One-Month versus 3-Month Heavy Silicone Oil Tamponade in Complex Rhegmatogenous Retinal Redetachment

Abstract

Introduction

The aim of the study was to compare functional and anatomical results after 1- vs. 3-month heavy silicone oil (HSO) tamponade to repair complex inferior recurrent rhegmatogenous retinal detachment (Re-RRD).

Methods

A retrospective, comparative, cohort study was conducted involving 46 eyes from 46 patients who were affected by complex inferior Re-RRD and had previously undergone tamponade with either gas or silicone oil. All the eyes were treated using HSO (Densiron® 68), which was removed after 1 (group A) or 3 months (group B). The outcomes included the attachment rate, best-corrected visual acuity (BCVA), and intraocular pressure (IOP), comparing these results at 3, 6, and 12 months after HSO removal.

Results

Out of 46 eyes that experienced a complex inferior Re-RRD after initial surgery and received HSO, 24 were in group A and 22 in group B, with HSO removal after 1 and 3 months, respectively. The reattachment rates were similar: 91.6% for group A and 81.8% for group B (p = 0.4). In group A, a significant visual gain occurred during all follow-up (p < 0.001); in group B, the significant improvement (p ≤ 0.03) was lost at 12 months. Mean BCVA was better in group A than B at 6 and 12 months (p ≤ 0.02). Group B exhibited a significant increase in mean IOP after 3 months (p < 0.001), consistently exceeding the values observed in group A throughout the follow-up (p ≤ 0.002). Macular edema occurred in 7 eyes, with no notable differences between the groups.

Conclusion

A 1-month HSO endotamponade has a similar reattachment rate but provides better visual recovery and controlled IOP than a 3-month endotamponade in complex Re-RRD with inferior involvement.

Introduction

The recurrence of rhegmatogenous retinal detachment (RRD) is one of the most common factors that impact the prognosis following initial surgical intervention. Existing literature indicates that more than 80% of recurrences occur within the first 6 weeks after primary surgery [1]. Recurrent rhegmatogenous retinal detachment (Re-RRD) after surgery is likely attributed to multiple mechanisms, including vitreoretinal traction and fluid passing through an untreated or newly formed retinal break [2]. Re-RRD related to inferior retinal breaks, particularly when accompanied by proliferative vitreoretinopathy (PVR), poses a surgical challenge in selecting an appropriate tamponade. Using endotamponades with higher specific gravity than the aqueous humor has been reported to aid in the treatment of Re-RRD [3, 4]. Various heavy silicone oils (HSOs) are available for use as endotamponade, including Densiron^® 68 (Fluoron, Neu Ulm, Germany), Densiron XTRA (Fluoron, Neu Ulm, Germany), Oxane HD (Bausch & Lomb, Toulouse, France), and Alaheavy (AlaMedics GmbH & Co. KG, Dornstadt, Germany) [5, 6]. Several studies assessed the effectiveness of HSO, mostly in eyes with complex RRD, although the majority of studies had heterogeneous cohorts, including either primary or Re-RRDs [7–14]. The number of studies exclusively focused on HSO for Re-RRD is limited, and even fewer involve the use of Densiron^® 68 [12, 14], a solution composed of 30% perfluorohexyloctane and 70% of 5,000 cSt silicone [4], characterized by high viscosity (1,400 mPa), a density of 1.06 g/cm³, and less tendency to disperse [15, 16]. The anatomical success rates after Densiron^® 68 removal for Re-RRD varied from 61% to 100% [12, 14], with an improved visual acuity observed over a follow-up ranging from 7 to 12 months [12, 14]. Several complications have been reported due to HSO endotamponade, including raised intraocular pressure (IOP), inflammatory response, cystoid macular edema, epiretinal membrane, oil dispersion/emulsification, and cataract formation [3, 5, 8, 13, 17]. A review by Russo et al. [17] suggested that inflammation may be influenced by the duration of tamponade. Specifically, in cases involving Densiron^® 68 for Re-RRD, the complication rate was higher (50% versus 36.3%) when the tamponade duration was extended (3 months as opposed to 1 month) [12, 14]. This study aimed to evaluate the rate of retinal attachment, visual recovery, and postoperative complications after 1 month or 3 months of HSO removal for Re-RRD with inferior involvement in eyes that previously underwent vitrectomy using different endotamponades (gas or standard silicone oil [SO]) over a 12-month follow-up period.

