Three-Year Safety Results of SAR422459 (EIAV-ABCA4) Gene Therapy in Patients With ABCA4-Associated Stargardt Disease: An Open-Label Dose-Escalation Phase I/IIa Clinical Trial, Cohorts 1-5.

PURPOSE: To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to mutations in ABCA4. DESIGN: Nonrandomized multicenter phase I/IIa clinical trial. METHODS: Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment. MAIN OUTCOME MEASURES: The primary end point was ocular and systemic adverse events. The secondary end points were best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, multifocal ERG, color fundus photography, short-wavelength fundus autofluorescence, and spectral domain optical coherence tomography. RESULTS: The subretinal injections were well tolerated by all 22 patients across 3 dose levels. There was 1 case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In 1 patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared with the untreated eye. However, in 6 patients, hypoautofluorescent changes were worse in the treated eye than in the untreated eye. Of these, 1 patient had retinal pigment epithelium atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, or multifocal ERG attributable to the treatment. CONCLUSIONS: Subretinal treatment with EIAV-ABCA4 was well tolerated with only 1 case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on fundus autofluorescence. There was a significant reduction in macular flecks in 1 treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.

Incidence and characteristics of rhegmatogenous retinal detachment during coronavirus-19 pandemic: A French study.

PURPOSE: To assess the impact of the Covid-19 pandemic and subsequent lockdown on the number and clinical characteristics of patients with retinal detachment (RD) in a French public university eye hospital. METHODS: Single-center, retrospective non-interventional study. Patients consulting at the emergency room (ER) of Quinze-Vingts Hospital (France) for rhegmatogenous RD before and after instauration of the lockdown were reviewed. We compared the characteristics of patients with RD between the containment period (March17th - April27th,2020) and the period preceding the lockdown (February18th - March16th,2020). We compared the number of RD surgeries performed between the first month of lockdown (March17th - April19th,2020) and the corresponding period of 2019. Number of cases, delay between diagnosis and surgery, visual acuity was measured. RESULTS: During the first month of lockdown, 59 RDs were operated on, compared to 107 in the corresponding period in 2019 (-44,8%). Mean time from first symptoms to surgery was significantly higher during the lockdown 12.7 (11.3) days vs 7.6 (7.8) days (p = 0.031) before. During the lockdown, the mean BCVA was lower albeit the difference did not reach statistical significance (1.16 (0.9) during pre-containment vs 1.5 (0.9) during containment; p = 0.09). Reasonsfor delayed consultation were: fear of Covid-19 (31%; p = 0.0001), absence of referral doctor (31%; p = 0.003) and difficulties in getting to public transport (10.3%;p = 0.859). CONCLUSION: Despite maintaining accessto emergency eye care facilitiesin our hospital, the lockdown affected visual health. Should the lockdown be reinstated, we postulate that a better information about eye care access for non-Covid emergencies may attenuate its effect on visual health.

TREATMENT OF SUBRETINAL PERFLUOROCARBON LIQUID BUBBLES COMPLICATING RETINAL DETACHMENT SURGERY USING AIR FOR DRAINAGE.

PURPOSE: The authors describe an original technique for treating multiple subretinal perfluorocarbon liquid (PFCL) bubbles complicating previous surgery for rhegmatogenous retinal detachment. METHODS: To facilitate the induction of macular redetachment and peripheral displacement of the PFCL bubbles, we performed the subretinal injection of filtered air in addition to balanced salt solution. In this setting, the action of the PFCL in the vitreous cavity, combined with globe manipulation, allowed bubbles' displacement and full aspiration. RESULTS: A 57-year-old man had a history of repeated pars plana vitrectomies for recalcitrant rhegmatogenous retinal detachment, the latter leading to multiple subretinal PFCL bubbles retained at the posterior pole. The described technique was performed 8 weeks after the last pars plana vitrectomy. A complete flattening of the macular region was obtained with visual improvement. CONCLUSION: Direct injection of air into the subretinal space may represent an effective strategy to help the surgical management of multiple retained PFCL bubbles.

Choroidal and peripapillary changes in high myopic eyes with Stickler syndrome.

