García et al. BMC Ophthalmology (2022) 22:319 https://doi.org/10.1186/s12886-022-02536-2 RESEARCH ARTICLE Open Access Prevalence and implications of the presence of intraocular silicone oil droplets in patients treated with intravitreal injections of anti‑VEGF Sandra Banderas García1,2*† , Xavier Garrell‑Salat1†, Fernando Trejo‑Velasco1, David Aragón‑Roca1, Miguel Ángel Zapata1,2 and José García‑Arumí1,2 Abstract Background: To determine the percentage of patients who have silicone droplets in the vitreous after treatment with different anti-Vascular Endothelial Growth Factor (anti-VEGF) intravitreal injections (IVI) and how symptomatic they are. Methods: One hundred fifty-two eyes of 140 patients who had at least received an IVI were recruited for this study. Data collection included the number and type of IVI (aflibercept, ranibizumab and bevacizumab) and the follow-up time. A complete ophthalmologic examination was carried out and patients were classified in four groups accord‑ ing to the amount of silicone droplets found in dilated fundoscopy (nonexistent, scarce, moderate and abundant). Measurement of intraocular pressure (IOP) was also carried out. An interview was conducted to report the presence and intensity of the symptomatology. Results: Silicone oil droplets were reported in 109 eyes (71.7%). A positive correlation was found between the number of IVIs received and the quantity of droplets found, especially when aflibercept was used. Posterior vitreous detachment (PVD) was present in 65.8% of the patients, showing a positive correlation with the number of bubbles. Regarding the symptomatology, 60 eyes (39.5%) had floaters and the disturbance was reported to be 4 out of 10. The group with a moderate amount of silicone droplets had the highest percentage of floaters (60%). No statistical differ‑ ences in the IOP were found between groups, although the group with abundant droplets had a higher mean IOP. Conclusion: A high prevalence of silicone droplets in vitreous of patients who undergo IVI treatment was found. It appears to have little impact on symptomatology and rise of IOP. Keywords: Intravitreal injections, Silicone droplets, Anti-VEGF, Floaters, Intraocular pressure, Macular diseases Background neovascularization that appears in age-related macular The intravitreal injection of drugs that inhibit vas- degeneration (AMD), as well as in the treatment of dia- cular endothelial growth factor (anti-VEGF) is the betic macular edema and macular edema secondary to first therapeutic option in the treatment of choroidal retinal vein occlusion. Most patients receive several of these injections with a frequency that can vary between monthly and quarterly, depending on the severity of the † Sandra Banderas García and Xavier Garrell-Salat shared first authorship. macular damage they present, becoming a chronic treat- *Correspondence: sandrabanderasgarcia@gmail.com ment for a large percentage of these patients. 1 Department of Ophthalmology, Vall d’Hebron University Hospital, Passeig de The prevalence of some forms of AMD and diabetic la Vall d’Hebron, 119‑129, 08035 Barcelona, Spain retinopathy are 1.5% of the general population and Full list of author information is available at the end of the article © The Author(s) 2022. 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The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​ mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. García et al. BMC Ophthalmology (2022) 22:319 Page 2 of 8 35% of the diabetic population, respectively; and the We included patients who agreed to participate in the expected growing trend in the coming years will lead to study, were older than 18 years old, had received at least an immense number of patients exposed to these drop- 1 intravitreal injection of any anti-VEGF agent and had lets of silicone oil [1]. Since 2006, the presence of silicone a visual acuity better than hand-motion (0.005 in Snel- oil droplets has