Novel TA-IVIZ Patch and BSS Tamponade for Macular Hole Repair: A Pilot Study

Abstract

Purpose

This study evaluates the efficacy of minimal vitrectomy for full-thickness macular hole (FTMH) repair using a triamcinolone acetonide (TA)-IVIZ patch and balanced salt solution (BSS) tamponade.

Methods

An in vitro experiment was conducted to compare the adhesiveness and stability of the TA-IVIZ patch and the TA-DisCoVisc patch. Although the clinical arm of the study was a prospective study, an interventional cohort study was then performed on 24 eyes from 23 consecutive patients with FTMH. All eyes underwent minimal vitrectomy combined with internal limiting membrane (ILM) peeling, an inverted ILM flap, TA-IVIZ patch application, and BSS tamponade, without postoperative prone positioning. Outcomes, including anatomical closure rate, best-corrected visual acuity, and intraoperative and postoperative complications, were compared with a retrospective cohort of 25 eyes from 24 patients who underwent conventional surgery involving ILM peeling and grafting, gas tamponade, and postoperative prone positioning.

Results

The in vitro experiment demonstrated that TA-IVIZ exhibited stronger adhesion than the TA-DisCoVisc. The anatomical closure rate was comparable between groups (87.5% for TA-IVIZ vs. 92% for gas tamponade; P = 0.888), as were final best-corrected visual acuity improvements (P = 0.954) and mean postoperative intraocular pressure (P = 0.623). Notably, the TA-IVIZ group did not require postoperative prone positioning.

Conclusions

Minimal vitrectomy with ILM peeling, an inverted ILM flap, TA-IVIZ patch, and BSS tamponade achieves high closure rates, reduces the requirement for postoperative prone positioning, and facilitates faster visual recovery, presenting a promising alternative to conventional gas tamponade techniques.

Translational Relevance

We combined TA and IVIZ to provide an effective alternative to conventional techniques for the treatment of FTMH.

Introduction

Full-thickness macular hole (FTMH) is a defect in the neurosensory retinal tissue at the fovea, leading to central vision loss and significantly impacting patients’ daily activities and quality of life. FTMH can be categorized into idiopathic MHs, where the cause remains unknown, and secondary MHs, which are associated with identifiable factors such as high myopia, ocular trauma, or vitreomacular traction secondary to other retinal diseases.¹ The development of idiopathic MHs is thought to be associated with pathological vitreoretinal traction at the central macula. Tangential and anteroposterior vitreomacular traction can contribute to a more extensive, persistent, and intense set of forces on the perifoveal region, ultimately leading to FTMH formation.^2–4

Optical coherence tomography (OCT) has revealed various mechanisms of FTMH formation, which occur through tractional disruption of the inner layer of the foveola, leading to outer lamellar holes, and/or the external limiting membrane (ELM), resulting in degenerative lamellar holes. These disruptions are often accompanied by cystic cavities in the foveal walls, a consequence of impaired water clearance by the retinal pigment epithelium. The size of these cystic cavities is closely correlated with FTMH width, providing critical insights for diagnosis and monitoring.⁵ Thus, theoretically, the resolution of cystic cavities indicates the healing process of FTMHs.⁶ Recent advancements in medical therapy suggest that small-diameter FTMHs with macular cystoid hydration can be treated effectively with topical agents after the resolution of cystic cavities. Wang et al.⁷ demonstrated that a combination of topical steroids, nonsteroidal anti-inflammatory drugs, and carbonic anhydrase inhibitors achieved successful closure in select FTMH cases. Of course, progressive visual impairment and metamorphopsia typically necessitate surgical intervention.⁸

