Efficacy and Safety of Supraciliary Dexamethasone Implantation in Patients with Macular Edema: Preliminary and Comparative Study

Efficacy and Safety of Supraciliary Dexamethasone Implantation in Patients with Macular Edema: Preliminary and Comparative Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Efficacy and Safety of Supraciliary Dexamethasone Implantation in Patients with Macular Edema: Preliminary and Comparative Study Selim Doganay, Gamze Ucan Gunduz, Mehmet Omer Kiristioglu, Elif Kacmaz, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4462347/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Jan, 2025 Read the published version in Eye → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose To investigate the efficacy and safety of dexamethasone implantation (DEXI) in the supraciliary (SC) region, a potential new implantation site, compared to intravitreal (IVi) application. Methods This retrospective cohort study enrolled 39 eyes of 38 patients with macular edema who received DEXI between January and August 2023. Patients were randomized into SC and IVi treatment groups. All patients were followed up for 3 months after DEXI. The maximum retinal thickness (MRT) and central retinal thickness change (ΔCRT), intraocular pressure (IOP), and visual acuity (VA) were assessed preoperatively and postoperatively. Results The SC treatment group showed a significant reduction in MRT at 1st and 3rd month visits (p = 0.0002, p = 0.0002). IVi group showed a significant reduction at all postoperative visits (p = 0.0002, p = 0.0004, p = 0.0003). ΔCRT showed no significant difference between SC and IVi groups at any visit (p > 0.05). No significant IOP changes were observed (p > 0.05). No ocular hypertony or hypotony cases on day one post-SC DEXI. VA improved significantly in the SC group compared to the IVi group in the first week (p = 0.014). Subconjunctival hemorrhage was observed in all patients after IVi. No perioperative or postoperative complications were observed in any patients in either group other than subconjunctival hemorrhage. Conclusion SC DEXI appears to be a suitable alternative for managing macular edema. It offers comparable effectiveness to IVi administration with potentially fewer complications. Further larger-scale research is needed to validate its long-term safety and efficacy. Anterior segment optical coherence tomography can demonstrate SC DEXI. Health sciences/Diseases/Eye diseases/Retinal diseases Health sciences/Medical research/Outcomes research Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Corticosteroids are among the most potent and effective anti-inflammatory drugs. Corticosteroids have been widely utilized in ophthalmology due to their anti-inflammatory and anti-neovascularisation properties to anterior and posterior segment diseases ( 1 , 2 ). They are used via topical, intraocular, and periocular routes, particularly in posterior segment diseases such as non-infectious uveitis, macular edema following retinal vein occlusions or intraocular surgery, and diabetic macular edema ( 2 , 3 ). The supraciliary (anterior suprachoroidal) and suprachoroidal spaces form a continuous potential space. The supraciliary space (SC), an anterior route for aqueous humor outflow, lies between the ciliary body and the sclera and extends posteriorly into the suprachoroidal space after the pars plana ( 4 ). Suprachoroidal and intravitreal steroid applications are more effective as they bypass ocular barriers and, due to compartmentalization, result in less impact on surrounding tissues, leading to fewer systemic and local side effects ( 5 – 7 ). There has been significant interest in suprachoroidal drug delivery methods in ophthalmic treatments in recent years. This approach is being explored as a potential alternative for treating posterior segment diseases. Suprachoroidal injections allow ophthalmic drugs to reach target areas such as the choroid and retina more directly and locally, thereby potentially reducing systemic and ocular side effects ( 8 – 11 ). In this regard, the use of suprachoroidal triamcinolone acetonide (TA) was approved in 2021 by the Food and Drug Administration ( 12 ). To date, no study regarding the SC use of the DEX implant is available in the literature. We aim to compare the effectiveness and safety of DEX implant application via a SC route with its intravitreal (IVi) use, thereby determining whether there is an alternative treatment option, especially in selected cases such as aphakic patients or patients with capsular compromise. Materials and Methods This was a single-center, retrospective cohort study of data collected from patients with various causes of macular edema treated with one or more injections of 0,7 mg of DEX implants (Ozurdex® 0.7 mg, Allergan Inc., Irvine, CA, USA) at the outpatient retina clinic of Bursa Uludag University between January 2023 and August 2023. The local institutional review board of the Bursa Uludag University Medical Faculty approved the study protocol, which adhered to the tenets of the Declaration of Helsinki (2023-16/29). All patients were informed about the procedure, acknowledging the off-label application of the medication, and written informed consent was obtained before the injection. All cases were evaluated at pre-injection, during injection, postoperative day 1, postoperative week 1, first-month, and third-month visits, and findings and measurements were noted. Patient Eligibility We included patients aged 18 and above who received intraocular DEX injections for macular edema, had comprehensive medical records, and provided images of anterior segment optical coherence tomography (OCT). Exclusion criteria comprised patients under 18, those with concurrent ocular diseases (e.g., glaucoma, scleritis), recent ocular surgery within 3 months, and intraocular pressure (IOP) exceeding 21 mmHg. We also exclude patients who have received certain treatments recently, such as anti-vascular endothelial growth factor injections in the last month, DEX implant injections in the last 6 months, or other types of injections in the last 6 months (such as IVi, suprachoroidal, or SC, subtenon, or peribulbar TA injections). Patients currently undergoing pan-retinal laser photocoagulation therapy after injection, using a topical antiglaucoma medication, or those who are treatment-naive are also excluded. Additionally, individuals with best-corrected visual acuity (BCVA) less than or equal to 0.1 in the untreated fellow eye are not included. Patients with low-quality (< 20 dB) anterior and posterior segment OCT images were excluded from the study. Ophthalmic Examinations Before and after injections, patients in both the control and study groups will be retrospectively evaluated through medical records for comparison of refraction, BCVA via ETDRS chart, IOP measured with applanation tonometry and corrected according to pachymetric measurement, anterior segment biomicroscopic examinations, fundoscopic examinations, and anterior/posterior segment optical coherence tomography (OCT) images. To demonstrate the placement of the DEX implant in supraciliary space and to confirm its correct positioning, anterior segment OCT images were taken in the EDI mode of the anterior sclera in all cases, targeting the implantation site. Anterior segment OCT images were obtained using the Spectralis (Heidelberg Engineering, Heidelberg, Germany) Anterior Segment Module. We also utilized the Spectralis system for macular OCT imaging. All OCT images were taken by the same ophthalmologist. Measurements were made in a dimly lit room after pupil dilation. An automatic real-time eye tracker was installed during OCT image acquisitions. Before initiating the recording, careful attention was paid to ensure the patient's correct positioning, head alignment, clarity of the image focus, and scan area alignment. Spectralis was configured to perform volume scans of 30° × 25° dimensions, consisting of 32 lines with 512 A-scans each for macular cube measurements. The initial examination served as the reference, with subsequent follow-up examinations automatically applying the same scan settings and positions for consistency. After the imaging, the ophthalmologist reviewed all measurements to ensure fixation was at the fovea, and measurements with segmentation errors were manually corrected. Low-quality images were also adjusted. The ETDRS subfield measurements were performed using Spectralis maps, an inbuilt Spectralis software program, which divides the subfields into four quadrants and three different diameters of concentric circles (1-mm, 3-mm, and 6-mm diameter), measuring the average macular thickness in that area as done in similar studies before ( 13 ). The