been observed in the vitreous of those len Scale). We decided to take as sample all patients patients who received intravitreal injections [2] and the with a programmed appointment for intravitreal injec- quantity of these is directly proportional to the number tions of the Ophthalmology Department of the Vall of doses received [3, 4]. Macro-sized droplets (larger than d’Hebron University Hospital (Barcelona, Spain) within 100 μm) are typically visible to naked eye, while micro- 5 weeks between 1st of February and 4th of March 2021. sized droplets (up to 60 μm) can only be observed with Exclusion criteria were the impossibility of signing the technologies such as imaging flow cytometry [5]. In informed consent, eyes with prior vitrectomy, presence our study, we will always refer to macro-sized droplets of vitreous hemorrhage, synchysis scintillans or aster- because of the examination technique employed. Silicone oid hyalosis, known history or actual active uveitis, poor oil is used in the manufacture of disposable syringes, in mydriasis or severe allergic reaction to tropicamide, fluo- which the medication is pre-filled, to lubricate the piston rescein or oxybuprocaine. and thus prevent it from sticking to the syringe tube. Although these droplets generally do not generate Examinations performed symptoms, a percentage of patients report transient The examinations were performed at least 1 month golden floaters for an average of 1 week after intravitreal after the last intravitreal injection to the patient. The injection. On the other hand, silicone oil when used as following variables were recorded from the patient a plugger in retinal detachment surgeries can pass into files: age, sex, pathology treated, follow-up time since the anterior chamber and cause ocular hypertension the first intravitreal injection, and number and type of by blocking the iridocorneal angle. Most commercially intravitreal agents received. Consecutively, a careful available needles also are siliconized in their inner lumen examination at slit-lamp by an experienced ophthal- [5]. mologist (DAR, SBG, XGS and FTV) was performed The objective of our study was to determine the per- with pharmacologic mydriasis (one drop of tropicamide centage of patients who have silicone droplets in the 0.5%, single dose 10 minutes before the examination) vitreous after treatment with anti-VEGF intravitreal to determine the presence of silicone bubbles in ante- injections and how symptomatic they are for the patient. rior vitreous and with a superfield lens for bubbles in the posterior vitreous (Fig. 1). PVD was also ruled Methods out: visualization of posterior hyaloid membrane with Inclusion and selection of patients absence of gel posterior to it. Measurement of intraoc- This was a transversal study, which was approved by the ular pressure (IOP) by means of Goldmann tonometry clinical research Ethics Committee of our center. The was carried out. Every patient was then classified into tenets of the Declaration of Helsinki were followed and four categories: “Non-existent”, “Scarce” (less than an informed consent was obtained from the subjects. 10 bubbles in vitreous), “Moderate” (between 10 and Fig. 1 A careful slit-lamp examination with pharmacologic mydriasis reveals the presence of numerous silicone oil droplets (white arrow) in the anterior vitreous (A) and in the posterior vitreous (B) with blue arrow García et al. BMC Ophthalmology (2022) 22:319 Page 3 of 8 30 bubbles) and “Abundant” (more than 30 bubbles). Results Following the examination, a short interview was Study population conducted asking for symptoms including: vision of We included a total of 140 patients and 152 eyes. Men floaters, presence of a central scotoma and metamor- accounted for 53.3% of the patients were men and mean phopsia. If the answer to any of the last symptoms was age was 73.6 years. The mean follow-up time since the positive, a scale from 1 to 10 was used to indicate the