Methods

This is a retrospective, comparative, single-center cohort study. We reviewed the charts of consecutive patients affected by Re-RRD who underwent surgery at the Eye Clinic, University Hospital of Bari, Italy, between December 2021 and September 2023. This study was performed in accordance with the national legislation on retrospective studies.

Inclusion Criteria

Adult patients aged 18 years or older were selected. The study included adult patients with a Re-RRD complicated by inferior PVR after a first failed vitrectomy, which was performed using either 20% sulfur hexafluoride (SF₆) or 14% perfluoropropane (C₃F₈) gas endotamponade, or standard SO 1,000 cSt. All included patients had undergone only one vitreoretinal surgery prior to this study. During the second surgery, all eyes were treated with vitrectomy and HSO (Densiron^® 68, Fluoron, Neu Ulm, Germany) as per endotamponade at the end of each surgery.

Exclusion Criteria

Patients were excluded if they had a history of ocular hypertension, glaucoma, diabetic retinopathy, degenerative or dystrophic retinal diseases, eyes affected by traumatic retinal detachment, or were undergoing vitrectomy for causes other than RRD. Additionally, eyes undergoing any type of previous intraocular surgery, with the exception of those which had phacoemulsification and intraocular lens implantation, were excluded. Patients with an axial length greater than 26 mm (as measured with the ZEISS IOLMaster 500^® with a signal-to-noise ratio >200) or a myopic refractive error of −6.0 diopters or more were also excluded. Aphakic eyes were not included in the study. None of the eyes had received HSO endotamponade during the first surgery.

Surgical Procedure

All surgeries were performed by the same vitreoretinal surgeon (F.B.) using local retrobulbar anesthesia. The procedure involved the removal of peripheral vitreous remnants through a 25-gauge pars plana vitrectomy. A vital dye (Dual Blue, DORC, The Netherlands) was injected into the vitreous cavity to approach PVR. Perfluorodecalin (F Decalin, Fluoron Co, Neu Ulm, Germany) was used to flatten the retina during PVR peeling. The retinectomy was performed if the retinal contraction did not reduce during the peeling. Intraoperative endolaser treatment was performed in every retinal quadrant and around retinal breaks. Internal limiting membrane peeling was performed when necessary. Each case received Densiron^® 68 endotamponade (Fluoron Co, Neu Ulm, Germany). To prevent mechanical forces induced by HSO from affecting the optic nerve and the posterior pole structures, the patients were advised to maintain a standing position during the day and rest at 45° at night, avoiding a face-up position after surgery until the removal procedure. Medical postoperative therapy consisted of a combination of topical steroids and antibiotics (preservative-free dexamethasone eye drops, 1 mg/mL, and tobramycin, 3 mg/mL, administered four times daily), as well as topical nonsteroidal anti-inflammatory drugs (bromfenac eye drops, 0.9 mg/mL, twice daily) for at least 1 month in all patients. A 25-gauge vitrectomy was then used for HSO removal 1 or 3 months after its injection as per endotamponade. Written informed consent was obtained from all patients prior to surgery.

Assessment and Outcomes

All participants underwent a comprehensive ophthalmic examination before HSO removal, which included the collection of demographic and medical history data, measurement of best-corrected visual acuity (BCVA) and IOP, slit-lamp examination, and fundoscopy. Follow-up examinations were scheduled throughout a follow-up of at least 12 months after HSO removal. IOP was measured using a Goldmann tonometer. BCVA was assessed using a standardized Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, with ETDRS values converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. The main outcomes were BCVA and recurrence of retinal detachment over follow-up. Unscheduled appointments, complications, and additional interventions were recorded. According to the time duration of HSO endotamponade, the eyes were categorized in two groups: in group A, the HSO was removed after 1 month; in group B, HSO was removed after 3 months. The decision on when to remove the HSO was made on the surgeon’s discretion, considering factors such as the patient’s systemic condition, poor vision in the contralateral eye, poor compliance with maintaining the correct position, and the patient’s professional and social requirements.

