Recurrences and Macular Complications after Perfluorocarbon-Liquid-Free Vitrectomy for Primary Rhegmatogenous Retinal Detachment

Rhegmatogenous retinal detachment (RRD) is a sight-threatening condition affecting a significant number of individuals, with an annual incidence of 10 to 20 cases per 100,000 population in high-income countries [1, 2]. Pars plana vitrectomy (PPV) is a widely performed surgical procedure for RRD repair, with advancements in surgical techniques and tools leading to improved visual outcomes and long-term anatomical success [3].

Perfluorocarbon liquids (PFCLs) have historically played a critical role in vitreoretinal surgery, facilitating retina flattening, subretinal fluid (SRF) drainage, macular protection, and intraocular foreign body removal. However, the use of PFCLs has been associated with rare but severe complications, including inflammation, subretinal migration, and toxicity to the inner retina or retinal pigment epithelium (RPE) [4]. In recent years, PFCL-free PPV techniques, involving direct SRF aspiration through retinal breaks or surgical retinotomy, have gained popularity [5]. These techniques have demonstrated comparable visual outcomes and single-operation success rates to PFCL-assisted PPV for uncomplicated RRD [6‐13]. Nevertheless, data on PFCL-free PPV in complicated RRD cases are limited [14], and little is known about factors associated with RRD recurrence in this approach.

While previous studies, including the ELLIPSOID study, have explored macular complications associated with different SRF drainage techniques in PPV for primary RRD, none have specifically evaluated factors linked to outer retinal damage, cystoid macular edema (CME), and other macular complications in PFCL-free PPV [12]. At our center, PFCL-free PPV has been routinely performed for uncomplicated RRD since 2015, and this study aims to investigate factors related to RRD recurrence in PFCL-free PPV for both complicated and uncomplicated RRD cases. Additionally, the study seeks to estimate the prevalence of macular complications detected by spectral-domain optical coherence tomography (SD-OCT) and their associations with visual outcomes at 12 months.

The findings from this study are expected to serve as a valuable reference for surgeons adopting PFCL-free PPV approaches and provide provisional treatment recommendations for uncomplicated and complicated RRD cases. By shedding light on the factors influencing RRD recurrence and macular complications, this research contributes to a broader understanding and refinement of surgical strategies for managing RRD.

This longitudinal cohort study was conducted at a tertiary referral center, San Gerardo Hospital, Monza, Italy, from March 2017 to June 2021. The study included patients with RRD repaired using PFCL-free PPV. To be eligible, patients had to have at least one postoperative SD-OCT scan and a minimum follow-up duration of 6 months. Exclusion criteria comprised previous intraocular surgery (except uncomplicated phacoemulsification), other retinal or optic nerve diseases, ocular trauma, or prior retinal detachment.

Patients were categorized into two groups: complicated RRD and uncomplicated RRD. Complicated RRD encompassed cases with high myopia (≤ − 6.00 diopters or axial length > 26.5 mm) prior to cataract extraction, RRD originating from a macular hole or macular schisis, giant retinal tears, choroidal detachment, or proliferative vitreoretinopathy (PVR) worse than grade A [14, 15]. The remaining eyes were classified as uncomplicated RRD. The study adhered to the Declaration of Helsinki and received approval from the local Institutional Review Board (CE-MILAN-V1, approval date 01/28/2022).

Data, including patient demographics, concomitant cataract extraction, surgery duration, macular involvement, retinal break characteristics (e.g., presence of multiple breaks, location, and size), PVR grade, tamponading agent used, preoperative and postoperative visual acuity (converted into LogMAR), RRD recurrences, and complications, were extracted from the hospital’s electronic medical records. All available preoperative and postoperative SD-OCT scans were evaluated by a retina specialist (MVC).

A total of 346 eyes from 333 patients who underwent PFCL-free PPV for primary RRD were included in the study. Among them, 274 eyes (79%) had uncomplicated RRD, while 72 eyes (21%) had complicated RRD. The complicated RRD group comprised eyes with various complicating factors, including pathologic myopia (39 eyes, 54%), PVR grade B or worse (15 eyes, 21%), giant tears (15 eyes, 21%), RRD starting from a macular hole (11 eyes, 15%), and choroidal detachment (3 eyes, 4%). Notably, some patients with complicated RRD had multiple complicating factors. Peripheral schisis-associated RRD was not observed.