The hydration theory explains how pars plana vitrectomy (PPV) combined with intraocular gas tamponade facilitates FTMH closure. The gas bubble isolates the macular defect from vitreous fluid, reducing hydration at the site of the hole. Simultaneously, the postoperative facedown position enhances the activity of Müller cells and retinal pigment epithelium pumps, allowing effective fluid clearance and resolution of cystic cavities, ultimately promoting macular healing.⁹ Despite the high success rates of PPV, limitations such as the need for strict postoperative positioning and temporary visual impairment during gas tamponade have spurred interest in alternative approaches. The use of biological glue with anti-inflammatory properties to seal the MH appears to be a feasible option. Building on prior research, this study explores the innovative combination of internal limiting membrane (ILM) peeling and inverted ILM flap techniques with the application of a sodium hyaluronate hydrogel mixed with triamcinolone acetonide (TA). This approach eliminates the need for gas tamponade, used balanced salt solution (BSS) tamponade, and required only a postoperative nonstrict supine position in patients with FTMH.

Methods

Patients

This study, approved by the Sichuan Provincial People's Hospital Ethics Committee and adhering to the Declaration of Helsinki, was conducted on consecutive FTMH patients undergoing PPV at a tertiary ophthalmic hospital from January to August 2024.

Patients with FTMH requiring surgery for progressive vision loss or metamorphopsia and an axial length (AL) of less than 28 mm were included in the viscoelastic-assisted (VA) group. Exclusion criteria included FTMH from identifiable causes except for high myopia, significant corneal opacity, unrelated ocular conditions causing vision loss, or follow-up of less than 3 months. All findings and surgical details were documented in the electronic patient record. Those patients who underwent PPV combined with ILM peeling, inverted ILM flap technique, application of VA material, and BSS tamponade were classified as the VA group.

According to the electronic medical records, patients with FTMHs who underwent standard surgical intervention with gas tamponade within the 5 months preceding the initiation of this study were included in the gas group. The AL in this group was also limited to less than 28 mm. A comparison was made between the VA group and the gas tamponade group.

In Vitro Experiments

Ophthalmic viscosurgical devices (OVDs) are categorized by rheological properties into cohesive, dispersive, viscoadaptive, and cohesive–dispersive types. This study compared the underwater adhesion of cohesive (IVIZ; Bausch & Lomb, Shanghai, China) and cohesive–dispersive (DisCoVisc; Alcon Laboratories, Inc., Fort Worth, TX) OVDs. IVIZ, a medical sodium hyaluronate, is a 1.7% cohesive OVD used during eye surgeries to maintain the anterior chamber, capsular bag, and so on. It has a pH range of 6.8 to 7.6, ensuring biocompatibility with ocular tissues.¹⁰ DisCoVisc was introduced to the market in 2005, which is a combination of two main components: 1.6% sodium hyaluronate and 4% chondroitin sulfate. This formulation gives DisCoVisc both cohesive and dispersive properties, allowing it to act as a cohesive-–dispersive OVD.¹¹

Two patches were prepared by mixing 0.5 mL TA suspension (5 mL:50 mg, Zhejiang Xianju Pharmaceutical Co., Taizhou, China) with 1 mL of either IVIZ or DisCoVisc in a 2.0-mL syringe, leaving a small volume of air to facilitate thorough mixing. The syringe was shaken gently up and down to ensure uniform dispersion of the TA particles within the viscoelastic agent, as previously described by Fan et al.¹² During this process, air became incorporated into the solution, resulting in the formation of uniformly distributed microbubbles——an indicator that the TA-OVD mixture was thoroughly and homogeneously blended. A 10-mL culture flask, simulating the human eye, was filled with BSS and overlaid with perfluorocarbon liquid (PFCL) at the bottom. A 0.1-mL TA-IVIZ patch and a TA-DisCoVisc patch were injected beneath the PFCL. Subsequently, the PFCL was aspirated using a needle, facilitating direct contact between the patches and the BSS (Fig. 1). As shown in Figure 1, the TA-OVD patch adhered to the bottom of the flask. When the flask was placed upright (standing vertically), it simulated the supine position of a human body. Conversely, when the flask was laid flat (horizontally), it simulated the upright (standing) human position. Then the flask was laid flat for 120 minutes to simulate the upright human position, and patch displacement was observed at 0, 5, 10, 20, 30, 60, and 120 minutes. To provide a preliminary quantitative assessment, a simplified approach was used by measuring the vertical displacement of the upper edge of the patch at specific time points. Each experimental condition was repeated three times, and the differences in displacement between the two groups were analyzed statistically.