highest value in these quadrants was the maximum retinal thickness (MRT). Central retinal thickness changes (ΔCRT) were measured from the central fovea subfield within the inner 1-mm-diameter circle. Then, the ΔCRT value was calculated by subtracting the mathematical values at each postoperative visit from the mathematical value at the preoperative measurement [ΔCRT = [(preoperative CRT) - (postoperative CRT)]]. Surgical Procedure Supraciliary Injection Technique After topical anesthesia, the patient's eye is covered with a sterile drape. Then, under an operating microscope, marks are made 3.5 mm from the limbus in the temporal superior oblique quadrant for the right eye and the nasal superior oblique quadrant for the left eye. A 0.2–0.3 ml lidocaine injection is then administered subconjunctivally with a 27-gauge needle at these marks. The area is massaged with a cotton swab to reduce subconjunctival swelling. Next, using forceps to stabilize the eye at the limbus, a DEX implant injector is inserted at a 45-degree angle to the sclera, bevel-up, from the 10 o'clock quadrant, 3.5 mm from the limbus, aiming to keep it parallel to the limbus. The injector is advanced 2–3 mm until its metal part is hidden by the sclera, at which point the implant is injected. Pressure is then applied to the injection site with a sterile sponge (see supplementary material 1). Intravitreal Injection Technique After topical anesthesia, the patient's eye is covered with a sterile drape. Then, for the right eye, from the temporal superior oblique quadrant, and for the left eye, the nasal superior oblique quadrant, a mark is made on the sclera 3.5 mm from the limbus under an operating microscope. A 0.2–0.3 ml lidocaine injection is administered in the marked area with a 27-gauge needle subconjunctivally. The area is massaged with a cotton swab to reduce subconjunctival swelling. Then, using forceps to stabilize the eye from the limbus, a DEX injector is advanced through the sclera in a 1–2 mm tunnel at a 45-degree angle to the limbus, bevel-up until it reaches the pars plana and enters the vitreous where the implant is injected. Afterward, pressure is applied to the injection site with a sterile sponge. Statistical Analysis The Shapiro‒Wilk test was used to test normality, and continuous variables are expressed as median and range while categorical variables are presented as frequencies. Fisher's exact test was used to compare the distributions of categorical variables. Repeated measures ANOVA and one-way ANOVA were used for comparative statistical analysis. All the statistical tests were two-tailed, with a significance level of 0.05. All the statistical analyses were done using IBM SPSS version 28.0 (IBM Corp., released 2021). IBM SPSS Statistics for MacOS. Armonk, NY). The graphics were generated using GraphPad Prism (version 8; GraphPad Software, Inc.). Results Thirty-nine eyes of 38 patients were included in the study. Among them, 23 patients were female and 15 were male. Indications included diabetic macular edema in 22 eyes, BRVO in 4 eyes, CRVO in 3 eyes, uveitis in 7 eyes, and postoperative edema in three eyes. In the SC treatment group, the median age was 58 (31–79) years, while in the IVi group, it was 62 (36–79) years (Table 1 ). Table 1 Demographics and clinical characteristics of the patients in each group. Groups Supraciliary Intravitreal Age 58 (31–79) 62 (36–79) Lens Status Phakic Pseudophakic 10 9 8 11 Sex F M 10 9 13 6 Indications DME BRVO CRVO UCME PCME 10 1 1 5 2 12 3 2 2 1 Number of patients with capsule-lens compromise 1 (SFIOL) 1 (laser capsulotomy) BRVO: Branch retinal vein occlusion, CRVO: Central retinal vein occlusion, DME: Diabetic macular edema, F: Female, M: Male, PCME: Pseudophakic cystoid macular edema, SFIOL: Scleral fixated intraocular lens, UCME: Uveitic cystoid macular edema. When the two groups were compared with each other in terms of macular thickness measurements at each visit, no statistically significant difference in retinal thickness was observed in all visits and all macular subgroups (p > 0.05) (Supplementary material 2). Regarding ΔCRT, there was no statistically significant difference between the two groups at all visits (p-values at the 1st week, 1st month, and 3rd-month visits were respectively; p = 0.17, p = 0.4075, p = 0.9773) (Fig. 1 ). In the SC treatment group, there was a statistically significant reduction in maximum retinal thickness (MRT) at the 1st and 3rd-month visits, except for the postoperative 1st-week visit when compared to the preoperative visit (respectively; p = 0.0002, p = 0.0002, and p = 0.2517). Similarly, when comparing preoperative MRT with postoperative 1st week, 1st, and 3rd-month visits, there was a statistically significant reduction at all postoperative visits (respectively; p = 0.0002, p = 0.0004, and p = 0.0003) (Fig. 2 ). A significant difference was observed between the two groups in the postoperative 1st week (p = 0.014), while there was no significant difference in BCVA between the groups preoperatively (p = 0.639). However, no significant differences were found in BCVA between the postoperative 1st and 3rd months (p = 0.078 and p = 0.745). In the SC treatment group, compared to preoperative BCVA with postoperative 1st week, 1st and 3rd-month. BCVA, postoperative BCVA was higher than preoperative BCVA at 1st month (p = 0.0069), but no significant difference was observed at 1st week and 3rd month compared to the preoperative period (respectively; p = 0.0219 and p = 0.169). In the IVi group, no significant difference was observed between preoperative BCVA and BCVA in the postoperative 1st week, 1st and 3rd month (p = 0.2369, p = 0.1024, p = 0.6968, respectively) (Fig. 3 ). There were no significant differences in IOPs between preoperative and postoperative 1st week, 1st and 3rd month (p = 0.250, p = 0.078, p = 0.888, p = 0.260) (Fig. 1 ). No cases of ocular hypertony or hypotony were observed on the 1st day postoperatively in patients who received SC DEX implants. In the SC treatment group, IOP rose to the mid-thirties in one patient, while in the IVi treatment group, it increased to the forties in one patient and to the mid-twenties in two patients, all of whom responded to topical antiglaucoma treatment. After SC injection, anterior segment OCT showed the SC implant in all patients (Fig. 4 ). No suprachoroidal hemorrhage, choroidal detachment, ciliary body detachment, or endophthalmitis were observed among the patients with SC implantation. Similarly, none of the patients with IVi DEX implants exhibit sight-threatening complications such as endophthalmitis and retinal detachment. Nine patients (%47.3) who received SC DEX implants experienced pain during injections. All patients who underwent SC DEX implants developed subconjunctival hemorrhage. Of these patients, four (%21) had hemorrhage between 0 and 90 degrees on the clock dial, thirteen (%68.4) between 90 and 180 degrees, and two (%10.5) between 180 and 270 degrees. In the SC treatment group, 4 (21.05%) patients experienced clinically significant macular edema recurrence before three months, requiring additional IVi treatment. In the IVi treatment group, 2 (10%) patients required repeat treatment. Similarly, after three months, the number of patients needing further IVi treatment was 5 (26.32%) in the SC treatment group and 4 (20%) in the IVi treatment group. There was no statistically significant difference between the two treatment groups regarding the number of patients requiring treatment before and after three months (p = 0.318 and p = 0.832, respectively). Discussion The intravitreal DEX implant is innovatively designed to achieve a precise combination of potent effects and extended half-life. This biodegradable implant comprises a copolymer of lactic acid and glycolic acid (PLGA) and utilizes the Novadur® drug delivery technology to enable gradual dissolution within the vitreous gel. Through this sustained-release design, the DEX implant delivers preservative-free potent dexamethasone directly into the vitreous cavity, maintaining therapeutic levels for several months ( 14 – 16 ). In the context of the safety profile of the DEX implants, the Geneva study observed low rates of ocular hypertension, up to 12.6%. Ocular hypertensive episodes associated with the DEX implant are generally transient, with few patients requiring incisional glaucoma surgery ( 17 , 18 ). Other serious adverse events, such as retinal tear (one event in the 12-month data of the Geneva study) and endophthalmitis (0 events in the 12-month data), appear rare ( 17 ). Anterior migration or dislocation of the DEX implant is a rare complication, usually seen in vitrectomized eyes, aphakic eyes, eyes with reconstructed