beginning of intravitreal treatment in our center was intensity of the disturbance that that symptom would 34.7 months and the mean intravitreal injections per eye cause. was 10.11. The total amount of intravitreal injections was of 1544 with 876 aflibercept (56.7%), 553 ranibizumab (35.8%), 86 bevacizumab (5.6%) and 29 dexamethasone Characteristics of the agents intravitreal implants (1.9%). More characteristics from Aflibercept (Eylea: Regeneron Pharmaceuticals, Inc., our sample are available in Table 1. Tarrytown, NY, US) is administered to our hospital in a A total of 109 eyes (71.7%) presented silicone oil drop- vial which is split by the pharmacy of our center into 3 lets in the vitreous. Of these, 40 eyes (26.3%) accounted sterile disposable 0.3 mL BD Microfine + Demi syringes for the “Scarce” bubbles group, 35 eyes (23.0%) for the (BD, Franklin Laked, NJ, US). Each syringe is filled with “Moderate” group and 34 eyes (224%) for the “Abun- 0.06 mL of Eylea. These are stored between 5 °C and 8 °C dant” group. We examined differences between groups before use. Recently a prefilled glass syringe has been in terms of age, sex, visual acuity, pathology or follow- commercialized and used in our center. up time (Table 2), with no statistically significant differ- Ranibizumab (Lucentis: Genentech, San Francisco, CA, ences. Differences were found in terms of the presence of US) consists of a single-use, sealed sterile tray prefilled PVD among all groups (global p = 0.003). When exam- glass syringe containing 0.165 mL of sterile solution. The ining this difference, statistically significant proportions top is fabricated from bromobutyl recovered with a white were found between the “Scarce” and “Abundant” groups rubber cover stopper and includes a Luer Lock adapter. (47.5% vs. 88.3% with p < 0.05). These are stored between 5 °C and 8 °C before use. Bevacizumab (Avastin: Genentech, San Francisco, CA, US) is repacked from vials by the compounding phar- Table 1 Demographic features of the patients’ data macy of our hospital and then filled into 20 1.0 mL sterile N = 152 Descriptive disposable Luer Lock syringes (DH material médico, Bar- Eye (right, %) 79 (51.9%) celona, Spain). Each syringe is filled with 0.2 mL of Avas- Sex (male, %) 82 (53.3%) tin. These are stored between 5 °C and 8 °C before use. Age (mean, SD) 73.6 (SD 10.72) Dexamethasone implant (Ozurdex: Allergan Pharma- Pathology (number,%) ceuticals, Ireland) is a single use biodegradable intra- AMD 85 (55.9%) vitreal implant with 0.7 mg of dexamethasone located RVO 26 (17.1%) in the stainless-steel needle of a disposable applica- DME 24 (15.8%) tor. The product does not require of any special storage Myopia 4 (2.6%) conditions. Others 13 (8.6%) Snellen VA (mean, SD) 0.5 (SD 1.29) Follow-up time in months (mean, SD) 34.68 (SD 30.74) Statistical study IVI number (mean, SD) 1544 (10.1, SD 8.45) Statistical analyses were performed with the SPSS Aflibercept number (mean, SD) 876 (5.8, SD 5.94) (Armonk, NY, US, v23.0). The normality of the variables Ranibizumab number (mean, SD) 553 (3.6, SD 5.77) was tested with the test of Kolmogorov-Smirnov. The Bevacizumab number (mean, SD) 86 (0.6, SD 1.53) quantitative variables that followed a normal distribution Dexamethasone implant number (mean, SD) 29 (0.2, SD 0.99) were studied with analysis of variance (ANOVA) and if Presence of PVD (n, %) 100 (65.8%) significant, groups were separately tested using Bonfer- Symptoms roni correction. Kruskal-Wallis test was performed to Scotoma (n, %) 30 (19.7%) compare quantitative variables not normally distributed Metamorphopsia (n, %) 52 (34.2%) and if differences found to be significant, groups were Floaters (n, %) 60 (39.5%) tested separately using Mann-Whitney U test. Qualita- IOP (mean, SD) 16.07 (SD 8.81) tive variables were examined using the Χ2 test. Spearman correlation was used to explore correlation among vari- SD Standard deviation, AMD Age-related macular degeneration, DME