Statistical Analysis

Qualitative variables were presented as frequencies and percentages, whereas quantitative data were expressed as means and standard deviations. No sample size calculation was conducted. The chi-square test or Fisher’s exact test was used to compare the qualitative variables. We used the nonparametric Mann-Whitney test for variables with nonnormal distribution (Shapiro-Wilk test); otherwise, Student’s t test was utilized. A comparison of postoperative outcomes between the groups was performed at 3, 6, and 12 months after HSO removal. All statistical tests were conducted at the significance level of p values of <0.05. Statistical analysis was performed using SPSS Statistics for Windows, version 25.0 (SPSS Inc, Chicago, IL).

Results

Forty-six eyes of 46 patients with Re-RRD were included. The mean age of patients was 65.8 ± 13.2 years (range, 26–88), 20 females and 26 males. The mean axial length was 24.9 ± 0.8 mm (range, 22.5–25.9). Most of the eyes were pseudophakic (91.3%) and had an RRD involving the macula (67.4%) at the time of first vitrectomy, when retinectomy and internal limiting membrane peeling were performed in overall 9 (19.5%) eyes, respectively. Only four eyes, two for each group, had undergone cataract surgery during the first RRD repair. Twenty-seven (58.7%) eyes were tamponaded with gas (SF₆ or C₃F₈), while the remaining 19 (41.3%) with SO 1,000 cs at the first surgery. In all eyes, the Re-RRD involved the inferior quadrants and occurred after a mean time of 61.2 ± 36.2 days (range, 7–122). When Re-RRD occurred, PVR grade C 1 to 3 was observed in 12 patients (5 in group A; 7 in group B), while a PVR grade B was observed in the remaining patients (19 in group A; 15 in group B; 0.77). Nine patients (4 in group A; 5 in group B; 0.60) were subjected to retinectomy at the second surgery when contraction did not reduce during the PVR peeling. Eleven eyes underwent ILM peeling (7 in group A; 4 in group B; 0.38). Twenty-four eyes removed HSO after 1 month (group A), while 22 eyes (group B) had the HSO removed after 3 months. The time period of HSO tamponade was 32 ± 1.9 days (30–36) in group A and 94.6 ± 4.1 (90–104) days in group B (p < 0.001). The main characteristics of the eyes in both groups at their first surgery are displayed in Table 1. The mean follow-up was 52 ± 1.2 weeks (group A, 52.8 ± 1.1 weeks; group B, 53 ± 1.2 weeks; p 0.45). Overall, the rate of retinal reattachment after HSO endotamponade was 87% (40 eyes). Over all follow-up, the reattachment rate was 91.6% (22/24) in group A and 81.8% (18/22) in group B (p 0.40). The relapse of RRD occurred in two eyes after 3 months, in three eyes after 6 months, and in one eye after 12 months from HSO removal. The mean overall BCVA improved from 20/796 (1.6 ± 1.03 logMAR) before HSO removal to 20/200 (1.0 ± 0.79 logMAR; p = 0.001) at last follow-up after HSO removal. In group A, mean BCVA significantly improved from 20/957 (1.68 ± 1.03 logMAR) before HSO removal to 20/145 (0.86 ± 0.66 logMAR; p < 0.001), 20/112 (0.75 ± 0.63 logMAR; p < 0.001), and 20/126 (0.8 ± 0.76 logMAR; p < 0.001), at 3, 6, and 12 months after HSO removal, respectively. In group B, mean BCVA improved from 20/957 (1.57 ± 1.05 logMAR) before HSO removal to 20/289 (1.16 ± 0.82 logMAR; p 0.03), 20/303 (1.18 ± 0.78 logMAR; p 0.02), and 20/332 (1.22 ± 0.79 logMAR; p 0.07), at 3, 6, and 12 months after HSO removal, respectively. The BCVA was significantly better in group A than B at 6 (p 0.02) and 12 months (p 0.01) (shown in Fig. 1). Five patients in each group maintained the same visual acuity at last follow-up when compared to pre-HSO removal. Overall, 7 patients (2 in group A; 5 in group B) experienced a visual acuity impairment at last follow-up. In group A, mean IOP did not significantly change over follow-up. In group B, mean IOP significantly increased only after 3 months from HSO removal. The IOP was significantly higher in group B than A at 3 (p < 0.001), 6 (p < 0.01), and 12 months (p < 0.001) (Table 2). At month 3, all patients in group B had an IOP higher than 20 mm Hg (range, 21–28 mm Hg). In group A, only 2 patients had IOP higher than 20 mm Hg (range, 22–27). During the follow-up, only 3 patients (1 in group A; 2 in group B) experienced an IOP elevation (over 25 mm Hg), requiring medical managing with topical therapy (dorzolamide 2% eye drops administered 3 times daily in two cases; timolol 0.5%/dorzolamide 2% eye drops administered 2 times daily in one case). No eyes needed incisional glaucoma surgery. Cystoid macular edema occurred in 7 (15.2%) eyes (group A, 3 eyes; group B, 4 eyes). In all cases, macula edema occurrence and its relapse are medically managed with nonsteroidal anti-inflammatory drug eye drops over 2 months. No other complications were reported.