iris, or compromised posterior capsule or zonular dehiscence. This complication was notably linked to vitrectomized eyes and compromised posterior capsules, leading to corneal edema in about 81.9% of cases and corneal decompensation in 31.4% ( 15 ). New techniques have been proposed to enhance the safety of DEX implantation in these patients. One involves leaving a residual vitreous "pad" inferiorly to facilitate embedding the DEX implant, while another technique involves suturing the implant to the sclera with an absorbable suture intraoperatively ( 19 , 20 ). The success of these anchoring techniques highlights the need for further research into the adaptability of the DEX implant and ways to prevent anterior migration, particularly in vitrectomized, aphakic, and pseudophakic eyes. Thus, caution is advised when using DEX implants in high-risk eyes, and swift action to reposition or remove the implant is essential to prevent corneal complications ( 21 ). In our study, SC implant injection was performed in our cases, and no anterior migration was observed. SC injection of corticosteroids like triamcinolone acetonide (TA) and DEX appears to have a lower risk of increasing IOP compared to other routes of administration, such as IVi administration. Studies indicate that after SC injection of TA, the concentration of the drug in the posterior segment is 12-fold higher than with IVi injection, while only up to 3% enters the anterior chamber ( 9 , 10 ). This minimizes steroid exposure to the anterior segment and reduces the risk of IOP elevation and cataract formation ( 22 ). In a phase 3 trial of suprachoroidal delivery of TA for noninfectious uveitis, the rate of increased IOP was only 11.5%, which is lower than the 25–43% rates reported with IVi DEX implants for uveitic macular edema. These rates appear lower than those reported with IVi DEX implants for uveitic macular edema ( 9 , 10 ). Additionally, one study found that after a suprachoroidal injection of TA, IOP increased significantly at one month but returned to baseline by three months ( 8 ). Another study in rabbits showed acute IOP elevation after suprachoroidal injection that was volume-dependent ( 11 ). An anterior suprachoroidal polyurethane implant containing dexamethasone effectively prevented endotoxin-induced uveitis in rats without causing significant ocular toxicity ( 23 ). Although a study in rabbits found that suprachoroidal injection of TA caused volume-dependent acute IOP elevation, the overall risk of corticosteroid-related complications like cataracts seems to be reduced with suprachoroidal delivery compared to other routes. Our study showed no significant difference in the average IOP between cases treated with SC DEX implant and those treated with IVi DEX implant. However, ocular hypertension developed in one patient in the SC group, compared to two patients with higher levels of ocular hypertension in the IVi group. This difference suggests that the limited steroid exposure to the anterior segment in the SC group might be a factor. Existing studies support the possibility of this theory ( 8 – 11 ). Nonetheless, more randomized, controlled, prospective studies with larger patient groups and longer follow-ups are needed. While SC CS delivery can transiently increase IOP in some cases, the risk appears lower than IVi or periocular routes, likely due to the preferential delivery to the posterior segment and reduced exposure to the anterior chamber. More research is still needed to fully characterize the safety profile. It is known that IVi DEX implantation can cause cataract formation and that the risk increases with repeated injections ( 24 ). It has been reported that 12.4% of eyes treated with IVi DEX implants required cataract surgery during follow-ups ( 25 ). One limitation of our study is the short follow-up period; cataract progression in patients who underwent SC DEX implants was not assessed. Therefore, more extensive and longer-term studies are needed. However, there have been reports of patients developing rapidly progressing cataracts after IVi treatment, possibly due to lens capsule trauma during injection or wondering of the implant in the vitreous cavity around the lens capsule ( 26 ). Nevertheless, theoretically, such a risk does not exist in patients undergoing SC treatment. Different substances administered via suprachoroidal injection exhibit varying pharmacokinetic properties, with factors such as viscosity, particle size, and water solubility playing significant roles in these differences. Various biopolymers are biocompatible, effective, and capable of extending the half-life of drugs in the suprachoroidal space ( 27 ). There is currently no study in the recent literature concerning the DEX implant. In the group treated with SC DEX implantation, the effect of the DEX implant was relatively shorter compared to the IVi therapy group, and more patients in the SC treatment group required retreatment, yet it was not statistically significant. This could be related to the increased clearance of aqueous-soluble substances like DEX when injected into the suprachoroidal space ( 27 – 30 ). The highly vascular nature of the choroid and ciliary body might be responsible for the increased clearance ( 30 ). Similarly, the IVi DEX implant is less effective in vitrectomized eyes ( 31 ). Clinical trials have demonstrated a strong safety profile for suprachoroidal and SC implants, with no significant injection-related concerns such as suprachoroidal hemorrhage, endophthalmitis, or retinal and/or choroidal detachment, contributing to a smoother treatment process and potentially faster resolution of the condition ( 27 , 32 ). In our study, these complications were not observed in cases treated with SC treatment. We encountered no vision-threatening complications intraoperatively or postoperatively. However, all cases exhibited subconjunctival hemorrhage. This was observed at a higher rate compared to the subconjunctival hemorrhage rates (5.4%-16.6%) reported after IVi therapy in various studies ( 33 ). This may be related to the injection technique and use of microforceps that require more manipulation compared to IVi therapy. In conclusion, the effectiveness of SC and IVi DEX implant applications was similar in our study, with a few exceptions. Therefore, SC DEX implant application can be considered an alternative treatment option, particularly in cases with causes leading to anterior chamber migration, in young patients with high IOP or potential for its increase, and patients with glaucoma or ocular hypertension. Long-term studies and larger series can confirm the effectiveness and safety profile. A special design and drug application method specific to this area would be more appropriate for drug applications showing SC placement. Additionally, anterior segment OCT can be used to demonstrate SC implant placement. Declarations Prior publication: None Support: The authors have no sources of funding to declare for this manuscript. Conflicts of interest: The authors declare no conflicts of interest. Acknowledgment: None References Cunningham MA, Edelman JL, Kaushal S. Intravitreal steroids for macular edema: the past, the present, and the future. Surv Ophthalmol. 2008;53(2):139–49. 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Pharm Res. 2011;28(1):166–76. Saincher SS, Gottlieb C. Ozurdex (dexamethasone intravitreal implant) for the treatment of intermediate, posterior, and panuveitis: a systematic review of the current evidence. J Ophthalmic Inflamm Infect. 