Diabetic macular edema, IOP Intraocular pressure, IVI Intravitreal injections, PVD Posterior ables. P < 0.05 was considered statistically significant. vitreous detachment, RVO Retinal vein occlusion, VA Visual acuity García et al. BMC Ophthalmology (2022) 22:319 Page 4 of 8 Table 2 Main features in the four groups. Statistical analysis in the last column Non-Existent Scarce Moderate Abundant Significance N = 43 N = 40 N = 35 N = 34 among groups Age (mean, SD) 71.84 (SD 1.89) 74.60 (SD 1.65) 70.77 (SD 1.59) 77.71 (SD 1.51) p = 0.13a Male sex (number, %) 23 (53.5%) 19 (47.5%) 24 (68.6%) 15 (44.1%) p = 0.174b Snellen VA (n, SD) 0.32 (SD 0.03) 0.44 (SD 0.4) 0.92 (0.44) 0.34 (SD 0.04) p = 0.084a Pathology (n, %) p = 0.243b AMD 19 (44.2%) 27 (67.5%) 19 (54.3%) 20 (58.8%) RVO 5 (11.6%) 6 (15%) 7 (20%) 8 (23.5%) DME 9 (20.9%) 5 (12.5%) 6 (17.1%) 4 (11.3%) Myopia 2 (4.6%) 1 (2.5%) 0 (0%) 1 (2.8%) Other 8 (18.6%) 1 (2.5%) 3 (8.6%) 1 (2.8%) PVD 27 (62.8%) 19 (47.5%) 24 (68.6%) 30 (88.2%) p = 0.003b Present (n, %) IOP (mean, SD) 15.21 (SD 0.515) 16.05 (SD 0.765) 14.63 (SD 0.499) 18.68 (SD 2.94) p = 0.259a Follow-up time in months 27.79 (SD 4.97) 36.05 (4.61) 39.03 (5.4) 37.32 (SD 4.83) p = 0.066a (mean, SD) SD Standard deviation, VA Visual acuity, RVO Retinal vein occlusion, AMD Age-related macular degeneration, DME Diabetic macular edema, PVD Posterior vitreous detachment, IOP Intraocular pressure Statistically significant p < 0.05 in bold a Kruskal-Wallis b Χ2 test Intravitreal agent group regarding the number of bubbles (Spearman cor- The average number of intravitreal injections that the relation rs = 0.330; p < 0.001). patients with no silicone droplets received was 6.26, while Regarding the intravitreal agents that were used, we the patients with droplets had received a mean number analyzed the average number of aflibercept, ranibizumab, of 11.70 intravitreal injections (Table 1). Statistically sig- bevacizumab and dexamethasone injections that each nificant differences were found regarding the mean num- group had received (Table 3). Statistically significant dif- ber of intravitreal injections when comparing groups ferences were found for aflibercept (p < 0.001) and ranibi- (p < 0.001). All 3 groups with silicone oil bubbles had zumab (p = 0.006). Examining the correlation between received a significantly bigger mean number of injections the average number of intravitreal injections of these two when compared with the “Non-existent” droplets group drugs and the group regarding the number of droplets (“Non-existent” vs. “Scarce” p = 0.001; “Non-existent” by means of Spearman correlation factor, we detected a vs. “Moderate” p < 0.001; “Non-Existent” vs. “Abundant” negative weak correlation for ranibizumab (rs = − 0.228; p < 0.001). Moreover, a positive moderate correlation was p = 0.005) and a moderate positive one for aflibercept (rs found between the average number of injections and the =0.574; p < 0.001). Table 3 Mean number of anti-VEGF injections used in each group Non-existent Scarce Moderate Abundant Significance among groups Total number of intravitreal injections (n, SD) 6.26 (SD 1.06) 10.05 (SD 1.06) 13.09 (SD 1.77) 11.97 (SD 1.40) p < 0.001a Aflibercept intravitreal injection (n, SD) 1.51 (SD 0.33) 5.82 (SD 0.73) 7.45 (SD 1.02) 9.32 (SD 1.23) P < 0.001a Ranibizumab intravitreal injection (n, SD) 4.40 (SD 0.97) 3.78 (SD 0.790) 4.97 (SD 1.22) 1.15 (SD 0.49) p = 0.006a Bevacizumab intravitreal injection (n, SD) 0.30 (SD 0.113) 0.30 (SD 0.169) 0.51 (SD 0.176) 1.26 (SD 0.451) p = 0.069a Dexamethasone intravitreal implant (n, SD) 0.14 (SD 0.140) 0.23 (SD 0.166) 0.14 (SD 0.083) 0.26 (SD 0.236) p = 0.702a Statistically significant p < 0.05 in bold a Kruskal-Wallis and Mann-Whitney U test García et al. BMC Ophthalmology (2022) 22:319 Page 5 of 8 Symptomatology with floaters had received a higher amount of anti- In our interview, a total of 30 eyes (19.7%) had a central VEGF intravitreal agents. scotoma, 52 