Figure 1.

The steps of in vitro experiment. (A) A 10-mL culture flask filled with BSS, the PFCL was injected to the bottom. (B) The TA-OVD patch was injected to the bottom between the culture flask and PFCL. (C) The PFCL was removed to make direct contact between BSS and TA-OVD patch.

Patient Examination

Demographic data, including age, gender, affected eye, AL, symptom duration, MH stage, and medical and surgical history, were recorded. Patients underwent best-corrected visual acuity (BCVA), intraocular pressure (IOP), slit-lamp fundus examination, ultra-widefield photography, and swept-source OCT and OCT angiography (TowardPi BMizar, Beijing, China) preoperatively and postoperatively.

The FTMH diameter was measured as the distance between the ELM, and BCVA was converted to logarithm of the minimum angle of resolution (logMAR) for analysis. Patients were followed for at least 3 months; outcome measures included BCVA, IOP, slit-lamp fundus examination, OCT/OCT angiography, and postoperative complications. We provided the necessary treatment in case of complications, such as high IOP. The FTMH was classified according to the Gass staging system, which describes the progression of vitreomacular traction leading to MH formation. The main measure was the primary MH closure rate after at least 3 months of follow-up. Secondary outcome measures were the final BCVA and postoperative complications.

Surgical Procedure

All surgeries were performed by a single surgeon (JZ) under retrobulbar anesthesia using a 25G vitrectomy system (Constellation, Alcon) and a wide-angle viewing system (RESIGHT, Carl Zeiss, Jena, Germany). If cataract was present, phacoemulsification and intraocular lens implantation was performed simultaneously. All patients underwent minimal vitrectomy, defined as removal of the posterior vitreous within the vascular arcades after TA injection to visualize the vitreous cortex, followed by careful mechanical induction of posterior vitreous detachment using a vitrectomy cutter. Indocyanine green (25 mg, Dandong Yichuang Pharmaceutical Co., Dandong City, China) was applied to stain the ILM for 5 seconds.

In the VA group, PFCL was injected until it reached the vascular arcade. The ILM around the hole was peeled, a semicircular ILM flap at least 1 optic disc distance to the MH margin was created by peeling approximately 180° of the ILM around the MH, with the hinge positioned at the inferior edge. The flap was inverted gently to cover the MH in a downward orientation. The TA-IVIZ patch was applied beneath the PFCL over the inverted ILM flap, The amount of TA-IVIZ patch injection was determined according to the size of the inverted ILM flap (Fig. 2). After removal of PFCL, the procedure was completed with the infusion of BSS. The scleral incisions were left unsutured and gently massaged with cotton-tipped applicators. Patients were instructed to maintain a nonstrict supine position for 24 hours, after which they could adopt any comfortable position.

Figure 2.

The surgical step of application TA-IVIZ patch. (A) ICGA staining followed by peeling of the ILM. (B) Injection of PFCL. (C) ILM peeling and inverted ILM flaps. (D) Injection of TA-IVIZ between the inverted ILM flap and PFCL. (E) Aspiration of PFCL. (F) TA-IVIZ directly contacts the BSS.

In the gas group, ILM peeling and flap inversion were performed under BSS, followed by fluid–air exchange with sterile air filling the vitreous cavity. Patients maintained a strict prone position for 3 days postoperatively.