2020;10(1):1. Additional Declarations There is no conflict of interest Supplementary Files supracor.mp4 Supplementary Material 1. tabloxx.xlsx Supplementary Material 2. Cite Share Download PDF Status: Published Journal Publication published 07 Jan, 2025 Read the published version in Eye → Version 1 posted Editorial decision: revise 29 Aug, 2024 Review # 1 received at journal 20 Aug, 2024 Reviewer # 1 agreed at journal 07 Aug, 2024 Reviewers invited by journal 24 Jul, 2024 Editor assigned by journal 18 Jul, 2024 Submission checks completed at journal 23 May, 2024 First submitted to journal 22 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4462347","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":331055789,"identity":"12dbf7f3-ffca-4482-ad5c-cb809205ae23","order_by":0,"name":"Selim Doganay","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYFCCBAjFz8DYwMADZPAxE6tFsgGqhY1oLQYHgARYCyEN/OzJh1/83GGXuPlGctuDNxWH7dnYeQwfMNTYROPSItnzLM2y90xy4rYbie2Gc84cTmxj5jE2YDiWltuAQ4vBjRwzA9425sRttxPbpHnbbiewMbOlSTA2HMarxfBvW33i5tkQLfZALek/CGgxfszbdjhxgzREC2MbM/MxBnxaQH5hlm07bjzj/sM2yTln/gP9wnxYIgGPX0Ah9vFtW7Vsf8/xZxJvKtLs+fkPNn74UGODUwsQsEkACUdUBQm4lYMA8wcgYY9fzSgYBaNgFIxoAACrGltmjwc7/wAAAABJRU5ErkJggg==","orcid":"","institution":"Bursa Uludag University Medical Faculty","correspondingAuthor":true,"prefix":"","firstName":"Selim","middleName":"","lastName":"Doganay","suffix":""},{"id":331055790,"identity":"c1b9bb71-ed2d-4e15-bf36-d9aa7c6acb34","order_by":1,"name":"Gamze Ucan Gunduz","email":"","orcid":"https://orcid.org/0000-0002-5458-1686","institution":"Uludag University","correspondingAuthor":false,"prefix":"","firstName":"Gamze","middleName":"Ucan","lastName":"Gunduz","suffix":""},{"id":331055791,"identity":"1bbaeb14-f9a5-4698-b68c-c59f7d0215b1","order_by":2,"name":"Mehmet Omer Kiristioglu","email":"","orcid":"https://orcid.org/0000-0001-8010-0105","institution":"Uludag University","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"Omer","lastName":"Kiristioglu","suffix":""},{"id":331055792,"identity":"21ebaf49-adc6-409d-a943-7a2a0c9adbd8","order_by":3,"name":"Elif Kacmaz","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Elif","middleName":"","lastName":"Kacmaz","suffix":""},{"id":331055793,"identity":"9f65672f-759f-4aaf-b378-61a2acdae3ba","order_by":4,"name":"Ozgur Yalcinbayir","email":"","orcid":"https://orcid.org/0000-0002-7311-5277","institution":"Uludag University","correspondingAuthor":false,"prefix":"","firstName":"Ozgur","middleName":"","lastName":"Yalcinbayir","suffix":""}],"badges":[],"createdAt":"2024-05-22 16:51:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4462347/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4462347/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41433-024-03570-8","type":"published","date":"2025-01-07T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":63367762,"identity":"a6cd938a-6646-4047-8538-5c60a17fac42","added_by":"auto","created_at":"2024-08-27 11:33:22","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":163712,"visible":true,"origin":"","legend":"\u003cp\u003eDifferent charts show the CRT and IOP changes among different visits. \u003cem\u003eCRT: Central retinal thickness, IOP: Intraocular pressure\u003c/em\u003e\u003c/p\u003e","description":"","filename":"crtiopfigure.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4462347/v1/079122f2b4fe5f6b74bd755e.jpg"},{"id":63367763,"identity":"30b445f2-114c-4fc7-b679-23f749c3afcb","added_by":"auto","created_at":"2024-08-27 11:33:22","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":153427,"visible":true,"origin":"","legend":"\u003cp\u003eThe maximum retinal thickness of each group in every visit.\u003cstrong\u003e \u003c/strong\u003e\u003cem\u003eMRT: Maximum retinal thickness, IVi: Intravitreal, SC: Supraciliary\u003c/em\u003e\u003c/p\u003e","description":"","filename":"mrtler.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4462347/v1/06df80151414c6a8837c1838.jpg"},{"id":63367765,"identity":"a325c764-26d5-4162-a2e7-e883f040ca25","added_by":"auto","created_at":"2024-08-27 11:33:22","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":160794,"visible":true,"origin":"","legend":"\u003cp\u003eLogarithmic BCVA values of the study groups in each visit.\u003cem\u003e BCVA: Best-corrected visual acuity, IVi: Intravitreal, SC: Supraciliary.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"bcvalar.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4462347/v1/fd6fc669c091a97bedc888fa.jpg"},{"id":63367764,"identity":"d8d68ff2-04e0-48d5-9d44-09779336c509","added_by":"auto","created_at":"2024-08-27 11:33:22","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":78059,"visible":true,"origin":"","legend":"\u003cp\u003eAnterior segment optical coherence tomography of a patient with suprachoroidal DEX implantation in the postoperative first week. \u003cem\u003eThe anterior segment optical coherence tomography shows the implant (yellow asterisks). The image demonstrates that the suprachoroidal space, previously a potential space, has become visible due to implantation, indicated by yellow arrows. Cb: Ciliary Body. Sc: Sclera\u003c/em\u003e\u003c/p\u003e","description":"","filename":"figure4oct.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4462347/v1/0bead281370e67fc7f02131f.jpg"},{"id":73251441,"identity":"8f45d410-c0ff-43f2-b65e-502d8c6d313a","added_by":"auto","created_at":"2025-01-08 08:07:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":936116,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4462347/v1/e80227c0-d3dd-4290-aeb2-62890f29cd92.pdf"},{"id":63367766,"identity":"b4c02976-df4d-4f6e-9614-0675f012691d","added_by":"auto","created_at":"2024-08-27 11:33:24","extension":"mp4","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":94258341,"visible":true,"origin":"","legend":"Supplementary Material 1.","description":"","filename":"supracor.mp4","url":"https://assets-eu.researchsquare.com/files/rs-4462347/v1/117bdb3d33db7daed080d812.mp4"},{"id":63367761,"identity":"e5d46a21-3aa7-4075-9504-3d63cd63031d","added_by":"auto","created_at":"2024-08-27 11:33:22","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":11353,"visible":true,"origin":"","legend":"Supplementary Material 2.","description":"","filename":"tabloxx.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4462347/v1/c06d377e1265d458abedc9bf.xlsx"}],"financialInterests":"There is no conflict of interest","formattedTitle":"Efficacy and Safety of Supraciliary Dexamethasone Implantation in Patients with Macular Edema: Preliminary and Comparative Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCorticosteroids are among the most potent and effective anti-inflammatory drugs. Corticosteroids have been widely utilized in ophthalmology due to their anti-inflammatory and anti-neovascularisation properties to anterior and posterior segment diseases (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). They are used via topical, intraocular, and periocular routes, particularly in posterior segment diseases such as non-infectious uveitis, macular edema following retinal vein occlusions or intraocular surgery, and diabetic macular edema (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe supraciliary (anterior suprachoroidal) and suprachoroidal spaces form a continuous potential space. The supraciliary space (SC), an anterior route for aqueous humor outflow, lies between the ciliary body and the sclera and extends posteriorly into the suprachoroidal space after the pars plana (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Suprachoroidal and intravitreal steroid applications are more effective as they bypass ocular barriers and, due to compartmentalization, result in less impact on surrounding tissues, leading to fewer systemic and local side effects (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere has been significant interest in suprachoroidal drug delivery methods in ophthalmic treatments in recent years. This approach is being explored as a potential alternative for treating posterior segment diseases. Suprachoroidal injections allow ophthalmic drugs to reach target areas such as the choroid and retina more directly and locally, thereby potentially reducing systemic and ocular side effects (\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In this regard, the use of suprachoroidal triamcinolone acetonide (TA) was approved in 2021 by the Food and Drug Administration (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo date, no study regarding the SC use of the DEX implant is available in the literature. We aim to compare the effectiveness and safety of DEX implant application via a SC route with its intravitreal (IVi) use, thereby determining whether there is an alternative treatment option, especially in selected cases such as aphakic patients or patients with capsular compromise.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis was a single-center, retrospective cohort study of data collected from patients with various causes of macular edema treated with one or more injections of 0,7 mg of DEX implants (Ozurdex\u0026reg; 0.7 mg, Allergan Inc., Irvine, CA, USA) at the outpatient retina clinic of Bursa Uludag University between January 2023 and August 2023. The local institutional review board of the Bursa Uludag University Medical Faculty approved the study protocol, which adhered to the tenets of the Declaration of Helsinki (2023-16/29). All patients were informed about the procedure, acknowledging the off-label application of the medication, and written informed consent was obtained before the injection. All cases were evaluated at pre-injection, during injection, postoperative day 1, postoperative week 1, first-month, and third-month visits, and findings and measurements were noted.