eyes (34.2%) had metamorphopsia and 60 eyes (39.5%) had floaters (Table 1). We compared the Intraocular pressure presence of these symptoms in each group regarding Measures of intraocular pressure were also undergone by the number of bubbles that were found. No differences all patients. The mean IOP was 16.07 (SD 8.81), with the were found among groups when analyzing the presence “Abundant” group having the highest mean IOP (18.68, of central scotoma or metamorphopsia (Table 4). How- SD 2.94) (Table 2). There was no statistically significant ever, the presence of floaters statistically differed among difference in the mean IOP among groups and no cor- groups (global p = 0.026). Difference was only observed relation was found with the number of intravitreal injec- between “Scarce” vs. “Moderate” groups (27.5% vs. 60% tions (Rs = 0.021; p = 0.802). with p < 0.05). We also examined the possible relationship between Discussion the number of intravitreal injections received and the Intravitreal injections with anti-VEGF agents are cur- presence of floaters. Although no statistically signifi- rently used to treat multiple retinal pathologies. The cant difference among groups was found, the patients three most commonly used drugs are aflibercept, ranibi- with floaters had received a higher number of intravit- zumab and bevacizumab. Each of these injections is real anti-VEGF (Table 5). Similarly, no statistical dif- administered with a different syringe and needle, which ferences were found when analyzing the presence of were not initially designed for intravitreal use, and con- floaters in relation to the type of drug used, but patients tain small amounts of silicone oil. This material coats the inner surface of both syringes and needles, for smoother Table 4 Symptomatology reported in each group Non-Existent Scarce Moderate Abundant Significance N = 43 N = 40 N = 35 N = 34 among groups Central scotoma 12 (27.9%) 7 (17.5%) 6 (17.1%) 5 (14.7%) p = 0.452b Yes (n, %) N = 30 Scotoma discomfort (mean, SD) 6.92 (SD 0.88) 5.43 (SD 0.97) 5 (SD 1.36) 6.20 (SD 1.42) p = 0.492a Metamorphopsia 17 (27.9%) 13 (32.5%) 12 (34.3%) 10 (29.4%) p = 0.815b Yes (n, %) N = 52 Metamorphopsia discomfort (mean, SD) 5.18 (SD 0.64) 5.69 (SD 0.72) 5.08 (SD 0.71) 5.90 (SD 0.87) p = 0.890a Floaters 17 (27.9%) 11 (27.5%) 21 (60%) 11 (32.3%) p = 0.026b Yes (n, %) N = 60 Floaters discomfort (mean, SD) 3.29 (SD 0.56) 3.91 (SD 0.82) 3.33 (SD 0.45) 3.64 (SD 0.83) p = 0.957a Statistically significant p < 0.05 in bold a Kruskall-Wallis and Mann-Whitney U test b X2 test Table 5 Presence of floaters regarding the intravitreal agent used Floaters No Floaters Yes Significance N = 92 N = 60 Total number of intravitreal injections (mean, SD) 8.73 (SD 0.71) 12.22 (SD 1.31) p = 0.068a Aflibercept intravitreal injection number (mean, SD) 5.14 (SD 0.49) 6.71 (SD 0.94) p = 0.635a Ranibizumab intravitreal injection number (mean, SD) 2.87 (SD 0.49) 4.82 (SD 0.89) p = 0.131a Bevacizumab intravitreal injection number (mean, SD) 0.54 (SD 0.17) 0.60 (SD 0.16) p = 0.154a Dexamethasone intravitreal injection number (mean, SD) 0.28 (SD 0.13) 0.05 (SD 0.37) p = 0.370a Statistically significant p < 0.05 in bold a Mann-Whitney U test García et al. BMC Ophthalmology (2022) 22:319 Page 6 of 8 gliding of the plunger and facilitating injection. For this agreement with Thompson et al. However, they found a reason, the presence of silicone bubbles in the vitreous weak correlation, suggesting that the amount of silicone after repeated intravitreal administration of anti-VEGF oil in each injection could vary between the batches of drugs is studied. syringes [4]. The prevalence of silicone bubbles after intravitreal Bevacizumab injections with a BD 0.3 mL polypro- injections of anti-VEGF varies in the different studies. In pylene syringe produce the most bubbles in our sample. a recent article, Melo et al. found silicone oil droplets in Second are the injections of aflibercept with a 