Statistical Analyses

Statistical analysis was performed using SPSS 25.0 (IBM, Armonk, NY). Normally distributed data was expressed as mean ± standard deviation and non-normally distributed data as median (interquartile range). Categorical data were presented as proportions. The Mann-Whitney U test was used for nonparametric data, the independent samples t test for parametric data, and the χ² test for categorical variables. A P value of less than 0.05 was considered statistically significant.

Results

In Vitro Experiments

The results showed that, during the 120-minute horizontal placement of the culture flask, the spreading behavior of the TA-OVDs was diffuse and morphologically inconsistent (Fig. 3A). The flask diameter (33 mm) was used as a reference scale to quantify the vertical displacement of the upper margin of the TA-OVDs over time in both groups. The measured distances were subjected to statistical analyses. The findings revealed that the TA-DisCoVisc patch exhibited significantly greater displacement compared with the TA-IVIZ patch after more than 5 minutes (Fig. 3B and Supplementary Table S1).

Figure 3.

Time-dependent displacement of the upper margin of the TA-OVDs following flask rotation. (A) Representative images were captured at 0, 1, 5, 10, 30, 60, and 120 minutes. (B) Vertical displacement at each time point was quantified using the flask diameter (33 mm) as a reference scale. Data from three independent experiments were collected and subjected to statistical analysis using the Mann–Whitney U test to evaluate differences in displacement over time.

Patient Characteristics

Patients were divided into the VA and gas groups based on the surgical procedure. The VA group comprised 23 patients (24 eyes), with 4 males and 19 females (mean age, 62.2 ± 5.7 years; range, 29–76 years), including 10 right and 14 left eyes. The median AL was 23.57 ± 1.83 mm. MHs were classified as 3 stage II cases, 6 stage III cases, and 15 stage IV cases. The median preoperative ELM gap was 575.5 ± 369.5 µm (range, 273–1610 µm). The preoperative BCVA averaged 0.96 ± 0.44 logMAR (20/182; range, 0.40–2.22 logMAR), and the mean IOP was 15.1 ± 2.9 mm Hg (range, 10.6–22.0). Symptoms lasted 2 weeks to 10 years, and 14 eyes also underwent cataract surgery with lens implantation.

The gas group included 24 patients (25 eyes), with 7 males and 17 females (mean age, 64.7 ± 9.6 years; range, 46–85 years). Of the 25 eyes, 11 were right and 14 were left. The median AL was 23.52 ± 1.34 mm (range, 22.00–27.43 mm). MHs were classified as 4 stage II 4 cases, 4 stage III cases, and 17 stage IV cases. The preoperative ELM gap averaged 673.9 ± 310.2 µm (range, 126.1–1250.0 µm). The BCVA averaged 1.13 ± 0.43 logMAR (20/270; range, 0.60–2.17 logMAR), and the mean IOP was 15.0 ± 2.9 mm Hg (range, 10.4–20.5 mm Hg). Symptoms lasted 2 weeks to 4 years, and 14 eyes also underwent simultaneous cataract surgery with lens implantation. No significant baseline differences were observed between the groups (Table 1).

Table 1.

Demographic and Preoperative Clinical Characteristics of Patients

Characteristics	VA Group (n = 24)	Gas Group (n = 25)	P Value
Age, years	62.21 ± 5.69	64.72 ± 9.56	0.272
Gender (male/female)	4/19	7/17	0.543
Eye (right/left)	10/14	11/14	0.869
AL (mm)	23.57 (1.83)	23.52 (1.34)	0.704
MH stage (Ⅱ/Ⅲ/Ⅳ)	3/6/15	4/4/17	0.767
Duration of symptoms (weeks)	22.5 (43)	24 (44)	0.824
ELM gap (µm)	575.50 (369.5)	673.93 ± 310.23	0.465
Preoperative BCVA (logMAR)	0.96 ± 0.44	1.13 ± 0.43	0.164
Preoperative IOP (mm Hg)	15.07 ± 2.89	15.04 ± 2.88	0.974
Combined cataract extraction	14/24	14/25	0.869