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Eligibility\u003c/h2\u003e \u003cp\u003e We included patients aged 18 and above who received intraocular DEX injections for macular edema, had comprehensive medical records, and provided images of anterior segment optical coherence tomography (OCT). Exclusion criteria comprised patients under 18, those with concurrent ocular diseases (e.g., glaucoma, scleritis), recent ocular surgery within 3 months, and intraocular pressure (IOP) exceeding 21 mmHg. We also exclude patients who have received certain treatments recently, such as anti-vascular endothelial growth factor injections in the last month, DEX implant injections in the last 6 months, or other types of injections in the last 6 months (such as IVi, suprachoroidal, or SC, subtenon, or peribulbar TA injections). Patients currently undergoing pan-retinal laser photocoagulation therapy after injection, using a topical antiglaucoma medication, or those who are treatment-naive are also excluded. Additionally, individuals with best-corrected visual acuity (BCVA) less than or equal to 0.1 in the untreated fellow eye are not included. Patients with low-quality (\u0026lt;\u0026thinsp;20 dB) anterior and posterior segment OCT images were excluded from the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eOphthalmic Examinations\u003c/h2\u003e \u003cp\u003eBefore and after injections, patients in both the control and study groups will be retrospectively evaluated through medical records for comparison of refraction, BCVA via ETDRS chart, IOP measured with applanation tonometry and corrected according to pachymetric measurement, anterior segment biomicroscopic examinations, fundoscopic examinations, and anterior/posterior segment optical coherence tomography (OCT) images.\u003c/p\u003e \u003cp\u003eTo demonstrate the placement of the DEX implant in supraciliary space and to confirm its correct positioning, anterior segment OCT images were taken in the EDI mode of the anterior sclera in all cases, targeting the implantation site. Anterior segment OCT images were obtained using the Spectralis (Heidelberg Engineering, Heidelberg, Germany) Anterior Segment Module.\u003c/p\u003e \u003cp\u003eWe also utilized the Spectralis system for macular OCT imaging. All OCT images were taken by the same ophthalmologist. Measurements were made in a dimly lit room after pupil dilation. An automatic real-time eye tracker was installed during OCT image acquisitions. Before initiating the recording, careful attention was paid to ensure the patient's correct positioning, head alignment, clarity of the image focus, and scan area alignment. Spectralis was configured to perform volume scans of 30\u0026deg; \u0026times; 25\u0026deg; dimensions, consisting of 32 lines with 512 A-scans each for macular cube measurements. The initial examination served as the reference, with subsequent follow-up examinations automatically applying the same scan settings and positions for consistency. After the imaging, the ophthalmologist reviewed all measurements to ensure fixation was at the fovea, and measurements with segmentation errors were manually corrected. Low-quality images were also adjusted.\u003c/p\u003e \u003cp\u003eThe ETDRS subfield measurements were performed using Spectralis maps, an inbuilt Spectralis software program, which divides the subfields into four quadrants and three different diameters of concentric circles (1-mm, 3-mm, and 6-mm diameter), measuring the average macular thickness in that area as done in similar studies before (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The highest value in these quadrants was the maximum retinal thickness (MRT). Central retinal thickness changes (ΔCRT) were measured from the central fovea subfield within the inner 1-mm-diameter circle. Then, the ΔCRT value was calculated by subtracting the mathematical values at each postoperative visit from the mathematical value at the preoperative measurement [ΔCRT = [(preoperative CRT) - (postoperative CRT)]].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSurgical Procedure\u003c/h2\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eSupraciliary Injection Technique\u003c/h2\u003e \u003cp\u003eAfter topical anesthesia, the patient's eye is covered with a sterile drape. Then, under an operating microscope, marks are made 3.5 mm from the limbus in the temporal superior oblique quadrant for the right eye and the nasal superior oblique quadrant for the left eye. A 0.2\u0026ndash;0.3 ml lidocaine injection is then administered subconjunctivally with a 27-gauge needle at these marks. The area is massaged with a cotton swab to reduce subconjunctival swelling. Next, using forceps to stabilize the eye at the limbus, a DEX implant injector is inserted at a 45-degree angle to the sclera, bevel-up, from the 10 o'clock quadrant, 3.5 mm from the limbus, aiming to keep it parallel to the limbus. The injector is advanced 2\u0026ndash;3 mm until its metal part is hidden by the sclera, at which point the implant is injected. Pressure is then applied to the injection site with a sterile sponge (see supplementary material 1).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eIntravitreal Injection Technique\u003c/h2\u003e \u003cp\u003eAfter topical anesthesia, the patient's eye is covered with a sterile drape. Then, for the right eye, from the temporal superior oblique quadrant, and for the left eye, the nasal superior oblique quadrant, a mark is made on the sclera 3.5 mm from the limbus under an operating microscope. A 0.2\u0026ndash;0.3 ml lidocaine injection is administered in the marked area with a 27-gauge needle subconjunctivally. The area is massaged with a cotton swab to reduce subconjunctival swelling. Then, using forceps to stabilize the eye from the limbus, a DEX injector is advanced through the sclera in a 1\u0026ndash;2 mm tunnel at a 45-degree angle to the limbus, bevel-up until it reaches the pars plana and enters the vitreous where the implant is injected. Afterward, pressure is applied to the injection site with a sterile sponge.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe Shapiro‒Wilk test was used to test normality, and continuous variables are expressed as median and range while categorical variables are presented as frequencies. Fisher's exact test was used to compare the distributions of categorical variables. Repeated measures ANOVA and one-way ANOVA were used for comparative statistical analysis. All the statistical tests were two-tailed, with a significance level of 0.05. All the statistical analyses were done using IBM SPSS version 28.0 (IBM Corp., released 2021). IBM SPSS Statistics for MacOS. Armonk, NY). The graphics were generated using GraphPad Prism (version 8; GraphPad Software, Inc.).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThirty-nine eyes of 38 patients were included in the study. Among them, 23 patients were female and 15 were male. Indications included diabetic macular edema in 22 eyes, BRVO in 4 eyes, CRVO in 3 eyes, uveitis in 7 eyes, and postoperative edema in three eyes. In the SC treatment group, the median age was 58 (31\u0026ndash;79) years, while in the IVi group, it was 62 (36\u0026ndash;79) years (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics and clinical characteristics of the patients in each group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSupraciliary\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntravitreal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (31\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (36\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLens Status\u003c/p\u003e \u003cp\u003ePhakic\u003c/p\u003e \u003cp\u003ePseudophakic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003cp\u003eF\u003c/p\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndications\u003c/p\u003e \u003cp\u003eDME\u003c/p\u003e \u003cp\u003eBRVO\u003c/p\u003e \u003cp\u003eCRVO\u003c/p\u003e \u003cp\u003eUCME\u003c/p\u003e \u003cp\u003ePCME\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients with capsule-lens compromise\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (SFIOL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(laser capsulotomy)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cem\u003eBRVO: Branch retinal vein occlusion, CRVO: Central retinal vein occlusion, DME: Diabetic macular edema, F: Female, M: Male, PCME: Pseudophakic cystoid macular edema, SFIOL: Scleral fixated intraocular lens, UCME: Uveitic cystoid macular edema.