0.1 mL 25 out of 37 eyes (67.6%), although this prevalence rose polycarbonate BD syringe, and third are the ranibizumab to 75.7% when B-scan ultrasonography was performed injections with a 0.1 mL polypropylene BD syringe. It [6]. Sanabria et al. reported that 89.4% of 142 treated appears that these bubbles are not detected after injec- eyes presented silicone droplets in the vitreous [3]. In tions of prefilled ranibizumab [4]. In our study, despite our study we found that 71.7% of the treated eyes had not analyzing the prevalence of droplets regarding the droplets, however, in comparison to the study by Sana- agent, we could determine a moderate positive correla- bria et al., our patients had a lower mean follow up time tion between the number of aflibercept injections and (34.7 vs. 44.7 months) and had received a lower average the quantity of droplets, and a weak negative correlation of intravitreal injections (10.1 vs. 16.7). Furthermore, we between prefilled ranibizumab injections and the quan- included patients that had only received one intravitreal tity of them. In 2020 Olea et al. conducted a study with injection. silicone oil-free syringes and demonstrated absence of oil These variations in the prevalence of droplets can be droplets larger than 25 μm [9]. Other authors, like Mello attributed to many other factors, such as the form of et al. have found trace amounts of silicone oil released presentation, the repackaging, transport and manipu- from purportedly silicone oil-free syringes [5]. lation of the drug, or even the examination technique. With regard to the symptoms, most patients experi- Recently, and by means of fluorescence labelling and ence floaters immediately after the injection, however imaging flow cytometry, micro-sized droplets (0.1–10 μm their persistence is less usual. Except when the number size range) have been detected in the vitreous of patients of bubbles is greater, when these are large or aggregate [5]. These cannot be detected by slit-lamp observation between them, they cause no symptoms [3, 10]. Sanabria and recent literature point to its potential inflammatory et al. reported that 36.7% of the patients complained of power [6]. Another limitation of our examination tech- permanent floaters after injections [3]. This prevalence is nique is the different ability of quantifying for bubbles in accordance with our study (39.5% of eyes). It is inter- depending on media transparency, for example in the esting that the prevalence of symptoms is much lower case of a cortico-nuclear cataract or a posterior capsule than the prevalence of droplets. Furthermore, when ana- opacity in intraocular lenses carriers, which has not been lyzing the disturbance of floaters in the daily life of the regarded in our inclusion/exclusion criteria. Finally, the patients, it did not reach a score of 4 out of 10 in any own observer ability to detect the droplets, the different of the groups. Surprisingly, the group with “Moderate” use of the superfield lenses and slit lamp among physi- droplets in vitreous complained significantly more of cians also can influence the results of examination. floaters (60% of eyes). We believe that a reasonable cause The injection technique can also determine the amount could be that this group had a much better visual acuity of silicone bubbles injected. It has been shown that when than the rest, and they had also received a higher number the plunger is depressed to the end of the syringe, more of intravitreal injections. Thompson et al. also observed oil penetrates the vitreous [7]. Therefore, injections that that patients with very poor VA (20/400 or less) did not have less drug volume, such as aflibercept, transmit more complain of floaters [4]. silicone bubbles since the plunger has to be pushed all The higher prevalence of posterior vitreous detach- the way, unlike ranibizumab, in which there is a surplus ment in these patients must also be considered, which of