Operation Outcomes

At the last follow-up, the BCVA was 0.82 ± 0.25 logMAR (20/133; range, 0.40–1.30 logMAR) in the VA group and 0.98 ± 0.52 logMAR (20/190; range, 0.40–3.07 logMAR) in the gas group. The BCVA improved by 0.14 ± 0.44 logMAR in the VA group and 0.15 ± 0.64 logMAR in the gas group, with no significant difference (P = 0.954). Postoperative IOP averaged 14.23 ± 2.92 mm Hg (range, 10.50–21.00 mm Hg) in the VA group and 14.86 ± 2.74 mm Hg (range, 9.00–19.20 mm Hg) in the gas group, with no significant difference (P = 0.623). The ELM gap decreased by 498.4 ± 406.5 µm in the VA group and 556.2 ± 355.8 µm in the gas group, with no significant difference (P = 0.598). Postoperative changes are summarized in Table 2.

Table 2.

Treatment Effects of the Two Groups

Characteristics	VA Group	Gas Group	P Value
Type of MH closure (not closed/1/2)	3/18/3	2/20/3	0.888
Duration (days)	31 (43)	42 (80)	0.617
ΔBCVA (logMAR)	0.14 ± 0.44	0.15 ± 0.64	0.954
ΔIOP (mm Hg)	0.58 ± 3.41	0.19 ± 2.03	0.623
ΔELM gap (µm)	498.38 ± 406.52	556.22 ± 355.79	0.598

In the VA group, 21 of 24 eyes (87.5%) achieved closure, with 18 type 1 closures and 3 type 2 closures; a classic closure case and a nonclosure case are presented in Figure 4. In cases of successful closure, we observed from the first postoperative day that the inverted ILM remained in place. This was initially accompanied by the resolution of macular edema, followed by the sequential healing of the ELM, outer nuclear layer, and ellipsoid zone. In contrast, in cases of unsuccessful closure, the inverted ILM was absent, macular edema persisted, and the MH remained unclosed. In the gas group, 23 of 25 eyes (92%) achieved closure, with 20 type 1 closures and 3 type 2 closures (Fig. 5, Supplementary Table S2). Closure rates were comparable (P = 0.888). All persistent MH cases achieved closure after a second surgery. For ELM gaps of less than 400 µm, closure rates were 66.7% (4/6) in the VA group and 83.3% (5/6) in the gas group, all being type 1 closures (P = 0.518). For ELM gaps of 400 to 800 µm, closure rates were 92.3% (12/13) in the VA group, with 10 type 1 closures and 2 type 2 closures, and 90.9% (10/11) in the gas group, all type 1 closures (P = 0.731). For gaps of more than 800 µm, both groups achieved 100% closure (VA: 5/5, 4 type 1, 1 type 2; gas: 8/8, 5 type 1, 3 type 2; P = 1.000).

Figure 4.

The OCT images of classic closure case (No. 10) the nonclosure case (No. 21) at the preoperative and postoperative time points: day 1, day 3, day 15, and month 1.

Figure 5.

The proposition of different closure types in VA group (A) and gas group (B).

Discussion

In this study, we explored the use of the TA-IVIZ patch in the treatment of FTMH, building on its demonstrated adhesion in laboratory experiments. Patients underwent minimal posterior pole vitrectomy with ILM peeling, an inverted ILM flap technique, TA-IVIZ patching, and BSS tamponade, along with a nonstandard supine positioning postoperatively. When compared with a standard surgical approach involving conventional vitrectomy, ILM peeling, inverted ILM flap technique, gas tamponade, and prone positioning, the two methods showed similar outcomes in terms of MH closure and improvements in BCVA. These findings suggest that the combination of a TA-IVIZ patch and BSS tamponade offers a viable alternative to traditional approaches. Although preliminary results are promising, further studies with larger, more diverse populations are needed to confirm its efficacy.