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWhen the two groups were compared with each other in terms of macular thickness measurements at each visit, no statistically significant difference in retinal thickness was observed in all visits and all macular subgroups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Supplementary material 2). Regarding ΔCRT, there was no statistically significant difference between the two groups at all visits (p-values at the 1st week, 1st month, and 3rd-month visits were respectively; p\u0026thinsp;=\u0026thinsp;0.17, p\u0026thinsp;=\u0026thinsp;0.4075, p\u0026thinsp;=\u0026thinsp;0.9773) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In the SC treatment group, there was a statistically significant reduction in maximum retinal thickness (MRT) at the 1st and 3rd-month visits, except for the postoperative 1st-week visit when compared to the preoperative visit (respectively; p\u0026thinsp;=\u0026thinsp;0.0002, p\u0026thinsp;=\u0026thinsp;0.0002, and p\u0026thinsp;=\u0026thinsp;0.2517). Similarly, when comparing preoperative MRT with postoperative 1st week, 1st, and 3rd-month visits, there was a statistically significant reduction at all postoperative visits (respectively; p\u0026thinsp;=\u0026thinsp;0.0002, p\u0026thinsp;=\u0026thinsp;0.0004, and p\u0026thinsp;=\u0026thinsp;0.0003) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA significant difference was observed between the two groups in the postoperative 1st week (p\u0026thinsp;=\u0026thinsp;0.014), while there was no significant difference in BCVA between the groups preoperatively (p\u0026thinsp;=\u0026thinsp;0.639). However, no significant differences were found in BCVA between the postoperative 1st and 3rd months (p\u0026thinsp;=\u0026thinsp;0.078 and p\u0026thinsp;=\u0026thinsp;0.745). In the SC treatment group, compared to preoperative BCVA with postoperative 1st week, 1st and 3rd-month. BCVA, postoperative BCVA was higher than preoperative BCVA at 1st month (p\u0026thinsp;=\u0026thinsp;0.0069), but no significant difference was observed at 1st week and 3rd month compared to the preoperative period (respectively; p\u0026thinsp;=\u0026thinsp;0.0219 and p\u0026thinsp;=\u0026thinsp;0.169). In the IVi group, no significant difference was observed between preoperative BCVA and BCVA in the postoperative 1st week, 1st and 3rd month (p\u0026thinsp;=\u0026thinsp;0.2369, p\u0026thinsp;=\u0026thinsp;0.1024, p\u0026thinsp;=\u0026thinsp;0.6968, respectively) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThere were no significant differences in IOPs between preoperative and postoperative 1st week, 1st and 3rd month (p\u0026thinsp;=\u0026thinsp;0.250, p\u0026thinsp;=\u0026thinsp;0.078, p\u0026thinsp;=\u0026thinsp;0.888, p\u0026thinsp;=\u0026thinsp;0.260) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). No cases of ocular hypertony or hypotony were observed on the 1st day postoperatively in patients who received SC DEX implants. In the SC treatment group, IOP rose to the mid-thirties in one patient, while in the IVi treatment group, it increased to the forties in one patient and to the mid-twenties in two patients, all of whom responded to topical antiglaucoma treatment.\u003c/p\u003e \u003cp\u003eAfter SC injection, anterior segment OCT showed the SC implant in all patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). No suprachoroidal hemorrhage, choroidal detachment, ciliary body detachment, or endophthalmitis were observed among the patients with SC implantation. Similarly, none of the patients with IVi DEX implants exhibit sight-threatening complications such as endophthalmitis and retinal detachment.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eNine patients (%47.3) who received SC DEX implants experienced pain during injections. All patients who underwent SC DEX implants developed subconjunctival hemorrhage. Of these patients, four (%21) had hemorrhage between 0 and 90 degrees on the clock dial, thirteen (%68.4) between 90 and 180 degrees, and two (%10.5) between 180 and 270 degrees.\u003c/p\u003e \u003cp\u003eIn the SC treatment group, 4 (21.05%) patients experienced clinically significant macular edema recurrence before three months, requiring additional IVi treatment. In the IVi treatment group, 2 (10%) patients required repeat treatment. Similarly, after three months, the number of patients needing further IVi treatment was 5 (26.32%) in the SC treatment group and 4 (20%) in the IVi treatment group. There was no statistically significant difference between the two treatment groups regarding the number of patients requiring treatment before and after three months (p\u0026thinsp;=\u0026thinsp;0.318 and p\u0026thinsp;=\u0026thinsp;0.832, respectively).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe intravitreal DEX implant is innovatively designed to achieve a precise combination of potent effects and extended half-life. This biodegradable implant comprises a copolymer of lactic acid and glycolic acid (PLGA) and utilizes the Novadur\u0026reg; drug delivery technology to enable gradual dissolution within the vitreous gel. Through this sustained-release design, the DEX implant delivers preservative-free potent dexamethasone directly into the vitreous cavity, maintaining therapeutic levels for several months (\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the context of the safety profile of the DEX implants, the Geneva study observed low rates of ocular hypertension, up to 12.6%. Ocular hypertensive episodes associated with the DEX implant are generally transient, with few patients requiring incisional glaucoma surgery (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Other serious adverse events, such as retinal tear (one event in the 12-month data of the Geneva study) and endophthalmitis (0 events in the 12-month data), appear rare (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnterior migration or dislocation of the DEX implant is a rare complication, usually seen in vitrectomized eyes, aphakic eyes, eyes with reconstructed iris, or compromised posterior capsule or zonular dehiscence. This complication was notably linked to vitrectomized eyes and compromised posterior capsules, leading to corneal edema in about 81.9% of cases and corneal decompensation in 31.4% (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). New techniques have been proposed to enhance the safety of DEX implantation in these patients. One involves leaving a residual vitreous \"pad\" inferiorly to facilitate embedding the DEX implant, while another technique involves suturing the implant to the sclera with an absorbable suture intraoperatively (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). The success of these anchoring techniques highlights the need for further research into the adaptability of the DEX implant and ways to prevent anterior migration, particularly in vitrectomized, aphakic, and pseudophakic eyes. Thus, caution is advised when using DEX implants in high-risk eyes, and swift action to reposition or remove the implant is essential to prevent corneal complications (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In our study, SC implant injection was performed in our cases, and no anterior migration was observed.\u003c/p\u003e \u003cp\u003eSC injection of corticosteroids like triamcinolone acetonide (TA) and DEX appears to have a lower risk of increasing IOP compared to other routes of administration, such as IVi administration. Studies indicate that after SC injection of TA, the concentration of the drug in the posterior segment is 12-fold higher than with IVi injection, while only up to 3% enters the anterior chamber (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). This minimizes steroid exposure to the anterior segment and reduces the risk of IOP elevation and cataract formation (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). In a phase 3 trial of suprachoroidal delivery of TA for noninfectious uveitis, the rate of increased IOP was only 11.5%, which is lower than the 25\u0026ndash;43% rates reported with IVi DEX implants for uveitic macular edema. These rates appear lower than those reported with IVi DEX implants for uveitic macular edema (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Additionally, one study found that after a suprachoroidal injection of TA, IOP increased significantly at one month but returned to baseline by three months (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Another study in rabbits showed acute IOP elevation after suprachoroidal injection that was volume-dependent (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). An anterior suprachoroidal polyurethane implant containing dexamethasone effectively prevented endotoxin-induced uveitis in rats without causing significant ocular toxicity (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Although a study in rabbits found that suprachoroidal injection of TA caused volume-dependent acute IOP elevation, the overall risk of corticosteroid-related complications like cataracts seems to be reduced with suprachoroidal delivery compared to other routes.