BACKGROUND: To compare different clinical and Spectral-Domain Optical Coherence Tomography (SD-OCT) features of high myopic eyes with Stickler syndrome (STL) with matched controls. METHODS: Patients with genetically confirmed STL with axial length ≥ 26 mm and controls matched for axial length were included. The following data were obtained from SD-OCT scans and fundus photography: choroidal and retinal thickness (respectively, CT and RT), peripapillary atrophy area (PAA), presence of posterior staphyloma (PS). RESULTS: Twenty-six eyes of 17 patients with STL and 25 eyes of 19 controls were evaluated. Compared with controls, patients with STL showed a greater CT subfoveally, at 1000 µm from the fovea at both nasal and temporal location, and at 2000 and 3000 µm from the fovea in nasal location (respectively, 188.7±72.8 vs 126.0±88.7 µm, 172.5±77.7 vs 119.3±80.6 µm, 190.1±71.9 vs 134.9±79.7 µm, 141.3±56.0 vs 98.1±68.5 µm, and 110.9±51.0 vs 67.6±50.7 µm, always P< 0.05). Furthermore, patients with STL showed a lower prevalence of PS (11.5% vs 68%, P< 0.001) and a lower PAA (2.2±2.1 vs 5.4±5.8 mm2, P=0.03), compared with controls. CONCLUSIONS: This study shows that high myopic patients with STL show a greater CT, a lower PAA and a lower prevalence of PS, compared with controls matched for axial length. These findings could be relevant for the development and progression of myopic maculopathy in patients with STL.

Improved performance and safety from Argus II retinal prosthesis post-approval study in France.

PURPOSE: To evaluate the post-approval long-term outcomes of the Argus II Retinal Prosthesis, with a specific focus on its functional visual benefit in patients' daily activities. METHODS: Eighteen patients with bare light perception due to end-stage retinitis pigmentosa were included in a French prospective, multicentre, single-arm study and followed for 2 years. Visual benefit in patients' daily activities was monitored through the use of the Functional Low-vision Observer Rated Assessment (FLORA), and the final score at 2 years was the primary effectiveness outcome. Standardized visual assessments were also performed. Device- or procedure-related adverse events were recorded. RESULTS: Seventeen subjects completed the study. Positive impacts of the Argus II system on functional vision and well-being were demonstrated for over 70% of subjects on the FLORA. Among the daily activities/tasks tested, finding doorways was one of the most statistically significantly improved tasks (p < 0.001), along with estimating the size of an obstacle (p < 0.001), visually locating a place setting on a dining table (p < 0.001) and visually locating people in a non-crowded setting (p < 0.001). Visual function was improved on most standardized tests. Only two device- or procedure-related serious adverse events were observed (one vitreous haemorrhage and one endophthalmitis, both resolved with treatment). No explantation was required. CONCLUSION: This first report of a completed post-approval study of Argus II with a two-year follow-up demonstrates the safety and effectiveness of the Argus II System in a real-world cohort of patients and further highlights its real functional benefit in implanted patients' daily activities.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

TREATMENT OF MACULAR FOLDS COMPLICATING RETINAL DETACHMENT SURGERY USING AIR FOR RETINAL UNFOLDING.

PURPOSE: We discuss a modified surgical procedure for the treatment of macular folds complicating retinal reattachment surgery. METHODS: To facilitate the completion of the macular redetachment and the subsequent unrolling of the fold, we propose the subretinal injection, in addition to the conventional balanced salt solution, of filtered air as an original approach. In the presence of a subretinal air bubble, the action of gravity on the perfluorocarbon liquid in the vitreous cavity combined with an active globe manipulation proved to be very effective for flattening the central retina. Short-term tamponade with gas was successful at stabilizing the result. RESULTS: This technique has been used to treat symptomatic macular fold after surgery for rhegmatogenous retinal detachment in 3 consecutive eyes since 2014. Flattening of the macula with progressive visual recovery was achieved in all cases by the end of follow-up. CONCLUSION: Direct injection of air into the macular fold may represent an effective strategy to enhance the surgical management of such a vision-threatening complication. Air also minimizes the risks related to the forceful injection of fluid under the macula. An overview of recently reported surgical techniques is included, along with a brief discussion.

Adapted Surgical Procedure for Argus II Retinal Implantation: Feasibility, Safety, Efficiency, and Postoperative Anatomic Findings.

PURPOSE: To evaluate the feasibility, safety, and efficiency of an adapted surgical procedure used for postmarket Argus II implantations, so as to lower risks of postoperative hypotony or conjunctivoscleral erosion, and to describe the observed anatomic characteristics of the positioning of the implanted array. DESIGN: Single-arm prospective multicenter clinical trial. PARTICIPANTS: Eighteen consecutive patients with end-stage retinitis pigmentosa. METHODS: To protect the site of insertion of the cable of the device, a scleral flap was systematically added to the standardized implantation procedure. It was associated with temporalis fascia autograft, so as to cover the episcleral-fixed electronics case. Intraoperative and postoperative data at day 1, weeks 1 and 2, and months 1, 3, and 6 were collected. Postoperative distance between electrode-array and retina was measured on spectral-domain optical coherence tomography images. Position of the array was evaluated on fundus images between months 1 and 6. MAIN OUTCOME MEASURES: Feasibility of the modified surgical technique (time constraints, intraoperative complications), variations of intraocular pressure over time, postoperative ocular findings and adverse events, postoperative distance between the array and the retina, and rotation of the array between months 1 and 6 after implantation. RESULTS: The adapted surgical technique was performed easily without associated specific complications. No cases of chronic hypotony or conjunctivoscleral erosion were reported. One serious device/procedure-related adverse event was recorded (sterile posterior uveitis), which resolved after vitrectomy. Postoperative distance between array and retina was variable: full apposition was achieved in 4 patients (22.22%), partial apposition observed in 9 patients (50.00%), and absence of strict apposition noted in 5 patients (27.78%, 4 of whom had posterior staphyloma). A statistically significant slight rotation of the array was observed between months 1 and 6 (P < 0.0001), occurring downwardly in 68.75% of cases. CONCLUSIONS: The combined use of scleral flap and temporalis fascia autograft was easily achieved and effective in preventing hypotony and conjunctival erosion in our study. Postoperative distance between semirigid array and retinal surface was variable, and increased in the case of preoperative staphyloma. A slight rotation of the device occurred over time. Further studies based on larger samples are needed to confirm our findings and determine their functional consequences.