Table 1.

Demographic, clinical characteristics, and main steps of first surgery

​	Group A	Group B	p value
	(Densiron 1 month)	(Densiron 3 months)
	n = 24	n = 22
	n (%)	n (%)
Gender
Male	14 (30.4)	12 (26.1)	0.99
Female	10 (21.7)	10 (21.7)
Age, years	64.6±13.7	67.0±12.8	0.54*
Axial length, mm	25.0±0.84	24.9±0.95	0.91a
Lens status
Phakic	2 (4.3)	2 (4.3)	0.99
Pseudophakic	22 (47.8)	20 (43.5)
Retinal break	2.25±0.84	2.14±0.94	0.48a
Macular status
On	7 (15.2)	8 (17.4)	0.75
Off	17 (37.0)	14 (30.4)
PVR ≥ grade C
Yes	9 (19.6)	8 (17.4)	0.99
No	15 (32.6)	14 (30.4)
Phaco+IOL
Yes	2 (6.5)	2 (4.3)	0.99
No	22 (47.8)	20 (43.5)
Retinectomy
Yes	6 (13.0)	3 (6.5)	0.33
No	18 (11.9)	19 (16.7)
ILM peeling
Yes	5 (10.8)	4 (8.7)	0.99
No	19 (41.3)	18 (39.1)
First surgery tamponade
SF6	10 (21.7)	10 (21.7)	0.99
C3F8	4 (8.7)	3 (6.5)
SO	10 (21.7)	9 (19.6)
Days to recurrence from first surgery	59.7±37.2	62.8±35.9	0.69a

%, percentage of total study population; SF₆, sulfur hexafluoride; C₃F₈, perfluoropropane; SO, silicone oil; PVR, proliferative vitreoretinopathy; IOL, intraocular lens; p value, Fisher test.

*p, t test.

^a p, Mann-Whitney test.

Fig. 1.

Change in BCVA of both groups over time. Mean BCVA (logMAR); continuous line represents mean change from baseline in group A; dotted line represents mean change from baseline in group B. *p < 0.05 as compared to baseline. ***p < 0.001 as compared to baseline.

Table 2.

Mean IOP compared within and among the groups over follow-up

Parametersa	Baseline	3 months	6 months	12 months	p value
	(a)	(b)	(c)	(d)	(b) vs. (a)	(c) vs. (a)	(d) vs. (a)
IOP, mm Hg
Group A	15.8±1.61	17.0±3.28	15.3±2.48	15.3±1.33	0.17	0.39	0.21
Group B	16.5±1.53	22.5±1.65	17.6±4.24	17.7±2.86	<0.001	0.58	0.17
p valueb	0.11	<0.001	0.002	<0.001	​	​	​

IOP, intraocular pressure.

^aAs mean and standard deviation (mean ± SD).

^b p value for comparison within and among the groups, Mann-Whitney test.