volume that stays in the syringe. The same is seen can be a confounding factor when assessing these symp- when injections are shaken to remove air bubbles prior toms. Thus, not all floaters are explained by the presence to injection [8]. of droplets. In our study, floaters were reported in 39.5% In turn, a significant correlation has been demon- of the patients that had droplets, however, 27.9% of the strated in the literature between the number of injections patients without droplets also complained of this symp- and the presence of silicone oil bubbles in the vitreous tom. Geck et al. demonstrated that 24% of the patients [3, 4]. In our study we determined that those patients treated with intravitreal injections develop PVD during with droplets had received significantly more intravitreal the follow-up [11]. In our study, 65.8% of the patients had injections, and that the number of injections were corre- PVD, being 88.2% in the “Abundant” group. Interestingly, lated with the number of bubbles. These findings are in a positive correlation was demonstrated between PVD García et al. BMC Ophthalmology (2022) 22:319 Page 7 of 8 and the number of bubbles. We believe that PVD allows Funding No funding was obtained for this study. the silicone droplets to move freely in the vitreous, thus facilitating the examiner to visualize them. Availability of data and materials Other complications described in association with the All data relevant to this manuscript is included in the present paper, but further details and raw data can be provided up to reasonable request by presence of these droplets are ocular inflammation and contacting the corresponding author. ocular hypertension [12]. In previous studies in retinal surgeries, it has been shown that if silicone oil is kept Declarations in the vitreous for more than 12 to 18 months, it can be trapped by the cells of the trabecular meshwork, as well Ethics approval and consent to participate This study was performed in line with the principles of the Declaration of as by the Müller cells of the retina. For this reason, it has Helsinki. Approval was granted by the Ethics Committee of the Autonomous been hypothesized that direct obstruction of the tra- University of Barcelona (Code: PR(AG)182/2021). Informed written consent becular meshwork due to the presence of high molecular was obtained from all individual participants included in the study. weight proteins and the passage of these silicone bubbles Consent for publication into the anterior chamber could be a cause of increased Patients signed informed written consent regarding publishing their data and intraocular pressure [9, 13]. Our study analyzes for the photographs. first time differences in IOP in relation to the quantity of Competing interests droplets seen in vitreous. Although we did not observe The authors have no relevant financial or non-financial interests to disclose. statistically significant differences, the group “Abundant” Author details had a higher mean IOP than the rest of the groups. A fur- 1 Department of Ophthalmology, Vall d’Hebron University Hospital, Passeig de ther study, with a longer follow-up time, anterior cham- la Vall d’Hebron, 119‑129, 08035 Barcelona, Spain. 2 Departament de Cirurgia i ber inspection, gonioscopy and data of IOP values prior Ciències Morfològiques, Universitat Autònoma de Barcelona, Barcelona, Spain. IVI treatment could be of interest to confirm this trend Received: 2 December 2021 Accepted: 13 July 2022 and to determine the presence of silicone oil droplets in the trabecular meshwork of these patients. References Conclusions 1. Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, et al. Global preva‑ lence of age-related macular degeneration and disease burden projec‑ We found a high prevalence of silicone oil droplets in tion for 2020 and 2040: a systematic review and meta-analysis. Lancet the vitreous of our patients in the slit-lamp examina- Glob Health. 