The clinical characteristics of the patients are summarized in Table 1. Sixty-five eyes (24%) with uncomplicated RRD and 25 eyes (35%) with complicated RRD had macula-off RRD (p = 0.06). Eyes with complicated RRD were more myopic (− 8.60 ± 3.73 vs. − 2.40 ± 2.22 diopters, p < 0.001) and had longer PPV surgery durations (49.6 ± 17.8 vs. 43.3 ± 11.9 min, p = 0.005) than eyes with uncomplicated RRD. Silicone oil was used more frequently as a tamponading agent in complicated RRD cases (10% vs. 4%, p = 0.04), while 360° laser retinopexy was performed more often in uncomplicated RRD cases (88% vs. 75%, p = 0.005). There were no significant differences in other characteristics.

The mean postoperative follow-up duration was similar for uncomplicated and complicated patients with RRD (p = 0.8): 11 ± 2.0 months (range 6–44). A higher percentage of complicated RRD eyes underwent cataract extraction during follow-up (21% vs. 9%, p = 0.01).

The present study adds to the increasing body of evidence supporting the adoption of PFCL-free techniques in vitreoretinal surgery for retinal reattachment. PFCL-free procedures have gained popularity among vitreoretinal surgeons due to several potential advantages, such as avoiding retinal toxicity, reducing surgery times and costs, and minimizing intraoperative manipulations. Furthermore, procedures involving PFCLs carry a notable risk of accidental PFCL migration into the subretinal space, a potentially serious event that can lead to decreased visual acuity and scotomata. This global trend is evident in reports from various countries, including Canada [12], the United States [11], Italy [10], Israel [7], India [13], China [8], and Japan [9], all of which have shown widespread adoption of PFCL-free techniques.

This study contributes to the existing literature by presenting one of the largest series (n = 346) of PFCL-free PPV surgeries for both uncomplicated and complicated RRD. Previous studies have reported favorable outcomes with PFCL-free PPV, showing high single-operation success rates. For instance, Chen et al. conducted a small prospective study on uncomplicated RRD eyes managed with PPV and partial PFCL-free subretinal fluid drainage, achieving a single-operation success rate of 91.6% at 3 months [8]. Subsequent retrospective case series have further supported the positive outcomes of PFCL-free PPV. Additionally, it is important to consider the impact of surgeons’ experience and skills over time as well as the thoughtful selection of cases when analyzing surgical outcomes.

The main objective of this study was to investigate factors associated with RRD recurrence. In the analysis of uncomplicated RRD eyes, previous studies indicated that intraoperative 360° prophylactic laser photocoagulation was linked to a reduced risk of re-detachment [17, 18], suggesting its potential to prevent re-detachment from overlooked breaks. However, due to the small number of events, we could not perform a subset analysis of uncomplicated and complicated RRD regarding the role of 360° prophylactic laser photocoagulation. We acknowledge that 360° retinopexy was more commonly performed in cases perceived to have a higher risk of re-detachment compared to eyes where focal laser was used, leading to a potential selection bias that might have influenced the observed association between 360° retinopexy and a lower re-detachment rate. Moreover, the drawbacks of intraoperative 360° laser retinopexy include increased total operating time and the need for scleral depression to coagulate peripheral retinal locations. A navigated pattern laser (Navilas) could also have been used postoperatively [19]. A higher rate of RRD recurrence was observed in eyes filled with silicone oil, but this could also be attributed to a selection bias, as silicone oil is typically used in eyes perceived to be at a higher risk of re-detachment.

In cases of complicated RRD, including traumatic RRD, high myopia, choroidal detachment, recurrent RRD, a macular hole, high-grade PVR, and giant tears, the recurrence rate was estimated to be 7%, which aligns with a previous study by Bai et al. reporting a recurrence rate of 13% in complicated RRD managed with PFCL-free PPV [14]. While certain subgroups of complicated RRD, such as pathologic myopia, PVR, and giant tears, showed single-operation success rates similar to uncomplicated RRD, poorer outcomes were observed in cases with posterior retinal breaks, a macular hole, or concurrent choroidal detachment. These findings suggest that alternative surgical strategies may be necessary for such cases.