The pathogenesis and management of MHs remain controversial. The combined tractional–hydration theory and dynamic forces theory have been proposed to explain its development.^9,13 Wang et al.⁷ demonstrated that the size of a MH was directly correlated with the likelihood of closure after topical medical therapy; each 10-µm reduction in size increased the odds of closure by 1.2. FTMHs smaller than 200 µm achieved a 72.2% closure rate with topical therapy, especially in cases without vitreomacular traction but with macular cystoid edema. Additionally, the rates of MH narrowing and reduction in central foveal thickness were key predictors of drop therapy success.⁷ However, for larger MHs, vitrectomy and adjunctive therapies were necessary. Therefore, TA was combined with OVDs to leverage its anti-inflammatory properties, aiming to reduce central foveal thickness and promote better MH closure.

After Eckardt et al. introduced ILM peeling, it effectively improved anatomical and functional outcomes, with success rates of 80% to 95%.^1,14,15 A meta-analysis of 23 randomized controlled trials (RCTs) revealed that the inverted ILM flap technique resulted in better anatomical closure rates and improved postoperative vision at 3 months compared with ILM peeling alone.¹⁶ Based on these findings, our study applied vitrectomy combined with ILM peeling and inverted ILM flap technique in all patients. Gas tamponade is a mainstream choice, which aids in MH closure by preventing fluid leakage through the hole from the vitreous cavity, promoting the reabsorption of subretinal fluid through the retinal pigment epithelium. Additionally, the tamponade generates surface tension between the retina and the gas bubble, which helps to pull the edges of the hole together. This process supports glial cell migration, facilitating closure of the gap by creating a favorable surface for cellular activity.¹⁷ However, gas tamponade typically requires prone positioning postoperatively, particularly in phakic eyes. Although meta-analyses suggest that this maneuver may not be necessary for smaller MHs, further RCTs are needed to confirm these findings.^18–20 Our study used the adhesive properties of the TA-IVIZ patch, which also effectively isolates the vitreous cavity from the hole, preventing communication between them. Additionally, The TA-IVIZ patch helps to stabilize the inverted ILM flap, which functions as a scaffold for cellular proliferation and migration. Moreover, the anti-inflammatory properties of TA contribute to the resolution of retinal edema, thereby facilitating the healing process of FTMHs.^12,21,22,28 Importantly, no gas was introduced into the eye during the whole procedure, minimizing the risk of cataract progression and IOP elevation.^23,24 Previous studies have shown that minimal vitrectomy reduces peripheral retinal traction, thereby decreasing the risk of iatrogenic retinal tears and shortening overall operative time.²⁵ Accordingly, this technique was incorporated into the surgical approach used for the VA group. Postoperatively, patients were not required to maintain a strict prone position and could instead remain in a nonstrict supine position. Compared with the traditional approach of PPV combined with ILM peeling, inverted ILM flap, gas tamponade, and postoperative prone positioning, there were no differences between the two surgical methods in terms of MH healing rate and postoperative improvements in BCVA. Therefore, minimal posterior pole vitrectomy, ILM peeling, inverted ILM flap, the TA-IVIZ patch, BSS tamponade, and nonstrict supine position may provide a promising alternative for the treatment of FTMHs.

