed marginally significant association with the MH development (OR, 0.98; 95% CI, 0.97–1.00; p = 0.075).

Table 3.

Analysis of the associated clinical parameters for the development of macular hole after ERM surgery

Factor	Univariate analysis		Multivariate analysis
	OR (95% CI)	p-value	OR (95% CI)	p-value
Age (yr)	1.03 (0.93–1.14)	0.598
Female sex	1.17 (0.22–7.24)	0.849
Diabetes mellitus	0.20 (0.00–1.85)	0.186
Hypertension	0.90 (0.15–4.79)	0.904
Preoperative axial length (mm)	1.00 (1.00–1.00)	0.999
Preoperative BCVA (logMAR)	5.20 (0.33–45.83)	0.207
Preoperative foveal configuration of ERM
ERM only	1 (Reference)	-
ERM with cavitary change	14.07 (0.09–352.80)	0.219
ERM with foveoschisis	3.70 (0.02–74.62)	0.484
ERM with VMTS	7.81 (0.05–170.75)	0.309
ERM with MPH	14.07 (1.05–190.53)	0.046*	7.79 (0.52–115.99)	0.126
ERM with LH	25.91 (3.82–288.85)	0.001*	13.11 (1.56–160.50)	0.018*
Preoperative EP	1.54 (0.25–8.19)	0.618
Preoperative lens status (pseudophakic)	0.52 (0.00–4.85)	0.630
Preoperative CMT (μm)	0.98 (0.96–0.99)	0.002*	0.98 (0.97–1.00)	0.075
Intraoperative ILM peeling
No	1 (Reference)	-
Yes	0.58 (0.09–3.09)	0.518
Intraoperative air tamponade
No	1 (Reference)	-
Yes	5.76 (0.53–36.98)	0.130
Surgeons’ experience (yr)
≥10	1 (Reference)	-
≥3	0.70 (0.13–4.31)	0.673
Follow-up (mon)	1.02 (0.98–1.05)	0.281

Multivariate model was adjusted for preoperative foveal configuration of the ERM and preoperative CMT.

ERM = epiretinal membrane; OR = odds ratio; CI = confidence interval; BCVA = best-corrected visual acuity; logMAR = logarithm of the minimal angle of resolution; VMTS = vitreomacular traction syndrome; MPH = macular pseudohole; LH = lamellar hole; EP = epiretinal proliferation; CMT = central macular thickness; ILM = internal limiting membrane.

^*Statistically significant ( p < 0.05).

Discussion

In this study, the incidence of MH formation after vitrectomy for ERM removal was 3.5%. The interval from ERM surgery to detection of MH varied widely, ranging from 0.92 to 51.28 months. In the three patients who did not undergo ILM peeling, MH was found relatively early, between 0.92 and 10.82 months after surgery. In contrast, MH was found at a relatively later time in the ILM peeling group, at 42.64 and 51.28 months. The basal diameter of the MH also varied widely, ranging from 347 to 1,539 μm. In all five cases (100%) with MH formation, ERM was commonly observed at MH detection. This was due to residual or recurrent ERM following ERM surgery. In four of the five patients (80%), CME was present at the time of MH detection. Preoperative foveal configuration of ERM with LH was the significantly associated factors for MH formation after ERM surgery. Thin preoperative CMT was marginally significant factors for MH development. Among the four patients who underwent surgery for FTMH, MH was successfully closed in three cases (75%). There was no significant difference in BCVA before and after surgery among the four patients who underwent MH surgery.

Few studies have reported on the incidence of MH formation following ERM surgery. Moreover, most of these investigations analyzed the occurrence of nonfoveal, eccentric MHs, with reported incidence rates of 0.95%, 1.8%, and 5.6% [12,14,15]. In the study by Rush et al. [13], MH developed in 11 of 423 eyes (2.6%) that underwent PPV for removal of the ERM; among these, 2.1% were eccentric MHs and only 0.5% were central (foveal) MHs. In the present study, the overall incidence of MH following ERM surgery was 3.5%, which is relatively higher than the previous study (0.5%). In the study by Rush et al. [13], cases involving a combined procedure (i.e., cataract surgery performed concurrently with PPV) were excluded, and ILM peeling was performed in all cases. In contrast, the present study included cases with combined procedures and ILM peeling was performed in 55% of eyes.

In the present study, both the interval from ERM surgery to MH detection and the basal diameter of the MH varied widely. In contrast, in the study by Rush et al. [13], the two cases of foveal MH developed relatively early at 2 and 6 weeks postoperatively, and the hole diameters were comparatively small at 245 and 276 μm, respectively.