Improvements in vision-related quality of life in blind patients implanted with the Argus II Epiretinal Prosthesis.

BACKGROUND: The purpose of this analysis is to report the change in quality of life (QoL) after treatment with the Argus II Epiretinal Prosthesis in patients with end-stage retinitis pigmentosa. METHODS: The Vision and Quality of Life Index (VisQoL) was used to assess changes in QoL dimensions and overall utility score in a prospective 30-patient single-arm clinical study. VisQoL is a multi-attribute instrument consisting of six dimensions (injury, life, roles, assistance, activity and friendship) that may be affected by visual impairment. Within each dimension, patients were divided into two groups based on how much their QoL was affected by their blindness at baseline (moderate/severe or minimal). Outcomes were compared within each dimension sub-group between baseline and the combined follow-up periods using the Friedman test. In addition, data from the six dimensions were combined into a single utility score, with baseline data compared to the combined follow-up periods. RESULTS: Overall, 80 per cent of the patients reported difficulty in one or more dimensions pre-implant. Composite VisQoL utility scores at follow-up showed no statistically significant change from baseline; however, in three of the six VisQoL dimensions (injury, life and roles), patients with baseline deficits showed significant and lasting improvement after implantation with Argus II. In two of the three remaining dimensions (assistance and activity), data trended toward an improvement. In the final VisQoL dimension (friendship), none of the patients reported baseline deficits, suggesting that patients had largely adjusted to this attribute. CONCLUSION: Patients whose vision negatively affected them with respect to three VisQoL dimensions (that is, getting injured, coping with the demands of their life and fulfilling their life roles) reported significant improvement in QoL after implantation of the Argus II retinal prosthesis. Furthermore, the benefit did not deteriorate at any point during the 36-month follow-up, suggesting a long-term, durable improvement.

Argus II retinal prosthesis implantation with scleral flap and autogenous temporalis fascia as alternative patch graft material: a 4-year follow-up.

INTRODUCTION: The Argus II retinal prosthesis is composed of an epiretinal electrode array positioned over the macula and connected to an extrascleral electronics case via a silicone cable, running through a sclerotomy. During implantation, the manufacturer recommends to cover the sclerotomy site with a patch of processed human pericardium to prevent postoperative hypotony and conjunctival erosion by the underlying electronics case. Due to biomedical regulations prohibiting the use of this material in France, we developed an alternative technique combining a scleral flap protecting the sclerotomy and an autogenous graft of superior temporalis fascia overlying the electronics case. METHODS: The purpose of this study is to describe the 4-year outcomes of this modified procedure in three subjects who underwent Argus II Retinal Prosthesis System implantation. Clinical data consisting of intraocular pressure measurements and tolerance in terms of conjunctival erosion or inflammation were retrospectively assessed over a 4-year postoperative follow-up. RESULTS: None of the three patients implanted with the modified technique developed ocular hypotony over 4 years. A normal, transient conjunctival inflammation occurred during the first postoperative month but conjunctival erosion was not observed in any of the three patients over 4 years. Four years after implantation, the autogenous temporalis fascia graft remained well tolerated and the retinal prosthesis was functional in all three patients. CONCLUSION: The combination of an autograft of superficial temporalis fascia and a scleral flap efficiently prevented leakage through the sclerotomy site, ocular hypotony, and conjunctival erosion by the extrascleral electronics case. This modified technique is suitable for the implantation of existing and forthcoming retinal prostheses. Superficial temporalis fascia may also be used as alternative to commercial tectonic tissues for scleral wound repair in clinical settings where they are not available.

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

PURPOSE: The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. DESIGN: Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. PARTICIPANTS: Thirty participants in 10 centers in the United States and Europe. METHODS: The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. RESULTS: Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. CONCLUSIONS: The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada.