\u003c/p\u003e \u003cp\u003eOur study showed no significant difference in the average IOP between cases treated with SC DEX implant and those treated with IVi DEX implant. However, ocular hypertension developed in one patient in the SC group, compared to two patients with higher levels of ocular hypertension in the IVi group. This difference suggests that the limited steroid exposure to the anterior segment in the SC group might be a factor. Existing studies support the possibility of this theory (\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Nonetheless, more randomized, controlled, prospective studies with larger patient groups and longer follow-ups are needed. While SC CS delivery can transiently increase IOP in some cases, the risk appears lower than IVi or periocular routes, likely due to the preferential delivery to the posterior segment and reduced exposure to the anterior chamber. More research is still needed to fully characterize the safety profile.\u003c/p\u003e \u003cp\u003eIt is known that IVi DEX implantation can cause cataract formation and that the risk increases with repeated injections (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). It has been reported that 12.4% of eyes treated with IVi DEX implants required cataract surgery during follow-ups (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). One limitation of our study is the short follow-up period; cataract progression in patients who underwent SC DEX implants was not assessed. Therefore, more extensive and longer-term studies are needed. However, there have been reports of patients developing rapidly progressing cataracts after IVi treatment, possibly due to lens capsule trauma during injection or wondering of the implant in the vitreous cavity around the lens capsule (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Nevertheless, theoretically, such a risk does not exist in patients undergoing SC treatment.\u003c/p\u003e \u003cp\u003eDifferent substances administered via suprachoroidal injection exhibit varying pharmacokinetic properties, with factors such as viscosity, particle size, and water solubility playing significant roles in these differences. Various biopolymers are biocompatible, effective, and capable of extending the half-life of drugs in the suprachoroidal space (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). There is currently no study in the recent literature concerning the DEX implant.\u003c/p\u003e \u003cp\u003eIn the group treated with SC DEX implantation, the effect of the DEX implant was relatively shorter compared to the IVi therapy group, and more patients in the SC treatment group required retreatment, yet it was not statistically significant. This could be related to the increased clearance of aqueous-soluble substances like DEX when injected into the suprachoroidal space (\u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). The highly vascular nature of the choroid and ciliary body might be responsible for the increased clearance (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Similarly, the IVi DEX implant is less effective in vitrectomized eyes (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eClinical trials have demonstrated a strong safety profile for suprachoroidal and SC implants, with no significant injection-related concerns such as suprachoroidal hemorrhage, endophthalmitis, or retinal and/or choroidal detachment, contributing to a smoother treatment process and potentially faster resolution of the condition (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). In our study, these complications were not observed in cases treated with SC treatment. We encountered no vision-threatening complications intraoperatively or postoperatively. However, all cases exhibited subconjunctival hemorrhage. This was observed at a higher rate compared to the subconjunctival hemorrhage rates (5.4%-16.6%) reported after IVi therapy in various studies (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). This may be related to the injection technique and use of microforceps that require more manipulation compared to IVi therapy.\u003c/p\u003e \u003cp\u003eIn conclusion, the effectiveness of SC and IVi DEX implant applications was similar in our study, with a few exceptions. Therefore, SC DEX implant application can be considered an alternative treatment option, particularly in cases with causes leading to anterior chamber migration, in young patients with high IOP or potential for its increase, and patients with glaucoma or ocular hypertension. Long-term studies and larger series can confirm the effectiveness and safety profile. A special design and drug application method specific to this area would be more appropriate for drug applications showing SC placement. Additionally, anterior segment OCT can be used to demonstrate SC implant placement.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003ePrior publication:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupport:\u0026nbsp;\u003c/strong\u003eThe authors have no sources of funding to declare for this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u003c/strong\u003e None\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCunningham MA, Edelman JL, Kaushal S. Intravitreal steroids for macular edema: the past, the present, and the future. Surv Ophthalmol. 2008;53(2):139\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFung AT, Tran T, Lim LL, Samarawickrama C, Arnold J, Gillies M, et al. Local delivery of corticosteroids in clinical ophthalmology: A review. Clin Exp Ophthalmol. 2020;48(3):366\u0026ndash;401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThorne JE, Sugar EA, Holbrook JT, Burke AE, Altaweel MM, Vitale AT, et al. Periocular Triamcinolone vs. Intravitreal Triamcinolone vs. Intravitreal Dexamethasone Implant for the Treatment of Uveitic Macular Edema: The PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema (POINT) Trial. Ophthalmology. 2019;126(2):283\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEmi K, Pederson JE, Toris CB. Hydrostatic pressure of the suprachoroidal space. Invest Ophthalmol Vis Sci. 1989;30(2):233\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYeh S, Henry CR, Kapik B, Ciulla TA. Triamcinolone Acetonide Suprachoroidal Injectable Suspension for Uveitic Macular Edema: Integrated Analysis of Two Phase 3 Studies. Ophthalmol Ther. 2023;12(1):577\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomas J, Kim L, Albini T, Yeh S. Triamcinolone acetonide injectable suspension for suprachoroidal use in the treatment of macular edema associated with uveitis. Expert Rev Ophthalmol. 2022;17(3):165\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJose-Vieira R, Ferreira A, Meneres P, Sousa-Pinto B, Figueira L. Efficacy and safety of intravitreal and periocular injection of corticosteroids in noninfectious uveitis: a systematic review. Surv Ophthalmol. 2022;67(4):991\u0026ndash;1013.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNawar AE. Effectiveness of Suprachoroidal Injection of Triamcinolone Acetonide in Resistant Diabetic Macular Edema Using a Modified Microneedle. Clin Ophthalmol. 2022;16:3821\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoldstein DA, Do D, Noronha G, Kissner JM, Srivastava SK, Nguyen QD. Suprachoroidal Corticosteroid Administration: A Novel Route for Local Treatment of Noninfectious Uveitis. Transl Vis Sci Technol. 2016;5(6):14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarashi A, Baba M, Abu Ghedda S, Kitaz MN, Zazo A. A combination of suprachoroidal injection of triamcinolone using a custom-made needle and intravitreal Ziv-aflibercept every eight weeks to manage naive/denovo central DME: a single-center retrospective case series. Int J Retina Vitreous. 2024;10(1):30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen M, Li X, Liu J, Han Y, Cheng L. Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model. J Control Release. 2015;203:109\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCiulla TY, S. Microinjection via the suprachoroidal space: a review of a novel mode of administration. Am J Manag Care. 2022;28(13 Suppl):S243-S52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi ST, Wang XN, Du XH, Wu Q. Comparison of spectral-domain optical coherence tomography for intra-retinal layers thickness measurements between healthy and diabetic eyes among Chinese adults. PLoS One. 2017;12(5):e0177515.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRock D, Bartz-Schmidt KU, Rock T. Risk factors for and management of anterior chamber intravitreal dexamethasone implant migration. BMC Ophthalmol. 