Several mechanisms have been proposed to explain the development of eccentric MH following ERM surgery: (1) iatrogenic trauma occurring when grasping the ERM or ILM with microforceps; (2) Müller cell damage caused by ILM peeling itself, which may lead to glial cell and photoreceptor apoptosis, resulting in FTMH [12,20]; (3) contraction of residual ILM or ERM after surgery; and (4) concurrent CME, whereby the opening of intraretinal cysts may lead to MH formation [16]. Rush et al. [13] suggested the presumed mechanism for foveal MH formation after ERM removal. They suggested that postoperative contracture of the residual ILM or the presence of CME could be associated with the MH formation. However, they found no association between preoperative factors and the subsequent development of MH.

In the current study, preoperative configuration of the ERM with LH was significant risk factor for the development of FTMH after ERM surgery. There have been rare reports of FTMH formation following vitrectomy for LH. Witkin et al. [21] performed vitrectomy in 4 out of 19 eyes with LH that were associated with visual decline and reported FTMH formation in one case. Parolini et al. [22] reported that in 3 out of 19 eyes with LH-associated ERM, FTMH developed after PPV with ERM and ILM peeling. Neither of these studies provided a clear discussion on the mechanism of FTMH formation. Lim et al. [23] reported a case of ERM with LH where FTMH developed after PPV and combined ERM/ILM removal, but the FTMH spontaneously closed during follow-up. They hypothesized that CME may have contributed to FTMH formation, based on the presence of small cystic changes at the time of hole development. Chehaibou et al. [24] reported an observational study of 20 eyes with LH that progressed spontaneously to FTMH. While 70% of these eyes had accompanying ERM, 30% did not, suggesting that factors other than the tangential traction by ERM may play a role in the formation of FTMH. Under normal conditions, the structural stability of the fovea is maintained by Müller cells forming the Müller cell cone and Müller cells from the foveal wall. However, disruption of the Müller cell cone occurs in LH [25–27], and degenerative changes may occur in the outer nuclear layer, which is destabilized by the loss of central Müller cells [24]. These structural alterations may lead to progressive cavitation of the LH and eventual progression to FTMH [24,25]. Based on these findings, it is plausible that structural weakening of the fovea due to Müller cell cone disruption in LH could explain why preoperative LH may serve as a risk factor for FTMH formation following ERM surgery, as observed in our study.

Preoperative thin CMT is marginally significant risk factors for the development of MH after ERM surgery. There are two main theoretical mechanisms regarding the pathogenesis of secondary MH formation: tangential traction exerted by an ERM and the development of CME [28]. In CME, cysts can directly rupture to form a FTMH, or roof of the cysts slowly dehisce leading to a FTMH by degenerative forces [28]. When the preoperative CMT is thin, it is presumed that the increasing tangential traction from residual or recurrent ERM over time, or the postoperative development of CME in the thinned vulnerable foveal tissue, may lead to the formation of a FTMH. In the study by Kang et al. [29], among 38 eyes that developed secondary MHs after initial vitrectomy for various vitreoretinal disorders, 27 eyes (71%) had evidence of ERM formation, suggesting that tangential traction from ERM may significantly contribute to the formation of secondary MH. Additionally, it was proposed that the reopening of successfully closed MH may be caused by the proliferation of a secondary ERM around the hole in most cases [30]. In the present study, among three patients who did not undergo ILM peeling during ERM surgery, secondary MHs were found at 0.92, 1.38, and 10.82 months postoperatively. These intervals were comparatively shorter than those observed in two patients who had undergone ILM peeling, in whom MHs were detected at 42.64 and 51.28 months postoperatively. This finding may be related with the fact that postoperative contracture of residual ILM could be an additional contributing factor in MH formation [13]. Furthermore, Jain et al. [11] reported that CME was present in 12 out of 29 eyes (41.3%) with secondary MHs following vitrectomy. In another recent study, 14 patients with small FTMHs (mean diameter, 166 μm) accompanied by CME were treated with topical corticosteroids, nonsteroidal anti-inflammatory drugs, and carbonic anhydrase inhibitors, resulting in successful hole closure in all cases and visual improvement from a mean BCVA of 20 / 70 to 20 / 40 [31]. In the present study, recurred or residual ERM was observed in all five patients who developed secondary MHs after ERM surgery. CME was concurrently observed at the time of MH formation in four of the five patients (80%). These findings suggest that in eyes with thinner preoperative foveal tissue, tangential traction from ERM or the development of CME may have contributed to the progression to FTMH. Another possible mechanism may involve iatrogenic traumatic injury during ERM removal. In two patients (cases 2 and 3, 40%), MHs were detected at 0.92 and 1.38 months postoperatively. Although this raises the possibility of an iatrogenic mechanism during initial vitrectomy, no evidence of a FTMH was seen intraoperatively or on OCT at 1 week postoperatively for these two patients (Supplementary Figs. 1, 2).