Discussion

Re-RRD involving the inferior retinal periphery due to PVR can be effectively managed with HSO, which has a density greater than water [2, 4, 6, 8–15]. However, the visual recovery and complication rates following the removal of HSO can be disappointing, particularly if the tamponade is kept in place for three or more months [8, 12–14, 17]. This study aimed to compare the rates of reattachment, visual recovery, and postoperative complications between early (1 month) and late (3 months) removal of HSO endotamponade in eyes with Re-RRD that had previously undergone vitrectomy and been tamponaded with gas or standard SO. The results showed comparable anatomical success rates in both groups, with a slightly higher reattachment rate observed in the early removal group. Visual outcomes were significantly better in the early removal group at both 6 and 12 months post-HSO removal. Additionally, the early removal group had lower rates of postoperative IOP elevation. Our findings are consistent with existing literature on Re-RRD incidence in the weeks following primary surgery. Re-RRD often occurs shortly after the resolution of the tamponade effect. Specifically, redetachment happened after a median of 24.5 days with SF₆, 45 days with C₃F₈, and 94 days after SO removal. The clinical findings of RRD before the first surgery and the types of endotamponades used – either expandable fluorinated gases or standard SO – were evenly distributed between the two groups. Additionally, there were no significant differences between the groups in the clinical findings of complex Re-RRD, including PVR severity, or in the main surgical steps used to treat them. The clinical variables analyzed for comparison may also have limited the population within a narrow range. Additionally, the single-center, single-surgeon design may have further limited the study population, minimizing differences between the groups. Densiron^® 68 was utilized as a secondary option for cases of inferior Re-RRD that had previously been treated with gas or standard SO tamponade [12, 14]. Re-RRD occurs less frequently with HSO than with other endotamponades [18–22]. Our results revealed an overall reattachment rate of 87% (40 out of 46), which is comparable to and, in some cases, better than previous studies that reported reattachment rates from 49% to 100% [2, 4, 6, 8, 11, 12, 14], involving a study population with a major number of eyes with recurrent detachment, and regardless the duration of HSO tamponade. During a second surgery, using HSO may reduce the risk of PVR in the inferior quadrant by displacing a proliferative mixture of residual aqueous and inflammatory and RPE cells away from the lower retina [12]. Moussa et al. [23] found that retinal redetachment and the need for retinectomy appear to be less frequent after HSO usage compared with standard SO. Dirani et al. [24] conducted a systematic review analyzing 22 studies. They found that the usage of HSO tamponade was more frequently performed in eyes affected by secondary retinal detachment with inferior retinal breaks and PVR. This is likely because HSO is considered superior to standard SO. The “Heavy Silicone Oil Study” [25] revealed no statistically significant difference in anatomical outcomes between HSO and standard SO for addressing inferior PVR -related retinal detachments. However, the study failed to recruit a large number of patients, as previously suggested [24]. Indeed, the overall sample size for this comparative analysis was relatively modest (93 patients were recruited, 46 in the HSO group and 47 in the standard SO group). Despite six cases of a new Re-RRD during follow-up (four of which were in the late removal group), both groups had similar rates of retinal reattachment. These findings suggest that the timing of HSO removal may not significantly influence the anatomical outcome, as indicated by earlier studies where HSO was maintained for 1 to 4 months [2, 4, 6, 8, 11, 12, 14]. Two-thirds of patients had a macular detachment before the first retinal detachment repair. This may have contributed to the overall low visual acuity at the end of follow-up. However, we did not analyze the duration of macular involvement before the first diagnosis, as we did not have this information for all patients. Cataract surgery was performed on 4 of 46 patients during the first surgery. This may have influenced functional outcomes to a limited extent. Notably, one of these patients had a macula-off RRD before the first surgery. Two of these patients had functional impairment at the last follow-up, and only one had stable visual acuity. Approximately 74% of patients showed an improved visual acuity at the last follow-up, while only 7 patients experienced a decline in visual acuity (two in the early removal group and five in the late removal group). The early removal group had significantly better average of visual acuity at 6 and 12 months compared to the other group. The overall improvement aligns with previous studies demonstrating better visual recovery regardless of the duration of HSO tamponade [2, 4, 6, 8, 11, 12, 14]. However, no prior research has specifically compared functional recovery based on the duration of HSO tamponade. Our results suggest that prolonged HSO tamponade may negatively impact on the final sight recovery. Previous studies have identified disorganization of the outer retinal layers and retinal pigment epithelium due to mechanical stress and the toxic effects of SO [26–28]. SO can lead to retinal thinning, particularly at the macula, although this change may regress after the tamponade is removed [29]. Hostovsky et al. [30] noted that prolonged HSO tamponade for up to 6 months may induce reversible retinal thinning due to mechanical effects, suggesting that short-term use could prevent damage to the fovea. Additionally, the toxic effects of different SO