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind.

PURPOSE: Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN: The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS: There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS: The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. RESULTS: A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS: The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

Extraction of retinal tacks from subjects implanted with an epiretinal visual prosthesis.

BACKGROUND: Retinal tacks, first developed for the treatment of complex retinal detachments, have more recently been used for the fixation of epiretinal electrode arrays as part of implanted visual prostheses. Here, we report on the clinical experience of extracting four such tacks after chronic implantation. The ability to safely extract retinal tacks ensures that epiretinal devices can be repositioned or removed if necessary. METHODS: Custom-built, titanium alloy retinal tacks were mechanically removed from the posterior coats after prolonged implantation (up to 19 months). The resulting wound was characterized by clinical evaluation, fundus photography, and fluorescein angiography while being monitored for stability over time. The wounds were also compared to earlier published reports of the healing response around retinal tacks in human subjects. RESULTS: Tack extraction was accomplished successfully, without complication, in all four subjects. The wound site was readily identified by pale scar tissue. No change in the wound size or appearance was noted over many months of post-operative observation (up to 22 months after explant). No adverse effects on overall ocular health were detected. CONCLUSION: Extraction of retinal tacks from subjects implanted with epiretinal prostheses can be performed without significant complication. The long-term healing response appears to be stable and localized in eyes afflicted with retinitis pigmentosa or choroideremia. There was also minimal, if any, impact on the local circulatory system. These cases suggest that the use of retinal tacks for anchoring epiretinal visual prostheses does not preclude safe repositioning or removal of the device more than a year after implant.

Epiretinal membrane recurrence: incidence, characteristics, evolution, and preventive and risk factors.

BACKGROUND: To evaluate the incidence, evolution, clinical characteristics, possible risk factors or preventive factors, and visual outcomes of epiretinal membrane (ERM) recurrence. METHODS: Retrospective study of 440 consecutive patients (440 eyes) who underwent pars plana vitrectomy for ERM. The internal limiting membrane (ILM) was peeled in 266 cases, with the help of indocyanine green in 27 cases and brilliant blue in 45 cases. Cases of symptomatic ERM recurrence were reoperated. RESULTS: The incidence of ERM recurrence was 5% (22/440), and 2% of the patients were reoperated (9/440). Epiretinal membrane recurrence was symptomatic in 9 cases (41%) and asymptomatic in 13 cases (59%). ILM peeling was the only factor preventing ERM recurrence (adjusted odds ratio = 0.33, P = 0.026). The use of staining dyes did not prevent recurrence (adjusted odds ratio = 0.35, P = 0.338). In the case of ERM reproliferation, the absence of ILM peeling, the existence of ERM on the fellow eye, and poor visual acuity before surgery seemed to be associated with a high risk of symptomatic recurrence and reoperation. The mean duration for follow-up was 3.5 ± 1.7 years. CONCLUSION: ILM peeling not only reduces the likelihood of reproliferation of ERM but also seems to improve the visual prognosis of recurrent ERMs. The use of dyes did not reduce the rate of recurrence compared with when ILM was peeled without dyes.

Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.

BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.

25-, 23-, and 20-gauge vitrectomy in epiretinal membrane surgery: a comparative study of 553 cases.

PURPOSE: To compare the safety and functional outcomes of 25-gauge and 23-gauge (G) micro-incision vitrectomy surgery (MIVS) instrumentation with the standard 20-G vitrectomy system in the treatment of epiretinal membranes (ERM). METHODS: A retrospective comparative study of 553 consecutive cases with epiretinal membrane who underwent pars plana vitrectomy. Twenty-gauge, 25-gauge and 23-gauge vitrectomy was performed respectively in 347, 91, and 115 eyes. Surgery duration, visual acuity improvement, intraocular pressure variation, intraoperative and postoperative complications were analyzed. RESULTS: The mean surgical time in the 23-G group and in the 25-G group was shorter than in the 20-G group (P < 0.001). Visual improvement was higher 8 days postoperatively in the 25-G group than in the 20-G and 23-G groups (P = 0.035), but not at 6 weeks postoperatively (P = 0.186). In the 20-G group, the IOP increased significantly on the first day postoperatively (P < 0.001), while in the 23-G group, the IOP decreased on the first day postoperatively (P = 0.073). In the 25-G group, the IOP did not change significantly (P = 0.807). The incidence of complications was not statistically significant between the three groups. Retinal breaks were significantly related to the induction of posterior vitreous detachment, independent of the system gauge. CONCLUSION: In ERM surgery, 23-G and 25-G (MIVS) systems are as safe and effective as the 20-G system, and significantly reduce surgical time. Although the 25-G system provides an earlier visual improvement, the 23- and 25- gauge systems are comparable, and the selection will depend on the surgeon's preference.