EP is primarily derived from Müller glial cells in the inner retina, distinguishing it from ERM, which is composed of myofibroblasts and demonstrates contractile properties. Yang et al. [32] suggested that the presence of EP may indicate chronic and severe gliosis accompanied by neurodegenerative changes. They reported patients with hole marginal ERM combined with EP are more likely to have failed closure of the MH (38%) compared with patients with no ERM (11.8%). This suggests that EP may also have a potential role in the development of MH after ERM surgery. However, in the present study, there was no statistically significant difference in the proportion of EP between the MH and non-MH groups, and the presence of preoperative EP was not a significant factor for MH formation following ERM surgery.

Among the four patients who underwent surgery for FTMH in the present study, MH was successfully closed in three cases. There was no significant difference in BCVA before and after surgery among the four patients who underwent MH surgery. However, in two cases, visual acuity measurements were incomplete: case 1 lacked postoperative BCVA, and case 2 lacked preoperative BCVA. Even when only cases 3 and 4, for which both preoperative and postoperative BCVA measurements were available, were analyzed, no significant difference was observed between preoperative and postoperative BCVA. Rush et al. [13] previously reported two cases of foveal FTMH development following ERM surgery, both of which achieved successful closure of MH. However, preoperative BCVA for MH surgery was not separately measured in that study; instead, the authors compared preoperative BCVA for ERM surgery and postoperative BCVA for MH surgery, showing a decrease from 0.5 to 0.4 and from 0.6 to 0.4, respectively, for the two cases of foveal FTMH. The hole diameters in those two cases were 245 and 276 μm. Additionally, those holes were detected at 2 and 6 weeks after ERM surgery and the postoperative BCVA were reported at 6 months postoperatively after ERM surgery, indicating a relatively short follow-up period after MH surgery. These differences in study design and timing make direct comparison with our study difficult. Further systematic studies with larger case numbers are warranted to better understand the anatomical and functional outcomes after MH formation following ERM surgery.

This study has several limitations. First, this study had a retrospective design and had an inherent risk of selection bias. Second, the size of the cases in the MH group was small. This may make the reliability of conventional logistic regression analysis questionable due to insufficient statistical power. Therefore, we analyzed the data using Firth bias-reduced logistic regression, which is more suitable for rare event data. The subgroup analysis by ILM peeling included fewer cases per subgroup, which may have limited the statistical robustness of the logistic regression model, even when applying Firth bias-reduced logistic regression. Therefore, we did not present a logistic regression model for the subgroup analysis by ILM peeling; instead, we provided only the comparison of the clinical parameters between the MH and non-MH groups for the subgroup analysis. Although Firth bias-reduced logistic regression was applied to account for rare events, the limited number of outcome cases and the heterogeneity of surgical techniques restrict the generalizability of the results. In addition, variations in instrumentation, dye usage, and peeling methods, which were not standardized across cases, may also have influenced the outcomes. Given these considerations, the current results should be interpreted with caution. However, this study included all analyzable cases of MH that developed following ERM surgery performed at our institution. The study subjects were comprehensively identified from the entire cohort of patients diagnosed with and treated surgically for ERM at our institution without data loss by extracting data by combining clinical data warehouse and electronic medical records. The study included all surgically treated ERM cases with available Heidelberg OCT data collected since the device was introduced at our hospital in January 2012. Lastly, ILM peeling was not consistently performed during ERM surgery but was selected based on the surgeon’s preference and the individual characteristics of each patient case. Despite these limitations, to our knowledge, this study is the first study to systematically report the largest cohort of foveal FTMH, rather than eccentric cases, that occurred following ERM surgery.

In conclusion, ERM with LH was identified as a significant factor associated with MH formation after ERM surgery, while thin preoperative CMT showed a marginal association. At the time of MH detection, recurred or residual ERM and postoperative CME were observed in most cases, suggesting that tangential traction caused by postoperative ERM or, postoperative CME may represent possible etiologies for MH formation. Therefore, in patients with ERM with LH or thin preoperative CMT, the possibility of MH formation after ERM surgery should be taken into account, and these patients may warrant closer postoperative monitoring for the early detection of MH development.

Supplementary Materials

Supplementary materials are available from https://doi.org/10.3341/kjo.2025.0107.