Optical coherence tomography imaging was utilized to assess postoperative outcomes in this study. Common findings after retinal reattachment surgery, as observed in previous studies [20], include residual pockets of SRF, CME, ORF, a macular hole, ERM, and EZ/IZ damage [21, 22]. The prevalence rates of these complications in PFCL-free PPV eyes were estimated to be 4% for SRF, 5% for ORF, 6% for EZ/IZ damage, and 3% for a macular hole. These rates are in line with previous reports, although caution should be exercised when comparing studies due to potential variations in the timing of OCT assessments [7‐10]. Nevertheless, these findings underscore the importance of vigilant postoperative monitoring and timely intervention to address macular complications in PFCL-free PPV cases.

The ELLIPSOID study, which included 300 eyes with RRD that underwent PPV with different SRF drainage techniques, reported a lower proportion of EZ/IZ damage at 12 months in eyes undergoing PFCL-free PPV [12]. These findings support the idea that PFCL-free PPV may be associated with less retinal turbulence, SRF currents, and forced retinal repositioning compared to PFCL-assisted PPV [23]. However, it is important to note that the occurrence of CME, ERM, and EZ/IZ damage together suggests that outer retinal damage is multifactorial, and epiretinal traction may also contribute to outer retinal disruption. The dynamic changes in EZ/IZ reflectivity after retinal reattachment and the timing of SD-OCT assessment can influence the rate of EZ/IZ damage [21].

The presence of PVR preoperatively and RRD recurrence were identified as risk factors for CME, consistent with previous studies [24]. ERM was found more frequently in eyes with giant tears, likely due to the higher chances of RPE dispersion and vitreous hemorrhage in these cases [25]. ERM was also associated with the use of large-caliber vitrectomy probes (23-gauge), which may be related to the complexity of the cases operated using these probes [26]. ORF was more frequently observed in association with ERM, suggesting that epiretinal traction could impede retinal relaxation after reattachment, favoring ORF formation.

Visual acuity significantly improved from baseline to 12 months in this study, and final VA scores were comparable to those reported in other PFCL-free cohorts [7, 11]. Postoperative EZ/IZ damage was associated with worse vision after adjusting for confounding variables such as cataract extraction during or after PPV. These results align with previous studies, indicating a link between functional outcomes of RRD repair and the integrity of photoreceptors on SD-OCT [27, 28].

The present study has several strengths, including a relatively large sample size and the comprehensive availability of SD-OCT data for all study eyes, allowing for objective and repeatable functional and prognostic assessments. However, there are some limitations that need to be acknowledged. The retrospective design of the study may introduce selection bias due to loss to follow-up, favoring more complicated or recurrent RRD cases. Additionally, the dropout rate limited the use of more sophisticated statistical analyses, and certain functional and anatomical outcomes, such as metamorphopsia and retinal vessel displacement, were not evaluated. The analysis focused on a 26-scan macular volume, potentially underestimating extra-macular pathology. Clinically relevant details, including the time elapsed between RRD and repair surgery, were missing, and this factor could have influenced visual outcomes, especially in cases with macular detachment at the time of surgery. The classification of pseudophakic eyes based on refraction status prior to cataract surgery was not possible for all patients due to unavailable data. Furthermore, postoperative SD-OCT data were analyzed at different postoperative times, which may have led to an underestimation of some postoperative complications, such as ERM or CME development.

In conclusion, the study contributes valuable insights into the efficacy of PFCL-free PPV for both uncomplicated and complicated RRD. The prevalence of macular complications was low, and they were predominantly observed in complicated RRD cases. Outer retinal damage was identified as a crucial predictor of postoperative vision. The analysis of risk factors for RRD recurrence provided provisional recommendations for PFCL-free approaches, suggesting that heavy liquid retinal reattachment may be necessary in cases with posterior retinal breaks, macular holes, and concurrent choroidal detachment. The use of SD-OCT imaging allowed for an objective assessment of postoperative outcomes and confirmed the association between EZ/IZ damage and visual outcomes. However, the retrospective design and limitations of the study warrant further prospective investigations to validate these findings and explore additional functional and anatomical outcomes.