The term OVDs for viscoelastic substances was introduced in the beginning of this century, which are a class of nonactive, clear, gel-like chemical compounds with viscous and elastic properties.²⁶ One of the new applications of OVDs in ophthalmology is in PPV. Initial attempts were made in 2013 and Hirata et al.²⁷ used dispersive OVD (Viscoat; Alcon Japan) as a retinal patch after vitrectomy surgery in rabbit retinal tear models, no postoperative inflammation was seen and all rabbit eyes treated with an OVD achieved patching of the retinal tear for more than 3 days. Moreover, Liu et al.²⁸ conducted an exploratory study on MH treatment using DisCoVisc to cover the inverted ILM flap, combined with BSS tamponade, achieving a 100% closure rate. Thus, we are exploring the use of OVDs mixed with TA to cover MHs to isolate MHs from the fluid in the vitreous cavity while promoting the disappearance of MH edema. To identify the optimal TA-OVDs for covering the inverted ILM flap without displacement, we conducted an in vitro experiment comparing TA-IVIZ and TA- DisCoVisc. The results demonstrated that, after placing the culture flask horizontally to simulate the upright position of the human body, TA-DisCoVisc exhibited significantly greater displacement after 30 minutes. Therefore, TA-IVIZ was selected for clinical trials. Moreover, we initially attempted to directly inject the TA-OVDs patch onto the bottom of a flask filled with BSS in the in vitro experiment. However, the results indicated that the TA-OVDs patch did not adhere well owing to the excessively moist environment and gradually floated in the BSS over time (Supplementary Figure S1). To prevent air introduction throughout the whole procedure, we modified our approach by incorporating PFCL. As shown in Figure 3, this adjustment enabled the TA-OVD patch to adhere effectively to the target area. Consequently, PFCL was introduced into the surgical procedure.

In our surgical approach, the most critical step is ensuring that the TA-IVIZ patch adheres to the inverted ILM flap and retina. The macula and inverted ILM flap are isolated with BSS via PFCL before the TA-IVIZ is injected. Injecting TA-IVIZ between the PFCL and the retinal surface helps to prevent adhesion loss owing to excess moisture.²⁷ In cases of successful closure, facilitated by BSS tamponade, we could clearly observe the inverted ILM remaining in place. Within a short period, we documented changes in each retinal layer and the recovery of the ellipsoid zone. The sequence of healing was consistent with that reported in the literature, beginning with the ELM, followed by the outer nuclear layer, and finally the ellipsoid zone. However, owing to the addition of TA in the patch, macular edema resolved rapidly, leading to a shorter healing time compared with previously reported findings.^29,30 However, on the first postoperative day, displacement of the TA-IVIZ patch and the inverted ILM flap was observed in five patients, resulting in direct communication between the BSS and the hole. Consequently, these MHs did not heal. Based on the results of the in vitro experiments, after placing the flask horizontally to simulate the upright position of the human body, the TA-IVIZ patch exhibited slight movement after 30 minutes. Therefore, we recommend that postoperative patients maintain a supine position, limiting upright activities to 30 minutes daily. Prolonged upright positioning risks TA-IVIZ and inverted ILM flap displacement, thereby reducing the success rate of MH closure.

Limitations of this study are as follows. First, the quantification of patch displacement in the in vitro experiment was based on a simplified method, in which only the vertical displacement of the upper margin was measured over time. In future studies, we plan to use image analysis tools to objectively measure the speed and pattern of patch displacement. Second, this is an exploratory investigation, and the findings were compared only with retrospective case data. Our conclusions are preliminary and RCTs are needed to confirm noninferiority. Third, concerning postoperative positioning, we recommend that patients maintain a supine position after surgery; upright activities should be limited to 30 minutes at a time. Fourth, although gas was avoided to reduce cataract and IOP risks during the surgical procedure, TA may still promote cataract progression, especially in phakic eyes. The use of PFCL adds to surgical cost and carries a risk of residual intraocular bubbles, which should be considered a limitation of the technique. Finally, the mixing of TA with OVDs may alter the properties of OVDs, such as their adhesiveness and cohesiveness, warranting further research to elucidate these effects. Moreover, developing a hydrogel with improved adhesive properties and integrated anti-inflammatory characteristics may represent a promising direction for future research.

This novel approach provides an effective alternative to conventional techniques, achieving similar outcomes while improving patient comfort and minimizing postoperative risks. However, additional RCTs are essential to validate its effectiveness. It may be a promising direction in further that a hydrogel with excellent adhesive properties and integrated anti-inflammatory characteristics.