2019;19(1):120.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsoutsanis P, Kapantais D. Anterior migration of Ozurdex implant: a review on risk factors, complications, and management. Int J Retina Vitreous. 2023;9(1):74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZafar A, Aslanides IM, Selimis V, Tsoulnaras KI, Tabibian D, Kymionis GD. Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty. Case Rep Ophthalmol. 2018;9(1):143\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaller JA, Bandello F, Belfort R, Jr., Blumenkranz MS, Gillies M, Heier J, et al. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology. 2011;118(12):2453\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChin EK, Almeida DRP, Velez G, Xu K, Peraire M, Corbella M, et al. Ocular Hypertension after Intravitreal Dexamethasone (Ozurdex) Sustained-Release Implant. Retina. 2017;37(7):1345\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMateo C, Alkabes M, Bures-Jelstrup A. Scleral fixation of dexamethasone intravitreal implant (OZURDEX(R)) in a case of angle-supported lens implantation. Int Ophthalmol. 2014;34(3):661\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKapoor KG, Shultz RW, Iezzi R. Vitreous pillow for sustained-release intravitreous drug delivery implants. Ophthalmic Surg Lasers Imaging Retina. 2013;44(2):181\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhor HG, Lott PW, Wan Ab Kadir AJ, Singh S, Iqbal T. Review of Risk Factors and Complications of Anterior Migration of Ozurdex Implant: Lessons Learnt from the Previous Reports. J Ocul Pharmacol Ther. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFung S, Syed YY. Suprachoroidal Space Triamcinolone Acetonide: A Review in Uveitic Macular Edema. Drugs. 2022;82(13):1403\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarbosa Saliba J, Vieira L, Fernandes-Cunha GM, Rodrigues Da Silva G, Lig\u0026oacute;rio Fialho S, Silva-Cunha A, et al. Anti-Inflammatory Effect of Dexamethasone Controlled Released From Anterior Suprachoroidal Polyurethane Implants on Endotoxin-Induced Uveitis in Rats. Investigative Ophthalmology \u0026amp; Visual Science. 2016;57(4):1671\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIovino C, Mastropasqua R, Lupidi M, Bacherini D, Pellegrini M, Bernabei F, et al. Intravitreal Dexamethasone Implant as a Sustained Release Drug Delivery Device for the Treatment of Ocular Diseases: A Comprehensive Review of the Literature. Pharmaceutics. 2020;12(8).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosenblatt A, Udaondo P, Cunha-Vaz J, Sivaprasad S, Bandello F, Lanzetta P, et al. A Collaborative Retrospective Study on the Efficacy and Safety of Intravitreal Dexamethasone Implant (Ozurdex) in Patients with Diabetic Macular Edema: The European DME Registry Study. Ophthalmology. 2020;127(3):377\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee JH, Park JY, Kim JS, Hwang JH. Rapid progression of cataract to mature stage after intravitreal dexamethasone implant injection: a case report. BMC Ophthalmol. 2019;19(1):1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaftali Ben Haim L, Moisseiev E. Drug Delivery via the Suprachoroidal Space for the Treatment of Retinal Diseases. Pharmaceutics. 2021;13(7).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang M, Liu W, Lu Q, Zeng H, Liu S, Yue Y, et al. Pharmacokinetic comparison of ketorolac after intracameral, intravitreal, and suprachoroidal administration in rabbits. Retina. 2012;32(10):2158\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlsen TW, Feng X, Wabner K, Csaky K, Pambuccian S, Cameron JD. Pharmacokinetics of pars plana intravitreal injections versus microcannula suprachoroidal injections of bevacizumab in a porcine model. Invest Ophthalmol Vis Sci. 2011;52(7):4749\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbarca EM, Salmon JH, Gilger BC. Effect of choroidal perfusion on ocular tissue distribution after intravitreal or suprachoroidal injection in an arterially perfused ex vivo pig eye model. J Ocul Pharmacol Ther. 2013;29(8):715\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCevik SG, Yilmaz S, Cevik MT, Akalp FD, Avci R. Comparison of the Effect of Intravitreal Dexamethasone Implant in Vitrectomized and Nonvitrectomized Eyes for the Treatment of Diabetic Macular Edema. J Ophthalmol. 2018;2018:1757494.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatel SR, Lin AS, Edelhauser HF, Prausnitz MR. Suprachoroidal drug delivery to the back of the eye using hollow microneedles. Pharm Res. 2011;28(1):166\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaincher SS, Gottlieb C. Ozurdex (dexamethasone intravitreal implant) for the treatment of intermediate, posterior, and panuveitis: a systematic review of the current evidence. J Ophthalmic Inflamm Infect. 2020;10(1):1.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4462347/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4462347/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo investigate the efficacy and safety of dexamethasone implantation (DEXI) in the supraciliary (SC) region, a potential new implantation site, compared to intravitreal (IVi) application.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study enrolled 39 eyes of 38 patients with macular edema who received DEXI between January and August 2023. Patients were randomized into SC and IVi treatment groups. All patients were followed up for 3 months after DEXI. The maximum retinal thickness (MRT) and central retinal thickness change (ΔCRT), intraocular pressure (IOP), and visual acuity (VA) were assessed preoperatively and postoperatively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe SC treatment group showed a significant reduction in MRT at 1st and 3rd month visits (p\u0026thinsp;=\u0026thinsp;0.0002, p\u0026thinsp;=\u0026thinsp;0.0002). IVi group showed a significant reduction at all postoperative visits (p\u0026thinsp;=\u0026thinsp;0.0002, p\u0026thinsp;=\u0026thinsp;0.0004, p\u0026thinsp;=\u0026thinsp;0.0003). ΔCRT showed no significant difference between SC and IVi groups at any visit (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). No significant IOP changes were observed (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). No ocular hypertony or hypotony cases on day one post-SC DEXI. VA improved significantly in the SC group compared to the IVi group in the first week (p\u0026thinsp;=\u0026thinsp;0.014). Subconjunctival hemorrhage was observed in all patients after IVi. No perioperative or postoperative complications were observed in any patients in either group other than subconjunctival hemorrhage.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSC DEXI appears to be a suitable alternative for managing macular edema. It offers comparable effectiveness to IVi administration with potentially fewer complications. Further larger-scale research is needed to validate its long-term safety and efficacy. Anterior segment optical coherence tomography can demonstrate SC DEXI.\u003c/p\u003e","manuscriptTitle":"Efficacy and Safety of Supraciliary Dexamethasone Implantation in Patients with Macular Edema: Preliminary and Comparative Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-27 11:33:17","doi":"10.21203/rs.3.rs-4462347/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2024-08-29T08:41:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-08-21T02:54:57+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-08-07T10:41:27+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2024-07-24T06:51:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-18T12:04:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-23T11:56:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Eye","date":"2024-05-22T16:49:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"19bb8e16-2f4b-4ca1-a318-15fe632e70ac","owner":[],"postedDate":"August 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":35048686,"name":"Health sciences/Diseases/Eye diseases/Retinal diseases"},{"id":35048687,"name":"Health sciences/Medical research/Outcomes research"}],"tags":[],"updatedAt":"2025-01-08T08:07:49+00:00","versionOfRecord":{"articleIdentity":"rs-4462347","link":"https://doi.org/10.1038/s41433-024-03570-8","journal":{"identity":"eye","isVorOnly":false,"title":"Eye"},"publishedOn":"2025-01-07 05:00:00","publishedOnDateReadable":"January 7th, 2025"},"versionCreatedAt":"2024-08-27 11:33:17","video":"","vorDoi":"10.1038/s41433-024-03570-8","vorDoiUrl":"https://doi.org/10.1038/s41433-024-03570-8","workflowStages":[]},"version":"v1","identity":"rs-4462347","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4462347","identity":"rs-4462347","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}