endotamponades on retinal cells and their impacts on visual recovery have been just reported [31, 32]. On the other hand, if Horozoglu et al. [33] observed that ellipsoid zone continuity was preserved in the long-term HSO endotamponade (15.3 ± 11.0 months), it can also elevate IOP [34], potentially contributing to visual function impairment due to glaucomatous optic neuropathy [35]. Moussa et al. [36] found no prognostic relevance in the use and duration of Densiron as endotamponade concerning visual reduction of ≥0.30 logMAR units. However, the use of SO endotamponade has been associated with a risk-adjusted increase in unexplained visual loss compared to gas tamponade. Therefore, early removal of the SO may limit the exposure time of the silicone endotamponade to the macula, potentially minimizing its toxic effects, as suggested by recent recommendations [37]. In this study, eyes that underwent late HSO removal experienced significantly higher IOP levels than those in the early removal group. All eyes that had late removal exhibited elevated IOP 3 months post-removal. In contrast, only 2 patients in the early removal group experienced IOP elevation during the follow-up. Ocular medication was necessary for only 3 patients (one in group A and two in group B) to manage IOP elevation. HSO is considered to carry a higher postoperative IOP elevation risk compared to standard SO [38, 39]. For instance, Caporossi et al. [12] observed ocular hypertension in 34.7% after the fill with HSO; of these, only 23.5% returned to normal IOP after HSO removal, while the remaining 76.5% required prolonged glaucoma therapy. Tognetto et al. [15] reported only five instances of ocular hypertension after HSO tamponade; three were treated with medication, while two required HSO removal. Wong et al. [40] noted IOP levels exceeding 30 mm Hg in 3 patients at the 5-week follow-up, and 3 patients had an IOP higher than 30 mm Hg after 3 months after the HSO removal. All cases were managed with glaucoma medications. Sandner et al. [41] described increased IOP in only 4 patients, but it persisted in three cases after HSO removal. The presence of emulsified HSO droplets has been identified as a contributor to inflammatory reactions and subsequent IOP elevation [38, 39, 42]. Emulsification of HSO occurs earlier compared to standard SO [8, 43, 44], affecting 32.5% to 42.2% of eyes treated with HSO [15, 45]. In all previous studies, the HSO remained in the eye between 3 and more months. Although the duration of SO tamponade does not seem to influence IOP increases [46–48], emulsification of the SO does play a significant role in the rise of IOP following vitrectomy for RRD, with emulsification observed between 4.3 and 5 months post-procedure [49, 50]. Notably, patients with oil emulsification show higher IOP values than those without [46], likely due to their prolonged exposure to dense HSO. Among the well-known complications associated with HSO [5], our study also noted occurrences of macular edema, with similar rates between groups. Our study reported a lower overall complication rate and fewer postoperative issues compared to the previous research on Densiron, likely due to the shorter duration of HSO endotamponade. This suggests that a shorter tamponade period is associated with fewer inflammatory complications [51, 52]. HSO may provoke a more pronounced inflammatory response, probably due to its higher tendency for emulsification compared to standard SO [39, 51], suggesting that HSO should be removed as soon as possible. There are limitations to our study that must be acknowledged. The retrospective analysis of the study may have introduced biases in data collection and selection. Furthermore, the small sample size may have limited statistical power and reduced the generalizability of results to all cases of Re-RRD. Additionally, the clinical variables used for comparison may have limited the study population. Notably, the lack of OCT analysis of macula status means that the functional results could not be corroborated. Moreover, HSO removal was determined on a case-by-case basis, which could potentially lead to selection bias. Therefore, prospective studies with larger cohorts and macular tomographic analysis are needed to validate these findings.

Conclusions

The early removal of Densiron^® 68 after 1 month from surgery for Re-RRD in selected cases may improve visual outcomes and reduce postoperative IOP elevation rates compared to late removal after 3 months. However, further prospective studies with larger sample sizes are required to confirm these findings and establish optimal protocols for HSO removal in cases of Re-RRD.

Statement of Ethics

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board as well as the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Institutional Review Board of the Eye Clinic of University of Bari, Bari, Italy, approved the study (Code: HSO Study 21-23). In line with national guidelines, the IRB waived the need for written informed consent for the retrospective study. However, verbal informed consent about study enrollment was obtained from all individual participants included in the study.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding was received for the study.

Author Contributions

Giancarlo Sborgia designed the study, collected the data, and prepared the first draft of the manuscript; Giacomo Boscia and Alfredo Niro prepared the first draft of the manuscript and performed statistical analysis; Camilla Di Pardo and Alessandra Sborgia collected the data; Pasquale Viggiano, Pierluigi Grenga, Marco Coassin, Alfonso Savastano, and Francesco Boscia revised the manuscript. All authors contributed to the study concept and design and read and approved the final manuscript.

Funding Statement

No funding was received for the study.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.