2014;2:e106–16. tion. However, the majority of patients did not report any 2. Freund KB, Laud K, Eandi CM, Spaide RF. Silicone oil droplets following intravitreal injection. Retina. 2006;26:701–3. symptomatology, especially those with poor VA. Moreo- 3. Sanabria MR, Alonso-Tarancón AM, Fernández I, et al. Silicone microbub‑ ver, we did not see a significant relation between the IOP bles after anti-vascular endothelial growth factor injections in patients and the number of bubbles. Further studies are needed to with wet age-related macular degeneration: incidence, quantification and secondary optical coherence tomography artfacts. Acta Ophthalmol. examine the prevalence of micro-droplets and eventually 2021. https://​doi.​org/​10.​1111/​aos.​14743. assess the safety of syringes containing particles of silicon 4. Thompson JT. Prospective study of silicone oil microdroplets in eyes oil. receiving intravitreal anti-vascular endothelial growth factor therapy in 3 different syringes. Ophthalmol Retina. 2020;5:234–40. 5. Melo GB, da Cruz NFS, et al. Silicone oil-free syringes, siliconized syringes and needles: quantitative assessment of silicone oil release with drugs Abbreviations used for intravitreal injection. Acta Ophthalmol. 2021;99(8):e1366–74. Anti-VEGF: Anti-Vascular Endothelial Growth Factor; IVI: Intravitreal injec‑ 6. Melo GB, Dias CS, Morais FB, et al. Prevalence of silicone oil droplets in tions; IOP: Intraocular pressure; PVD: Posterior vitreous detachment; AMD: eyes treated with intravitreal injection. Int J Retina Vitreous. 2019;5:34. Age-related macular degeneration; ANOVA: Analysis of variance; SD: Standard https://​doi.​org/​10.​1186/​s40942-​019-​0184-9. deviation; DME: Diabetic macular edema; RVO: Retinal vein occlusion; VA: 7. Pitcher JD, Roybal CN. Silicone oil microdroplets in repackaged bevaci‑ Visual acuity. zumab syringes: identification, quantification, and strategies for reducing clincal impact. Invest Ophthalmol Vis Sci. 2017;58(8):434. Acknowledgements 8. Melo GB, Dias CS, Maia M, et al. Release of silicone oil droplets from Not applicable. syringes. Int J Retina Vitreous. 2019;5:1. 9. Olea JL, Gómez-Resa M, Cervera-Peris MM, Aragón JA. Silicone oil drop‑ Authors’ contributions lets in repackaged anti-vascular endothelial growth factors for intravitreal JGA and MAZ contributed to the study conception and design. Material injections: in search of the main source of contamination. Eur J Ophthal‑ preparation and data collection were performed by DAR, SBG, XGS and FTV. mol. 2020;30:774–9. Statistical analysis was conducted by SBG and MAZ. DAR and XGS interpreted 10. Schargus M, Frings A. Issues with intravitreal Administration of Anti-VEGF the data. The first draft of the manuscript was written by SBG, XGS and FTV drugs. Clin Ophthalmol. 2020;14:897–904. and all authors commented on previous versions of the manuscript. XGS and 11. Geck U, Pustolla N, Baraki H, Atili A, Feltgen N, Hoerauf H. Posterior vitre‑ SBG contributed equally to the manuscript and therefore share first author‑ ous detachment following intravitreal drug injection. Graefes Arch Clin ship. All authors read and approved the final version of the manuscript. All Exp Ophthalmol. 2013;251:1691–5. authors have agreed to be personally accountable for the integrity of any part 12. Melo GB, Figueira ACM, Batista FAH, Filho AASL, Rodrigues EB, Belfort of this work. R Jr, et al. Inflammatory reaction after Aflibercept intravitreal injections García et al. BMC Ophthalmology (2022) 22:319 Page 8 of 8 associated with silicone oil droplets released from syringes: a case-con‑ trol study. Ophthalmic Surg Lasers Imaging Retina. 2019;50:288–94. 13. Liu L, Ammar DA, Ross LA, Mandava N, Kahook MY, Carpenter JF. Silicone oil microdroplets and protein aggregates in repackaged bevacizumab and ranibizumab: effects of long-term storage and product mishandling. Invest Ophthalmol Vis Sci. 2011;52:1023–34. 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